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['Pentobarbital (PB) is widely used as a short-term sedative and anticonvulsive drug with a side-effect of relaxing muscle tone. We investigated block of nicotinic acetylcholine receptor (nAChR) channel currents by PB using the patch-clamp technique in combination with an ultrafast system for solution exchange. As a preparation, recombinant rat adult-type nAChR channels transiently expressed in HEK293 cells were used. Appli-cation of 1 mM acetylcholine to small cells or outside-out patches showed a transient current with fast activation and desensitization kinetics. Adding PB to the acetylcholine-containing solution resulted in a decrease of the time constant of current decay and of the peak current amplitude starting at concentrations >0.01 mM PB. Preincubation of nAChR channels with PB led to a decrease of the peak current amplitude without alteration of activation and desensitization kinetics caused by competitive block of nAChR channels. In conclusion, similar to the effect of d-Tubocurarine, block of nAChR channel currents by PB can be explained by a combination of open-channel and competitive block.'] |
['Porphyromonas gingivalis, a periodontal pathogen, has inter-strain variability in virulence. The aim of this study was to determine the contribution of the cell invasion ability and proteolytic activity of P. gingivalis to its virulence in a murine model of periodontitis.', 'Three clinical isolates, including KUMC-P1 (P1: low cell invasion ability and low proteolytic activity), KUMC-P4 (P4: low cell invasion ability and high proteolytic activity), and KUMC-P8 (P8: high cell invasion ability and low proteolytic activity), were orally administered into mice. Alveolar bone loss and bacterial invasion of gingival tissues were then measured. Additionally, the effects of the three strains on transepithelial electrical resistance and the levels of tight junction proteins in gingival epithelial cells were evaluated in vitro.', 'The alveolar bone loss induced by the three strains was in the sequence P4 > P8 > P1, and the difference between P8 and P1 was not significant. The amounts of P. gingivalis detected within the gingival tissues were increased by all three strains compared with the sham group, and the bacterial level was positively correlated with alveolar bone loss. In vitro, P4 had a greater effect than the other strains on epithelial barrier disruption, as evidenced by the reduced levels of tight junction proteins and transepithelial electrical resistance.'] |
['Gallstone composition has changed over the past decades in East Asian countries with a prominent increase in the prevalence of cholesterol gallstones. This trend is possibly due to the westernization of dietary habits. This study was undertaken to delineate the changing trends in gallstone composition in Japan since the 1920s and to assess dietary influences on gallstone composition.', 'Between 1971 and 1999, 1264 Japanese patients underwent cholecystectomy for gallstone disease in Niigata University Medical Hospital. Gallbladder stones retrieved from each patient were classified into four types by gross inspection of the cut surface and infrared spectroscopy: cholesterol stone, black pigment stone, brown pigment stone, and other stones. The literature was reviewed to find both changing trends in gallstone composition before 1971 and dietary changes since 1950 in Japan.', 'The prevalence of cholesterol gallstones among Japanese patients undergoing cholecystectomy increased steadily until the 1970s and declined thereafter (P<0.001). Among dietary factors, only per capita daily total calorie intake strongly correlated with cholesterol gallstone prevalence (r=0.93, P=0.02).'] |
['Tubulointerstitial fibrosis is an important component of diabetic nephropathy, which is characterized by increased expression of interstitial extracellular matrix components and aberrant expression of the basement membrane component collagen type IV. The present study examined the effect of high ambient glucose and transforming growth factor-beta1 (TGF-beta1) on collagen secretion by human renal fibroblasts and proximal tubular epithelial cells (PTECs).', 'Human renal fibroblasts (TK173) and PTECs (HK2) were used to examine the effects of high glucose (25 mM d-glucose) and TGF-beta1 (1 ng/ml) on collagen type I, III and IV secretion compared with control medium (5.5 mM glucose). Matrix components were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR).', 'Renal fibroblasts are the main producers of the interstitial components collagen type I and type III, while collagen type IV was secreted predominantly by PTECs. However, renal fibroblasts were also able to secrete collagen type IV. Secretion of collagen type IV by fibroblasts was increased upon stimulation with TGF-beta1, reaching levels comparable with those secreted by TGF-beta1-induced PTECs. Moreover, high glucose stimulated increased collagen type IV secretion. Importantly, this could not be attenuated by neutralizing pan-specific anti-TGF-beta antibodies.'] |
['FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease.', 'Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice.', 'Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation.'] |
['Calcium ions are highly versatile spacial and temporal intracellular signals of non-excitable cells and have an important impact on nearly every aspect of cellular life controlling cell growth, metabolism, fluid secretion, information processing, transcription, apoptosis, and motility. Neurons and glia respond to stimuli, including neurotransmitters, neuromodulators, and hormones, which increase the intracellular calcium concentration. The function of intracellular calcium in gliomas is unknown. Lots of daily used drugs may act via receptors that can be linked to the intracellular calcium system and therefore could influence glioma biology.', 'Glioma cells were loaded with the calcium ion sensitive dye Fura 2-AM. Subsequently, cells were stimulated with 25 different medical drugs for 30 s. The increase of free intracellular calcium ions was measured and calculated by a microscope-camera-computer-unit.', 'Except for the buffer solution HEPES that served as negative control and for the cortisol derivative dexamethasone, all other 24 tested drugs induced a rise of intracellular calcium ions. The cellular calcium responses were classified into seven functional groups. The tested substances activated several types of calcium channels and receptors.'] |
['The appropriate management of gallstones in patients undergoing renal transplantation is controversial. Screening for gallstones and subsequent prophylactic cholecystectomy has been recommended by some authors for kidney transplant candidates. Our program does not practice routine pretransplant screening for gallstones, and we reviewed our data to determine the outcome of our management approach.', 'We reviewed the records of the 1,364 currently followed patients who have undergone kidney transplant at our institution since 1985 in order to evaluate the morbidity and mortality of biliary disease in the post-transplant period. We attempted to contact all patients by telephone or mail survey for the presence of biliary tract disease or operations.', 'Six hundred and sixty-two patients were fully evaluated. Fifty-two (7.85%) required cholecystectomy for stone disease. Seven patients underwent incidental cholecystectomy during other operations, 2 patients developed acalculus cholecystitis, and 14 patients with asymptomatic cholelithiasis are being followed up. Surgical indications included 38 biliary colic, 9 acute cholcystitis, 3 gallstone pancreatitis, and 2 patients who were asymptomatic. Fifty-two patients underwent 30 laparoscopic cholecystectomies, 20 open cholecystectomies, and 2 conversions. Surgery occurred from 7 days to 9.6 years following transplantation. Overall, the median hospital stay (no postoperative stay) was 4 days (range 1 to 57). Patients undergoing laparoscopy had a median stay of 2 days compared with 7 days for those undergoing an open procedure. Complications were seen in 6 patients (11.5%) with no morbidity and no graft loss. The 1-, 2-, and 5-year graft survival was 98%, 96%, and 85%, respectively, in patients undergoing cholecystectomy.'] |
['It remains unclear whether exercise-induced muscle damage (EIMD) increases heat strain during subsequent exercise heat stress, which in turn may increase the risk of exertional heat illness. We examined heat strain during exercise heat stress 30 min after EIMD to coincide with increases in circulating pyrogens (e.g., interleukin-6 [IL-6]) and 24 h after EIMD to coincide with the delayed muscle inflammatory response when a higher rate of metabolic energy expenditure (M˙) and thus decreased economy might also increase heat strain.', 'Thirteen non-heat-acclimated males (mean ± SD, age = 20 ± 2 yr) performed exercise heat stress tests (running for 40 min at 65% V˙O2max in 33°C, 50% humidity) 30 min (HS1) and 24 h (HS2) after treatment, involving running for 60 min at 65% V˙O2max on either -10% gradient (EIMD) or +1% gradient (CON) in a crossover design. Rectal (Tre) and skin (Tsk) temperature, local sweating rate, and M˙ were measured throughout HS tests.', 'Compared with CON, EIMD evoked higher circulating IL-6 pre-HS1 (P < 0.01) and greater plasma creatine kinase and muscle soreness pre-HS2 (P < 0.01). The ΔTre was greater after EIMD than CON during HS1 (0.35°C, 95% confidence interval = 0.11°C-0.58°C, P < 0.01) and HS2 (0.17°C, 95% confidence interval = 0.07°C-0.28°C, P < 0.01). M˙ was higher on EIMD throughout HS1 and HS2 (P < 0.001). Thermoeffector responses (Tsk, sweating rate) were not altered by EIMD. Thermal sensation and RPE were higher on EIMD after 25 min during HS1 (P < 0.05). The final Tre during HS1 correlated with the pre-HS1 circulating IL-6 concentration (r = 0.67).'] |
['Entoprocta (Kamptozoa) is an enigmatic, acoelomate, tentacle-bearing phylum with indirect development, either via a swimming- or a creeping-type larva and still debated phylogenetic position within Lophotrochozoa. Recent morphological and neuro-anatomical studies on the creeping-type larva support a close relationship of Entoprocta and Mollusca, with a number of shared apomorphies including a tetraneurous nervous system and a complex serotonin-expressing apical organ. However, many morphological traits of entoproct larvae, in particular of the putative basal creeping-type larva, remain elusive.', 'Applying fluorescent markers and 3D modeling, we found that this larval type has the most complex musculature hitherto described for any lophotrochozoan larva. The muscle systems identified include numerous novel and most likely creeping-type larva-specific structures such as frontal organ retractors, several other muscle fibers originating from the frontal organ, and longitudinal prototroch muscles. Interestingly, we found distinct muscle sets that are also present in several mollusks. These include paired sets of dorso-ventral muscles that intercross ventrally above the foot sole and a paired enrolling muscle that is distinct from the musculature of the body wall.'] |
["Recent histopathological studies have shown that neurodegenerative processes in Alzheimer's and Parkinson's Disease develop along neuronal networks and that hallmarks could propagate trans-synaptically through neuronal pathways. The underlying molecular mechanisms are still unknown, and investigations have been impeded by the complexity of brain connectivity and the need for experimental models allowing a fine manipulation of the local microenvironment at the subcellular level.", 'In this study, we have grown primary cortical mouse neurons in microfluidic (μFD) devices to separate soma from axonal projections in fluidically isolated microenvironments, and applied β-amyloid (Aβ) peptides locally to the different cellular compartments. We observed that Aβ application to the somato-dendritic compartment triggers a "dying-back" process, involving caspase and NAD(+) signalling pathways, whereas exposure of the axonal/distal compartment to Aβ deposits did not induce axonal degeneration. In contrast, co-treatment with somatic sub-toxic glutamate and axonal Aβ peptide triggered axonal degeneration. To study the consequences of such subcellular/local Aβ stress at the network level we developed new μFD multi-chamber devices containing funnel-shaped micro-channels which force unidirectional axon growth and used them to recreate in vitro an oriented cortico-hippocampal pathway. Aβ application to the cortical somato-dendritic chamber leads to a rapid cortical pre-synaptic loss. This happens concomitantly with a post-synaptic hippocampal tau-phosphorylation which could be prevented by the NMDA-receptor antagonist, MK-801, before any sign of axonal and somato-dendritic cortical alteration.'] |
['Taking the family history helps the doctor in estimating the probability of disease in individual patients. However, significant barriers to obtaining adequate family history information remain. Tools overcoming these barriers might support family physicians in this task.', 'To review systematically the characteristics of existing family history tools and discuss their potential use in primary care.', 'Studies were identified through searches of PubMed, Embase and Cinahl from 1 January 2002 until May 2012. All authors independently screened studies and included original research papers on family history tools of which assessment had been performed or was planned. We reviewed diseases for which family history information was collected, study setting, tool design, type of family history collection, presence of risk-assessment and recommendations for management, and assessment (categorized as either validity or benefit).', 'Eighteen family history tools were identified: six generic, two on cardiovascular disease and ten on cancer. The six generic tools were partly tested in primary care (3x), are mainly computerized (4x), rarely include management recommendations for the physician (1x) and were partly validated against a reference standard (genetic counsellor) (3x, plus one planned). Of the five specific tools studied in primary care, none was validated. No family history tool allows electronic transfer of family history information to electronic medical record systems. Use of a family history tool improved identification of patients at risk for disease.'] |
['This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery.', 'Blood eosinophil numbers and serum interleukin-5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed.', 'Blood eosinophil numbers and serum interleukin-5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 ± 26.1 vs 443.9 ± 76.6 cells/μl, p < 0.05), and decreased significantly after surgery (825.7 ± 26.1 vs 76.7 ± 25.8 cells/μl, p < 0.05).'] |
['Sequential events of endometrial tumorigenesis can be studied by comparison of genetic lesions seen in normal, premalignant, and malignant tissues. The distribution of k-ras mutations in microsatellite stable and unstable premalignant lesions was studied to determine whether this gene is implicated in both tumorigenic pathways.', 'K-ras mutations were analysed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing in matched endometrial normal, premalignant (atypical hyperplasias), and adenocarcinoma tissues from individual patients. Identification of precancers solely by their appearance as atypical endometrial hyperplasias is very subjective; therefore, in addition to histopathological assessment, we performed molecular testing (non-random X inactivation or clonal altered microsatellites) for an expected feature of precancers--that is, monoclonality.', 'Equivalent K-ras mutation frequencies were seen in microsatellite stable (six of 33) and unstable (three of 23) cancers. In both types, K-ras mutation in monoclonal precancers usually corresponded to a change from normal to an equivocal (two of 12) or hyperplastic (10 of 12) histology. Divergent K-ras genotypes among multiple neoplastic tissues of individual patients (two of six patients) are exceptions explained either by multicentric premalignant disease, or acquisition of K-ras mutation late in neoplastic progression.'] |
['Capsular contracture is the most common side effect of breast implant insertion and the problem that breast surgeons seek to avoid the most. Previous animal studies have proved that an antiadhesive barrier solution (AABS) prevents peri-implant capsule formation. In this study, the authors sought to explore the effect that Guardix-SG(®), an AABS that can encapsulate implants in the form of a gel, can have on capsular contracture.', "This study used 12 female New Zealand white rabbits weighing 2.5-3 kg. Implants were inserted into the subpanniculus carnosus plane through an incision in the bilateral midback area. Once the implant was inserted, 3 g of Guardix-SG(®) and normal saline were instilled into the left and right sides, respectively. The rabbits were killed 6 months after the procedure. The intracapsular pressure was measured using tonometry with a 38.2-g circular glass piece, and capsular thickness was measured by dyeing the biopsy specimen with hematoxylin and eosin and Masson's trichrome stain. The myofibroblasts were quantitatively analyzed through monoclonal anti-alpha smooth muscle actin antibody immunohistochemistry staining.", 'The intracapsular pressure in the control group (4.51 ± 0.98 mmHg) was significantly higher (p = 0.002) than in the study group (3.51 ± 0.4 mmHg). The average capsular thickness was significantly greater in the control group (0.33 ± 0.15 mm; p = 0.015). In the analysis, the interrelation between capsular thickness and intracapsular pressure was insignificant in both groups, as was the number of myofibroblasts in both groups (p = 0.582).'] |
