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pubmed_207_57
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The Portex infant breathing/ventilation systems with 8.5 mm and 15 mm internal diameter connectors were compared with a standard T-piece which had a 15 mm connector and 22 mm internal diameter tubing. The differential pressures across each system were measured at constant fresh gas flows up to 30 l.min-1 dry air. Resistance was calculated at flows compatible with quiet respiration and peak inspiratory flow. Flow resistance of the 3.0 mm internal diameter tracheal tube in conjunction with the minilink breathing systems were similar to those previously reported for tracheal tubes alone. However, the minilink breathing system assumed a greater influence on resistance when tracheal tubes of larger internal diameter were used. It added considerably more resistance than the standard tubing. This may have a deleterious effect during spontaneous ventilation in older children.
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10.1111/j.1365-2044.1993.tb06910.x
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pubmed_399_10779
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The explanation of apparent misalignment in the Poggendorff figure, based on underestimation of the intertransversal distance, was investigated in two experiments. In Experiment 1, subjects judged the intertransversal distance in the traditional Poggendorff figure and two of its variants. The size of the acute angle and the intertransversal distance were manipulated. Half of the subjects made the judgments with the method used by Wilson and Pressey (1976) and the other half made their judgments with the method used by Greist-Bousquet and Schiffman (1981). The results indicated that perceived intertransversal distance was greater with the former method. In Experiment 2, subjects adjusted the transversals to apparent collinearity in the same displays as were used in Experiment 1. The collinearity judgments were transformed to allow comparison with the results of Experiment 1. Comparison of the collinearity judgments with the distance judgments indicated that they did not follow similar trends. For each Poggendorff variant, proportional distance judgments increased as the size of the acute angle increased, and decreased as the intertransversal distance increased. Collinearity judgments did not vary as a function of intertransversal distance. As the size of the acute angle increased, collinearity judgments increased for two of the Poggendorff variants but decreased for the third. It was concluded that the findings did not support the explanation of apparent misalignment based on underestimation of the intertransversal distance.
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10.3758/bf03208056
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pubmed_781_21618
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The local structure of as-synthesised silicalite-1 zeolites is modified using asymmetric R(Pr)3N(+) structure directing agents. Using multi-nuclear NMR ((1)H, (13)C, (14)N, (19)F, (29)Si), we show for the first time the ability of these cations to adopt preferential orientations at the zeolite channels' crossing.
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10.1039/c5dt02558c
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pubmed_156_3137
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PURPOSE
Oxidative stress is increased in the retina in diabetes, and antioxidants inhibit activation of caspase-3 and the development of retinopathy. The purpose of this study was to investigate the effect of diabetes on the release of cytochrome c from mitochondria and translocation of Bax into mitochondria in the rat retina and in the isolated retinal capillary cells.
METHODS
Mitochondria and cytosol fractions were prepared from retina of rats with streptozotocin-induced diabetes and from the isolated retinal endothelial cells and pericytes incubated in 5 or 20 mM glucose medium for up to 10 days in the presence of superoxide dismutase (SOD) or a synthetic mimetic of SOD (MnTBAP). The release of cytochrome c into the cytosol and translocation of the proapoptotic protein Bax into the mitochondria were determined by the Western blot technique and cell death by caspase-3 activity and ELISA assay.
RESULTS
Diabetes of 8 months' duration in rats increased the release of cytochrome c into the cytosol and Bax into the mitochondria prepared from the retina, and this phenomenon was not observed at 2 months of diabetes. Incubation of isolated retinal capillary cells with 20 mM glucose increased cytochrome c content in the cytosol and Bax in the mitochondria, and these abnormalities were accompanied by increased cell apoptosis. Inclusion of SOD or its mimetic inhibited glucose-induced release of cytochrome c, translocation of Bax, and apoptosis.
CONCLUSIONS
Retinal mitochondria become leaky when the duration of diabetes is such that capillary cell apoptosis can be observed; cytochrome c starts to accumulate in the cytosol and Bax into the mitochondria. Inhibition of superoxides inhibits glucose-induced release of cytochrome c and Bax and inhibits apoptosis in both endothelial cells and pericytes. Identifying the mechanism by which retinal capillary cells undergo apoptosis may reveal novel therapies to inhibit the development of retinopathy in diabetes.
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10.1167/iovs.03-0353
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pubmed_1113_542
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Bilateral inguinal adenitis and penoscrotal elephantiasis are uncommonly encountered presentations of Lymphogranuloma venereum. Herein, we report a male who presented with bilateral inguinal bubos along with penoscrotal elephantiasis that developed within 6 months of the primary lesion.
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pubmed_1113_542
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pubmed_224_9184
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A case of Mönckeberg's arteriosclerosis associated with Raynaud's phenomenon and diabetes is reported. It is probable that Mönckeberg's arteriosclerosis could provoke a Raynaud's phenomenon when predisposing local conditions, such as microvasculature and/or haemorheological alterations, are present. Finally our findings seem to demonstrate that xeroradiographic investigation is most important for the early diagnosis of the disease.
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pubmed_224_9184
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pubmed_1052_24389
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BACKGROUND & AIMS
The dilemma of early diagnosis of biliary Atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis is challenging. The aim was to design and validate a scoring system for early discrimination of BA from other causes of neonatal cholestasis.
METHODS
A twelve-point scoring system was proposed according to clinical, laboratory, ultrasonographic, and histopathological parameters. A total of 135 patients with neonatal cholestasis in two sets were recruited to design (n=60) and validate (n=75) a scoring system. Parameters with significant statistical difference between BA (n=30) and non-BA (n=30) patients in the design set were analyzed by logistic regression to predict the presence or absence of BA then a scoring system was designed and validated.
RESULTS
The total score ranged from 0 to 37.18 and a cut-off value of >23.927 could discriminate BA from other causes of neonatal cholestasis with sensitivity and specificity of 100% each. By applying this score in the validation set, the accuracy was 98.83% in predicting BA. The diagnosis of BA was proposed correctly in 100% and the diagnosis of non-BA was proposed correctly in 97.67% of patients. By applying this model, unnecessary intraoperative cholangiography would be avoided in non-BA patients.
CONCLUSIONS
This scoring system accurately separates infants with BA and those with non-BA, rendering intraoperative cholangiography for confirming or excluding BA unnecessary in a substantial proportion of patients.
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pubmed_1052_24389
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pubmed_373_14927
|
Three female patients without type B or type C viral hepatitis, alcoholic, metabolic or autoimmune liver disease, were selected from 250 cases with histologically proven liver cirrhosis (M:F = 183:67). All three cases showed at least one positive aspect among three parameters of serum anti-HBc (RPHA, x1), HBV-DNA (gene S, nested PCR) and liver HBs and/or pre-S2 antigen (immunoperoxidase methods). Two cases may suggest a spontaneous disappearance of HBV from sera. Another case may suggest a contribution of mutant HBV which can not be detected by the routine tests. These HBV-related cirrhotic patients have done well clinically and have not been associated with hepatocellular carcinoma during the period from 6 to 12 years of follow-up when compared with 59.6% and 65.4% prevalence of hepatocarcinogenesis in type B and type C hepatitis-associated cirrhosis during the observation period of six and seven years on average, respectively.
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pubmed_373_14927
|
pubmed_406_3318
|
Channel catfish, Ictalurus punctatus, measuring 150 (+/- 5)mm were exposed continuously to dieldrin for 70 days to determine if equilibrium between dieldrin uptake and elimination was reached by muscle tissue. Fish exposed to 13 parts per trillion (pptr) dieldrin reached equilibrium in 56 days, fish exposed to 27 pptr dieldrin were near equilibrium after 56 days, and fish exposed to 49 pptr dieldrin did not reach a balance between uptake and elimination after 70 days of exposure. Evidence of this study showed that balance between uptake and elimination was reached in less time at lower exposure levels than at higher levels.
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10.1007/BF01686080
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pubmed_156_19316
|
1. The relative roles of various members of the human sulfotransferase (SULT) enzyme family in the metabolism of apomorphine, a dopamine receptor antagonist used in the treatment of Parkinson's disease and, more recently, erectile dysfunction, were examined. In humans, sulfation is the major route of metabolism of this drug. 2. Using recombinant SULTs expressed in Escherichia coli, R(--)-apomorphine sulfation was studied using the universal barium precipitation assay in the presence of [35S] 3'-phosphoadenosine 5'-phosphosulfate and SULTs 1A1, 1A2, 1A3, 1B1, 1C2, 1E1 and 2A1. It was shown that SULTs 1A1, 1A2, 1A3 and 1E1 all sulfated apomorphine to varying extents. Low activity with SULT1B1 was only seen at the highest concentration (100 microM) and no activity with SULT1C2 or SULT2A1 was observed. 3. Kinetic analysis using purified recombinant SULTs showed that 1A1, 1A3 and 1E1 all had similar Vmax/Km values, although SULT1E1 had a slightly lower Km at around 1 microM compared with approximately 4 microM for the other SULTs. 4. By correlating apomorphine sulfation (at 10 microM) in a bank of 28 liver cytosols with SULT activity towards 10 microM 4-nitrophenol (SULT1A1) and 0.2 microM 17beta-oestradiol (SULT1E1), a strong correlation with SULT1A1 activity was clearly demonstrated, suggesting this enzyme was primarily responsible for hepatic apomorphine sulfation. 5. These findings were confirmed using immuno-inhibition experiments with antibodies against SULT1A and SULT1E1, which showed preferential inhibition of apomorphine sulfation in human liver cytosol by anti-SULT1A. 6. The results strongly implicate SULT1A1 as the major enzyme responsible for hepatic apomorphine metabolism. As SULT1A1 is subject to a common functional polymorphism, sulfation phenotype may be an important determinant of susceptibility to side-effects of apomorphine and/or efficacy of treatment.
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10.1080/00498250310001609192
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pubmed_1095_8703
|
During evolution vertebrates had to evolve in order to perform more and more complex tasks. To achieve this goal, they developed specialized tissues: a highly branched vascular system to ensure that all tissues receive adequate blood supply, and an intricate nervous system in which nerves branch to transmit electrical signals to peripheral organs. The development of both systems is tightly controlled by a series of developmental cues, which ensure the accomplishment of a complex and highly stereotyped mature network. Vessels and nerves use similar signals and principles to grow, differentiate, and navigate toward their final targets. Both systems share several molecular pathways, highlighting an important link between vascular biology and neuroscience. Moreover, the vascular and the nervous system crosstalk and, when deregulated, contribute to medically relevant diseases. This new phenomenon, named the neurovascular link, promises to accelerate the discovery of new pathogenetic insights and therapeutic strategies for the treatment of both vascular and neurological diseases. To study the development of both systems, scientists are taking advantage of the use of several vertebrate and invertebrate animal models. In the first part of this chapter, we will discuss the more commonly used animal models; in the second part, the striking similarities occurring during the development of the vascular and the neural systems will be revised.
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10.1016/S0070-2153(07)80001-9
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pubmed_249_17080
|
Not only have the systemic mycoses clearly increased in number but also mycoses of the skin are more common than presumed in the past. Today onychomycosis is found in up to 10% of human beings. Onychomycosis can compromise quality of life markedly. Common tinea pedis is one of the most important risk factors for erysipelas of the lower legs. The clinical presentation of oral candidosis in HIV-infected patients is changing; Candida dubliniensis has been identified as another important causative microorganism. Onychomycosis today in most cases can be cured using terbinafine or itraconazole. When choosing the ideal drug in a given case, both the benefit risk ratio and the benefit cost ratio have to be taken into account. Liposomally encapsulated amphotericin B represents a major breakthrough in the treatment of systemic mycoses or fever of unknown origin. The same applies to liposomally encapsulated econazole with respect to tinea pedis. In regard to the pathogenesis of Candida infections the family of secreted aspartic proteinases plays a major role as a virulence factor and possible future target for antimycotic treatment.
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10.1007/s001050051271
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pubmed_873_6355
|
Purpose Transplant recipients who develop cutaneous squamous cell carcinomas are at high risk for multiple subsequent skin cancers. Sirolimus has been shown to reduce the occurrence of secondary skin cancers, but no study included a follow-up exceeding 2 years. We extended at 5 years the TUMORAPA randomized trial of sirolimus-based immunosuppressive regimen versus calcineurin inhibitor-based immunosuppression. Methods Kidney transplant recipients receiving calcineurin inhibitors who had at least one cutaneous squamous cell carcinoma were randomly assigned to receive sirolimus as a substitute for calcineurin inhibitors (n = 64) or to maintain their initial treatment (n = 56). The primary end point was survival free of squamous cell carcinoma at 5 years. Secondary end points included the occurrence of other skin cancers, renal function, patient and graft survival, and treatment tolerance. Results Survival free of cutaneous squamous cell carcinoma was significantly longer in the sirolimus group than in the calcineurin inhibitor group ( P = .007). In the sirolimus group, the number of patients with new skin cancers was significantly lower compared with the calcineurin inhibitor group: 22% versus 59% for squamous cell carcinomas ( P < .001), 34% versus 66% for other skin cancers ( P < .001), and 20% versus 37.5% for basal cell carcinomas ( P < .05). Kidney graft function, patients, and graft survival were similar in both groups. In the sirolimus group, the mean number of serious adverse effects per patient decreased from 1.16 during the first 2 years, to 0.83 between years 2 and 5. Conclusion In kidney transplant recipients with previous cutaneous squamous cell carcinomas, the antitumoral effect of conversion from calcineurin inhibitors to sirolimus was maintained at 5 years, and sirolimus tolerance was satisfactory.