['Temperature increase, oxidative stress, and inflammatory reactions after endurance exercise were expected to stimulate the synthesis of heat shock proteins (HSP) in peripheral blood leukocytes. Furthermore, it was of interest whether regular endurance training influences HSP expression.', 'The expression of HSP27, HSP60, HSP70, constitutive HSC70, and HSP90 in the cytoplasma and surface of lymphocytes, monocytes, and granulocytes of 12 trained athletes was analyzed by flow cytometry before and after (0, 3, and 24 h) a half marathon. Twelve untrained persons at rest were included as control.', 'After the race, there was a significantly greater percentage of leukocytes expressing cytoplasmic HSP27, HSP60, and HSP70 (P < 0.01), whereas HSC70 and HSP90 remained unchanged. The fluorescence intensity increased significantly in monocytes for HSP27 (0 and 3 h) and HSP70 (0, 3, and 24 h) and in granulocytes, only 24 h postexercise for HSP70. The percent values of trained athletes at rest were significantly lower compared with untrained persons (P < 0,01).'] |
['To identify patients with severe extra-articular RA (ExRA) in an early RA cohort and to investigate potential risk factors.', 'From a cohort (n = 2900) in a structured programme for newly diagnosed RA, 40 patients with severe ExRA after RA diagnosis were identified. Disease activity score (DAS28), functional disability (HAQ) and treatment with glucocorticosteroids (GCs) and DMARDs were assessed regularly. Cases with ExRA were compared with RA controls from the same cohort matched for age, sex and duration of symptoms at inclusion.', 'Patients who developed severe ExRA were more often current smokers and had higher mean DAS28, HAQ and CRP at baseline. Among the ExRA cases, 93% had a positive RF vs 59% of the controls. The area under the curve (AUC) of DAS28 odds ratio (OR) 7.79/S.D.; 95% CI 3.04, 19.95, HAQ (OR 2.30/S.D.; 95% CI 1.37, 3.88) and CRP (OR 3.05/S.D.; 95% CI 1.77, 5.26) during the first 2 years of follow-up were strong predictors of subsequent development of ExRA. The most frequently used DMARDs were MTX and SSZ, with similar frequency and duration of treatment among cases and controls. The cases were treated with GC before onset of ExRA more frequently (73 vs 47%; P = 0.005) and with higher mean cumulative dose (3667 vs 2037 mg, P = 0.015).'] |
['Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTex project (GBM and Experimental Therapeutics) a GBM patient-derived cell line (GBM-PDCL) library. A multi-omic approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors.', 'Single nucleotide polymorphism array, expression arrays, exome sequencing, and RNA sequencing were used to measure and compare the molecular landscapes of 20 samples representing 10 human GBM tumors and paired GBM-PDCLs.', 'Copy number variations were similar for a median of 85% of the genome and for 59% of the major focal events. Somatic point mutations were similar in a median of 41%. Mutations in GBM driver and "druggable" genes were maintained in 67% of events. Mutations that were not conserved in the PDCL were mainly low allelic fraction and/or non-driver mutations. Based on RNA expression profiling, PDCLs cluster closely to their parental tumor with overexpression of pathways associated with cancer progression in PDCL.'] |
['We have previously demonstrated in a coculture model that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) morphology. This study was performed to test the hypothesis that ECs inhibit transforming growth factor-beta 2 (TGF-beta 1) activation through the release of plasminogen activator inhibitor (PAI-1).', 'Bovine SMCs were cultured on a thin, semipermeable membrane, either alone or opposite ECs in coculture (SMC/EC). Conditioned media and cell lysates at 1, 5, and 21 days were assayed for TGF-beta 1 and PAI-1 by enzyme-linked immunoabsorbent assay. Cell proliferation rates, protein, and DNA content were measured and compared with SMC morphology.', 'Activation of TGF-beta 1 was significantly decreased (1.2% versus 18.9% active TGF-beta 1 p < 0.05) and PAI-1 was increased (659 pg/ml versus 343 pg/ml p < 0.05) in SMC/EC medium on day 1, compared with the medium of SMC alone. Significantly higher levels of PAI-1 were measured in cell lysates of cocultured ECs (128 pg/micrograms DNA) than in cocultured SMCs (5.8 pg/micrograms DNA, p < 0.05). SMC/EC coculture prevented the SMC hill-and-valley growth morphology seen in SMCs cultured alone.'] |
['Older adults and patients with dementia often have disrupted circadian activity rhythms (CARs). Disrupted CARs are associated with health declines and could affect cognitive aging. We hypothesized that among older women, weaker CARs would be associated with poorer cognitive function 5 y later.', 'Prospective observational study.', 'Three US clinical sites.', 'There were 1,287 community-dwelling older women (82.8 ± 3.1 y) participating in an ongoing prospective study who were free of dementia at the baseline visit.', 'Baseline actigraphy was used to determine CAR measures (amplitude, mesor, and rhythm robustness, analyzed as quartiles; acrophase analyzed by peak activity time < 13:34 and > 15:51). Five years later, cognitive performance was assessed with the Modified Mini-Mental Status Examination (3MS), California Verbal Learning Task (CVLT), digit span, Trail Making Test B (Trails B), categorical fluency, and letter fluency. We compared cognitive performance with CARs using analyses of covariance adjusted for a number of health factors and comorbidities. Women in the lowest quartile for CAR amplitude performed worse on Trails B and categorical fluency compared to women in the highest quartile (group difference (d) = 30.42 sec, d = -1.01 words respectively, P < 0.05). Women in the lowest quartile for mesor performed worse on categorical fluency (d = -0.86 words, P < 0.05). Women with a later acrophase performed worse on categorical fluency (d = -0.69 words, P < 0.05). Controlling for baseline Mini-Mental State Examination and sleep factors had little effect on our results.'] |
['Obesity is a risk factor for cardiovascular disease (CVD) and is also associated with an increased risk of death in subjects without CVD. However, in heart failure (HF), elevated body mass index (BMI) has been shown to be associated with better prognosis, but it is unknown whether this is the case in unselected HF patients encountered in routine clinical practice in Japan.', 'The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed for 2.1 years. Study cohort (n=2,488) was classified into 3 groups according to baseline BMI: <20.3kg/m(2) (n=829), 20.3-23.49kg/m(2) (n=832), and ≥23.5kg/m(2) (n=827). The mean BMI was 22.3±4.1kg/m(2). Patients with higher BMI had lower rates of all-cause death, cardiac death, and rehospitalization because of worsening HF. After multivariable adjustment, the risk for all-cause death and cardiac death significantly increased with decreased BMI levels compared with patients with BMI ≥23.5kg/m(2). However, BMI levels were not associated with rehospitalization for worsening HF.'] |
['Bcl-2 protects cells from apoptosis and provides a survival advantage to cells over-expressing this oncogene. In addition, over expression of Bcl-2 renders cell resistant to radiation therapy. Recently, dichloroacetate (DCA) was proven to potentiate the apoptotic machinery by interacting with Bcl-2. In this study, we investigated whether treating human prostate cancer cells with DCA could modulate Bcl-2 expression and if the modulation in Bcl-2 expression could render the Bcl-2 over expressing cells more susceptible to cytotoxicity effects of radiation.', 'PC-3-Bcl-2 and PC-3-Neo human prostate cancer cells treated with DCA in addition to irradiation were analyzed in vitro for changes in proliferation, clonogenic survival, apoptosis, cell cycle phase distribution, mitochondrial membrane potential, and expression of Bcl-2, Bcl-xL, Bax, or Bak proteins.', "DCA alone produced significant cytotoxic effects and was associated with G1 cell cycle arrest. Furthermore, DCA was associated with an increased rate of apoptosis. The combination of DCA with irradiation sensitized both cell lines to radiation's killing effects. Treatment of PC-3-Bcl-2 or PC-3-Neo with DCA and irradiation resulted in marked changes in various members of the Bcl-2 family. In addition, DCA therapy resulted in a significant change in mitochondria membrane potential, thus supporting the notion that DCAs effect is on the mitochondria."] |
['Animal studies and anecdotal human case reports have indicated that the subthalamic nucleus (STN) may be a site of anticonvulsant action.', 'We tested the hypothesis that continuous electrical stimulation of the STN inhibits seizures acutely. We determined the effects of three stimulation frequencies, 130 Hz, 260 Hz, and 800 Hz, on generalized clonic and tonic-clonic flurothyl seizures. Adult male rats were implanted with concentric bipolar stimulating electrodes in the STN bilaterally. After recovery, rats underwent flurothyl seizures to compare the effects of each stimulation frequency on seizure threshold. Rats were tested 4 times, twice in the stimulated condition, and twice in the unstimulated condition. The order of trials was random, except that stimulation trials alternated with control trials. Flurothyl seizure thresholds under each stimulation condition were compared with control values from the same animal.', 'Bilateral stimulation of the STN at 130 Hz produced a significant increase in the seizure threshold for clonic flurothyl seizures, whereas stimulation at 260 Hz did not appear to have any effect on seizures. STN stimulation at 800 Hz significantly lowered seizure threshold for tonic-clonic seizures.'] |
['The nature of the inflammatory change within ruptured AAA has not been extensively reported. The aim of this study was to compare the inflammatory response in non-ruptured and ruptured aneurysms with emphasis on the site of rupture.', 'Non-rupture site biopsies were taken from the anterior aneurysm sac of non-ruptured (n=31) and ruptured AAA (n=20). In 12 ruptured AAA, a further biopsy was taken from the rupture site. Enzyme-linked immunosorbent assay was used to quantify IL-6, IL-1beta and TNF-alpha. Quantitative immunohistochemistry was undertaken for generic lymphocytes, T-cells, and B-cells.', 'Comparing biopsies in non-ruptured AAA versus a non-rupture site biopsy from ruptured AAA; there was no significant difference in IL-6, IL-1beta, TNF-alpha, generic lymphocytes, T-cell or B-cell content. Comparing ruptured AAA--non-rupture site with rupture site; IL-6 and TNF-alpha were unchanged. By contrast IL-1beta and lymphocytes were lower at the rupture site compared to the non-rupture site (IL-1beta 1.39 ng/mg [0.97-2.29] vs. 1.92 ng/mg [1.46-2.57], p=0.027; generic lymphocytes 2.89% [0.51-5.51] vs. 4.73% [2.27-12.40], p=0.018; T-cells 0.28% [0.04-1.18] vs. 0.82% [0.40-1.36], p=0.027; B-cells 0.16% [0.04-1.14] vs. 1.30% [0.32-5.40], p=0.021).'] |
['Because loss of Nkx2-8 increases lung cancer in the mouse, we studied suppressive mechanisms in human lung cancer.', 'NKX2-8 is located within 14q13.3, adjacent to its close relative TTF1/NKX2-1. We first analyzed LOH of 14q13.3 in forty-five matched human lung cancer and control specimens. DNA from tumors with LOH was then analyzed with high-density single-nucleotide polymorphism (SNP) arrays. For correlation with this genetic analysis, we quantified expression of Nkx2-8 and TTF1 mRNA in tumors. Finally, suppressive function of Nkx2-8 was assessed via colony formation assays in five lung cancer cell lines.', 'Thirteen of forty-five (29%) tumors had LOH. In six tumors, most adenocarcinomas, LOH was caused by gene amplification. The 0.8-Mb common region of amplification included MBIP, SFTA, TTF1, NKX2-8, and PAX9. In 4 squamous or adenosquamous cancers, LOH was caused by deletion. In three other tumors, LOH resulted from whole chromosome mechanisms (14(-), 14(+), or aneuploidy). The 1.2-Mb common region of deletion included MBIP, SFTA, TTF1, NKX2-8, PAX9, SLC25A21, and MIPOL1. Most tumors had low expression of Nkx2-8. Nevertheless, sequencing did not show NKX2-8 mutations that could explain the low expression. TTF1 overexpression, in contrast, was common and usually independent of Nkx2-8 expression. Finally, stable transfection of Nkx2-8 selectively inhibited growth of H522 lung cancer cells.'] |
['Previous studies have suggested that in vivo Th2 lymphocyte activation is related to increased soluble CD30 (sCD30) plasma levels. As various hormones (dehydroepiandrosterone, glucocorticoids, progesterone) can regulate the Th1/Th2 balance, and because growth hormone (GH) enhances lymphocyte function, we measured sCD30 plasma levels, before and after treatment with recombinant human GH (rhGH), in children with growth failure due to chronic renal failure (CRF) or to isolated GH deficiency in order to evaluate the potential effects of rhGH treatment on Th1/Th2 balance.', 'sCD30 plasma levels were determined by ELISA assay in 30 children with CRF (mean age 10.7+/-3.7 years), in five children with isolated GH deficiency (mean age 11.4+/-2.6 years), and in 10 normal controls (mean age 10.1+/-3.5 years).', 'sCD30 levels were higher in the 30 children with CRF than in the 10 controls (179.8+/-79.4 vs 11.3+/-10.9 U/ml, P<0.001) exhibiting an inverse correlation with glomerular filtration rate (GFR) (r=-0.7860, P<0.001). In 11 children with CRF, after 19.9+/-16.7 months of rhGH treatment, a decrease of sCD30 plasma level (170+/-50 vs 134+/-49 U/ml, P<0.01) was observed. The five children with primary GH deficiency had higher sCD30 plasma level than controls (mean 147+/-105 vs 11+/-10 U/ml, P<0.004) and sCD30 plasma levels decreased to 95.2+/-109.6 U/ml after rhGH treatment.'] |
['The use of tongue ties in racing is common, yet there are few data to support their efficacy. In order to make appropriate recommendations for clinical practice and policy on tongue ties, data documenting their effect on upper airway structure are necessary.', 'To determine the effect of a tongue tie on the resting laryngohyoid position of the standing horse.', 'Experimental study.', 'Twelve normal Standardbred horses were subjected to ultrasonographic measures of laryngohyoid position during 3 phases of tack application: Phase I--halter and lead; Phase II--bit, bridle, harness and check applied; and Phase III--as in Phase II but with the tongue tie added.', 'Compared to Phase I, during Phase III with the application of a tongue tie a significant difference between lingual process position was noted both rostrally and caudally (P<0.001 and P<0.001), such that the tongue tie resulted in an increase in lingual process depth. The tongue tie in Phase III resulted in a decrease in depth of the thyroid cartilage and basihyoid bone compared to the Phase I location (P = 0.007 and P = 0.0047).'] |
['Direct microscopy, anaerobic culture and DNA-DNA hybridization have previously demonstrated an association between microorganisms and osteoradionecrosis (ORN). The purpose of our study was to use culture independent molecular techniques to detect bacteria in necrotic bone lesions of the mandible after radiation therapy.', 'Bacterial DNA was extracted from eight deep medullar specimens from resected mandibles (six cases), including one patient with relapse. 16S rRNA genes were PCR amplified, cloned, transformed into Escherichia coli and sequenced to determine species identity and closest relatives.', 'From the analysis of 438 clones, 59 predominant species were detected, 27% of which have not been cultivated. The predominant species detected from radionecrotic mandibles were Campylobacter gracilis, Streptococcus intermedius, Peptostreptococcus sp. oral clone FG014, uncultured bacterium clone RL178, Fusobacterium nucleatum, and Prevotella spp. The study demonstrated intersubject variability of the bacteria present in ORN. In contrast to the diverse bacterial profile detected in primary infection, only a few members of the oral indigenous flora were identified from the relapse case.'] |