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10.1200/JCO.2017.76.6691
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pubmed_950_5805
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We use a simple model to study the static and dynamic efficiency of alternative regulation regimes for the reimbursement of medical innovations when responses to a new treatment (effectiveness) are heterogeneous across the eligible population. When the rational behavior of profit-maximizing firms is taken into account, only average value-based prices can ensure both static and dynamic efficiency, but they imply higher expenditure and lower consumer surplus. Ignoring dynamic efficiency, if patients' responses are sufficiently homogeneous, marginal value-based prices may dominate from the payer's perspective. We also present a refinement of average value-based prices that could reverse this result. Overall, the cost of ensuring static and dynamic efficiency is increasing in the degree of heterogeneity. A real-world example is used to illustrate these results.
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10.1002/hec.4033
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pubmed_1127_4889
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Obesity plays a causative role in the pathogenesis of the metabolic syndrome. Adipokines may link obesity to its co-morbidities. Most adipokines with pro-inflammatory properties are overproduced with increasing adiposity, while some adipokines with anti-inflammatory or insulin-sensitizing properties, like adiponectin are decreased. This dysregulation of adipokine production may promote obesity-linked metabolic disorders and cardiovascular disease. Besides considering adipokines, this review will also highlight the cellular key players and molecular mechanisms involved in adipose inflammation. Targeting the changes in the cellular composition of adipose tissue, the underlying molecular mechanisms, and the altered production of adipokines may have therapeutic potential in the management of the metabolic syndrome.
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10.1016/j.mce.2009.07.031
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pubmed_217_1587
|
BACKGROUND
Patients with sickle cell anemia (SCA) have a high incidence of cholelithiasis and choledocholithiasis. This report is an analysis of our experience with laparoscopic cholecystectomy (LC) for children with SCA and the role of endoscopic retrograde cholangiopancreatography (ERCP).
PATIENTS AND METHODS
The records of children with SCA who had cholecystectomy were retrospectively reviewed for age, sex, hemoglobin level, hemoglobin electrophoresis, indication for cholecystectomy, operative time, hospital stay, and postoperative complications. They were divided into 2 groups, open cholecystectomy (OC) group and LC group, and the 2 were compared in terms of operative time, hospital stay, and postoperative complications.
RESULTS
Over a period of 15 years (January 1995 and December 2009), 94 children with SCA had cholecystectomy. Thirty-five (19 males and 16 females) had OC, 52 (28 males and 24 females) had LC, and 7 (4 males and 3 females) had LC and splenectomy. Their age ranged from 4 to 15 years (mean, 11.4 y). The indications for cholecystectomy were biliary dyspepsia and biliary colic (55), acute cholecystitis (7), obstructive jaundice (17), asymptomatic (12), and biliary pancreatitis (3). All those who had OC underwent intraoperative cholangiogram, 9 of them (25.7%) had common bile duct (CBD) exploration and 2 transduodenal sphincterotomy. Of those who had LC, 13 (25%) underwent preoperative ERCP, which was normal in 1, showed dilated CBD with no stones in 2, and dilated CBD with stones in 7. In 3, ERCP showed dilated CBD with enlarged, inflammed papilla suggestive of recent stone passage. Nine underwent endoscopic sphincterotomy and stone extraction followed by LC. There was no mortality; 1 (2.1%) required conversion to OC and another underwent postoperative exploration because of bleeding from an accessory cystic artery. In the LC group, 4 (7.7%) developed minor postoperative complications, whereas 8 (22.9%) in the OC group developed complications.
CONCLUSIONS
With proper perioperative management, LC is feasible, safe, and superior to OC in children with SCA with regard to postoperative complications, duration of hospital stay, cosmetic appearance, and postoperative recovery. LC should be the treatment of choice for both symptomatic and asymptomatic cholelithiasis in children with SCA. ERCP is a valuable diagnostic and therapeutic investigation both preoperatively and postoperatively. The sequential approach of endoscopic sphincterotomy and stone extraction followed by LC is a safe and effective approach for the management of cholelithiasis and choledocholithiasis in children with SCA.
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10.1097/SLE.0b013e3182471b1c
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pubmed_829_10320
|
This paper describes the effect on Sun Protection Factor (SPF) of the combination of inorganic and organic filters in sunscreen products as determined by an in vitro method. O/W emulsions containing inorganic filters, such as titanium dioxide and zinc oxide, combined with 18 EU-authorized UV-B organic filters were tested. SPF measurements were carried out using a spectrophotometer equipped with an integrating sphere. This study observed a synergic effect when titanium dioxide was combined with either anisotriazine or octyldimethylPABA. The combination of zinc oxide with 11 UV-B organic filters also exhibited a similar synergy; however, the measured SPF was systematically lower than the protection factor achieved with titanium dioxide.
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10.1016/j.ijpharm.2007.05.047
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pubmed_702_19593
|
BACKGROUND
It is speculated that the exposure to Mycobacterium tuberculosis, either by infection or by Bacillus Calmette-Guérin vaccination, may inhibit the onset of atopy by the modification of immune profiles leading to a shift of T(H)1/T(H)2 balance to the T(H)1 side.
OBJECTIVE
One hundred eighty-six patients hyperreactive at tuberculin skin test (TST) were examined in order to investigate the prevalence of atopic disorder, particularly referring to the association between the size of the TST induration and the prevalence of sensitization and manifest atopic disorder.
METHODS
The study consisted of a family history record, patients' medical history assessment and clinical examination, skin prick test (SPT), serum total and allergen-specific IgE (sIgE) measurement and eosinophil count.
RESULTS
Atopic disorder was present in 49 (26.3%) patients tested. No significant difference between the groups based on the TST induration size (15-24 mm vs. > or =25 mm) was found for gender distribution, family atopy history, total IgE measurement, eosinophil count, positive SPT, and the presence of sIgE. A significant difference was found for the age median (14.0 years vs. 13.0 years), childhood atopy record, and manifest atopic disorder. No association between the size of the TST induration and the incidence of allergic sensitization was demonstrated. However, a significant inverse association between the size of the TST induration and manifest atopic disorder was demonstrated.
CONCLUSION
In patients highly hyperreactive at TST, the size of the induration is inversely associated with manifest atopic disorder.
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10.1002/ppul.21043
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pubmed_585_618
|
The addition of 2.8 μg/ml algal extracts enhanced both scu-PA production and cell growth in a serum-free medium, compared to a conventional serum-free medium for the cultivation of recombinant CHO cells. The growth rate and scu-PA production were relatively lower in the serum-free medium than 5% serum containing medium: however, specific scu-PA production rate was higher in the serum-free medium due to the long-term period of cultivation (3.66×10(-4) vs. 2.48×10(-4) IU/cell/day). Overall scu-PA production rate was also greater in an enforced serum-free medium as 25,000 IU/day over 50 d of perfusion cultivation. The conversion ratio of scu-PA to tcu-PA was greatly reduced in the serum-free medium during perfusion cultivation (10% compared to 20% conversion in a serum containing medium).
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10.1007/BF00749654
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pubmed_244_1948
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Infectious diseases of the upper airway can lead to emergency situations with partial up to complete obstruction and respiratory insufficiency, especially in infants and toddlers. This necessitates a cool-headed and calm approach; however, at times a prompt intervention is required by the primary care physician. Important questions concerning patient history include the onset of symptoms, severity and duration of fever and for orientation possible previously known respiratory problems since birth or in the first weeks afterwards (e.g. congenital malformations of the larynx or trachea). The examination should begin by careful observation of the child's position of comfort and by noting all vital signs. A child with inspiratory or biphasic stridor at rest already has some degree of airway obstruction that can progress to complete obstruction over time. Systemic steroids and inhalation of nebulized epinephrine (adrenaline) are the best therapeutic options for viral laryngotracheobronchitis, which is the most common cause of acute stridor in childhood. Rare differential diagnoses, such as bacterial tracheitis, epiglottitis (supraglottitis), retropharyngeal and parapharyngeal infections necessitate disease-specific management.
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10.1007/s00608-015-0240-0
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pubmed_783_5823
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The regulation of D₃ receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D₃-preferring radioligand [(3)H]WC-10 and a D₂-preferring radioligand [(3)H]raclopride were used and the absolute densities of the dopamine D₃ and D₂ receptors were determined in the striatal regions and substantia nigra (SN) from postmortem brains from five cases of DLBD, which included dementia with Lewy bodies (DLB, n=4) and Parkinson disease dementia (PDD, n=1). The densities of the dopamine D₁ receptor, vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT) were also measured by quantitative autoradiography using [(3)H]SCH23390, [(3)H]dihydrotetrabenazine, and [(3)H]WIN35428, respectively. The densities of these dopaminergic markers were also measured in the same brain regions in 10 age-matched control cases. Dopamine D₃ receptor density was significantly increased in the striatal regions including caudate, putamen and nucleus accumbens (NAc). There were no significant changes in the dopamine D₁ and D₂ receptor densities in any brain regions measured. VMAT2 and DAT densities were reduced in all the brain regions measured in DLB/PDD, however, the significant reduction was found in the putamen for DAT and in the NAc and SN for VMAT2. The decrease of dopamine pre-synaptic markers implies neuronal loss in the substantia nigra pars compacta (SNpc) in these DLB/PDD cases, while the increase of D₃ receptors in striatal regions could be attributed to dopaminergic medication history and psychiatric states such as hallucinations. Whether it also reflects compensatory regulation upon dopaminergic denervation warrants further confirmations on larger populations.
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pubmed_783_5823
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pubmed_670_14588
|
The effects of repeated ip administration of diethylenetriaminepentaacetic acid (DTPA), Kryptofix 222, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), ethylenglycol-bis-(beta-amino-ethylether)-N,N'-tetraacetic acid (EGTA), and Kryptofix 5 on the distribution and excretion of sc-injected strontium were investigated in male Swiss mice. Groups of 20 animals received 95 mg strontium nitrate/kg, and 10 min later ip treatment with one of the chelators or 0.9% saline was initiated and continued for 10 d. The animals were housed in plastic metabolism cages, and urine and feces were collected daily during the period of treatment. At the end of this period, the animals were killed and the concentration of strontium determined in their tissues. Only Kryptofix 5 and EGTA significantly increased the amount of strontium excreted into feces, whereas none of the chelators significantly enhanced the urinary elimination of strontium. Treatment with Kryptofix 5 significantly decreased the concentration of strontium in all tissues analyzed. Kryptofix 5 was the most effective agent of those tested in the removal of strontium after a single dose of strontium nitrate.
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pubmed_670_14588
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pubmed_698_11311
|
This article reports on a qualitative social constructionist analysis that aims to examine the ways in which menopause and women's bodies are represented in self-help texts. In particular, we aim to compare texts with a more traditional 'medical' approach and others taking a more 'woman-centred' perspective. Four diverse self-help books on menopause and HRT available in England were analysed to examine the ways in which women, menopause and midlife were portrayed, and to investigate the construction of notions of knowledge, expertise and responsibility. The selected texts were published between 1992 and 1996 and covered a range of perspectives, including medical, alternative and feminist. Results showed that menopause was constructed as a 'deficiency disease' in all four texts, although in three of the texts this 'disease' discourse was counterposed by the simultaneous use of a 'menopause as natural' discourse. Menopause was also constructed as inherently complex and confusing, as were women's bodies. A discourse of 'change' was drawn upon in which menopause was portrayed as only one of the stressful events women must cope with at midlife. Finally, most of the texts drew on a discourse of 'management' rather than one of 'treatment' or 'cure' when discussing how menopause, and women's relationship to menopause should be handled. The medical profession was constructed as the primary source of expertise on menopause and women's bodies, although responsibility for the 'management' of menopause as a chronic condition lay solely with individual women. Although there were a number of differences in representations of menopause in medically oriented self-help texts and those adopting a more woman-centred perspective, our analysis also revealed several areas of similarity and overlap with regard to the construction of menopause and its 'management'. The implications of these findings for the construction of menopause in self-help texts for women are discussed.
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10.1016/s0277-9536(02)00165-x
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pubmed_534_2562
|
BACKGROUND
Transseptal puncture for left atrial (LA) access is still mainly performed using fluoroscopy and transesophageal or intracardiac echocardiography. We present an easily applicable approach for the guidance of transseptal puncture that uses the combination of a 3D-mapping system and CT-derived 3D-overlayed anatomy.
METHODS AND RESULTS
A computer tomographic (CT) LA-angiography was performed in n = 65 patients prior to a scheduled atrial fibrillation ablation procedure. The CARTO3 (Biosense Webster, Diamond Bar, CA, USA) segmentation tool was used to create a 3D-reconstruction of cardiac anatomy and the spine. The CARTO UNIVU module was then used to overlay and register the segmented 3D-anatomy onto fluoroscopy. The 3D-reconstructed spine and cardiac anatomy were congruently aligned to their fluoroscopic counterparts in fluoroscopic views. The feasibility of the technique, its safety, and accuracy (assessed as contour offsets between 3D-overlay and angiographic LA anatomy) were evaluated. Overlay registration accuracy was analyzed by CARTO3 registration matrices. Transseptal puncture was feasible without complications in all 65 patients using the new 3D-overlay technique. Three-dimensional-overlay contour offsets were 1.6 ± 1.2 mm in left PV, 1.7 ± 1.2 mm in right PV, and 1.3 ± 1.0 mm in the LA roof region. Overlay registration accuracy was 4.9 ± 2.7 mm. The average time needed for anatomy segmentation was 204 ± 61 seconds, time needed for overlay registration was 18 ± 8 seconds.
CONCLUSIONS
Three-dimensional-augmented fluoroscopy is feasible, safe, and easy to apply as guidance for transseptal puncture and demonstrates a high level of accuracy.
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10.1111/jce.12885
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pubmed_184_5779
|
Following renal transplantation, hepatic glucocerebroside deposits in a child with Gaucher disease were reduced. This suggests that enzyme replacement had been achieved.
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pubmed_184_5779
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pubmed_1082_16922
|
alpha 1-Antitrypsin (alpha 1-AT) is one of the major proteinase inhibitors in serum. Its primary physiological function is to inhibit neutrophil elastase activity in lung, but it also inhibits other serine proteases including trypsin, chymotrypsin, thrombin, and cathepsin. We have previously reported a novel alpha 1-AT, S-2 isoform, from rabbit that is induced up to 100-fold in the liver during acute inflammatory condition (Ray, B. K., Gao, X., and Ray, A. (1994) J. Biol. Chem. 269, 22080-22086). Here, we present evidence that the expression of this alpha 1-AT S-2 gene is also induced in lipopolysaccharide (LPS)-treated peripheral blood monocytes. From the cloned genomic DNA, we have identified a distal LPS-responsive enhancer located between -2438 and -1990 base pairs upstream of the transcription start site. In vitro DNA-binding studies demonstrated an interaction of an LPS-inducible NF-kappa B-like nuclear factor with a kappa B-element present in this enhancer region. Antibodies against p65 and p50 subunits of NF-kappa B supershifted the DNA-protein complex. A mutation of the NF-kappa B-binding element virtually abolished the LPS-responsive induction of the chimeric promoter in monocytic cells. Furthermore, overexpression of NF-kappa B induced the wild-type promoter activity. Taken together, these results demonstrated that during LPS-mediated inflammation, NF-kappa B/Rel family of transcription factors play a crucial role in the transcriptional induction of the inflammation responsive alpha 1-AT gene.
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10.1074/jbc.270.49.29201
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pubmed_900_2909
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Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where major histocompatibility complex (MHC) genes and the insulin-linked polymorphic region have been shown to play major roles. We report here an integrated effect of tumor necrosis factor (TNF) alpha with other cytokine genes. The TNF-alpha-308 GA and AA (high secretor) polymorphisms were significantly increased in the patients with T1D (n = 235) [P < 7 x 10(-6), odds ratio (OR) = 3.04, 95% confidence interval (CI) = 1.8-5.3] compared with the controls (n= 128). The variants of interferon-gamma (IFN-gamma) (A(+874)T), interleukin (IL)-6 (G(-174)C), IL-10 (A(-1082)G, T(-819)C, C(-592)A) and transforming growth factor (TGF) beta1 (T(cdn10)C, G(cdn25)C) did not show a significant difference between patients and controls. However, simultaneous presence of TNF-alpha-308 GA+AA along with both high and low secretor genotypes of IFN-gamma (P < 0.003) was significantly increased in patients. Simultaneous presence of TNF-alpha-308 GA + AA along with high secretor genotypes of IL-6 (P < 0.0001, OR = 2.61, 95% CI = 1.5-4.56), IL-10 (P < 0.0001, OR = 4.26, 95% CI = 1.9-10.1) and TGF-beta1 (P < 0.00004, OR = 2.8, 95% CI = 1.6-4.86) was also significantly increased in patients with T1D. Low secretor genotype of TNF-alpha-308 GG along with low secretor genotypes of IFN-gamma (P < 0.001, OR = 0.465, 95% CI = 0.28-0.77), high secretor genotypes of IL-6 (P < 0.000004, OR = 0.76, 95% CI = 0.227-0.621) and TGF-beta1 (P < 0.000006, OR = 0.336, 95% CI = 0.198-0.568) was protective. The TNF-alpha-308 G allele was in linkage disequilibrium (LD) with the human leukocyte antigen (HLA)-B*0801-DRB1*0301 haplotype, while TNF-alpha-308 A allele was in LD with the HLA-B*5001-DRB1*0301 and B*5801-DRB1*0301 haplotypes, suggesting that the effect of TNF-alpha -308 A allele is not because of its being in LD with any HLA alleles, but because of its functional role and its integrated effect with other cytokines.
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10.1111/j.1399-0039.2007.00817.x
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pubmed_189_24199
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BACKGROUND
Joubert syndrome (JS) is a genetically heterogeneous disorder; its genetic etiology involves more than 35 genes, and a limited number of studies have investigated the pathogenic mechanism of variants in patients with JS. RNA splicing analysis is critical to determine the functional significance for noncanonical splicing variants.
METHODS
Whole exome sequencing was performed to screen the causative gene variants in a JS family. Sanger sequencing was used to verify the variants. cDNA PCR products were analyzed and functional experiments were performed to determine the pathogenicity of the variants.
RESULTS
The clinical phenotypes and CPLANE1 variants in the JS patient were analyzed and proved consistent. We identified two novel heterozygous variants of CPLANE1 in the proband first, including c.4459del (frameshift variant) and c.7534-14G > A (intronic variant). We analyzed the pathogenic consequences of the 2 variants and classified the c.4459del as likely pathogenic according to the ACMG/AMP guidelines; however, the pathogenic significance of c.7534-14G > A was uncertain. Furthermore, we performed RNA splicing analysis and revealed that the noncanonical splicing variant (c.7534-14G > A) caused aberrant exon 37 skipping. It produced an aberrant transcript that was predicted to encode a C-terminal truncated protein.
CONCLUSIONS
The genetic variation spectrum of JS caused by CPLANE1 was updated. Two novel variants further deepened our insight into the disease's molecular mechanism and confirmed the significance of diagnostic whole-exome sequencing.
|
10.1002/mgg3.1877
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pubmed_159_2711
|
BACKGROUND
The recurrence of endoscopically resected intramucosal colorectal cancer (CRC) is quite rare, and data regarding metastasis in intramucosal tumors are still lacking. We herein report a case of presacral lymph node recurrence of intramucosal rectal cancer after curative endoscopic resection.
CASE PRESENTATION
A 53-year-old man underwent endoscopic mucosal resection (EMR) for rectal intramucosal adenocarcinoma. Thirty-nine months after the procedure, follow-up computed tomography (CT) revealed a swollen anterior sacral lymph node with an abnormal fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). He underwent laparoscopic low anterior resection (LAR) and was discharged on postoperative day 11 without any complications. The pathological examination confirmed solitary lymph node metastasis (moderately differentiated adenocarcinoma) without a residual tumor in the rectal epithelium. We diagnosed him with lymph node metastasis of rectal cancer. Pathological examination of the resected lymph node confirmed moderately differentiated adenocarcinoma. He has not experienced any re-recurrence in the 6 months since surgery.
CONCLUSIONS
This is a rare case of local lymph node recurrence of intramucosal rectal cancer after successful EMR that was salvaged with surgery. Surveillance after successful endoscopic resection of rectal cancer using both endoscopy and CT is necessary.
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10.1186/s40792-020-00836-7
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pubmed_1121_9164
|
Limb salvage surgery is now the preferred procedure for bone tumor surgery. To decrease the risk of local recurrence, it is crucial to obtain adequate resection margins. The obtained margins must be evaluated postoperatively because they influence what treatment is given subsequently when margins are not adequate (e.g., surgical revision and radiotherapy). The study aims to evaluate margin assessment of tumor specimen by MRI compared to conventional histology (to establish the viability of using MRI) and assess the accuracy of a patient-specific instrument when narrow margins were aimed. The resection margins in 12 consecutive patients that were operated on for bone tumor resection were prospectively analyzed using three methods: MRI of the resection specimen, macroscopic evaluation of specimen slices, and microscopic pathological evaluation. The assessments were qualitative (R0, R1, and R2) and quantitative (distance in mm). MRI, macroscopic, and microscopic margins generated similar results for both the qualitative (all resections were R0) and quantitative assessments. The median error in safe margins was 2 mm with a surgical guide (PSI) and 5 mm without a surgical guide. Local recurrences were not detected after a mean follow-up period of 3.7 years (range, 2.1-5 years); however, four patients died during the study. In conclusion, MRI is a valuable tool for assessing safe margins. When specimens are not available for pathological assessment (e.g., extracorporeally irradiated autograft or autoclaved autograft), MRI could be used to evaluate margins. In particular, when tumor volume is high, MRI could also help to focus the pathological examination on areas of concern.
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10.1155/2020/5289547
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pubmed_665_6635
|
OBJECTIVE
To determine the risk for TB infection among nurses exposed to TB patients and non-exposed employees, and to evaluate associated aspects to initiate TB prevention in a teaching hospital in Brazil.
DESIGN
A cross-sectional tuberculin skin test (TST) survey and assessment questionnaire of 169 nurses exposed to patients (exposed group [EG]) and 164 administrative employees (comparative group [CG]).
RESULTS
The prevalence of positive TST was 59.7% in the EG and 53.7% in the CG (P = 0.26). Univariate analysis revealed, in the CG, association of TST positivity with BCG scar (P = 0.002), and, in the EG, with male sex (P = 0.02) and working at that hospital for >2 years (P < 0.001). On multivariate analysis, male sex (P = 0.0444), working at the institution for >2 years (P < 0.0001) and BCG scar (P = 0.0004) were associated with positive TST, while occupational exposure was not.
CONCLUSIONS
The results suggest that all health care workers should be evaluated in an institutional TB prevention programme because community exposure to TB and BCG vaccination may have influenced TST positivity in the studied population.
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pubmed_665_6635
|
pubmed_100_17298
|
Q fever is a worldwide zoonosis caused by Coxiella burnetii. The disease most frequently manifests clinically as a self-limited febrile illness, as pneumonia (acute Q fever) or as a chronic illness that presents mainly as infective endocarditis. The extreme infectivity of the bacterium results in large outbreaks, and the recent outbreak in the Netherlands underlines its impact on public health. Recent studies on the bacterium have included genome sequencing, the investigation of host-bacterium interactions, the development of cellular and animal models of infection, and the comprehensive analysis of different clinical isolates by whole genome and proteomic approaches. Current approaches for diagnosing Q fever are based on serological methods and PCR techniques, but the diagnosis of early stage disease lacks specificity and sensitivity. Consequently, different platforms have been created to explore Q fever biomarkers. Several studies using a combination of proteomics and recombinant protein screening approaches have been undertaken for the development of diagnostics and vaccines. In this review, we highlight advances in the field of C. burnetii proteomics, focusing mainly on the contribution of these technologies to the development and improvement of Q fever diagnostics.
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10.1186/gm266
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pubmed_201_8177
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The aim of this study is to demonstrate that improving the mitochondrial function can inhibite the loss of chondrocyte phenotype by regulating the expression of uncoupling protein 2(UCP2) and NADPH oxidase1/4(NOX1/4) to reduce the production of reactive oxygen species(ROS). The effects of mitochondrial biogenesis "master regular" peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcriptional factor A (TFAM), UCP2, and NOX1/4 on chondrocyte phenotype was examined. It was found that when the chondrocyte phenotype was lost, PGC-1α, UCP2, and TFAM expression decreased, while NOX1/4 expression increased. Inhibiting UCP2 expression promoted the loss of chondrocyte phenotype, and inhibiting NOX1/4 relieved the loss of the chondrocyte phenotype. After activating the PGC-1α-TFAM pathway, UCP2 increased and NOX1/4 decreased, which suppressed loss of the chondrocyte phenotype. After inhibiting NOX1/4, UCP2 expression increased. Increasing and decreasing UCP2 and NOX1/4 expression, respectively, helps maintain the chondrocyte phenotype and improve mitochondrial functioning by reducing reactive oxygen species production.