['Although new treatments for rheumatoid arthritis (RA) are extremely effective in preventing disease progression, rates of total knee replacement (TKR) continue to rise. The ongoing need for TKR is problematic, especially as functional outcomes in patients with RA have been reported to be worse than in patients with osteoarthritis (OA). The purpose of this study is to assess pain, function, and quality of life 2 years after TKR in contemporary patients with RA compared with patients with OA.', 'Primary TKR cases enrolled between May 1, 2007 and July 1, 2010 in a single institution TKR registry were eligible for this study. Validated RA cases were compared with OA at baseline and at 2 years.', 'We identified 4456 eligible TKR, including 136 RA. Compared with OA, RA TKR had significantly worse preoperative Western Ontario and McMaster Universities Osteoarthritis Index pain (55.9 vs 46.6, p < 0.0001) and function (58.7 vs 47.3, p < 0.0001); however, there were no differences at 2 years. Within RA, there was no difference for patients who were treated with biologic disease-modifying antirheumatic drugs versus those who did not in pain (p = 0.41) or function (p = 0.39) at 2 years. In a multivariate regression, controlling for multiple potential confounders, there was no independent association of RA with 2-year pain (p = 0.18) or function (p = 0.71). Satisfaction was high for both RA and OA.'] |
['To evaluate the antiproliferative activity of 3-(2-chlorophenyl)-1-(2-hydroxy-4, 6-dimethoxy-3-((ethyl(methyl) amino) methyl) phenyl) prop-2-en-1-one (DMF) against human androgen-independent prostate cancer PC3 cells in vitro and its underlying mechanisms.', 'The cytotoxic effect of DMF on PC3 cells was measured by MTT assay. Induction of apoptosis was assessed by propidium iodide staining and flow cytometric analysis. Changes of mitochondrial membrane potential (DeltaPsim) were detected by JC-1 staining. The levels of apoptosis related proteins were analyzed by Western blot.', 'DMF exhibited high efficiency on cell growth inhibition in PC3 cells with an IC50 value of (9.5 +/- 0.2)micromol/L. Flow cytometric analysis indicated that DMF could induce apoptosis in PC3 cells. A significant decrease of mitochondrial membrane potential was observed in PC3 cells treated with DMF, which was in a time- and dose-dependent manner. The results of Western blot indicated that DMF induced the activation of caspase-3, increased the ratio of Bax/Bcl-2 and downregulated the expression of phosphate-p38.'] |
['Serum levels of retinol-binding protein 4 (RBP4) are associated with insulin resistance and type 2 diabetes mellitus (T2DM) and may impact on β-cell function. Thus, the present study investigated the relationship between serum RBP4 and insulin secretion in Chinese people with and without T2DM.', 'A 75 g oral glucose tolerance test was administered to all 867 subjects and serum RBP4 concentrations were determined. Insulin secretion was assessed by ΔI/ΔG (increment in plasma insulin concentration/plasma glucose concentration 30 min after the oral administration of 75 g glucose) and the total area under the curve for insulin over 180 min (AUC-I). Magnetic resonance imaging was used to measure visceral fat area (VFA) at L4-L5; subjects with VFA ≥80 cm(2) were considered to have visceral obesity (VO).', 'Serum RBP4 concentrations were significantly higher in subjects with VO than without, regardless of the presence of T2DM. In addition, in the entire group with normal glucose tolerance (NGT), serum RBP4 was positively correlated with ΔI/ΔG (r = 0.152; P < 0.01) and AUC-I (r = 0.218; P < 0.01) after adjustment for gender. The correlation between RBP4 and ΔI/ΔG (r =\u200a 0.162; P < 0.05) and AUC-I (r = 0.195; P < 0.01) remained in NGT non-VO subjects. No correlation was found between serum RBP4 and ΔI/ΔG or AUC-I in T2DM patients. Stepwise multiple regression analysis showed that serum RBP4 is an independent factor that contributes to ΔI/ΔG (β = 0.176) and AUC-I (β = 0.204) in NGT non-VO subjects.'] |
['C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients.', 'We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels >/=3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H-CRP and prognosis in HCC patients.', 'The survival rate of patients of the H-CRP-positive group was lower than that of H-CRP-negative patients. Tumour stage (stages 3 or 4), total bilirubin >/=1.2 mg/dL, albumin (Alb) <3.5 g/dL, des-gamma-carboxy prothrombin >/=40 mAU/mL, positive H-CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H-CRP [hazard ratio (HR), 1.58; P=0.048], Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis.'] |
['Although in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized.', 'Helios (ikzf2), a member of the Ikaros transcription regulator family, is expressed in thymocytes and some antigen-matured T cells as well as in regulatory T cells. It has been proposed that Helios is a specific marker for thymus-derived regulatory T cells. Here, we show that mouse ovalbumin-specific CD4 (OTII) cells responding to alum-precipitated ovalbumin (alumOVA) upregulate Th2 features - GATA-3 and IL-4 - as well as Helios mRNA and protein. Helios is also upregulated in follicular helper T (TFh) cells in this response. By contrast, OTII cells responding to the Th1 antigen - live attenuated ovalbumin-expressing Salmonella - upregulate Th1 features - T-bet and IFN-γ - but not Helios. In addition, CD4 T cells induced to produce Th2 cytokines in vitro do not express Helios. The kinetics of Helios mRNA and protein induction mirrors that of GATA-3. The induction of IL-4, IL-13 and CXCR5 by alumOVA requires NF-κB1 and this is also needed for Helios upregulation. Importantly, Helios is induced in Th2 and TFh cells without parallel upregulation of Foxp3. These findings suggested a key role for Helios in Th2 and TFh development in response to alum-protein vaccines. We tested this possibility using Helios-deficient OTII cells and found this deficiency had no discernable impact on Th2 and TFh differentiation in response to alumOVA.'] |
['Adult patients with nasal polyps often have comorbid asthma, adding to the serious effect on the quality of life of these patients. Nasal polyps and asthma might represent a therapeutic challenge; inflammation in both diseases shares many features, such as airway eosinophilia, local IgE formation, and a T(H)2 cytokine profile. Omalizumab is a human anti-IgE mAb with proved efficacy in patients with severe allergic asthma. Omalizumab could be a treatment option for patients with nasal polyps and asthma.', 'The goal of this study was to investigate the clinical efficacy of omalizumab in patients with nasal polyps and comorbid asthma.', 'A randomized, double-blind, placebo-controlled study of allergic and nonallergic patients with nasal polyps and comorbid asthma (n = 24) was conducted. Subjects received 4 to 8 (subcutaneous) doses of omalizumab (n = 16) or placebo (n = 8). The primary end point was reduction in total nasal endoscopic polyp scores after 16 weeks. Secondary end points included a change in sinus computed tomographic scans, nasal and asthma symptoms, results of validated questionnaires (Short-Form Health Questionnaire, 31-item Rhinosinusitis Outcome Measuring Instrument, and Asthma Quality of Life Questionnaire), and serum/nasal secretion biomarker levels.', 'There was a significant decrease in total nasal endoscopic polyp scores after 16 weeks in the omalizumab-treated group (-2.67, P = .001), which was confirmed by means of computed tomographic scanning (Lund-Mackay score). Omalizumab had a beneficial effect on airway symptoms (nasal congestion, anterior rhinorrhea, loss of sense of smell, wheezing, and dyspnea) and on quality-of-life scores, irrespective of the presence of allergy.'] |
['Neuregulin-1 (NRG-1) has been shown to act as a neuroprotectant in animal models of nerve agent intoxication and other acute brain injuries. We recently demonstrated that NRG-1 blocked delayed neuronal death in rats intoxicated with the organophosphate (OP) neurotoxin diisopropylflurophosphate (DFP). It has been proposed that inflammatory mediators are involved in the pathogenesis of OP neurotoxin-mediated brain damage.', 'We examined the influence of NRG-1 on inflammatory responses in the rat brain following DFP intoxication. Microglial activation was determined by immunohistchemistry using anti-CD11b and anti-ED1 antibodies. Gene expression profiling was performed with brain tissues using Affymetrix gene arrays and analyzed using the Ingenuity Pathway Analysis software. Cytokine mRNA levels following DFP and NRG-1 treatment was validated by real-time reverse transcription polymerase chain reaction (RT-PCR).', 'DFP administration resulted in microglial activation in multiple brain regions, and this response was suppressed by treatment with NRG-1. Using microarray gene expression profiling, we observed that DFP increased mRNA levels of approximately 1,300 genes in the hippocampus 24\xa0h after administration. NRG-1 treatment suppressed by 50% or more a small fraction of DFP-induced genes, which were primarily associated with inflammatory responses. Real-time RT-PCR confirmed that the mRNAs for pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-6 (IL-6) were significantly increased following DFP exposure and that NRG-1 significantly attenuated this transcriptional response. In contrast, tumor necrosis factor α (TNFα) transcript levels were unchanged in both DFP and DFP\u2009+\u2009NRG-1 treated brains relative to controls.'] |
['Treatment with glucocorticoids and mineralocorticoids has changed congenital adrenal hyperplasia (CAH) from a fatal to a chronic lifelong disease. Long-term treatment, in particular the chronic (over-)treatment with glucocorticoids, may have an adverse effect on the cardiovascular risk profile in adult CAH patients. The objective of this study was to evaluate the cardiovascular risk profile of adult CAH patients.', 'Case-control study.', 'In this case-control study the cardiovascular risk profile of 27 adult CAH patients and 27 controls, matched for age, sex and body mass index was evaluated by measuring ambulatory 24-hour blood pressure, insulin sensitivity (HOMA-IR), lipid profiles, albuminuria and circulating cardiovascular risk markers (PAI-1, tPA, uPA, tPA/PAI-1 complex, hsCRP, adiponectin, IL-6, IL-18 and leptin).', '24-Hour systolic (126.3 mmHg±15.5 vs 124.8 mmHg±15.1 in controls, P\u200a=\u200a0.019) and diastolic (76.4 mmHg±12.7 vs 73.5 mmHg±12.4 in controls, P<0.001) blood pressure was significantly elevated in CAH patients compared to the control population. CAH patients had higher HDL cholesterol levels (P<0.01), lower hsCRP levels (P\u200a=\u200a0.03) and there was a trend toward elevated adiponectin levels compared to controls. Other cardiovascular risk factors were similar in both groups.'] |
['Generation of thrombin occurs in response to parenchymal injury. Thrombin not only converts plasma fibrinogen into an insoluble fibrin clot, but also potentially augments inflammation through receptor-mediated activity. This study examines whether thrombin may potentially exacerbate fibrosis by upregulating the function of interstitial fibroblasts in vitro.', "Fibroblasts were isolated by explant outgrowth culture of rat kidneys. Subcultured cells were grown in DMEM+10% FCS supplemented with 0.1-0.5 U/ml thrombin. Functional parameters examined included kinetics (thymidine incorporation and change in cell number), differentiation (Western blotting for alpha-smooth muscle actin; alphaSMA), expression of procollagen alpha1(I) (Northern blotting) and contraction of collagen I lattices. RT-PCR was used to characterise expression of protease-activated receptors (PAR) previously implicated in thrombin's cellular effects.", 'Cell population growth was increased 66 +/- 41 and 47 +/- 41% by 0.1 and 0.5 U/ml thrombin respectively (both p < 0.05 vs. basal). Likewise, 0.5 U/ml thrombin increased corrected procollagen alpha1(I) expression 2.4-fold (p < 0.05 vs. basal) and exacerbated the ability of fibroblasts to contract collagen matrix (p < 0.05 vs. basal). These effects were not associated with any change in expression of the myofibroblast marker alphaSMA. Effects on cell number were inhibited by treatment with (D)-Phe-Pro-Arg-chloromethylketone HCl (PPACK) suggesting that functional effects were mediated by serine protease activity. PAR-1 was the only fully functional known thrombin receptor expressed by these cells.'] |
['Antiphospholipid antibodies are associated with increased risk of thrombosis, particularly as in antiphospholipid syndrome. This study aims to determine the acute effects of anticardiolipin antibodies on nitric oxide production and vascular function.', 'Ex vivo aortic rings from male Sprague Dawley rats were incubated with IgG monoclonal anticardiolipin antibody (IS4) or a non-specific IgG control. In organ baths, response to phenylephrine and acetlycholine was determined alone and with nitro-L-arginine methyl ester (L-NAME), 1,400 W, D-arginine, L-arginine, sodium nitroprusside and cardiolipin. In vivo antibodies were injected into anaesthetised, spontaneously breathing male Sprague Dawley rats. Haemodynamic variables and serum nitric oxide were measured. Immunohistochemistry for iNOS and eNOS was performed in kidney vessels.', 'Phenylepherine contraction was decreased in the IS4 group compared to controls (p < 0.001). L-NAME, 1,400 W and cardiolipin, abolished this effect. L-Arginine caused significant relaxation in the IS4 group (p = 0.005). Mean arterial pressure in rats injected with IS4 was reduced compared to IgG and saline controls (p < 0.001). NO in plasma increased significantly after IS4 administration (p < 0.001). Immunohistochemistry showed increased iNOS expression in kidney arteries in the IS4 group, with no change in eNOS.'] |
['There is limited evidence supporting the hypothesized environment-disability link. The objectives of this study were to (a) identify the prevalence of community mobility barriers and transportation facilitators and (b) examine whether barriers and facilitators were associated with disability among older adults with functional limitations.', 'Four hundred and thirty-five participants aged 65+ years old with functional limitations were recruited from the Multicenter Osteoarthritis Study, a prospective study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis. Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey. Two domains of disability, (a) daily activity limitation (DAL) and (b) daily activity frequency (DAF), were assessed with the Late-Life Disability Instrument. Covariates included age, gender, education, race, comorbidity, body mass index, knee pain, and functional limitation. Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF.', 'Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators. High mobility barriers was associated with greater odds of DAL (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.2-3.1) after adjusting for covariates, and high transportation facilitators was associated with lower odds of DAL (OR = 0.5, 95% CI 0.3-0.8) but not with DAF in adjusted models.'] |
['Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been considered to be one of the most promising candidates in research on treatments for cancer, including renal cell carcinoma (RCC). However, many cells are resistant to TRAIL-induced apoptosis which limits the potential application of TRAIL in cancer therapy. Luteolin, a naturally occurring flavonoid, has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity. In this study, we investigated whether luteolin treatment could modulate TRAIL-induced apoptosis in RCC.', 'The effect of luteolin on TRAIL sensitivity was assessed in human RCC 786-O, ACHN, and A498 cells. The underlying regulatory cascades were approached by biochemical and pharmacological strategies.', 'We found that nontoxic concentration of luteolin alone had no effect on the level of apoptosis, but a combination treatment of TRAIL and luteolin caused significant extrinsic and intrinsic apoptosis. The sensitization was accompanied by Bid cleavage, Mcl-1 and FLIP down-regulation, DR4/DR5 protein expression and cell surface presentation, and Akt and signal transducer and activator of transcription-3 (STAT3) inactivation. Among these phenomena, changes in FLIP, Akt, and, STAT3 are more prone to the effects of luteolin treatment. Studies have further demonstrated that inactivation of Akt or STAT3 alone was sufficient to down-regulate FLIP expression and sensitized 786-O cells to TRAIL-induced apoptosis.'] |