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10.18632/oncotarget.18908
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pubmed_16_11061
|
Antibiotic resistance data, made available from laboratory records during eight cholera outbreaks between 1990 and 2004 showed Vibrio cholerae serogroup O1 to have a low level of resistance (2-3%) to tetracycline during 1990-1991. Resistance increased for tetracycline (95%), chloramphenicol (78%), doxycycline (70%) and trimethoprim-sulphamethoxazole (97%) in subsequent outbreaks. A significant drop in resistance to tetracycline and chloramphenicol followed the adoption of a national policy to replace tetracycline with erythromycin for treating cholera. Sixty-nine strains from cholera outbreaks in Zambia between 1996 and 2004, were examined for antibiotic resistance and basic molecular traits. A 140 MDa conjugative, multidrug-resistant plasmid was found to encode tetracycline resistance in strains from 1996/1997 whereas strains from 2003/2004 were resistant to furazolidone, but susceptible to tetracycline, and lacked this plasmid. PCR revealed 25 of 27 strains from 1996/1997 harboured the intl1 class 1 integron but lacked SXT, a conjugative transposon element. Similar screening of 42 strains from 2003/2004 revealed all carried SXT but not the intl1 class 1 integron. All 69 strains, except two, one lacking ctxA and the other rstR and thus presumably truncated in the CTX prophage region, were positive for important epidemic markers namely rfbO1, ctxA, rstR2, and tcpA of El Tor biotype. Effective cholera management is dependent on updated reports on culture and sensitivity to inform the choice of antibiotic. Since the emergence of antibiotic resistance may significantly influence strategies for controlling cholera, continuous monitoring of epidemic strains is crucial.
|
10.1017/S0950268806007254
|
pubmed_299_20740
|
Reproductive management is necessary to prevent deleterious genetic disorders in purebred dogs, but comprehensive studies aimed at prevention of multiple underlying genetic disorders in a single breed have not been performed. The aims of this study were to examine mutant allele frequencies associated with multiple genetic disorders, using Border collies as a representative breed, and to make recommendations for prevention of the disorders. Genotyping of known mutations associated with seven recessive genetic disorders was performed using PCR assays. More than half (56%) of the Border collies had no mutant alleles associated with any of the seven disorders, suggesting that these disorders can be removed from the population over several generations. Since frequencies of each mutant allele differed among disorders, reproductive management should be performed after the establishment of prevention schemes that are appropriate for each disorder, the type and specificity of genetic test available, and the effective population size in each breeding colony.
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pubmed_299_20740
|
pubmed_994_21152
|
PURPOSE
This study evaluated the effect of delayed bonding and antioxidant application (AA, 10% sodium ascorbate) after internal bleaching (35% carbamide peroxide) on the shear bond strength of an adhesive cement to enamel.
MATERIALS AND METHODS
Eighty-four human maxillary central incisors were endodontically treated. The control group remained unbleached with no AA. Experimental groups were all internally bleached. The buccal enamel was finished and polished with metallographic paper to a refinement of #600, in order to obtain a 5-mm(2) flat bonding area. An adhesive cement (Clearfil Esthetic) was placed into a plastic tube with internal diameter of 3 mm and a 3-mm height and cured on the enamel. Bonding occurred either immediately after bleaching (group Im), a 7-day delay (group 7), or a 14-day delay (group 14), and half the specimens were treated with antioxidant application (groups Im-AA, 7-AA, and 14-AA). Shear bond strength testing was performed on a universal testing machine, and data were analyzed with ANOVA and Fisher test (5%).
RESULTS
Delaying of bonding is a useful factor for enhancing shear bond strength (p < 0.05), whereas AA only enhanced shear bond strength after 7 days delayed bleaching (p < 0.05). The highest bond strength was noted in groups 7-AA (20.51 ± 4.5 MPa), 14 (19.82 ± 4.6), 14-AA (20.27 ± 4.4), and control (20.51 ± 5.1), which were not significantly different from each other.
CONCLUSIONS
After internal bleaching, adhesive cementation to enamel is recommended only when delayed 14 days, or delayed 7 days with sodium ascorbate application.
|
10.1111/jopr.12303
|
pubmed_418_3894
|
Chronic kynurenine pathway (KP) activation is implicated in Alzheimer's disease (AD) pathophysiology and results in quinolinic acid-induced excitotoxic stimulation of the N-methyl-D-aspartate receptor. However, most studies focus on plasma and it is unclear if peripheral concentrations reflect brain concentrations and how these may correlate to the AD biomarkers amyloid-β, total-tau (t-tau), or phosphorylated-tau (p-tau). We characterized the KP in matched plasma and cerebrospinal fluid (CSF) samples from 20 AD patients and 18 age-matched control subjects. Plasma concentrations of kynurenine (KYN), 3-hydroxykynurenine, anthranilic acid, picolinic acid, and neopterin significantly correlated with their respective CSF levels. In patients with AD, plasma KYN (r = -0.48, p = 0.033) and picolinic acid (r = -0.57, p = 0.009) inversely correlated with CSF p-tau and t-tau, respectively. Furthermore, in AD CSF, increased 3-hydroxykynurenine/KYN ratio correlated with t-tau (r = 0.58, p = 0.009) and p-tau (r = 0.52, p = 0.020). These data support KP involvement in AD pathogenesis and add to the case for the therapeutic modulation of the KP in AD.
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10.1016/j.neurobiolaging.2019.03.015
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pubmed_854_22485
|
PURPOSE
The purpose of this study was to compare the clinical success of stainless steel crowns (SSCs) made esthetic by open facing or veneering on posterior primary teeth.
METHODS
Thirty-three crowns (18 open-face and 15 veneered) were placed and followed up for 18 months with semiannual evaluations.
RESULTS
Crowns made esthetic with the open-face method showed a success of 95%, while the veneered crowns showed a success of 80% based on greater than two thirds facing retention. Statistical evaluation by 2 proportion test showed no significant difference between groups (P>.05). In addition, a statistically significant difference was found between upper and lower crowns by Fisher's exact test (P<.05).
CONCLUSIONS
This study showed that open-face SSCs had a higher but not significantly different success rate than veneered SSCs. Upper-arch crowns exhibited a higher success rate than those in the lower arch.
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pubmed_854_22485
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pubmed_588_14139
|
In the present work, we have studied the kinetic properties of the catalytic domain of CtBP1, a co-repressor belonging to the d-2-hydroxyacid dehydrogenase family and known to reduce pyruvate in the presence of NADH. CtBP1 acted on a variety of alpha-keto acids, for which it displayed biphasic curves with inhibition at elevated concentrations, as observed with other dehydrogenases of the same family. Based on catalytic efficiencies, the best substrate was 2-keto-4-methylthiobutyrate, an intermediate of the methionine salvage pathway. It was about 20-fold better than 2-ketoisocaproate and glyoxylate, and 80-fold better than pyruvate. From these data we conclude that 2-keto-4-methylthiobutyrate may be an important regulator of CtBP activity, possibly linking gene repression to the activity of the methionine salvage and spermine synthesis pathways.
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10.1016/j.bbrc.2006.11.111
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pubmed_533_9555
|
BACKGROUND AND AIMS
Brain death is defined as irreversible and complete cessation of all brain function including that of the brainstem. The aim of this study was to assess the level of knowledge and awareness about brain-death declaration among resident doctors.
METHODS
This was an observational questionnaire-based study conducted in single institute in which 112 junior residents and 46 senior resident doctors in various medical specialities were included by universal sampling method. A prevalidated questionnaire consisting of questions related to knowledge, attitude and performance of brain-death declaration were distributed among residents as per the inclusion criteria to fill in the time limit of 30 min. Statistical tools used were mean and standard deviation, proportion and Chi-square test.
RESULTS
A total 87 resident doctors consisting of 71.26% males and 28.73% females responded to the questionnaire. About 91.95% correctly defined it as complete cessation of brain activity including brainstem reflexes. Most of the resident doctors (80.45%) knew about the documentation of absence of brainstem reflexes at 6 h intervals and 64.36% were aware about positive apnoea test. When asked about whether there is legal sanction for disconnecting life support in India, 56.32% said no, and 43.67% said yes. Only 12.64% of resident doctors were aware about a panel of 4 physicians are mandatory to declare brain death in India.
CONCLUSION
Awareness and attitude towards the identification of brain death and possible deceased donor organ transplantation were lacking amongst resident doctors.
|
10.4103/ija.IJA_430_17
|
pubmed_921_5178
|
OBJECTIVE
Providing relief of symptomatic radiculopathy resulting from sacral perineural cysts has proven difficult. Our goal was to improve the treatment of these cysts with microsurgical cyst fenestration and imbrication, while minimizing functional damage to neural tissues.
METHODS
We retrospectively reviewed the records for eight adult patients with large (2-3-cm) sacral perineural cysts who were treated at the University of California, San Francisco, between October 1992 and April 1999. All patients presented with radicular pain that was refractory to medical treatment. Three patients also reported urinary incontinence. We performed sacral laminectomies with microsurgical cyst fenestration and cyst imbrication for all patients, using intraoperative electromyography to minimize damage to the sacral nerve roots. For seven patients, we reinforced the closures with epidural fat or muscle grafts and fibrin glue application. For five patients with cysts that communicated with the subarachnoid space in computed tomographic myelograms, we placed lumbar drains for cerebrospinal fluid diversion for several days postoperatively. We assessed outcomes, using telephone questionnaires and periodic postoperative physical examinations, 3 to 73 months after surgery.
RESULTS
After surgery, radicular pain improved markedly for four patients and moderately for three patients; one patient with initial improvement experienced pain recurrence 9 months later. Bladder control improved markedly for two of the three patients with bladder dysfunction. There were no cerebrospinal fluid leaks and no new postoperative neurological deficits.
CONCLUSION
Microsurgical cyst fenestration and imbrication are effective treatments for long-term relief of refractory painful radiculopathy and urinary incontinence associated with large sacral perineural cysts.
|
10.1097/00006123-200007000-00016
|
pubmed_167_14063
|
Research has examined various cognitive processes underlying ethical decision-making, and has recently begun to focus on the differential effects of specific emotions. The present study examines three self-focused moral emotions and their influence on ethical decision-making: guilt, shame, and embarrassment. Given the potential of these discrete emotions to exert positive or negative effects in decision-making contexts, we also examined their effects on ethical decisions after a cognitive reappraisal emotion regulation intervention. Participants in the study were presented with an ethical scenario and were induced, or not induced, to feel guilt, shame, or embarrassment, and were asked to reappraise, or not reappraise, the situation giving rise to those emotions. Responses to questions about the ethical case were evaluated for the quality of ethical sensemaking, perceptions of moral intensity, and decision ethicality. Findings indicate that guilt, shame, and embarrassment are associated with different sensemaking processes and metacognitive reasoning strategies, and resulted in different perceptions of moral intensity. Additionally, cognitive reappraisal had a negative impact on each of these factors. Implications of these findings for ethical decision-making research are discussed.
|
10.1007/s11948-018-00082-z
|
pubmed_1003_11296
|
OBJECTIVES
Resident physician knowledge of financial reimbursement guidelines for patient encounters is limited. We determined whether the use of standardized history and physical examination forms by residents for hospital admissions plus a brief lecture would increase the level of billing codes, increase billable income, and increase resident awareness of billing guidelines.
METHODS
Residents used history and physical examination forms after a brief documentation lecture. Pretrial and posttrial surveys measured awareness of billing guidelines. The admission billing codes for a 6-month period were obtained, and the percentages were compared with a control 6-month period.
RESULTS
There was an absolute increase of 14.5% in the highest code between the two study periods (P < 0.0001). Billable income increased by $10,385. Resident documentation awareness also increased (P < 0.001).
CONCLUSIONS
The use of history and physical examination forms, combined with a brief lecture, significantly increased the percentage of highest billing codes, which increased billable income. Resident awareness of documentation requirements significantly improved.
|
10.1097/01.SMJ.0000149388.95575.72
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pubmed_21_14504
|
Attentional biases for drug-related stimuli play a prominent role in addiction, predicting treatment outcomes. Attentional biases also develop for stimuli that have been paired with nondrug rewards in adults without a history of addiction, the magnitude of which is predicted by visual working-memory capacity and impulsiveness. We tested the hypothesis that addiction is associated with an increased attentional bias for nondrug (monetary) reward relative to that of healthy controls, and that this bias is related to working-memory impairments and increased impulsiveness. Seventeen patients receiving methadone-maintenance treatment for opioid dependence and 17 healthy controls participated. Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11; Patton, Stanford, & Barratt, 1995), visual working-memory capacity was measured as the ability to recognize briefly presented color stimuli, and attentional bias was measured as the magnitude of response time slowing caused by irrelevant but previously reward-associated distractors in a visual-search task. The results showed that attention was biased toward the distractors across all participants, replicating previous findings. It is important to note, this bias was significantly greater in the patients than in the controls and was negatively correlated with visual working-memory capacity. Patients were also significantly more impulsive than controls as a group. Our findings demonstrate that patients in treatment for addiction experience greater difficulty ignoring stimuli associated with nondrug reward. This nonspecific reward-related bias could mediate the distracting quality of drug-related stimuli previously observed in addiction.
|
10.1037/a0034575
|
pubmed_164_13067
|
We report the synthesis of a GDP analogue, SML-8-73-1, and a prodrug derivative, SML-10-70-1, which are selective, direct-acting covalent inhibitors of the K-Ras G12C mutant relative to wild-type Ras. Biochemical and biophysical measurements suggest that modification of K-Ras with SML-8-73-1 renders the protein in an inactive state. These first-in-class covalent K-Ras inhibitors demonstrate that irreversible targeting of the K-Ras guanine-nucleotide binding site is potentially a viable therapeutic strategy for inhibition of Ras signaling.
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10.1002/anie.201307387
|
pubmed_1019_20909
|
OBJECTIVE
To identify factors associated with general satisfaction among clients attending outpatient clinics in a referral hospital in Uganda.
DESIGN
Cross-sectional exit survey of patients and care-givers in selected outpatient clinics.
SETTING
Seven outpatients' clinics at Mulago National Referral and Teaching Hospital.
MAIN OUTCOME MEASURES
Mean score of clients' general satisfaction with health-care services.
RESULTS
Overall the clients' general satisfaction was suboptimal. Average satisfaction was higher among clients with a primary or secondary education compared with none, those attending HIV treatment and research clinic compared with general outpatient clients, and returning relative to new clients. Conversely, satisfaction was lower among clients incurring costs of at least $1.5 during the visit, and those reporting longer waiting time (>2 h). Client's perceived technical competence of provider, accessibility, convenience and availability of services especially prescribed drugs were the strongest predictor of general satisfaction.
CONCLUSIONS
This study highlights the important findings about outpatient services at Mulago hospital. The sub-optimal satisfaction scores for outpatient care strongly suggest that more could be done to assure that services provided are more patient centered. Significant factors including category of clinic visited, waiting time, costs incurred, accessibility of services and perceived providers' technical competence at this hospital should be explored by the Makerere University College of Health Sciences and Mulago hospital for potential improvements in quality of the health service delivered.
|
10.1093/intqhc/mzr040
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pubmed_616_17074
|
The performance of a bioreactor landfill is highly influenced by the simultaneous interactions of several coupled processes that occur within the landfill. In addition, the high uncertainty and spatial variability in the geotechnical properties of municipal solid waste (MSW) poses significant challenge in accurately predicting the performance of bioreactor landfills. In this study, a 2D coupled hydro-bio-mechanical (CHBM) model was employed to predict the behavior of MSW in bioreactor landfills. The numerical model integrated a two-phase flow hydraulic model, a plane-strain formulation of Mohr-Coulomb constitutive model, and a first order decay biodegradation model. The statistical ranges (mean and standard deviation) of some of the major influential MSW properties were derived from the published studies. Random fields of spatially variable MSW properties were generated following the log-normal distribution. Reliability-based analysis was carried out by performing several realizations of Monte-Carlo simulations and the statistical response of the output results including the moisture distribution, pore fluid pressures, landfill settlement, and interface shear response of the composite liner system were quantified. The results clearly indicate the importance of considering spatial variability of the geotechnical MSW properties and its influence on the performance of bioreactor landfills during leachate injection operations. A comparison of the results with the deterministic analysis was performed to evaluate the relative benefits and to emphasize the need for reliability-based analysis for effective design of bioreactor landfills.
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10.1016/j.wasman.2017.11.010
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pubmed_272_286
|
We characterized 67 newly admitted patients in manic or mixed episodes of bipolar I disorder on categorical and continuous measures of smoking and psychosis to test the hypothesis that patients who were smokers would be more likely to demonstrate psychotic features. Smoking did not associate with psychosis in any of our analyses.
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10.1053/comp.2002.29847
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pubmed_65_14608
|
As use of alternative therapies grows, there appears to be heightened concern among health care professionals about the liability implications of delivering these therapies. Little is known about malpractice law in this area. We begin by reviewing the type and frequency of claims brought against alternative medicine practitioners and by analyzing the standard of care to which these practitioners are held when sued. Next we turn to the standard of care question as it relates to physicians (MDs/DOs) who incorporate alternative therapies into their practices. Few cases have addressed this question to date. We argue, however, that when courts decide cases at the intersection between conventional and alternative medicine, they may judge conduct according to standards enunciated by: 1) alternative medicine practitioners who regularly deliver the treatment at issue, 2) physicians who have established similar practices, or 3) conventional practitioners. This latter possibility should be taken seriously; it raises troubling questions for physicians at the outset of the negligence inquiry. Available case law highlights the importance of ensuring that patients are fully informed about any alternative therapies they elect to receive, as well as any conventional treatments they may be foregoing, and that patients expressly consent to treatment in light of this information, preferably in writing.
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pubmed_65_14608
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pubmed_959_18823
|
Wearable sensors to continuously measure blood pressure and derived cardiovascular variables have the potential to revolutionize patient monitoring. Current wearable methods analyzing time components (e.g., pulse transit time) still lack clinical accuracy, whereas existing technologies for direct blood pressure measurement are too bulky. Here we present an innovative art of continuous noninvasive hemodynamic monitoring (CNAP2GO). It directly measures blood pressure by using a volume control technique and could be used for small wearable sensors integrated in a finger-ring. As a software prototype, CNAP2GO showed excellent blood pressure measurement performance in comparison with invasive reference measurements in 46 patients having surgery. The resulting pulsatile blood pressure signal carries information to derive cardiac output and other hemodynamic variables. We show that CNAP2GO can self-calibrate and be miniaturized for wearable approaches. CNAP2GO potentially constitutes the breakthrough for wearable sensors for blood pressure and flow monitoring in both ambulatory and in-hospital clinical settings.
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10.1038/s41467-021-21271-8
|
pubmed_669_5787
|
The purpose of this study was to explore the kinematical characteristics of jumping discus throwing. Eight male right-handed discus throwers who used to practice the jumping throwing technique were recruited as participants. Two high-speed digital cameras with 120 Hz sampling rate were synchronized to capture the movement. The captured images were processed using a motion analysis suite, and the markers attached to joints on images were digitized manually. Based on the results, throwers should keep smaller the shoulder-hip twisting and the right anterior superior iliac spine (abbreviated: ASIS) in front of the right acromion (for right-handed throwers) from the instant the right foot lands to the instant the left foot lands, before the instant of the right foot lands; keep the discus at a depressed position; and reduce the time before discus release, particularly the time of the non-support phase and the second single-support phase. Additionally, release velocity must be improved because throwing distance is directly proportional to squared release velocity. In conclusion, the current study demonstrated comprehensive kinematical analyses, which can be used to instruct the jumping discus throwing technique with duration and angle characteristics of throwing movement for athletes by coaches with videos.
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10.3390/ijerph182413414
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pubmed_81_20641
|
Angiopoietin-like protein 3 (ANGPTL3) is a 70 kDa secretory glycoprotein, which has been identified as a plasma triacylglycerol (TG)-increasing factor in KK/San mice. In this study, we have characterized the expression profile and activity of ANGPTL3 in the chicken, Gallus gallus. This is the first report of this protein in a pre-mammalian species and reveals novel details about the molecular structure of, and specific features of the expression of, important molecules in lipid metabolism. Recombinant chicken ANGPTL3 inhibited chicken lipoprotein lipase activity in vitro and increased plasma TG concentrations in vivo. Chicken ANGPTL3 mRNA expression was detected only in the liver. ANGPTL3 mRNA expression was significantly higher in mature (i.e. egg producing) chickens than in immature chickens. However, this increase was not associated with estradiol, although estradiol does enhance triacylglycerol and very low density lipoprotein secretion by the chicken liver. Changes in chicken ANGPTL3 mRNA expression with nutritional state were examined. ANGPLT3 expression was affected by certain nutritional treatments, i.e. fasting and re-feeding, and ANGPTL3 gene expression in the livers of chickens fed a cholesterol-supplemented diet was lower than that in the livers of chickens fed a control diet. The present study is the first to molecularly characterize and analyze the gene expression of ANGPTL3, and suggests that in avian species ANGPTL3 plays a key role in lipid delivery to the yolk.
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10.1016/j.ygcen.2008.06.005
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pubmed_798_11876
|
Antiplatelet therapies for the treatment of acute coronary syndromes (ACS) act to interrupt various pathways of platelet activation. Clopidogrel, an established thienopyridine antiplatelet medication, inhibits adenosine diphosphate (ADP)-induced platelet aggregation to a modest degree and with wide variability in platelet response. Accumulating data suggest that a 600-mg loading dose of clopidogrel may help overcome the suboptimal response to the standard 300-mg dose seen in some patients. Prasugrel is a third-generation investigational thienopyridine that demonstrates more potent inhibition of platelet aggregation and more consistent platelet response compared with standard- and high-dose clopidogrel. A large clinical trial showed prasugrel to be superior to standard-dose clopidogrel in reducing ischemic events in patients with ACS scheduled for percutaneous coronary intervention, although prasugrel was associated with a significantly higher risk of major bleeding events. Other investigational antiplatelet agents also display more potent and consistent inhibition of platelet aggregation than is seen with clopidogrel. These include AZD6140, a reversible ADP receptor blocker; cangrelor, a rapidly acting intravenous ADP receptor blocker; and the thrombin receptor antagonist SCH 530348.
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10.3949/ccjm.76.s1.02
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pubmed_327_5920
|
The effects of calcium channel blockers (CCBs) verapamil and diltiazem on the toxicity of rubratoxin B in HL60 cells were investigated. Treatment of rubratoxin B caused a considerable rate of blebbing, fragmentation and condensation of cells. The rate of this morphological change was much lower in the concomitant rubratoxin B and CCBs-treated cells than in the cells treated only with rubratoxin B. Cell viability was determined by measuring mitochondrial succinic dehydrogenase activity and the rate of cell proliferation. The results of these assays were of the same tendency as that of the morphological study. CCBs attenuated rubratoxin B's toxicity on cell viability because of their protective action. Rubratoxin B induced apoptosis in the presence of internucleosomal fragmentation. In contrast, concomitant rubratoxin B and CCBs treatment did not. Taken together, the above results indicated that CCBs impaired the toxicity including morphological change, cell viability and apoptosis caused by rubratoxin B.
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10.1016/s0378-4274(00)00266-6
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pubmed_433_17878
|
Atrazine is frequently detected in surface waters and negatively affect physiological function in aquatic organisms. Even though numerous authors have intensively studied its toxicity, only limited information concerning the long-term fish exposure is available. The aim of this study was evaluation of chronic exposure in common carp. Fish were exposed to a range of atrazine concentrations (0.3 - environmentally relevant concentration; 300; 1000; and 3000 µg/l) for twelve weeks. The potential impact of atrazine exposure was studied using various markers (behaviour; biometrical characteristics; haematological, biochemical and oxidative stress indices and histopathological changes). Most alterations were recorded at the highest concentration (3000 µg/l) which is probably due to a combined effect of both the herbicide exposure and intensive parasite infection development during second week. This group was cancelled after three weeks due to adverse health status, which partly confirmed atrazine immunotoxicity. Chronic exposure resulted in long-term reduction in feed intake followed by a significant decrease in body weight and morphological changes in gill at 1000 µg/l. At the same concentration, significant alterations in haematological (e.g. increase in erythrocyte, leukocyte, lymphocytes and neutrophil counts as well as decrease in monocyte counts) and biochemical (e.g. changes in enzyme activities; increase in glucose; decrease in ammonia) indices were documented, especially during first three weeks. Similar trend, but not so intensive, was observed at 300 µg/l. Moreover, significant changes were observed in various indicators of oxidative stress. These alterations were highly variable with both increasing and decreasing trends depending on dose and analysed tissue. Significant changes, especially in white blood profile, enzyme activities and oxidative stress indices, were proven even at 0.3 µg/l. Obtained results indicate that chronic atrazine exposure of common carp can negatively influence many indicators of health status such as behaviour, immune response, haematological and biochemical profile, oxidative stress indices and organ histopathology.
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10.1016/j.scitotenv.2019.135059
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pubmed_201_12442
|
The Production Effect (PE) represents superior memory for produced (read aloud) relative to non-produced (silently read) items. Another method of improving memory is taking a test on the study material - the Testing Effect. We evaluated the combined influence of both effects on free recall memory, using delayed vocal production, in which study words were vocally produced only after their disappearance. Such procedure involves an initial instant test since participants had to vocally retrieve the words (rather than read them aloud). In five experiments, participants were presented with study words that they were instructed to learn by no-production (reading silently), immediate production (reading aloud), delayed reading aloud, or delayed vocal production (instant retrieval). The results showed superior recall for delayed production over all other conditions. We suggest that the source of this superiority is the desirable difficulty induced by the addition of the initial test (retrieval effort) to the vocal production. The novel delayed production condition forms a superior mnemonic.
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10.1080/09658211.2017.1384496
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pubmed_665_17118
|
OBJECTIVE
To use in vivo gene transfer into the testis by electroporation to express a fluorescent recombinant form of a testis-specific gene in the mature epididymal sperm of mice and thus study the pattern of gene localization.
DESIGN
Controlled animal study.
SETTING
Research laboratory at the University of Oxford.
ANIMAL(S)
Four- to 6-week-old male mice.
INTERVENTION(S)
Phospholipase C zeta (PLCzeta), the putative mammalian egg activation factor, was fused to enhanced yellow fluorescent protein (EYFP), and in vivo gene transfer by electroporation was used to introduce this transgene (PLCzeta-EYFP) into mouse testis. Transgene expression in testis and sperm were analyzed at 20 and 40 days after electroporation.
MAIN OUTCOME MEASURE(S)
Transgene expression in testis and epididymal sperm was analyzed by fluorescence microscopy and an excitation light source suitable for EYFP.