['Tendon vibration has been shown to enhance muscle activity and to increase muscular endurance times. The impact of vibration on recovery from fatigue, however, is not known. This study aims to determine whether tendon vibration reduces recovery time following fatiguing contractions.', 'Eight sedentary males (22 ± 2.8 yr) performed a fatiguing protocol of ankle dorsiflexor muscles on two separate days, with a minimum of 48 h between visits. Surface EMG was recorded from the tibialis anterior muscle while participants were performing 25 maximal voluntary contractions (MVCs), each lasting 5 s and separated by 2 s. Following the fatiguing protocol, recovery was assessed with 3-s MVC each minute over a 10-min period. Recovery time was defined as the time at which force had returned to 90% of baseline values. At one visit, vibration was applied to the distal tendon of the tibialis anterior muscle between MVCs (throughout recovery). The alternate visit involved a sham condition in which no vibration was applied.', 'MVC force (P = 0.48) and EMG amplitude (P = 0.26) were not significantly different across testing days. Both MVC force (P < 0.001) and EMG amplitude (P < 0.001) declined significantly at the end of the fatigue protocol. However, there were no significant interaction effects for MVC force (P = 0.82) or EMG amplitude (P = 0.09), indicating similar levels of fatigue across days. With tendon vibration, MVC force recovered within 4.0 ± 2.5 min, which was not different from the sham condition (5.3 ± 1.8 min; P = 0.42). Similarly, EMG recovery time was not different between vibration condition (3.9 ± 3.8 min) and sham condition (4.9 ± 2.5 min) (P = 0.41).'] |
['Hydrogen sulfide (H(2) S), the third endogenous gaseous transmitter, may be a crucial mediator in airway hyper-responsiveness and airway inflammation, including asthma. To elucidate the role of H(2) S in allergic rhinitis, the present study was undertaken to determine the level of expression of H(2) S in healthy nasal mucosa and mild and moderate/severe persistent allergic nasal mucosa as well as peripheral blood obtained from each patient. The expression and distribution pattern of the H(2) S-synthesizing enzymes cystathione γ-lyase (CSE) and cystathione β-synthase (CBS) were investigated in healthy and allergic nasal mucosa.', 'Controlled, prospective study.', 'The concentration of H(2) S in nasal mucosa and plasma was determined by zinc trap spectrophotometry. The expression levels and patterns of distribution of CSE and CBS mRNA and proteins were evaluated using real time polymerase chain reaction, Western blot, and immunohistochemistry.', 'The levels of expression of H(2) S in nasal mucosa and plasma were increased in patients with mild and moderate/severe persistent allergic rhinitis compared with healthy controls. CSE was localized in vascular endothelium and surrounding muscles, and submucosal glands, whereas CBS was exclusively distributed in the superficial epithelium and submucosal glands. Their expression levels were increased in mild and moderate/severe persistent allergic rhinitis.'] |
['To document the properties of the voltage-gated ion channels in human pancreatic alpha-cells and their role in glucagon release.', 'Glucagon release was measured from intact islets. [Ca(2+)](i) was recorded in cells showing spontaneous activity at 1 mmol/l glucose. Membrane currents and potential were measured by whole-cell patch-clamping in isolated alpha-cells identified by immunocytochemistry.', 'Glucose inhibited glucagon secretion from human islets; maximal inhibition was observed at 6 mmol/l glucose. Glucagon secretion at 1 mmol/l glucose was inhibited by insulin but not by ZnCl(2). Glucose remained inhibitory in the presence of ZnCl(2) and after blockade of type-2 somatostatin receptors. Human alpha-cells are electrically active at 1 mmol/l glucose. Inhibition of K(ATP)-channels with tolbutamide depolarized alpha-cells by 10 mV and reduced the action potential amplitude. Human alpha-cells contain heteropodatoxin-sensitive A-type K(+)-channels, stromatoxin-sensitive delayed rectifying K(+)-channels, tetrodotoxin-sensitive Na(+)-currents, and low-threshold T-type, isradipine-sensitive L-type, and omega-agatoxin-sensitive P/Q-type Ca(2+)-channels. Glucagon secretion at 1 mmol/l glucose was inhibited by 40-70% by tetrodotoxin, heteropodatoxin-2, stromatoxin, omega-agatoxin, and isradipine. The [Ca(2+)](i) oscillations depend principally on Ca(2+)-influx via L-type Ca(2+)-channels. Capacitance measurements revealed a rapid (<50 ms) component of exocytosis. Exocytosis was negligible at voltages below -20 mV and peaked at 0 mV. Blocking P/Q-type Ca(2+)-currents abolished depolarization-evoked exocytosis.'] |
['Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures.', 'The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3× upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI(4 mm) ≥500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI(4 mm) ≥500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI(4 mm) (P=0.0002).'] |
['Corneal polarization axis (CPA) has been reported to affect retardation measurements obtained with scanning laser polarimetry (SLP). The purpose of this investigation was to prospectively determine whether correction for CPA improves the discriminating power of SLP for detection of mild-to-moderate glaucoma.', 'Cross-sectional analysis of normal and glaucomatous eyes.', 'We constructed a noninvasive slit-lamp-mounted device incorporating two crossed linear polarizers and an optical retarder to measure the slow axis of corneal polarization. Complete ocular examination, standard automated perimetry, SLP imaging, and CPA measurements were performed on normal and glaucomatous eyes. One eye/subject was enrolled; if both eyes of a patient were eligible for the study, the right eye was selected. For each of the 13 SLP parameters, logistic regression was used to determine if including CPA in the model influenced the ability to discriminate between normal and glaucomatous eyes.', 'Forty-three normal eyes (average visual field mean defect, -0.53 +/- 1.4 dB) and 33 glaucomatous eyes (average visual field mean defect, -5.93 +/- 6.5 dB) were enrolled. CPA was significantly correlated with summary retardation parameters (average thickness and integral values) in normal (r = 0.72-0.83, P <.001 for all values) and glaucomatous eyes (r = 0.43-0.62, P =.013 to <.001). Including CPA in the model improved the ability to discriminate between normal and glaucomatous eyes for five retardation parameters quantifying retinal nerve fiber layer (RNFL) thickness (range of P values: 0.045-0.001). For inferior average thickness, area under the receiver operating characteristic (ROC) curve increased significantly (P =.002) from 0.70 to 0.78 after accounting for CPA; with a sensitivity set at 80% specificity improved from 33% to 72%. Correlations between visual field corrected pattern standard deviation and average thickness, ellipse average, superior average, and inferior average significantly increased (range of P values,.018-.001) after adjustment for CPA (r = -0.35 and -0.45, -0.38 and -0.47, -0.46 and -0.57, and -0.42 and -0.49, respectively).'] |
['Historically, Q-wave myocardial infarction (MI) has been equated with transmural MI. This association have, however, recently been rejected. The endocardial extent of MI is another potential determinant of pathological Q waves, since the first part of the QRS complex where the Q wave appears reflects depolarization of subendocardial myocardium. Therefore, the aim of the present study was to test the hypothesis that endocardial extent of MI is more predictive of pathological Q waves than is MI transmurality and to investigate the relationship between QRS scoring of the ECG and MI characteristics.', 'Twenty-nine patients with reperfused first-time MI were prospectively enrolled. One week after admission, delayed contrast-enhanced magnetic resonance imaging (DE-MRI) was performed and 12-lead ECG was recorded. Size, transmurality and endocardial extent of MI were assessed by DE-MRI. Q waves were identified with Minnesota coding and electrocardiographic MI size was estimated by QRS scoring of the ECG.', 'There was a significant difference between patients with and without Q waves with regard to MI size (P = 0.03) and endocardial extent of MI (P = 0.01), but not to mean and maximum MI transmurality (P = 0.09 and P = 0.14). Endocardial extent was the only independent predictor of pathological Q waves. Endocardial extent of MI was most strongly correlated to QRS score (r = 0.86, P<0.001) of the MI variables tested.'] |
['To compare the in vitro effect of plasma from normal pregnant women and women with pre-eclampsia on the endothelium-dependent behaviour of myometrial resistance arteries from normal pregnant women.', 'An in vitro comparative study.', 'Nottingham City Hospital.', 'Uterine biopsy specimens were obtained from normal pregnant women delivered by elective caesarean section at term. Plasma was collected from nulliparous women with pre-eclampsia (n = 18), and from multiparous normal pregnant women (n = 18), all samples being matched for maternal age and gestation at venepuncture. Pools of plasma from women with pre-eclampsia and normal pregnant women were formed from these samples and were used in all the experiments.', 'Myometrial resistance vessels obtained from the uterine biopsies were incubated with normal pregnant plasma, plasma from women with pre-eclampsia, or without plasma. Wire myography was employed to study the effect of plasma on the endothelium-dependent behaviour of these vessels.', 'Incubation of vessels from normal pregnant women with plasma from women with pre-eclampsia resulted in a significant reduction in endothelium-dependent relaxation, compared with vessels incubated either with plasma from normal pregnant women or without plasma. This alteration in endothelial function occurred after an incubation period of one hour and required a threshold concentration for its effect to become established. Removal of the vascular endothelium abolished these changes in vessel behaviour. There were no plasma-induced alterations in the endothelium-independent behaviour of the vascular smooth muscle.'] |
['Seizures and antiepileptic drugs (AEDs) are the main causes for cognitive impairment in persons with epilepsy. It is still a matter of debate whether carbamazepine (CBZ) improves cognition because of its own psychotropic effects or because it is more effective to treat temporal epilepsy. Our objective was to analyze the performance of CBZ-treated or nontreated pilocarpine epileptic rats in an object-recognition test.', 'Twelve chronic pilocarpine-induced epileptic rats were treated with CBZ, 40 mg/kg, or saline, t.i.d. for 8 days. Twenty-one nonepileptic controls were treated with CBZ or saline. On day 8 of treatment, all rats were tested with an object-recognition paradigm.', 'No locomotor impairment was detected in chronic epilepsy or CBZ treatment, as exploration during training was not affected. Exploratory behaviors during the choice session were not decreased in rats treated with CBZ; therefore CBZ does not compromise procedural memory. Epileptic rats showed a nonsignificant change in the discrimination performance, and prolonged treatment with CBZ in epileptic rats induced a significant increase in object discrimination during the choice session.'] |
["Fibrinogen is a major determinant of plasma viscosity. The increased risk of atherothrombotic disease associated with a high fibrinogen concentration may partly be attributed to its effect on viscosity. Since the ratio between the three main fibrinogen subfractions high molecular weight (HMW)-, low molecular weight (LMW)-, and very low molecular weight (LMW')-fibrinogen is altered during acute phase conditions, and an increased HMW/LMW-fibrinogen ratio is associated with increased thromboembolic risk, we have examined how these subfractions affect viscosity. The viscosity of plasma is usually determined in ethylenediaminetetra-acetic acid (EDTA) plasma at 37 degrees C. Under such conditions the clotting properties of fibrinogen is affected due to denaturation. Denaturation of plasma proteins may affect their viscosity. Therefore, we have also investigated the effects of EDTA on the viscosity of fibrinogen.", 'Purified fibrinogen was obtained by beta-alanine precipitation of plasma from healthy donors. Separation of the fibrinogen fractions was performed by gradual precipitation of purified fibrinogen by ammonium sulphate. The viscosity was determined using a Haake Microvisco 2 viscometer.', 'There was no statistically significant difference between the viscosity of native fibrinogen and the three fibrinogen subfractions. A substantial prolongation of the thrombin clotting time was observed in the fibrinogen solution containing EDTA at 37 degrees C compared to 20 degrees C. However, the viscosity of EDTA anticoagulated purified fibrinogen and plasma samples did not differ from that of heparin anticoagulated samples.'] |
['Verbal short-term memory (STM) and working memory (WM) skills predict speech and language outcomes in children with cochlear implants (CIs) even after conventional demographic, device, and medical factors are taken into account. However, prior research has focused on single end point outcomes as opposed to the longitudinal process of development of verbal STM/WM and speech-language skills. In this study, the authors investigated relations between profiles of verbal STM/WM development and speech-language development over time.', 'Profiles of verbal STM/WM development were identified through the use of group-based trajectory analysis of repeated digit span measures over at least a 2-year time period in a sample of 66 children (ages 6-16 years) with CIs. Subjects also completed repeated assessments of speech and language skills during the same time period.', 'Clusters representing different patterns of development of verbal STM (digit span forward scores) were related to the growth rate of vocabulary and language comprehension skills over time. Clusters representing different patterns of development of verbal WM (digit span backward scores) were related to the growth rate of vocabulary and spoken word recognition skills over time.'] |
['Attention-deficit/hyperactivity disorder (ADHD) is associated with a 3- to 4-fold increase in both driving-related accidents and associated injuries. Methylphenidate (MPH) is the most commonly prescribed psychostimulant medication for ADHD. It has been demonstrated to improve performance on a driving simulator. This study investigated whether a once-daily, long-acting, osmotic, controlled-release MPH formulation improves the driving performance of ADHD adolescents while driving their own car on an actual road segment.', 'Twelve ADHD-diagnosed male adolescent drivers (mean age, 17.8 years) prescribed a standard dose of 1.0 mg/kg (if they were not already taking methylphenidate) of controlled-release MPH participated in this repeated-measures crossover study. On 2 separate occasions (off/on medication randomized), participants drove a standard 16-mile road course incorporating rural, highway, and urban streets. A rater, blind to medication conditions, sat in the back seat and rated impulsive (eg, "cutting off" another driver) and inattentive (eg, drove past designated turn) driving errors.', 'Impulsive driving errors were observed to occur rarely under both medication and no medication conditions. Inattentive driving errors were more common and were significantly reduced while the subject was on medication (4.6 versus 7.8; P <.01). The improvement in driving performance (change in number of errors recorded) from first to second testing was positively correlated with medication dosage (r = 0.60; P <.01).'] |
['Poisoning events, including exposures to hazardous materials, can involve multiple victims. Regional poison centers often are contacted in such events involving multiple victims.', 'We searched our poison center database over a nine-year time period for all calls involving a poisoning event in which more than two people were exposed to the same substance. We then matched each product to the generic category used by the National Poison Data System. We analyzed this data to find the most frequent substances reported as primary substances in the multiple exposures.', 'We identified 6,695 calls between 2000 and 2008 that had more than two people exposed to the same substance. In these calls, 25,926 people were exposed (3.6% of the 715,701 human exposure calls for this period). These calls involved 64 of the 67 NPDS substance group codes. Some substances were much more commonly involved than others. The top three categories causing the most exposures were Fumes/Gases/Vapors, Food Products/Food Poisoning and Pesticides. Of the patients exposed, 69.4 % were not followed due to minimal effects possible or judged as nontoxic, 0.3% had major effects, 8.6% had no effects, and 9.3% had minimal to moderate effects. Eight people expired.'] |
['To study the effects of platelet activating factor (PAF) antagonism on cardiovascular function in Escherichia coli endotoxaemia in non-hypotensive anaesthetised pigs.', 'Experimental study.', 'Trauma research unit, Sweden.', '24 Domestic juvenile pigs.', '18 Pigs received a continuous infusion of E coli endotoxin in a dose of 36 micrograms/kg/hour for 5 hours. They were allocated to two groups of 9 each. The first group (BB-882 group) received a continuous infusion of BB-882 (a novel potent PAF antagonist) 33 mg/kg/hour 30 minutes before the endotoxin while the second group (placebo group) received vehicle alone. Another 6 pigs (control group) received only BB-882.', 'Blood temperature, rigors, heart rate, intravascular pressure, cardiac and stroke volume indices and systemic vascular resistance.', 'Animals in the BB-882 group had significantly fewer rigors (p < 0.001) and episodes of tachycardia (p < 0.001) than the placebo group. BB-882 significantly reduced the endotoxin-induced systemic hypertension (p < 0.001) and the rise in systemic vascular resistance (p < 0.001). BB-882 group had significantly higher central venous pressure (p < 0.05), pulmonary capillary wedge pressure (p < 0.001), cardiac index (p < 0.02), and stroke volume index (p < 0.001).'] |
['Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment and differentiation towards CD163 expressing macrophages ex vivo, in vitro and in human AAA.', 'CD163 mRNA and protein expression was significantly higher in human AAA (n=7) vs. healthy wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich in hemosiderin and adjacent to neoangiogenic microvessels. Dual CD14/CD163 expression was observed in recently infiltrated monocytes surrounding microvessels. A higher release of soluble CD163 was observed in the conditioned medium from AAA (AAA-CM, n=10), mainly in the adventitial layer. Similar to Hb, AAA-CM induced CD163-dependent monocyte chemotaxis, especially on circulating monocytes from AAA patients. Hb or AAA-CM promoted differentiation towards CD163(high)/HLA-DR(low)-expressing macrophages, with enhanced Hb uptake, increased anti-inflammatory IL-10 secretion and decreased pro-inflammatory IL-12p40 release. All these effects were partially suppressed when Hb was removed from AAA-CM. Separate analysis on circulating monocytes reported increased percentage of pre-infiltrating CD14(++)CD16(+) monocytes in patients with AAA (n=21), as compared to controls (n=14). A significant increase in CD163 expression in CD14(++)CD16(+) monocyte subpopulation was observed in AAA patients.'] |
['The aim of this study was to evaluate the impact of the optimal diabetes control on the left ventricular parameters and ambulatory blood pressure in women with gestational diabetes mellitus (GDM).', 'The patients with GDM were followed up according to predetermined protocol in order to optimize blood glucose and optimal weight gain. Ambulatory blood pressure monitoring (ABPM) and transthoracal and tissue echocardiography were examined in 36th week of pregnancy.', 'The age of 35 women with GDM was 33.1±3 and 30.5±4.4 years in 31 healthy control subjects (p=0.2). Fasting plasma glucose (FPG) in the patients with GDM was 5.0±0.5 mmol/L compared to 4.6±0.3 mmol/L in control subjects (p=0.002). Average weight gain during pregnancy was significantly lower in women with GDM; 10±7.6 kg vs. 13.1±3.7 kg in healthy pregnant women (p=0.05). No significant differences were recorded in 24 hours mean heart rate, systolic and diastolic blood pressure and number of nondippers between both groups. The significant correlation was detected between FPG and blood pressure dipping in subjects with GDM. Interventricular septal, posterior wall and relative wall thickness of the left ventricle were significantly higher in patients with GDM comparing to healthy pregnant women but no significant differences of the left ventricular functions were recorded.'] |
['The study aimed to determine whether isolated heart rate (HR) reduction with ivabradine reduces afterload of patients with systolic heart failure.', 'The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden.', 'Among the patients with systolic heart failure (ejection fraction ≤35%) randomized to either placebo or ivabradine in the SHIFT (Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial), 275 patients (n = 132, placebo; n = 143, ivabradine 7.5 mg twice a day) were included in the echocardiographic substudy. Ea, total arterial compliance (TAC), and end-systolic elastance (Ees) were calculated at baseline and after 8 months of treatment. Blood pressure was measured by arm cuff; stroke volume (SV), ejection fraction, and end-diastolic volume were assessed by echocardiography.', 'At baseline Ea, TAC, HR, and Ees did not differ significantly between ivabradine- and placebo-treated patients. After 8 months of treatment, HR was significantly reduced in the ivabradine group (p < 0.0001) and was accompanied by marked reduction in Ea (p < 0.0001) and improved TAC (p = 0.004) compared with placebo. Although contractility remained unchanged, ventricular-arterial coupling was markedly improved (p = 0.002), resulting in a higher SV (p < 0.0001) in the ivabradine-treated patients.'] |
['HNA-3a-specific antibodies can cause severe, sometimes fatal, transfusion-related acute lung injury when present in transfused blood. The HNA3-a/b antigens are determined by an R154Q polymorphism in the first of five extracellular (EC) loops of the 10-membrane-spanning choline transporter-like protein 2 (CTL2) expressed on neutrophils, lymphocytes, and other tissues. Approximately 50% of HNA-3a antibodies (Type 1) can be detected using CTL2 Loop 1 peptides containing R154; the remaining 50% (Type 2) fail to recognize this target. Understanding the basis for this difference could guide efforts to develop practical assays to screen blood donors for HNA-3 antibodies.', 'Reactions of HNA-3a antibodies against recombinant versions of human, mouse, and human/mouse (chimeric) CTL2 were characterized using flow cytometry and various solid-phase assays.', 'The findings show that, for binding to CTL2, Type 2 HNA-3a antibodies require nonpolymorphic amino acid residues in the third, and possibly the second, EC loops of CTL2 to be in a configuration comparable to that found naturally in the cell membrane. In contrast, Type 1 antibodies require only peptides from the first EC loop that contain R154 for recognition.'] |
['To evaluate the risk of radiation pneumonitis (RP) after stereotactic radiotherapy (SBRT) for patients presenting with severe pulmonary emphysema.', "This study included 40 patients with Stage I non-small-cell lung cancer who underwent SBRT, 75\u2009Gy given in 30 fractions, at the Tokyo Medical University, Tokyo, Japan, between February 2010 and February 2013. The median age of the patients was 79 years (range, 49-90 years), and the male:female ratio was 24:16. There were 20 T1 and 20 T2 tumours. 17 patients had emphysema, 6 had slight interstitial changes on CT images and the remaining 17 had no underlying lung disease. The level of emphysema was classified into three groups according to the modified Goddard's criteria (severe: three patients, moderate: eight patients and mild: six patients). Changes in the irradiated lung following SBRT were evaluated by CT.", 'On CT images, RP was detected in 34 (85%) patients, and not in 6 (15%) patients, during a median observation period of 313 days. Of the six patients, three had severe emphysema and three had no underlying lung disease. Patients with severe emphysema had lower risk of RP than those with moderate emphysema (p\u2009=\u20090.01), mild emphysema (p\u2009=\u20090.04) and no underlying lung disease (p\u2009=\u20090.01).'] |
['Adult stem cells provide a promising alternative for the treatment of injured tissues. We aimed to investigate the effect of in vivo transplantation of bone marrow mesenchymal stem cells (BMMSCs) on injured gastric mucosa in rats.', 'The gastric ulcer in rats was induced by indomethacin. BMMSCs from male rats, labeled with the fluorescent cell linker 5,6-carboxyfluorescein diacetate succinimidyl ester (CFDA SE), were transplanted into the female rats via tail vein injection. The healing process of gastric ulcers was monitored by HE staining. The protein levels of vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) in the injured gastric mucosa were determined by immunohistochemistry.', 'At 48 and 72 hours after BMMSCs transplantation, the CFDA SE labeled cells were found scattered in the injured gastric mucosa, but not in the gastric mucosa of control rats. At 72 hours after BMMSCs transplantation, the mean ulcer index was 12.67 ± 2.16 in the BMMSCs transplanted group and 17.33 ± 1.97 in vehicle-treated controls (P < 0.01). Both VEGF and EGFR protein expression levels were significantly higher in the gastric section from the rats that received BMMSCs transplantation as compared to rats without BMMSCs transplantation.'] |
['The role of single micronutrient deficiencies in the etiology of growth retardation has recently gained attention. However, because multiple micronutrient deficiencies are common in children in developing countries, it is possible that more than one micronutrient may limit growth and, hence, the correction of a single deficiency may not be enough to improve growth substantially.', 'The objective was to evaluate the effect of multiple micronutrient supplementation on the growth of children aged 8-14 mo whose diets were poor in several micronutrients.', 'Children were randomly assigned to 1 of 2 groups. One group received a multiple micronutrient supplement containing the recommended dietary allowance (RDA) or 1.5 times the RDA of vitamins A, D, E, K, C, B-1, B-6, B-12, riboflavin, niacin, biotin, folic acid, and pantothenic acid, and iron, zinc, iodine, copper, manganese, and selenium. The other group received a placebo. Supplements were administered 6 d/wk for an average of 12.2 mo. Body length was measured at baseline and monthly thereafter until the end of supplementation.', 'Supplemented infants initially aged <12 mo had significantly greater length gains than did the placebo group, with a difference of 8.2 mm (length-for-age z score: 0.3) at the end of supplementation. In contrast, differences in length gains between the supplemented and placebo groups initially aged > or =12 mo were not significant.'] |
['Aim of this study is to find subgroup of early gastric cancer with lymph node metastasis for which successive further surgical operation is needed after endoscopic resection.', 'A total of 559 lesions of early gastric cancer, which had undergone curative gastrectomy, were enrolled in this study. We retrospectively investigated 10 clinicopathological factors predictive of lymph node metastasis by univariate and multivariate analysis. We showed the frequency of lymph node metastasis of subgroups in combination of independent factors selected by multivariate analysis.', 'Lymph node metastases were detected in 57 lesions (10.2%). Univariate analysis revealed that lesion size > 30 mm, undifferentiated components, sm massive invasion, lymphatic invasion and venous invasion were factors significantly correlated with lymph node metastasis. By multivariate analysis, risk factors for lymph node metastasis were lesion size > 30 mm, undifferentiated components, sm massive invasion, and lymphatic invasion, with odds ratios of 2.17, 2.30, 5.88 and 8.24, respectively. In lesions with undifferentiated components, LNM were found in all subgroups.'] |
['To determine whether children with unilateral hearing loss (UHL) demonstrate worse language skills than their siblings with normal hearing, and whether children with UHL are more likely to receive extra assistance at school.', 'We conducted a case-control study of 6- to 12-year-old children with UHL compared with sibling controls (74 pairs, n = 148). Scores on the oral portion of the Oral and Written Language Scales (OWLS) were the primary outcome measure. Multivariable analysis was used to determine whether UHL independently predicted OWLS scores after we controlled for potential confounding variables.', 'Children with UHL had worse scores than their siblings on language comprehension (91 vs 98; P = .003), oral expression (94 vs 101; P = .007), and oral composite (90 vs 99; P < .001). UHL independently predicted these OWLS scores when multivariable regression was used with moderate effect sizes of 0.3 to 0.7. Family income and maternal education were also independent predictors of oral expression and oral composite scores. No differences were found between children with right- or left-ear UHL or with varying severity of hearing loss. Children with UHL were more likely to have an individualized education plan (odds ratio: 4.4 [95% confidence interval: 2.0-9.5]) and to have received speech-language therapy (odds ratio: 2.6 [95% confidence interval: 1.3-5.4]).'] |
["WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: In a recent rtMRI study, we were able to show that, during initiation of voiding, there was both funnelling of the bladder neck and simultaneous contraction of the ventral prostate. We presumed that the vertical contraction of the ventral prostate contributes to the initiation of successful micturition. The question remained as to whether this shortening of the ventral prostate is predominantly caused by contractile elements in the organ itself, or by surrounding contractile elements of the pelvic floor. In our study we provide insight in to anatomical changes, and biometric and functional analysis of the prostate during micturition. A sagittal contraction of the ventral prostate and the longitudinal smooth muscle elements at the onset of voiding, which can be observed on MRI, is likely to shorten and open up the prostatic urethra.", 'To investigate if in vitro contractile strength of the prostate and the prostatic urethra might correlate with the shortening of the ventral prostate seen on real-time magnetic resonance imaging (rtMRI). Micturition is a complex process that includes anatomical and neurological interactions for successful voiding. Recently we described on rtMRI that vertical contraction of the ventral prostate precedes initiation of male micturition and may contribute to the funnelling of the bladder neck.', 'In all, 10 patients undergoing radical prostatectomy (RP) were enrolled. Approval was obtained from all patients and by the local Ethics Committee. Preoperative rtMRI during voiding was performed as described before in eight patients undergoing RP, measuring the difference of the cranio-caudal distance of the ventral prostate (VP). To roughly estimate the amount of force required to deform the prostate in a vertical direction as seen on rtMRI, we uniaxially compressed the organ immediately after surgery by the same distance, assuming incompressibility and isotropy of prostatic tissue. A muscle strip (3 × 3\u2009mm) from the ventral prostate, dorsal prostate and prostatic urethra was obtained after pathological evaluation. Contraction was elicited by electrical-field stimulation (EFS: 0.1\u2009ms pulses at 2, 4, 8, 16, 32 and 64\u2009Hz for 4\u2009s).', 'There was a mean cranio-caudal contraction of the ventral prostate by 7.6\u2009mm at the onset of micturition on rtMRI (P = 0.002). The mean (sd) contractile force of strips elicited by EFS at 32\u2009Hz was 1472.44\u2009(706.88)\u2009mN for the ventral prostate, 1044.24\u2009(894.66)\u2009mN for the dorsal prostate, and 639.10\u2009(785.06)\u2009mN for the prostatic urethra (P = 0.02). Extrapolating these values to the whole organ diameter, we calculated comparable force as observed in compression experiments.'] |
['The outcome of non-surgical periodontal therapy is known to be inferior in smokers compared to non-smokers. In the present study, the question was asked whether such a difference in healing response may be less evident following adjunctive use of locally delivered controlled-release doxycycline.', 'One hundred and three patients (42 smokers, 61 non-smokers), each having at least eight periodontal sites with PPD (probing pocket depth) > or =5 mm, were following stratification for smoking randomly assigned to two different treatment protocols; non-surgical scaling/root planing (Control) or ultrasonic instrumentation+application of a 8.5% w/w doxycycline gel (Atridox trade mark ) (Test). Instructions in oral hygiene were given to all patients. Clinical examinations of plaque, PPD, clinical attachment level (CAL) and bleeding following pocket probing were performed at baseline and after 3 months. Primary efficacy endpoints were changes in PPD and CAL. Patient mean values were calculated as basis for statistical analysis (multiple regression analyses).', 'The baseline examination revealed no significant difference in mean PPD between treatment groups or between smokers and non-smokers (mean PPD 5.7-5.9 mm). The mean PPD reduction in the control group at 3-month was 1.1 mm (SD=0.45) for smokers and 1.5 mm (0.67) for non-smokers. In the test group the PPD reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non-smokers, respectively. The mean CAL gain for smokers and non-smokers amounted to 0.5 mm (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression analysis revealed that smoking and initial PPD negatively influenced the treatment outcome in terms of PPD reduction and CAL gain, while the use of doxycycline had a significant positive effect.'] |