RESULT(S)
Phospholipase C zeta-EYFP was successfully expressed in epididymal sperm when analyzed 40 days after gene transfer and was localized to the head and midpiece regions.
CONCLUSION(S)
Our results provide the first demonstration that in vivo gene transfer can be used to study the localization of proteins in mature sperm and that this represents a powerful new technique for studying male infertility and gene function in sperm.
|
10.1016/j.fertnstert.2005.12.012
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pubmed_934_22381
|
History of childhood trauma (CT) is highly prevalent and may lead to long-term consequences on physical and mental health. This study investigated the independent association of CT with symptoms of adult depression and posttraumatic stress disorder (PTSD), mental and physical health-related quality of life (HRQoL), as well as current tobacco consumption and alcohol abuse in a large homogenous cohort of 1254 never-deployed, young male Marines enrolled in the Marine Resiliency Study. Independent effects of CT history, number and type of CT on outcomes were analyzed using hierarchical multivariate logistic regression models. Our results suggested dose-dependent negative effect of an increasing number of trauma types of CT on depression, PTSD and HRQoL. Experience of single CT type demonstrated overall weak effects, while history of multiple CT types distinctively increased the likelihood of adult PTSD symptomology (OR: 3.1, 95% CI: 1.5-6.2), poor mental (OR: 2.3, 95% CI: 1.7-3.1) and physical HRQoL (OR: 1.4, 95% CI: 1.1-1.9). Risk for depression symptoms was similar for both single and multiple CT (OR: 2.2, 95% CI: 1.3-3.8 and OR: 2.1, 95% CI: 1.2-3.5 respectively). CT history had no effects on current tobacco use and alcohol abuse. Our study thus provides evidence for substantial additive effect of different CT types on adult mental and physical health with increasing levels of exposure.
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pubmed_934_22381
|
pubmed_425_23849
|
The Supplemental Nutrition Assistance Program (SNAP) is a highly effective program, vital to our nation's health and well-being. SNAP's entitlement funding structure allows it to provide benefits to anyone who meets the program's eligibility requirements, and this structure also enables SNAP to respond quickly when need increases. Research shows that SNAP reduces poverty for millions, improves food security, and is linked with improved health.Despite SNAP's successes, there is room to build on its considerable accomplishments. Evidence suggests that current benefit levels are not adequate for many households. Some vulnerable groups have limited SNAP eligibility, and some eligible individuals face barriers to SNAP participation.Policymakers should address these shortcomings by increasing SNAP benefits and expanding SNAP eligibility to underserved groups. The federal government and states should also continue improving policies and procedures to improve access for eligible individuals.
|
10.2105/AJPH.2019.305325
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pubmed_400_5152
|
Design of a neural-net-based regulator for nonlinear plants is considered. Both state and output feedback regulators with deterministic and stochastic disturbances have been investigated. A Multilayered Feedforward Neural Network (MFNN) has been employed as the nonlinear controller. The training of the MFNN utilizes the recently developed concept of Block Partial Derivatives (BPDs).
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10.1016/s0893-6080(98)00097-5
|
pubmed_929_18297
|
To understand striatal function, it is essential to know the functional organization of the numerous inputs targeting the diverse population of striatal neurons. Using optogenetics, we activated terminals from ipsi- or contralateral primary somatosensory cortex (S1) or primary motor cortex (M1), or thalamus while obtaining simultaneous whole-cell recordings from pairs or triplets of striatal medium spiny neurons (MSNs) and adjacent interneurons. Ipsilateral corticostriatal projections provided stronger excitation to fast-spiking interneurons (FSIs) than to MSNs and only sparse and weak excitation to low threshold-spiking interneurons (LTSIs) and cholinergic interneurons (ChINs). Projections from contralateral M1 evoked the strongest responses in LTSIs but none in ChINs, whereas thalamus provided the strongest excitation to ChINs but none to LTSIs. In addition, inputs varied in their glutamate receptor composition and their short-term plasticity. Our data revealed a highly selective organization of excitatory striatal afferents, which is determined by both pre- and postsynaptic neuronal identity.
|
10.1016/j.celrep.2019.12.095
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pubmed_301_8080
|
OBJECTIVE
The purpose of this study was to evaluate whether a combined resistance and aerobic training program would improve insulin sensitivity compared with aerobic training alone in postmenopausal women with type 2 diabetes. A second objective was to relate the improved insulin sensitivity to changes in abdominal adipose tissue (AT) and thigh muscle density.
RESEARCH DESIGN AND METHODS
A total of 28 obese postmenopausal women with type 2 diabetes were randomly assigned to one of three 16-week treatments: control, aerobic only training (Ae only), or aerobic plus resistance training (Ae+RT). Pre- and posttreatment outcome measures included glucose disposal by hyperinsulinemic-euglycemic clamp and computed tomography scans of abdominal AT and mid-thigh skeletal muscle.
RESULTS
Glucose infusion rates increased significantly (P < 0.05) in the Ae+RT group. Both exercise groups had reduced abdominal subcutaneous and visceral AT and increased muscle density. The Ae+RT training group exhibited a significantly greater increase in muscle density than the Ae only group. Improved glucose disposal was independently associated with changes in subcutaneous AT, visceral AT, and muscle density. Muscle density retained a relationship with glucose disposal after controlling for abdominal AT.
CONCLUSIONS
Adding resistance training to aerobic training enhanced glucose disposal in postmenopausal women with type 2 diabetes. The improved insulin sensitivity is related to loss of abdominal subcutaneous and visceral AT and to increased muscle density.
|
10.2337/diacare.26.11.2977
|
pubmed_822_4649
|
The effects of feeding a diet supplemented with zinc oxide (ZnO) or a blend of organic acids, cinnamaldehyde and a permeabilizing complex (OACP) on post-weaning diarrhoea (PWD) and performance in pigs infected with enterotoxigenic E. coli (ETEC) were examined. Additionally, changes in selected bacterial populations and blood measures were assessed. A total of 72 pigs weaned at 22 d of age and weighing 7.2 ± 1.02 kg (mean ± SEM) was used. Treatments were: base diet (no antimicrobial compounds); base diet + 3 g ZnO/kg; base diet + 1.5 g OACP/kg. Dietary treatments started on the day of weaning and were fed ad libitum for 3 weeks. All pigs were infected with an F4 ETEC on d 4, 5 and 6 after weaning. The incidence of PWD was lower in pigs fed ZnO ( p = 0.026). Overall, pigs fed ZnO grew faster ( p = 0.013) and ate more ( p = 0.004) than the base diet-fed pigs, with OACP-fed pigs performing the same ( p > 0.05) as both the ZnO- and base diet-fed pigs. Feed conversion ratio was similar for all diets ( p > 0.05). The percentage of E. coli with F4 fimbriae was affected a day by treatment interaction ( p = 0.037), with more E. coli with F4 fimbriae found in pigs fed ZnO on d 11 ( p = 0.011) compared to base diet-fed pigs. Only significant time effects ( p < 0.05) occurred for blood measures. Under the conditions of this study, inclusion of OACP gave statistically similar production responses to pigs fed ZnO, however pigs fed ZnO had less PWD compared to OACP- and the base diet-fed pigs.
|
10.3390/ani5040403
|
pubmed_91_14754
|
The heat of reaction of CO gas with the alpha2Mmetbeta2 and alpha2Mbeta2 species of the alpha-chain mutant hemoglobin M Iwate has been studied in buffers with different heats of ionization of 25degrees and in the absence of organic phosphates. For the alpha2Mmetbeta2deoxy species we find a small Bohr effect (0.12 mol of H+/mol of CO) which is in correspondence with that found in equilibrium studies. The heat of reaction, when corrected for proton reaction with buffer, is -18.4 +/- 0.3 kcal/mol of CO at pH 7.4 At pH 9 the same value is observed within experimental error. This value compares closely with heats of reaction of CO with myoglobin and with van't Hoff determinations of the heat of oxygen binding to isolated hemoglobin alpha and beta chains after correction for the heat of replacement of O2 by CO. Furthermore, an analysis of the differential heat of ligand binding as a function of the extent of reaction indicated that, within experimental error, the heat of reaction with the first beta-chain heme in alpha2Mmetbeta2deoxy is the same as the second. Since the quaternary Tleads to R transition is blocked in this mutant hemoglobin, we compared it with Hb A to estimate the enthalpic component of the allosteric T leads to R transition in Hb A. The heats of reaction with CO(g) and Hb A are -15.7 +/- 0.5 and -20.9 +/- 0.5 kcal/mol at pH 7.4 and 9.0, respectively. In going from the T to the R state we find an enthalpy of transition of 9 +/- 2.5 kcal at pH 7.4 and -12 +/- 2.5 kcal at pH 9.0. From published free energies of transsition we conclude the T leads to R transition is enthalpically controlled at p/ 7.4 but entropically controlled at pH 9.0 A near normal Bohr effect is estimated from heats of reaction of CO with alpha2Mdeoxybeta2deoxy in various buffers. A large than normal heat of reaction (-21.6 +/- 0.5 kcal/mol of CO) is attributed to the abnormal alpha chains in Hb M Iwate.
|
10.1021/bi00692a005
|
pubmed_74_4317
|
Scorpion envenomation is a public health problem in several countries in the tropics and subtropics, with high mortality in the severe forms involving multiple organ failure. The correlation between young age and clinical manifestations of severe scorpion envenomation is well established. We report the case of a 3-month-old infant admitted for severe scorpion envenomation who rapidly developed fatal multiple organ failure, and we discuss the different physiopathological aspects of severe scorpion envenomation.
|
10.1684/mst.2019.0936
|
pubmed_1111_4395
|
To clarify the effect of environmental cadmium (Cd) exposure on the life prognosis of inhabitants living in a Cd-polluted area, the standardized mortality ratio (SMR) according to cause of death in urinary β 2-microglobulin (β2-MG)-positive subjects (≥1000 μg/gCr) was compared to that of the Japanese general population and β2-MG-negative subjects (β 1000 μg/gCr).The SMR for all causes of death of both sexes was higher than that of the Japanese general population and β 2-MG-negative subjects. Among women, the SMR for malignant neoplasms was higher than that of β 2-MG-negative subjects. For cardiovascular disease and cerebrovascular disease, especially heart failure and cerebral infarction, SMRs were significantly higher in both sexes. The SMR for renal diseases was significantly high in the men and tended to be high in the women.These results suggest that the prognosis of urinary β 2-MG-positive subjects with Cd-induced renal tubular dysfunction is unfavorable, with higher mortality rates due to renal diseases, cerebral infarction and heart failure contributing to this. Although the increase of the mortality rate was slight, Cd might affect cancer mortality in women.
|
10.1007/BF02931206
|
pubmed_200_9010
|
Solid-state NMR transitions involving outer energy levels of the spin-1 (14)N nucleus are immune, to first order in perturbation theory, to the broadening caused by the nuclear quadrupole interaction. The corresponding overtone spectra, when acquired in conjunction with magic-angle sample spinning, result in lines, which are just a few kHz wide, permitting the direct detection of nitrogen compounds without the need for labeling. Despite the success of this technique, "overtone" resonances are still broadened due to indirect, second order effects arising from the large quadrupolar interaction. Here we demonstrate that another order of magnitude in spectral resolution may be gained by using double rotation. This brings the width of the (14)N solid-state NMR lines much closer to the region commonly associated with high-resolution solid-state NMR spectroscopy of (15)N and demonstrates the improvements in resolution that may be possible through the development of pulsed methodologies to suppress these second order effects.
|
10.1039/c5cp03266k
|
pubmed_446_7034
|
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by sterile abscesses and fistulae predominantly affecting the axillae and groin. Various biologic agents have been attempted for HS, but there is still no definitive treatment.
OBJECTIVES
We sought to evaluate the efficacy, safety, and tolerability of anakinra in the treatment of moderate to severe HS.
METHODS
Six patients with moderate to severe HS were enrolled in an open-label study with all patients receiving active treatment for 8 weeks with an additional 8 weeks of follow-up off therapy.
RESULTS
The 5 patients who completed the 8-week therapy showed a significant mean decrease in their modified Sartorius score of 34.8 points. The physician and patient global assessment of overall activity showed significant reductions between baseline and 8 weeks of therapy: 45.8 points and 35.6 points, respectively. The Dermatology Life Quality Index showed a significant reduction after 8 weeks of treatment with anakinra. Functional T-cell analysis revealed that patients had increased percentages of CD3(+) T cells in lesional skin compared with nonlesional skin before therapy.
LIMITATIONS
The limited number of patients and lack of control group are limitations.
CONCLUSIONS
Anakinra demonstrated decreased HS disease activity by both objective and subjective measures.
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pubmed_446_7034
|
pubmed_63_20437
|
Pregnancy is a state that changes the physiology of various organs and systems. The occurrence of concomitant diseases, or their presence prior to pregnancy, requires an understanding of such changes and their influence on the disease, the impact of the disease and the diagnostic and therapeutic measures on pregnant women and on the foetus. The aim of this paper is to provide a concise outline of the course of action recommended in dealing with pregnant women who attend the emergency department presenting symptoms of non-specific morbidity of pregnancy. Some of the most frequent pathologies classified by systems are presented.