['Age-related macular degeneration (AMD) is characterized clinically by changes in the retinal pigment epithelium (RPE), formation of drusen between the RPE and the underlying vasculature, geographic atrophy, and choroidal neovascularization. Later clinical stages are accompanied by impaired central vision. A limited understanding of the molecular events responsible for AMD has constrained the development of effective treatments. A proteomics approach was used to investigate the underlying mechanisms of AMD and to identify proteins exhibiting significant changes in expression with disease onset and progression.', 'Human donor eyes were categorized into one of four progressive stages of AMD. Proteins from the RPE were resolved and quantified by two-dimensional (2-D) gel electrophoresis. Proteins exhibiting significant expression changes at different disease stages were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. 2-D and semiquantitative one dimensional (1-D) Western blot analyses were used to determine whether changes identified by the proteomic analysis were specific for a protein subpopulation or representative of the entire protein population.', 'Proteins were identified from several critical pathways that changed at early and late disease stages, indicating potential causal mechanisms and secondary consequences of AMD, respectively. Proteins involved in protecting from stress-induced protein unfolding and aggregation, mitochondrial trafficking and refolding, and regulating apoptosis changed early in the disease process. Late-stage changes occurred in proteins that regulate retinoic acid and regeneration of the rhodopsin chromophore.'] |
['Since variations on the renin angiotensin (RA) system tend to exert effects on blood pressure, we investigated the association of the common ACE and AT1R polymorphisms with response to a multivariate pharmacotherapy.', 'This prospective study involved 169 hypertensive, community-dwelling older women. Genotypes were obtained by length analysis or direct sequencing of PCR products. Blood pressure-lowering pharmacotherapy was conducted according to current Brazilian Guidelines on Hypertension.', 'Genotype frequencies were in agreement to the Hardy-Weinberg equilibrium. Interventions were found to represent actual hypertension-management practices in Brazil, and accounted for a significant reduction in both systolic (P<0.001) and diastolic (P<0.001) blood pressure. Concerning the effect of polymorphisms, no influence of the ACE and AT1R genotypes were found on the magnitude of the treatment-induced blood pressure reduction (P>0.05). Nonetheless, the clinical result varied according to the ACE alleles since mean systolic pressure was roughly 10 mm Hg higher in insertion (I) homozygotes than in the deletion (D) counterparts either in baseline (P=0.001) and endpoint (P=0.010).'] |
['Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal destruction. COX-2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL-1beta). Little is known about IL-1beta-stimulated AgP fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1beta-stimulated gingival fibroblasts.', 'Gingival fibroblasts (2.5 x 10(4)) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1beta (10(-11)M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture supernatants were determined by specific enzyme-linked immunosorbent assay (ELISA)s.', 'All of the COX inhibitors caused dose-dependent decreases in IL-1beta-stimulated PGE2, to a maximum of > 90% in all cell lines (P < or = 0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60%), dose-dependent decreases in IL-1beta-stimulated IL-6 in all cell lines (P < or = 0.003). When exogenous PGE2 was added concurrently with COX-2 inhibitors before addition of IL-1beta, IL-6 production returned to levels at or approaching that produced by cells exposed only to IL-1beta (P < or = 0.04).'] |
['The study objective was to compare the effect of a standard calorie- and fat-restricted diet (STD-D) and a calorie- and fat-restricted lacto-ovo-vegetarian diet (LOV-D) on total and high-molecular-weight (HMW) adiponectin levels after 6 months of behavioral intervention.', 'This study is an ancillary study to a randomized clinical trial.', 'Subjects included 143 overweight/obese adults (STD-D = 79; LOV-D = 64).', 'Both groups received the same standard behavioral intervention; the only difference was that LOV-D participants were instructed to eliminate meat, poultry, and fish from their diet.', 'Weight, dietary intake with the 3-day food diary, and total and HMW adiponectin levels were measured.', 'Both groups significantly increased total (STD-D +7.2 ± 17.8%; LOV-D +9.4 ± 21.8%) and HMW adiponectin levels (STD-D +18.5 ± 32.9%; LOV-D +15.8 ± 34.5%; ps < 0.05) with no significant differences between the groups. We found significant associations between weight loss and increases in total (β (SE) = -.071(.27); p = 0.003) and HMW adiponectin (β (SE) = -1.37(.47); p = 0.001) levels independent of the diet type. Weight loss at the higher quartile was associated with improvements of adiponectin levels (p < 0.05).'] |
['To evaluate whether post-operative blood loss in patients with benign prostatic hyperplasia, undergoing transurethral resection of the prostate (TURP), depends on in situ fibrinolysis in urine, and to determine the relative contributions of the urokinase and tissue-type plasminogen activator systems.', 'TURP was performed in 24 men (median age 68.5 years, range 52-78) and the weight of resected tissue, the operative and post-operative blood loss determined. The concentrations of the urokinase- (u-PA) and tissue-type plasminogen activator (t-PA)-related fibrinolysis in their urine was followed using sensitive and specific assays, and the changes related to post-operative blood loss. Measurements of the urinary concentrations of free t-PA activity, t-PA antigen, free u-PA activity, u-PA antigen and fibrin degradation products (FbDP) were determined and the area under the curve for each of these quantities correlated with the post-operative blood loss.', 'The post-operative blood loss correlated significantly with the per-operative loss (P = 0.047) and the weight of resected tissue (P = 0.029). There was a highly significant correlation between the area under the curve of FbDP in the urine and the post-operative blood loss (P < 0.005), while there was no significant positive correlation between the PA concentration or activity in the urine and post-operative blood loss. There was a significant correlation between the urinary t-PA activity and the amount of FbDP in the urine (P = 0.047), and a significant correlation between the weight of resected tissue and the amount of FbDP in the urine (P = 0.014).'] |
['The growing epidemic of metabolic syndrome has been related to the increased use of fructose by the food industry. In fact, the use of fructose as an ingredient has increased in sweetened beverages, such as sodas and juices. We thus hypothesized that fructose intake by hypertensive rats would have a worse prognosis in developing metabolic disorder and non-alcoholic fatty liver disease.', 'Male Wistar and SHR rats aged 6weeks were given water or fructose (10%) for 6weeks. Blood glucose was measured every two weeks, and insulin and glucose sensitivity tests were assessed at the end of the follow-up. Systolic blood pressure was measure by plethysmography. Lean mass and abdominal fat mass were collected and weighed. Liver tissue was analyzed to determine interstitial fat deposition and fibrosis.', 'Fasting glucose increased in animals that underwent a high fructose intake, independent of blood pressure levels. Also, insulin resistance was observed in normotensive and mostly in hypertensive rats after fructose intake. Fructose intake caused a 2.5-fold increase in triglycerides levels in both groups. Fructose intake did not change lean mass. However, we found that fructose intake significantly increased abdominal fat mass deposition in normotensive but not in hypertensive rats. Nevertheless, chronic fructose intake only increased fat deposition and fibrosis in the liver in hypertensive rats.'] |
['Hepatic forkhead box q1 (FOXQ1) expression levels are regulated by nutritional and pathophysiological status. In this study we investigated the role of FOXQ1 in the regulation of hepatic gluconeogenesis.', 'We used multiple mouse and cell models to study the role of FOXQ1 in regulating expression of gluconeogenic genes, and cellular and hepatic glucose production.', 'Expression of hepatic FOXQ1 was regulated by fasting in normal mice and was dysregulated in diabetic mice. Overexpression of FOXQ1 in primary hepatocytes inhibited expression of gluconeogenic genes and decreased cellular glucose output. Hepatic FOXQ1 rescue in db/db and high-fat diet-induced obese mice markedly decreased blood glucose level and improved glucose intolerance. In contrast, wild-type C57 mice with hepatic FOXQ1 deficiency displayed increased blood glucose levels and impaired glucose tolerance. Interestingly, studies into molecular mechanisms indicated that FOXQ1 interacts with FOXO1, thereby blocking FOXO1 activity on hepatic gluconeogenesis, preventing it from directly binding to insulin response elements mapped in the promoter region of gluconeogenic genes.'] |
['The majority of patients with node-negative colorectal cancer have excellent 5-year survival prospects, but up to a third relapse. Strategies to identify patients at higher risk of adverse outcomes are desirable to enable optimal treatment and follow-up. The aim of this study was to examine postoperative mortality and longer-term survival by mode of presentation for patients with node-negative colorectal cancer undergoing surgery with curative intent.', 'Patients from 16 hospitals in the west of Scotland between 2001 and 2004 were identified from a prospectively maintained regional clinical audit database. Postoperative mortality and 5-year relative survival by mode of presentation were recorded.', 'Of 1,877 patients with node-negative disease, 251 (13.4%) presented as an emergency. Those presenting as an emergency were more likely to be older (P\u2009=\u20090.023), have colon rather than rectal cancer (P\u2009<\u20090.001), have pT4 stage disease (P\u2009<\u20090.001), have extramural vascular invasion (P\u2009=\u20090.001), and receive surgery under the care of a nonspecialist surgeon (P\u2009<\u20090.001) compared to those presenting electively. The postoperative mortality rate was 3.3% after elective and 12.8% after emergency presentation (P\u2009<\u20090.001). Five-year relative survival was 91.8% after elective and 66.8% after emergency presentation (P\u2009<\u20090.001). The adjusted relative excess risk ratio for 5-year relative survival after emergency relative to elective presentation was 2.59 (95% CI 1.67-4.01; P\u2009<\u20090.001) and 1.90 (95% CI 1.00-3.62; P\u2009=\u20090.049) after exclusion of postoperative deaths.'] |
['Correlation of increased copeptin levels with various cardiovascular diseases has been described. The clinical use of copeptin levels in patients with hypertrophic cardiomyopathy (HCM) has not been investigated before.', 'In this study, we aimed to investigate the prognostic value of copeptin levels in patients with hypertrophic cardiomyopathy (HCM).', 'HCM was defined as presence of left ventricular wall thickness ≥15\u2009mm in a subject without any concomitant disease that may cause left ventricular hypertrophy. Levels of copeptin and plasma N-terminal probrain natriuretic peptide (NT-proBNP) were evaluated prospectively in 24 obstructive HCM patients, 36 nonobstructive HCM patients, and 36 age- and sex-matched control subjects. Blood samples were collected in the morning between 7 and 9\u2009am after overnight fasting. Patients were followed for 24 months. Hospitalization with diagnosis of heart failure/arrhythmia, implantable cardioverter-defibrillator implantation, and cardiac mortality were accepted as adverse cardiac events.', 'Copeptin and NT-proBNP levels were higher in the HCM group compared with controls (14.1 vs 8.4 pmol/L, P < 0.01; and 383 vs 44\u2009pg/mL, P < 0.01, respectively). Copeptin and NT-proBNP levels were higher in the obstructive HCM subgroup compared with the nonobstructive HCM subgroup (18.3 vs 13.1 pmol/L, P < 0.01; and 717 vs 223\u2009pg/mL, P < 0.01, respectively). In multivariable logistic regression analysis, copeptin and NT-proBNP levels remained as independent predictors of heart failure (P < 0.01 for both) and adverse cardiac events (P < 0.01 for both).'] |
['Flurbiprofen, a nonsteroidal antiinflammatory drug (NSAID), has been used to treat rheumatic and osteoarthritic pain and to reduce postoperative pain. Although other NSAIDs, such as indomethacin, reduce cerebral blood flow (CBF), the effect of flurbiprofen on CBF is unknown. In the present study, we investigated the effects of flurbiprofen on cerebral blood flow velocity (CBFV) and cerebral oxygenation under isoflurane or propofol anesthesia. Forty-eight patients undergoing orthopedic or abdominal surgery were enrolled. Patients were randomly allocated to receive either propofol (target control infusion: target site effect concentration 3 microg/mL) or isoflurane (1 MAC) for maintenance of anesthesia. In each group (n = 12), 1 mg/kg of flurbiprofen (PROP-F and ISO-F groups) or 0.1 mL/kg saline (PROP-S and ISO-S groups) was administered i.v. for 5 min. During and after the administration of flurbiprofen or saline, cerebral oxygenation variables (tissue oxygen index [TOI], total hemoglobin change [Delta cHb], oxygenated hemoglobin changes [Delta O(2)Hb], and deoxygenated hemoglobin changes [Delta HHb]), and middle cerebral artery flow velocity (Vmca) were measured using a cerebral oximeter (NIRO 300) and transcranial Doppler, respectively, from 5 min before study drug administration to 60 min post-administration. Before the administration of flurbiprofen, control values of TOI in the ISO-S and ISO-F groups were significantly higher than those in the PROP-S and PROP-F groups, respectively (ISO-S versus PROP-S, 67% +/- 4% versus 60% +/- 7%; IOS-F versus PROP-F, 69% +/- 4% versus 63% +/- 8%; P < 0.05). However, values of TOI, Delta cHb, Delta O(2)Hb, Delta HHb, and Vmca did not change significantly during and after the administration of flurbiprofen under propofol or isoflurane anesthesia, and these values were similar to those during and after the administration of saline in the same anesthesia group. These data indicate that flurbiprofen does not affect CBFV and cerebral oxygenation under propofol or isoflurane anesthesia.'] |
['The aim of this retrospective study was to investigate the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) gene mutations in lung adenocarcinomas of Chinese patients.', 'There were 200 lung adenocarcinoma patients who were enrolled in this study. Tumor specimens of these patients were investigated for TTF-1 expression and mutations in EGFR using immunohistochemistry and a liquid chip platform for DNA analysis of slides with sections of formalin-fixed, paraffin-embedded specimens.', 'The rates of TTF-1 expression and EGFR mutations were 81.5% and 45.5%, respectively, in the lung adenocarcinoma specimens of the recruited patients. Among female nonsmokers (n=72), 93.1% of specimens were positive for TTF-1 expression, and 63.9% had EGFR mutations. Of 89 patients with EGFR mutations, 83 (50.9%) specimens were simultaneously positive for TTF-1 expression. Kaplan-Meier analysis of all patient specimens found that postoperative survival time was not significantly associated with TTF-1 expression and the presence of EGFR mutations. However, patients with disease stages III-IV whose tumors were positive for TTF-1 expression and EGFR mutations had better postoperative survival than similar patients whose tumors were negative for TTF-1 expression and EGFR mutations.'] |
['To investigate the therapeutic potential of administration of gelatin hydrogel microspheres containing platelet-rich plasma (PRP), by examining its effects on progression of osteoarthritis (OA) in a rabbit model.', 'PRP and platelet-poor plasma (PPP) were prepared from rabbit blood. Adult rabbit chondrocytes were cultured in the alginate beads with the presence of 3% PRP or 3% PPP. Glycosaminoglycan (GAG) synthesis was quantified using dimethylmethylene blue assay. To confirm the anabolic effect of PRP in vivo, cartilage matrix gene expression was examined after intraarticular administration of PRP contained in gelatin hydrogel microspheres. The PRP contained in gelatin hydrogel microspheres was administered into the rabbit knee joint twice with an interval of 3 weeks, beginning 4 weeks after anterior cruciate ligament transection (ACLT). Ten weeks after ACLT, gross morphological and histological examinations were performed.', 'PRP significantly stimulated chondrocyte GAG synthesis in vitro. In the knee joint, expression of proteoglycan core protein mRNA in the articular cartilage increased after administration of PRP contained in microspheres. Intraarticular injections of PRP in gelatin hydrogel microspheres significantly suppressed progression of OA in the ACLT rabbit model morphologically and histologically.'] |
['We previously established that six sequence-specific transcription factors that initiate anterior/posterior patterning in Drosophila bind to overlapping sets of thousands of genomic regions in blastoderm embryos. While regions bound at high levels include known and probable functional targets, more poorly bound regions are preferentially associated with housekeeping genes and/or genes not transcribed in the blastoderm, and are frequently found in protein coding sequences or in less conserved non-coding DNA, suggesting that many are likely non-functional.', 'Here we show that an additional 15 transcription factors that regulate other aspects of embryo patterning show a similar quantitative continuum of function and binding to thousands of genomic regions in vivo. Collectively, the 21 regulators show a surprisingly high overlap in the regions they bind given that they belong to 11 DNA binding domain families, specify distinct developmental fates, and can act via different cis-regulatory modules. We demonstrate, however, that quantitative differences in relative levels of binding to shared targets correlate with the known biological and transcriptional regulatory specificities of these factors.'] |
['To evaluate the effect of Collagen cross-linking on the prevention of melting in rabbit corneas after alkali burn.', 'Twenty New Zealand white rabbits were randomly divided into model control group and collagen cross-linking treatment group. The second group of rabbits received collagen cross linked treatment. Both groups were applied with antibiotic eye drops to prevent infection. The corneas were evaluated for melting, opacity, pathological and immunohistochemistry, record the changes when 28 days after the animals were killed.', 'In the control group, 6 out of 8 rabbits showed corneal melting after injury (14±4) days, while two corneal perforated. In collagen cross-linking treatment group, one rabbit showed corneal melting after injury 23 days, without corneal perforation; corneal dissolution rate between the two groups was significantly different (P <0.05). Pathological examination suggested that in the treatment group, mild corneal edema, mild damage to collagen fibers, inflammatory cell infiltration was significantly less than the control group. Immunohistochemistry showed that corneal collagen fibers arranged in neat rows in the control group.'] |
['Obstructive sleep apnea (OSA) is associated with increased mortality, for which impaired functional capacity (IFC) has been established as a surrogate. We sought to assess whether IFC is associated with increased mortality in patients with OSA and whether IFC is predictive of increased mortality after accounting for coronary artery disease.', 'Patients with OSA who underwent both polysomnography testing and exercise stress echocardiogram were selected. Records were reviewed retrospectively for demographics, comorbidities, stress echocardiographic parameters, and polysomnography data. Univariable and multivariable logistic regression analysis was used to evaluate the association between IFC and overall mortality. We then evaluated the variables associated with IFC in the overall population and in the subgroup with normal Duke treadmill score (DTS).', 'In our cohort, 404 (26%) patients had IFC. The best predictors of IFC were female sex, history of smoking, ejection fraction less than 55, increased body mass index, presence of comorbidities, abnormal exercise echocardiogram, abnormal heart rate recovery, and abnormal DTS. Compared with those without IFC, patients with IFC were 5.1 times more likely to die (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.5-10.5; P < 0.0001) by univariate analysis and 2.7 times more likely to die (OR, 2.7; 95% CI, 1.2-6.1; P = 0.02) by multivariate analysis, when accounting for heart rate recovery, DTS, and sleep apnea severity. Among those without coronary artery disease, patients with IFC were at significantly increased risk of mortality (OR, 4.3; 95% CI, 1.35-13.79; P = 0.0088) compared with those with preserved functional capacity.'] |
['Previous studies suggest that angiotensin II (Ang II) upregulates the expression of tumor necrosis factor (TNF) in nonmyocyte cell types; however, the effect of Ang II on TNF expression in the adult mammalian heart is not known.', 'To determine whether Ang II was sufficient to provoke TNF biosynthesis in the adult heart, we examined the effects of Ang II in isolated buffer-perfused Langendorff feline hearts. Ang II (10(-7) mol/L) treatment resulted in a time- and dose-dependent increase in myocardial TNF mRNA and protein biosynthesis in the heart as well as in cultured adult cardiac myocytes. The effects of Ang II on myocardial TNF mRNA and protein synthesis were mediated through the angiotensin type 1 receptor (AT1R), insofar as an AT1R antagonist (AT1a) blocked the effects of Ang II, whereas an angiotensin type 2 receptor (AT2R) antagonist (AT2a) had no effect. Stimulation with Ang II led to the activation of nuclear factor-kappaB and activator protein-1 (AP-1), two transcription factors that are important for TNF gene expression. Nuclear factor-kappaB activation was accompanied by phosphorylation of IkappaBalpha on serine 32 as well as degradation of IkappaBalpha, suggesting that the effects of Ang II were mediated through an IkappaBalpha-dependent pathway. The important role of protein kinase C (PKC) was suggested by studies in which a phorbol ester triggered TNF biosynthesis, and a PKC inhibitor abrogated Ang II-induced TNF biosynthesis.'] |
['Recent reports have indicated that single-stranded DNA (ssDNA) viruses in the taxonomic families Geminiviridae, Parvoviridae and Anellovirus may be evolving at rates of approximately 10(-4) substitutions per site per year (subs/site/year). These evolution rates are similar to those of RNA viruses and are surprisingly high given that ssDNA virus replication involves host DNA polymerases with fidelities approximately 10,000 times greater than those of error-prone viral RNA polymerases. Although high ssDNA virus evolution rates were first suggested in evolution experiments involving the geminivirus maize streak virus (MSV), the evolution rate of this virus has never been accurately measured. Also, questions regarding both the mechanistic basis and adaptive value of high geminivirus mutation rates remain unanswered.', 'We determined the short-term evolution rate of MSV using full genome analysis of virus populations initiated from cloned genomes. Three wild type viruses and three defective artificial chimaeric viruses were maintained in planta for up to five years and displayed evolution rates of between 7.4 x 10(-4) and 7.9 x 10-4 subs/site/year.'] |
['Aberrant CXC chemokine receptor 2 (CXCR2) expression has been shown to promote angiogenesis and proliferation in renal cell carcinoma (RCC). Our current study aims to evaluate the prognostic significance of CXCR2 in patients with non-metastatic clear-cell renal cell carcinoma (ccRCC).', 'We retrospectively enrolled 375 patients with non-metastatic ccRCC undergoing nephrectomy at Zhongshan Hospital, Fudan University between 2003 and 2008. The cohort was split into a training set (n=184) and a validation set (n=191). CXCR2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated.', 'CXCR2 expression was significantly associated with tumour size (P=0.036 and P=0.016, respectively) and Fuhrman grade (P=0.009 and P=0.001, respectively) in the training and validation sets. Moreover, high CXCR2 expression indicated poor overall survival (OS) (P<0.001 and P=0.001, respectively) and recurrence-free survival (P<0.001 and P<0.001, respectively) in the training and validation sets. The incorporation of CXCR2 into the T stage and Fuhrman grade would help to refine individual risk stratification. Furthermore, CXCR2 expression was identified as an independent adverse prognostic factor for survival (P<0.001) and recurrence (P<0.001). A predictive nomogram was generated with identified independent prognosticators to assess patient recurrence-free survival at 5 and 10 years.'] |
['While reducing the potential for bacterial contamination, the storage of platelet concentrates (PCs) at refrigerated temperatures is not routine, because of the induction of the so-called platelet storage lesion. As the modulation of second-messenger levels might help to overcome this drawback, a quality assessment of PCs treated with a mixture of second-messengers effectors known as ThromboSol was performed.', "The PCs were supplemented with ThromboSol or phosphate-buffered saline, and stored in parallel at 22 degrees C with continuous agitation or at 4 degrees C. At 1, 5, and 9 days, an in vitro quality assessment of the PCs was performed, including measurement of cell number, metabolic and integrity markers, platelet surface expression of glycoproteins, platelet response to ristocetin and thrombin, and levels of cyclic adenosine 3', 5' monophosphate (cAMP) and thromboxane B2 (TxB2).", 'Control PCs stored at 4 degrees C underwent aggregation and displayed a significant decrease in the platelet number (40% on Day 5). By contrast, the ThromboSol-treated PCs maintained 80 percent of their initial platelet concentration after 9 days of storage at 4 degrees C. Compared to PCs stored at 22 degrees C, refrigerated PCs exhibited minor changes in metabolic values throughout storage, but the addition of ThromboSol induced a rise in metabolic rate during storage at 22 degrees C. Platelet responsiveness to both ristocetin and thrombin was maximally preserved in the ThromboSol-treated PCs stored at 4 degrees C. These units also maintained high levels of cAMP and low concentrations of TxB2 during storage.'] |
['Air-displacement plethysmography (ADP) systems can either measure or predict lung volume (LV) in their test trials. The repeatability of the predicted and the measured value is an important factor in the accuracy of the final test result.', 'Compare the variability and accuracy of ADP tests using predicted and measured LV over a protracted period of time.', 'Twenty-four adults (18-30 years) participated in the study. Each subject underwent three ADP tests over a period of 3 weeks, with 1 week between tests. At each testing session, subjects were tested using a predicted LV protocol and a measured LV protocol in random order. LV, body volume (BV) and per cent body fat (% BF) were compared between testing modes and between assessment times.', 'A two-way ANOVA examined the effect of the mode of LV assessment (measured or predicted) and trial (week) for LV and BV and the effect of the LV mode assessment (measured or predicted) and trial (week) on % BF results. LV and BV did not differ significantly (P>0.05) between the two modes of assessment (measured or predicted). Time (day of assessment) also was not significantly different between trials (P>0.05). Neither mode nor trial was significant (P>0.05), therefore neither had an effect on the % BF results.'] |
['Protein denitrosylation by thioredoxin reductase (TrxR) is key for maintaining S-nitrosothiol (SNO) homeostasis, although its role in tumor progression is unknown. Therefore, the present study aimed to assess the role of altered SNO homeostasis in breast cancer cells.', 'The impairment of SNO homeostasis in breast cancer cells was achieved with the highly specific TrxR inhibitor auranofin and/or exposure to S-nitroso-L-cysteine. S-nitrosylated proteins were detected using the biotin switch assay. Estrogen receptor (ER) alpha knockdown was achieved using RNA silencing technologies and subcellular localization of ERα was analyzed by confocal microscopy. The Oncomine database was explored for TrxR1 (TXNRD1) expression in breast tumors and TrxR1, ER and p53 expression was analyzed by immunohistochemistry in a panel of breast tumors.', 'The impairment of SNO homeostasis enhanced cell proliferation and survival of ER+ MCF-7 cells, but not of MDA-MB-231 (ER-, mut p53) or BT-474 (ER+, mut p53) cells. This enhanced cell growth and survival was associated with Akt, Erk1/2 phosphorylation, and augmented cyclin D1 expression and was abolished by the ER antagonist fulvestrant or the p53 specific inhibitor pifithrin-α. The specific silencing of ERα expression in MCF-7 cells also abrogated the growth effect of TrxR inhibition. Estrogenic deprivation in MCF-7 cells potentiated the pro-proliferative effect of impaired SNO homeostasis. Moreover, the subcellular distribution of ERα was altered, with a predominant nuclear localization associated with phosphorylation at Thr311 in those cells with impaired SNO homeostasis. The impairment of SNO homeostasis also expanded a cancer stem cell-like subpopulation in MCF-7 cells, as indicated by the increase of percentage of CD44+ cells and the augmented capability to form mammospheres in vitro. Notably, ER+ status in breast tumors was significantly associated with lower TXNDR1 mRNA expression and immunohistochemical studies confirmed this association, particularly when p53 abnormalities were absent.'] |
['The relationship between low estimated glomerular filtration rate (eGFR) and the outcome of ischemic stroke remains controversial, despite the close association between kidney dysfunction and atherosclerosis.', 'This study conducted subgroup analysis using data from the prospective Taiwan Stroke Registry to investigate the relationship between eGFR at the time of admission and 6-month functional outcomes in patients with the large artery atherosclerotic (LAA) subtype of acute ischemic stroke. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and outcomes were defined as modified Rankin Scale and mortality status at 6 months post stroke.', 'Of the 8052 patients with the LAA subtype of acute ischemic stroke in this study, 3312 (41.1%) had eGFR <60 mL/min/1.73 m(2). The adjusted odds ratios of worse functional outcomes following a stroke were 1.10 (95% confidence interval [CI], 0.95-1.28), 1.60 (95% CI, 1.22-2.11) and 1.60 (95% CI, 1.10-2.33) in patients with eGFR 30-59, 15-29, and <15 as compared with those with eGFR 60-119 mL/min/1.73 m(2), respectively. Increased risk of mortality was closely and independently related to high NIHSS scores and low eGFR levels. Stroke severity and eGFR were also synergistically related to 6-month mortality, with an adjusted hazard ratio of 21.19 (95% CI, 9.69-46.35) in patients with NIHSS >15 and eGFR <15 mL/min/1.73 m(2), compared with those with NIHSS 0-5 and eGFR 60-119 mL/min/1.73 m(2).'] |
['Depression is common in persons with HIV infection and with alcohol problems, and it has important prognostic implications. Neurocognitive dysfunction has been reported with chronic hepatitis C virus (HCV) infection. We hypothesized that HCV infection is associated with more depressive symptoms in HIV-infected persons with a history of alcohol problems.', 'We performed a cross-sectional analysis of baseline data from a prospective cohort study of 391 HIV-infected subjects with a history of alcohol problems, of whom 59% were HCV antibody (Ab) positive and 49% were HCV RNA-positive. We assessed depressive symptoms (Center for Epidemiologic Studies Depression [CES-D]) and past month alcohol consumption. In the primary analysis, we evaluated whether there were more depressive symptoms in HCV Ab-positive and RNA-positive subjects in unadjusted analyses and adjusting for alcohol consumption, gender, age, race, CD4 count, homelessness, drug dependence, and medical comorbidity.', 'Mean CES-D scores were higher in subjects who were HCV Ab-positive compared with those who were HCV Ab-negative (24.3 vs 19.0; p < 0.001). In adjusted analyses, the difference in CES-D scores between HCV Ab-positive and Ab-negative subjects persisted (24.0 vs 19.0; p < 0.001). Unadjusted mean CES-D scores were also significantly higher in HCV RNA-positive subjects compared with those who were RNA-negative, and the difference remained significant (24.6 vs 19.3; p < 0.001) in adjusted analyses.'] |
['The value of sequential thoracic metastasectomies is unknown. We evaluate repeat metastasectomy for limited recurrences within the thorax.', 'From July 1988 to September 1998, 54 patients underwent 2 to 6 separate sequential procedures to excise metastases after recurrence isolated to the thorax. Kaplan-Meier survival and Cox modeling determined prognostic variables.', 'Thirty-three men and 21 women, 22 to 76 years underwent 2 (100%, n = 54), 3 (50%), 4 (22%), or 5 to 6 (11%) metastasectomies. Fifty-four percent of patients had carcinoma, 35% sarcoma, 9% germ cell, and 2% melanoma. There were no operative deaths; all late deaths occurred from cancer. Median follow-up was 48 months. Cumulative 5-year survival from the second procedure was 57%. After the second, third, fourth, and fifth procedures, respectively, permanent control was achieved in 15 (27%) of 54 patients, 5 (19%) of 27, 1 (8%) of 12, and 0 of 7. Recurrence amenable to additional surgery occurred in 27 (50%) of 54, 12 (44%) of 27, 6 (50%) of 12, and 1 (17%) of 6. Mean hazard for the development of unresectable recurrence increased from 0.21 after the second procedure to 0.91 after the fifth procedure. The 5-year survival for the 27 patients undergoing only 2 metastasectomies was 60% (median not yet reached), 33% for the 15 patients undergoing only 3 metastasectomies (median 34.7 months), and 38% for the 12 patients undergoing 4 or more (median 45.6 months). From the time a recurrence was declared unresectable, patients had a 19% 2-year survival (median 8 months).'] |