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10.23938/ASSN.0187
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pubmed_92_359
|
Microfluidic bioreactors are expected to impact cell therapy and biopharmaceutical production due to their ability to control cellular microenvironments. This work presents a novel approach for continuous cell culture in a microfluidic system. Microcarriers (i.e., microbeads) are used as growth support for anchorage-dependent mammalian cells. This approach eases the manipulation of cells within the system and enables harmless extraction of cells. Moreover, the microbioreactor uses a perfusion function based on the biocompatible integration of a porous membrane to continuously feed the cells. The perfusion rate is optimized through simulations to provide a stable biochemical environment. Thermal management is also addressed to ensure a homogeneous bioreactor temperature. Eventually, incubator-free cell cultures of Drosophila S2 and PC3 cells are achieved over the course of a week using this bioreactor. In future applications, a more efficient alternative to harvesting cells from microcarriers is also anticipated as suggested by our positive results from the microcarrier digestion experiments.
|
10.1039/c4lc00570h
|
pubmed_1089_10781
|
AIM
To determine the receptor status of tumors as prognostic factor in development of bilateral breast cancer (BBC) and factor of prognosis of disease.
PATIENTS AND METHODS
272 cases of BBC during the period from 1995 to 2011 in different oncological institutions of Ukraine have been analyzed.
RESULTS
Patients with metachronous BBC with positive status of hormone receptors (HR) of tumors have significantly better indices of overall and progression-free survival (three-years - 95%, five-years - 72%), than patients with HR-negative status (among them nobody has survived over 5 years). In patients with synchronous BBC, the receptor status of tumors has similar influence on the prognosis of survival. Nevertheless, indices of overall survival (65%) and progression-free survival (66%) in HR-positive patients were lower than that at metachronous BBC (overall survival and progression-free survival - 72%).
CONCLUSIONS
Synchronous breast cancer has more aggressive clinical course than metachronous one. It was determined significant influence of receptor status of tumors on the overall survival and progression-free survival in patients with BBC.
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pubmed_1089_10781
|
pubmed_686_13562
|
Parasitic agents determine some of the most common skin disorders. Although well known, they could present different manifestations or be modified by individual or external factors that make their diagnosis or treatment difficult. This review will discuss some of the most prevalent parasitic infections, scabies, and pediculosis and also mention reactions determined by contact with certain insects that, although rarely found, could induce important skin reactions.
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10.1016/j.clindermatol.2005.01.013
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pubmed_408_8547
|
Incubation of HeLa cells for 24 hr with [3H]choline resulted in extensive labeling of the phosphorylcholine and phosphatidylcholine pools. 12-O-Tetradecanoylphorbol-13-acetate (TPA), other phorbol ester tumor promoters, and mezerein stimulated the release of [3H]choline and [3H]phosphorylcholine from such prelabeled cells. The release was accompanied by decreased radioactivity in the phosphorylcholine pool, raising the possibility that the released materials were derived by leakage from this pool. However, TPA did not induce the release of radioactivity from cells containing a prelabeled nucleotide pool. Similarly, the TPA-stimulated release of radioactivity from prelabeled cells closely paralleled the label present in the phospholipid pool rather than the phosphocholine pool. Consequently, it is suggested that the primary source of the released material is phosphatidylcholine acting as a substrate for a phospholipase C enzyme. TPA also simulated the incorporation of [3H]choline into phospholipids, but a time-course study indicated that phospholipase C activation preceded this event. This was supported by the observation that incorporation of [3H]choline was also stimulated by exogenously added phospholipase C.
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pubmed_408_8547
|
pubmed_622_18056
|
OBJECTIVE
To compare risk prediction models for death in hospital based on an administrative database with published results based on data derived from three national clinical databases: the national cardiac surgical database, the national vascular database and the colorectal cancer study.
DESIGN
Analysis of inpatient hospital episode statistics. Predictive model developed using multiple logistic regression.
SETTING
NHS hospital trusts in England.
PATIENTS
All patients admitted to an NHS hospital within England for isolated coronary artery bypass graft (CABG), repair of abdominal aortic aneurysm, and colorectal excision for cancer from 1996-7 to 2003-4.
MAIN OUTCOME MEASURES
Deaths in hospital. Performance of models assessed with receiver operating characteristic (ROC) curve scores measuring discrimination (<0.7=poor, 0.7-0.8=reasonable, >0.8=good) and both Hosmer-Lemeshow statistics and standardised residuals measuring goodness of fit.
RESULTS
During the study period 152 523 cases of isolated CABG with 3247 deaths in hospital (2.1%), 12 781 repairs of ruptured abdominal aortic aneurysm (5987 deaths, 46.8%), 31 705 repairs of unruptured abdominal aortic aneurysm (3246 deaths, 10.2%), and 144,370 colorectal resections for cancer (10,424 deaths, 7.2%) were recorded. The power of the complex predictive model was comparable with that of models based on clinical datasets with ROC curve scores of 0.77 (v 0.78 from clinical database) for isolated CABG, 0.66 (v 0.65) and 0.74 (v 0.70) for repairs of ruptured and unruptured abdominal aortic aneurysm, respectively, and 0.80 (v 0.78) for colorectal excision for cancer. Calibration plots generally showed good agreement between observed and predicted mortality.
CONCLUSIONS
Routinely collected administrative data can be used to predict risk with similar discrimination to clinical databases. The creative use of such data to adjust for case mix would be useful for monitoring healthcare performance and could usefully complement clinical databases. Further work on other procedures and diagnoses could result in a suite of models for performance adjusted for case mix for a range of specialties and procedures.
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10.1136/bmj.39168.496366.55
|
pubmed_689_19124
|
Memantine's benefits in Alzheimer's disease (AD) are modest and heterogeneous. We tested the feasibility of using sensitivity to acute memantine challenge to predict an individual's clinical response. Eight participants completed a double-blind challenge study of memantine (placebo versus 20 mg) effects on autonomic, subjective, cognitive, and neurophysiological measures, followed by a 24-week unblinded active-dose therapeutic trial (10 mg bid). Study participation was well tolerated. Subgroups based on memantine sensitivity on specific laboratory measures differed in their clinical response to memantine, some by large effect sizes. It appears feasible to use biomarkers to predict clinical sensitivity to memantine.
|
10.3233/JAD-215029
|
pubmed_635_1945
|
INTRODUCTION
Effective communication is critical to successful large-scale change. Yet, in our experience, communications strategies are not formally incorporated into quality improvement (QI) frameworks. The 1000 Lives Campaign ('Campaign') was a large-scale national QI collaborative that aimed to save an additional 1000 lives and prevent 50 000 episodes of harm in Welsh health care over a 2-year period. We use the Campaign as a case study to describe the development, application, and impact of a communications strategy embedded in a large-scale QI initiative.
METHODS
A comprehensive communications strategy guided communications work during the Campaign. The main aims of the communications strategy were to engage the hearts and minds of frontline National Health Service (NHS) staff in the Campaign and promote their awareness and understanding of specific QI interventions and the wider patient safety agenda. We used qualitative and quantitative measures to monitor communications outputs and assess how the communications strategy influenced awareness and knowledge of frontline NHS staff.
RESULTS
The communications strategy facilitated clear and consistent framing of Campaign messages and allowed dissemination of information related to the range of QI interventions. It reaffirmed the aim and value of the Campaign to frontline staff, thereby promoting sustained engagement with Campaign activities. The communications strategy also built the profile of the Campaign both internally with NHS organizations across Wales and externally with the media, and played a pivotal role in improving awareness and understanding of the patient safety agenda. Ultimately, outcomes from the communications strategy could not be separated from overall Campaign outcomes.
CONCLUSION AND RECOMMENDATIONS
Systematic and structured communications can support and enhance QI initiatives. From our experience, we developed a 'communications bundle' consisting of six core components. We recommend that communications bundles be incorporated into existing QI methodology, though details should be tailored to the specific context and available resource.
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10.1179/1753807615Y.0000000006
|
pubmed_1012_4822
|
Low-speed accidents with buses in public transport in the city of Uppsala during the years 1986-2000 are coded in 17 variables concerning mainly physical properties of the accident. The taxonomy uses classifications from existing schemes, but some are altered and some new are added to capture common features of reports of bus accidents in this population. It is found that side contacts and singles are the most common accidents, and that more than a quarter of all accident involvements occurs at bus stops. Inter-rater reliability calculations for the categories show that all except one have reliabilities above 80%. The level of internal validity, calculated as agreement of frequencies between time periods, is acceptable, despite many possible sources of change and bias. It is argued that the validity of this database far exceeds that of the, for research purposes normally used, non-company self-reports, state- and police-archives, due to more extensive reporting and corroborating evidence. The practical usefulness of these results and accident taxonomies in general is discussed.
|
10.1016/s0001-4575(01)00063-x
|
pubmed_1138_1649
|
Although catalase is a major intracellular antioxidant, the expression of the human catalase gene appears to be limited in the airway epithelium, making these cells vulnerable to oxidant stress. The basis for this limited gene expression was examined by evaluation of the expression of the endogenous gene in human bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "house-keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites). Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia. Importantly, using a replication-deficient recombinant adenoviral vector containing the human catalase cDNA, levels of catalase were significantly increased in human airway epithelial cells and this was associated with increased survival of the cells when exposed to hyperoxia. These observations provide a basis for understanding the sensitivity of the human airway epithelium to oxidant stress and a strategy for protecting the epithelium from such injury.
|
10.1172/JCI116959
|
pubmed_385_15511
|
An endotoxin (lipopolysaccharide, LPS) is known to activate the hypothalamo-pituitary adrenocortical axis, as well as norepinephrine and indolamine metabolism. Systemically administered LPS produces depression in the forced swimming-induced despair behaviour model in mice. The present study was designed to investigate the effect of green tea extract (GTE) on LPS-induced despair behaviour and to explore the mechanism involved in modulation of LPS-induced immobility by GTE. GTE (10-100 mg/kg) pretreatment reversed LPS-induced immobility in a dose-dependent manner. Rofecoxib (2 mg/kg) and nimesulide (2 mg/kg), COX-2 inhibitors, also reversed the LPS-induced immobility, which was significantly potentiated by concomitant administration of GTE. On the other hand, GTE did not show any potentiating effect on immobility with naproxen (10 mg/kg), which is a nonselective COX blocker. Interestingly the antioxidant, carvedilol (2 mg/kg) did not produce any effect on immobility either in normal or in LPS treated mice. The results of the study implicate the role of COX-2 inhibition by GTE in the reversal of LPS-induced immobility.
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10.1002/ptr.1520
|
pubmed_897_9744
|
PURPOSE
Sepsis has a high mortality rate despite the recent advances in intensive care medicine and antibiotics. Honokiol, a low molecular weight natural product, is known to possess anti-inflammatory activity. Here, we investigate whether honokiol can ameliorate acute lung injury and lethal response in murine models of sepsis.
METHODS
Mice were intraperitoneally given vehicle or honokiol 30 min after the induction of sepsis by cecal ligation and puncture (CLP) and endotoxemia by administration of E. coli lipopolysaccharide (LPS).
RESULTS
The productions of serum tumor necrosis factor-α (TNF-α), nitric oxide (NO), and high mobility group box 1 (HMGB 1) were increased in mice during sepsis, which could be reversed by honokiol. Honokiol could also effectively reduce the increased blood lipid peroxidation and nitrotyrosine in septic mice. Honokiol significantly reversed the inductions of inducible NO synthase and nuclear factor-κB (NF-κB) activation in the lungs of mice during sepsis. Honokiol also effectively rescued the lung edema, lung pathological changes, and lethality in septic mice.
CONCLUSIONS
These findings suggest that honokiol is capable of suppressing the lethal response and acute lung injury associated with sepsis, and support the potential use of honokiol as a therapeutic agent for the conditions associated with septic shock.
|
10.1007/s00134-010-2104-1
|
pubmed_398_14113
|
The B cell Ag receptor is a multimeric protein complex consisting of the ligand binding mlg and the Ig alpha/lg beta heterodimer. The cytoplasmic tails of Ig alpha and Ig beta both contain a consensus sequence termed the immunoreceptor tyrosine-based activation motif (ITAM). This motif is believed to play a critical role in the receptor-mediated signal transduction. To explore the role of ITAM in signaling for B cell death (apoptosis), we transfected CH31 cells, an immature B lymphoma cell line, with expression vectors encoding for the CD8 extracellular/transmembrane domains and the cytoplasmic signal-transducing domain (ITAM) of Ig alpha or Ig beta, respectively. Here, we demonstrate that cross-linking of CD8:Ig alpha or CD:Ig beta with anti-CD8 mAb effectively induced cell growth arrest and apoptosis characterized by [3H]thymidine release and DNA fragmentation; in contrast, CD8:gamma 2a or truncated CD8:Ig alpha lacking the ITAM could not do so. Moreover, selective point mutation of either of the two conserved tyrosine residues within the ITAM, but not the nonconserved tyrosine, completely abrogated the ability of this motif to mediate cell death signals. These findings clearly indicate that ITAM is a critical component required for transmitting growth arrest and apoptotic signals, and that these functions of ITAM are positively regulated by tyrosine phosphorylation.