['α-momorcharin (α-MMC), a type I ribosome-inactivating protein (RIP) from Momordica charantia, is well known for its antitumor and antivirus activities. However, the immunotoxicity and hepatotoxicity hampers its potential therapeutic usage. In order to reduce its toxicity, we had modified the α-MMC with polyethylene glycol (PEG), and detected the toxicity of the PEGylated α-MMC conjugates (α-MMC-PEG) in vivo.', 'After α-MMC purified from bitter melon seeds, α-MMC-PEG was constructed with a branched 20 kDa (mPEG) 2-Lys-NHS, the tests of immunogenicity, immunotoxicity, and general toxicity of α-MMC-PEG were conducted in guinea pig and rat.', 'The titer of specific IgG in rats, immunized by α-MMC-PEG, were approximately one-third of those that by α-MMC, all the guinea pigs treated with α-MMC died of anaphylaxis shock within 5 min, while no animals treated with α-MMC-PEG died in the active systemic anaphylaxis (ASA) test. The passive cutaneous anaphylaxis (PCA) reaction of α-MMC-PEG challenge in rats was significantly smaller than that of the α-MMC. The liver damage was greatly released, such as the change of globulin (GLB), aspartate aminotransferase (AST), total bilirubin (TBIL) cholesterol (CHOL), albumin (ALB), and the degree of hepatocyte necrosis in repeated toxicity study.'] |
['This study sought to evaluate the initial management of children with parapneumonic effusion admitted to all French university hospitals.', 'A nationwide survey of all 35 university hospitals took place in 2011 to assess practices for children with parapneumonic effusion, using a hypothetical clinical vignette and a standardised questionnaire. Two to four paediatricians per hospital were interviewed and asked about their initial management, probabilistic antibiotic therapy and its adaptation to microbiological results and subsequent course. Answers from paediatricians working in emergency departments, intensive care units and conventional paediatric units were compared.', 'Of the 100 paediatricians contacted, 95 responded. Of these, 98% would order an initial blood test, 70% would order diagnostic thoracentesis, and all would start immediate antibiotic therapy: 31% with a single drug, 67% with two drugs and 2% with three drugs. The most frequent initial choices were third-generation cephalosporin alone (17%) or combined with rifampicin (34%) or vancomycin (24%). Adaptation varied according to drug used, dose and duration, especially when the microorganism was not Streptococcus pneumoniae. Practices did not differ significantly among the different groups of paediatricians.'] |
['Vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) are recognized as the most frequent and bothersome symptoms associated with menopause. There are different treatments for both groups of symptoms, being necessary to individualize them.', 'There are different therapies for VMS including hormonal treatments with estrogen, with and without progestins; the new alternative, tissue-selective estrogen complex (TSEC), tibolone, phytoestrogens and only progestins. Evidence also shows efficacy with selective serotonin reuptake inhibitors. Other nonhormonal alternatives exist as second-line treatments, all with not conclusive results. The GSM can be treated with nonhormonal treatments such as vaginal lubricants and moisturizers, other alternatives as vaginal laser needs to have more evidence. On the other hand, there is the possibility to use the hormonal treatments with systemic or local estrogen, which are the most effective treatment, the TSEC and the newest selective estrogen receptor modulator (SERM), ospemifene. Therapies with testosterone and dehydroepiandrosterone (DHEA) are still under study. The GSM can be treated with nonhormonal treatments such as vaginal lubricants and moisturizers, and other alternatives as vaginal laser need to have more evidence. On the other hand, there is the possibility to use the hormonal treatments with systemic or local estrogen, which are the most effective treatment, the TSEC and the newest SERM, ospemifene. Therapies with testosterone and DHEA are still under study.'] |
['Staphylococcus aureus is a common human bacterial pathogen that causes skin and soft tissue infections. Methicillin-resistant Staph.\xa0aureus (MRSA) are increasingly drug-resistant, and thus there is great need for new therapeutics to treat Staph.\xa0aureus infections. Attention has focused on potential utility of natural products, such as extracts of marine macroalgae, as a source of novel antimicrobial compounds. The green macroalgae Ulva lactuca produces compounds inhibitory to human pathogens, although the effectiveness of U.\xa0lactuca extracts against clinically relevant strains of Staph.\xa0aureus is poorly understood. In addition, macroalgae produce secondary metabolites that may be influenced by exogenous factors including lunar phase, but whether lunar phase affects U.\xa0lactuca antimicrobial capacity is unknown. We sought to evaluate the antibacterial properties of U.\xa0lactuca extracts against medically important Staphylococci, and to determine the effect of lunar phase on antimicrobial activity. We report that U.\xa0lactuca methanolic extracts inhibit a range of Staphylococci, and that lunar phase of macrolagae harvest significantly impacts antimicrobial activity, suggesting that antimicrobial properties can be maximized by manipulating time of algal harvest. These findings provide useful parameters for future studies aimed at isolating and characterizing U.\xa0lactuca anti-Staphylococcal agents.'] |
['We hypothesize that different resuscitative fluids may immediately affect the degree of apoptosis after hemorrhagic shock.', "Rats (n = 35) were hemorrhaged 27 mL/kg over 5 minutes followed by 1 hour of shock, then resuscitation over 1 hour. The six treatment groups were sham hemorrhage, sham resuscitation, whole blood resuscitation, lactated Ringer's solution (LR) resuscitation with three times the volume bled, sham hemorrhage with LR infusion, and 7.5% hypertonic saline resuscitation (9.7 mL/kg). Liver and small intestine were harvested immediately after resuscitation. Apoptosis was evaluated by using in situ cell death detection method.", 'Resuscitation with LR resulted in a significant increase in small intestinal and liver apoptosis. Animals that received LR infusion without hemorrhage had an increased level of apoptosis in the intestine. Apoptosis in the intestine was observed in both the mucosa and muscularis externa. There was no increase in apoptosis in either organ in the animals resuscitated with sham resuscitation, whole blood, and hypertonic saline compared with the sham hemorrhage group.'] |
['The purpose of this prospective randomized trial was to examine the effect of tourniquet use on rehabilitation rate, return to work and sport activities, and muscle damage after arthroscopic meniscectomy.', 'Eighty patients who underwent arthroscopic partial meniscectomy were randomly allocated to the use of an inflated (group A, n = 40) or deflated (group B, n = 40) pneumatic tourniquet. Patients with concomitant ligamentous deficiency or grade III and IV chondral lesions were excluded. The primary outcome measures were pain, measured with a visual analog scale (VAS), and knee range of motion (ROM) on days 8 and 15 postoperatively; time required for patients to discontinue the use of crutches; time to return to light activities and moderate sporting activities such as jogging; and serum creatine phosphokinase (CPK) levels monitored preoperatively and on days 1, 8, and 15 postoperatively.', 'The 2 groups did not differ in terms of age; male-female ratio; body mass index; and preoperative International Knee Documentation Committee, Tegner, and Lysholm scores. Operative time was not significantly different between groups (mean, 27.5 for group A and 31.2 for group B; P = .83). VAS pain scores and knee ROM were not significant between groups (minimum P = .22). The patients progressed to weight-bearing without crutches within 13.4 and 12.9 days for groups A and B, respectively (P = .9). Return to work and jogging did not differ significantly between groups (minimum P = .34). Serum CPK values were also not significantly different between or within groups during consecutive measurements (P = .3). Tourniquet time did not significantly affect postoperative ROM, VAS pain scores, or serum CPK levels (minimum P = .14).'] |
['Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes, found in fungi and bacteria, which biosynthesize peptides without the aid of ribosomes. Although their metabolite products have been the subject of intense investigation due to their life-saving roles as medicinals and injurious roles as mycotoxins and virulence factors, little is known of the phylogenetic relationships of the corresponding NRPSs or whether they can be ranked into subgroups of common function. We identified genes (NPS) encoding NRPS and NRPS-like proteins in 38 fungal genomes and undertook phylogenomic analyses in order to identify fungal NRPS subfamilies, assess taxonomic distribution, evaluate levels of conservation across subfamilies, and address mechanisms of evolution of multimodular NRPSs. We also characterized relationships of fungal NRPSs, a representative sampling of bacterial NRPSs, and related adenylating enzymes, including alpha-aminoadipate reductases (AARs) involved in lysine biosynthesis in fungi.', 'Phylogenomic analysis identified nine major subfamilies of fungal NRPSs which fell into two main groups: one corresponds to NPS genes encoding primarily mono/bi-modular enzymes which grouped with bacterial NRPSs and the other includes genes encoding primarily multimodular and exclusively fungal NRPSs. AARs shared a closer phylogenetic relationship to NRPSs than to other acyl-adenylating enzymes. Phylogenetic analyses and taxonomic distribution suggest that several mono/bi-modular subfamilies arose either prior to, or early in, the evolution of fungi, while two multimodular groups appear restricted to and expanded in fungi. The older mono/bi-modular subfamilies show conserved domain architectures suggestive of functional conservation, while multimodular NRPSs, particularly those unique to euascomycetes, show a diversity of architectures and of genetic mechanisms generating this diversity.'] |
['Short-term elevations in fine particulate matter air pollution (PM2.5) are associated with increased risk of acute cerebrovascular events. Evidence from the peripheral circulation suggests that vascular dysfunction may be a central mechanism. However, the effects of PM2.5 on cerebrovascular function and hemodynamics are unknown.', 'We used transcranial Doppler ultrasound to measure beat-to-beat blood flow velocity in the middle cerebral artery at rest and in response to changes in end-tidal CO2 (cerebral vasoreactivity) and arterial blood pressure (cerebral autoregulation) in 482 participants from the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) of Boston study. We used linear mixed effects models with random subject intercepts to evaluate the association between cerebrovascular hemodynamic parameters and mean PM2.5 levels 1 to 28 days earlier adjusting for age, race, medical history, meteorologic covariates, day of week, temporal trends, and season.', 'An interquartile range increase (3.0 µg/m(3)) in mean PM2.5 levels during the previous 28 days was associated with an 8.6% (95% confidence interval, 3.7%-13.8%; P<0.001) higher cerebral vascular resistance and a 7.5% (95% confidence interval, 4.2%-10.6%; P<0.001) lower blood flow velocity at rest. Measures of cerebral vasoreactivity and autoregulation were not associated with PM2.5 levels.'] |
['Early nocturnal sleep enhances the consolidation of declarative memories acquired during prior wakefulness. Patients with type 1 diabetes frequently experience hypoglycemic episodes during sleep. We investigated whether short-lasting hypoglycemia during early nocturnal sleep affects the sleep-associated consolidation of declarative memories.', 'Sixteen type 1 diabetic patients and 16 healthy subjects matched for age and BMI were tested. On one condition, a linear fall of plasma glucose to 2.2 mmol/l was induced within 60 min by infusing insulin during early sleep. On the control condition, euglycemia (>3.86 mmol/l) was maintained throughout the night. In the morning, subjects recalled word pairs learned in the preceding evening. To assess mood and attention, a symptom questionnaire, an adjective check list, and the Stroop test were applied. Also, auditory event-related brain potentials were recorded.', 'After euglycemia, subjects recalled 1.5 +/- 0.5 more word pairs than after hypoglycemia (P < 0.01), remembering 2.0 +/- 0.6 more word pairs than at immediate recall before sleep (P = 0.002). Across the hypoglycemic night, no such gain occurred (+0.5 +/- 0.6 words; P = 0.41). Hypoglycemia during sleep also impaired mood (P < 0.05) but did not affect attention. Effects compared well between type 1 diabetic patients and healthy control subjects.'] |
['Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies.', 'The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS.', 'Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data (p<0.05 corrected).', 'Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with "low NFL levels" showed greater activity in the putamen compared with subjects with "high NFL levels" (p=0.001). These results are independent of cognitive impairment index.'] |
['The clinical relevance of the G1896A precore mutation in chronic hepatitis B is still poorly understood.', 'To assess the frequency of G1896A precore mutation in Brazilian patients with chronic hepatitis B, as well as its relation to the viral genotype, serum HBV-DNA levels and liver damage.', 'Fifty chronic hepatitis B patients (29 HBeAg-negative and 21 HBeAg-positive) were studied. HBV-DNA was quantified by the Amplicor HBV Monitor test and precore region and S gene were amplified and submitted to automatic sequencing. The histological activity index (HAI), degrees of hepatic fibrosis and distribution of core antigen (HBcAg) in hepatocytes were determined.', 'Precore mutation occurred in 1/21 (4.8%) HBeAg-positive patients and in 17/29 (58.6%) HBeAg-negative (p < 0.0001). Genotype D was identified in 56.5%, genotype A in 41.3%, and genotype F in 2.2%. The frequency of genotypes D and A, as well as serum levels of ALT and HBV-DNA were similar in patients infected with wild type and with precore mutant. Patients infected with precore mutant presented a higher frequency of moderate/severe HAI (p: 0.03) and moderate/severe fibrosis and cirrhosis (p: 0.03) than those infected with wild type. There was no association between G1896A mutation and cytoplasmic expression of HBcAg.'] |
['Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated.', 'To analyze the presence of SD in a large group of patients receiving long-term opioids.', 'A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects.', 'Sexual function was determined by the Female Sexual Function Index (FSFI; scores\xa0= 2-36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores\xa0= 1-30).', 'Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P < .05), although they reported having a regular partner (84% vs 70%, P\xa0= .03) and a sexually active life (69% vs 34%, respectively, P\xa0= .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median\xa0= 70 mg/d, interquartile range\xa0= 43.1-170, 115.5 ± 110.3 mg/d vs median\xa0= 60 mg/d, interquartile range\xa0= 30-100.6, 76.67 ± 63.79 mg/d, P\xa0= .016) at the same mean intensity of pain (P\xa0= .54), which correlated to FSFI scores (r\xa0=\xa0-0.313, P\xa0= .01).'] |
['Pancoast tumour is a rare neoplasia in which the optimal therapeutic management is still controversial. The traditional treatment of Pancoast tumour (surgery, radiotherapy or a combination of both) have led to an unsatisfactory outcome due to the high rate of incomplete resection and the lack of local and systemic control. The aim of the study was to determine the efficacy of the trimodality approach.', 'Fifty-six patients (male/female ratio: 47/9, median age: 64 years) in stage IIB to IIIB were treated during a period between 1994 and 2013. Induction therapy consisted of 2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30-44 Gy). After restaging, eligible patients underwent surgery 2 to 4-week post-radiation.', 'Thirty-two (57.1%) patients were cT3 and 24 (42.9%) cT4, 47 (83.9%) were N0 and 9 (16.1%) N+. Forty-eight (85.7%) patients underwent R0 resection and 10 (17.9%) had a complete pathological response (CPR). Thirty-day mortality rate was 5.4%, major surgical complications occurred in 6 (10.7%) patients. At the end of the follow-up, 17 (30.4%) patients were alive and 39 (69.6%) died (29 for cancer-related causes), with an overall 5-year survival of 38%. At statistical analysis, stage IIB (P = 0.003), R0 resection (P = 0.03), T3 tumour (P = 0.002) and CPR (P = 0.01) were significant independent predictors of better prognosis.'] |
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