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pubmed_398_14113
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pubmed_359_16124
|
Ophthalmic manifestations of neuroendocrine carcinoma. This case report describes the clinical presentation, diagnosis and treatment of a case of neuroendocrine carcinoma. A 43-year-old man presented with ocular manifestation due to orbital and brain metastasis of neuroendocrine carcinoma. The histopathologic and immunohistochemical analysis suggested the diagnosis. Partial and temporary remission of the symptoms occurred after the first chemotherapy cycle. We discuss the importance of creating treatment guidelines for this type of neoplasm, that can be very aggressive and fatal.
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10.1590/s0004-27492005000300019
|
pubmed_964_11322
|
Treatment of the pyridinium salts of heparin with N-methyltrimethylsilyl-trifluoroacetamide (MTSTFA) in pyridine for 2 h at various temperatures caused specific 6-O-desulfations from trisulfated disaccharide units to various degrees without detectable depolymerization or other chemical changes. In order to assess the importance of 6-O-sulfate groups in N-sulfated glucosamine (GlcNS) residues to promote FGF-1 and FGF-2 activities, various 6-O-desulfated (6-O-DS-) heparins were quantitatively examined for activity as enhancers or inhibitors of specific FGF-1- and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. The present results suggested that a high content of 6-O-sulfate groups in GlcNS residues was required for activation of FGF-1, but not FGF-2. However, complete 6-O-desulfation of trisulfated disaccharide units in heparin resulted in loss of the ability to activate FGF-2, although the desulfated product bound strongly to FGF-2.
|
10.1093/oxfordjournals.jbchem.a125015
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pubmed_974_20837
|
Student racial and ethnic diversity in higher education is an important and timely topic, as institutions, policy-makers, and economists increasingly recognize the value that accrues at many levels of having a skilled and diverse student body and workforce. Students benefit from learning in a diverse environment; firms may benefit from a diverse workforce; and more demographically diverse regions make experience higher rates of economic growth. However, the forces governing institution-level student diversity are poorly understood, as little prior research on the topic exists. This paper uses school enrollment data to parse out the contribution institutional characteristics, geographical setting, and local demographic characteristics make to student body diversity at each level of study. Results indicate that geographical location and local demographic composition play a role in student body diversity, as do the type and orientation of the institution. Institutional characteristics explain a lot of the variation in student body diversity and actual location of schools matters less than the demographic composition of young people around that location. Two broad conclusions emerge with regard to schools seeking to increase their student diversity. First, some may find their efforts hampered by circumstances outside their control (location, for example). Second, the influence of public/private status and even school size suggest further research on the ways in which these factors influence student diversity so that eventual policy action can be more effective.
|
10.1111/grow.12001
|
pubmed_137_13705
|
Bipolar disorder has the highest suicide attempt rate among psychiatric disorders. Many factors are associated with the risk of suicide attempt in patients with type 1 bipolar disorder, but the relation between them has still not been explicitly stated. This study aimed to examine the predictability of suicide attempt risk in BID patients based on quality of life, stressful life events, comorbidity of axis I disorders and medication compliance. We selected 140 inpatients with type 1 bipolar disorder by convenient sampling. Then they completed the WHOQOL-BREF questionnaire, Paykel's stressful life events scale and the medication adherence report scale (MARS). Logistic regression analysis showed that bipolar patients with axis I comorbidity are 40 times more likely to attempt suicide than those without axis I comorbidity. The higher the patients' quality of life, the lower the chance of attempt of suicide. Higher medication compliance reduces the likelihood of suicidal attempt in these patients. And, the increase of stressful life events would raise the risk of suicide attempts, but the relationship wasn't significant. So it can be concluded that quality of life, stressful life events and axis I comorbidity can predict the risk of suicide attempts in patients with type 1 bipolar disorder.
|
10.1016/j.psychres.2019.04.012
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pubmed_905_8043
|
This book aims to show readers that behaviours in people with dementia tend to be wrongly or poorly described and that this can lead to a misunderstanding of how best to understand or respond to both the behaviours and the person. The author makes a strong case for greater observation and assessment of a range of behaviours and their influencing factors. He also argues that interventions must be underpinned by a person-centred approach and with empathy for the subjective experience of people with dementia. The book should appeal to nurses, care assistants and other health care professionals as well as people working in the voluntary sector.
|
10.7748/nop.13.1.36.s23
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pubmed_73_20857
|
PURPOSE
The aim of this study was to describe the morphology, corneal topography and sensitivity in individuals with Dystrophia Helsinglandica. This autosomal dominant corneal disease is characterized by recurrent corneal erosive episodes and progressive subepithelial fibrosis not significantly affecting visual acuity.
METHODS
The corneas of nine affected and nine unaffected individuals were examined using slit-lamp biomicroscopy, in vivo confocal microscopy (IVCM) and videokeratography. Corneal mechanical sensitivity was also measured using a non-contact esthesiometer.
RESULTS
Slit-lamp biomicroscopy revealed that the affected individuals represented different stages of corneal changes, from a nearly normal cornea to subepithelial fibrosis of the central cornea. Corneal changes in affected individuals did not significantly decrease the best spectacle-corrected visual acuity. In vivo confocal microscopy detected morphological changes in the epithelium and stroma. Subepithelial opacity formation including altered keratocytes could be found in the anterior stroma in all affected eyes. With the exception of two eyes (one affected and one unaffected), all videokeratographies showed irregular astigmatism. Corneal sensitivity was significantly lower in affected individuals (p = 0.01). Age and corneal sensitivity showed no correlation.
CONCLUSION
The main morphological findings in affected individuals were discrete and progressive subepithelial fibrosis, in the in vivo confocal microscope corresponding to optically dense extracellular matrix and activated keratocytes. Subbasal nerve morphology was changed in the affected family members who also showed a decreased corneal sensitivity. The findings are per se not specific to the disease. The changes probably reflect a healing response to erosive events on the corneal surface influenced by the genotype.
|
10.1111/j.1755-3768.2009.01844.x
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pubmed_437_7985
|
Waldenström macroglobulinemia (WM) is a malignant lymphoplasma-proliferative disorder with IgM monoclonal gammopathy. A recent whole-genome study identified MYD88 L265P as the key mutation in WM. We investigated MYD88 mutations in conjunction with cytogenetic study in 22 consecutive Korean WM patients. Conventional G-banding and interphase fluorescence in situ hybridization (FISH) were performed at regions including 6q21 using bone marrow (BM) aspirates. Sixteen patients were subjected to Sanger sequencing-based MYD88 mutation study. Five patients (28%) showed cytogenetic aberrations in G-banding. The incidence of 6q21 deletion was 17% by conventional G-banding and 37% by FISH. Ten patients (45%) showed cytogenetic aberrations using FISH: 6q deletion in eight (37%) and IGH rearrangement in four (18%). Two patients had both the 6q deletion and IGH rearrangement, and two had only the IGH rearrangement. Eleven patients (69%) presented with the MYD88 L265P mutation. MYD88 mutations were significantly associated with the presence of 6q deletions (P = 0.037). Six patients with the 6q deletion for whom sequencing was possible were found to harbor MYD88 mutations. The MYD88 L265P mutation was also associated with increased lymphocyte burden in BM biopsy. This is the first report of high frequency MYD88 L265P mutations in Korean WM patients.
|
10.1155/2014/363540
|
pubmed_428_24453
|
Palbociclib (Ibrance®) is the first-in-class CDK4/6 inhibitor which has been introduced into clinical practice for the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). It is an orally administered drug, which acts by selectively inhibiting cyclin-dependant kinases CDK4 and CDK6. Given together with anti-estrogens like letrozole and fulvestrant it enhances the antiproliferative effect of these drugs without compromising the favorable toxicity profile of endocrine therapy. Areas covered: This review gives a concise overview of the current available preclinical and clinical data about pabociclib including its chemistry, mechanism of action, pharmacokinetics and evidence of its substantial anti-tumor efficacy and safety profile when combined with endocrine therapy Expert commentary: Palbociclib doubles treatment efficacy of letrozole and fulvestrant with a restricted and well manageable toxicity profile. Efficacy as well as safety results from the three registration trials are remarkably consistent. Patients' quality of life is maintained on palbociclib treatment. The treatment landscape in ER+ HER2- MBC will be highly influenced by this compound and development of two other CDK4/6 inhibitors.
|
10.1080/14737140.2017.1347506
|
pubmed_601_1480
|
The wild mouse ecotropic virus, Cas-Br-M murine leukemia virus, induces myeloid and erythroid leukemias as well as T-cell and B-cell lymphomas in NFS mice. The ability to establish long-term cell lines from these tumors in the presence or absence of the T-cell-derived lymphokine interleukin 3 (IL-3) was examined. IL-3-dependent cell lines were readily obtained from the majority of the myeloid or erythroid leukemias and immunoblastic lymphomas. In the absence of IL-3, only one long-term factor-independent cell line was obtained from a myelogenous leukemia. The majority of the thymic T-cell lymphomas or B-lineage lymphomas could not be cultured in the presence or absence of IL-3. The results suggest that transformation of hematopoietic lineages does not necessarily obviate the requirement for normal growth factors. The acquisition of independence from growth factors may require additional transforming events.
|
10.1073/pnas.82.19.6687
|
pubmed_1134_5394
|
The cochlear efferent feedback system exerts direct impact on cochlear nerve activity and balances interaural sensitivity. So far, acetylcholine, GABA and dopamine are known to be transmitters of the inhibitory efferent system. Despite the wealth of information about glycinergic neurotransmission in the central auditory system, the inhibitory glycine receptor (GlyR) has not yet been regarded as a target molecule of efferent transmission in the cochlea. Using RT-PCR, in situ hybridization and immunohistochemistry, we show that GlyRalpha3, GlyRbeta and gephyrin are expressed in the organ of Corti and spiral ganglion neurons. Furthermore, two alternative splice variants of GlyRalpha3, corresponding to the long (alpha3_L) and short (alpha3_K) human isoforms, could be distinguished. The localization of glycine receptors below inner hair cells and in outer hair cells of the adult cochlea suggests that these inhibitory receptors may serve as target molecules of the efferent olivocochlear bundle.
|
10.1007/s00418-008-0387-x
|
pubmed_1031_16574
|
BACKGROUND
Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance.
METHODS
In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-).
RESULTS
Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group.
CONCLUSIONS
We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.
|
10.1016/s1053-2498(02)00646-0
|
pubmed_1051_18517
|
Cell tracking is one of the most critical tools for time-lapse image analysis to observe cell behavior and cell lineages over a long period of time. However, the accompanying graphical user interfaces are often difficult to use and do not incorporate seamless manual correction, data analysis tools, or simple training set design tools if it is machine learning based. In this paper, we introduce our cell tracking software "LIM Tracker". This software has a conventional tracking function consisting of recognition processing and link processing, a sequential search-type tracking function based on pattern matching, and a manual tracking function. LIM Tracker enables the seamless use of these functions. In addition, the system incorporates a highly interactive and interlocking data visualization method, which displays analysis result in real time, making it possible to flexibly correct the data and reduce the burden of tracking work. Moreover, recognition functions with deep learning (DL) are also available, which can be used for a wide range of targets including stain-free images. LIM Tracker allows researchers to track living objects with good usability and high versatility for various targets. We present a tracking case study based on fluorescence microscopy images (NRK-52E/EKAREV-NLS cells or MCF-10A/H2B-iRFP-P2A-mScarlet-I-hGem-P2A-PIP-NLS-mNeonGreen cells) and phase contrast microscopy images (Glioblastoma-astrocytoma U373 cells). LIM Tracker is implemented as a plugin for ImageJ/Fiji. The software can be downloaded from https://github.com/LIMT34/LIM-Tracker .
|
10.1038/s41598-022-06269-6
|
pubmed_656_15556
|
PURPOSE OF REVIEW
The current report aims to summarize recent advances about the relationship between non-suicidal self-injury (NSSI) and eating disordered (ED) behaviors and highlights meaningful directions for future research.
RECENT FINDINGS
While there is solid evidence indicating a robust cross-sectional association between NSSI and ED behaviors, emerging evidence suggests that the temporal relationship between these behaviors may be bidirectional. Shared functions and risk factors may explain why these behaviors often co-develop. At the same time, little is still known about the psychosocial consequences of comorbid NSSI and ED engagement, and there is a lack of intervention studies that target these behaviors simultaneously. It is well-established that NSSI and ED behaviors frequently co-occur. The field should now turn to longitudinal designs to advance our understanding of the longer-term developmental and the shorter-term momentary relationship of these behaviors in daily life. Providing insight into these areas will help guide the deployment of evidence-based interventions that match the needs of clients who report comorbid NSSI and ED behaviors.
|
10.1007/s11920-020-01191-y
|
pubmed_13_6255
|
Fe-Co-Ni gradient-diameter magnetic nanowire arrays were fabricated via direct-current electrodeposition into a tapered anodic aluminium oxide template. In contrast to the magnetic behaviors of uniform-diameter nanowire arrays, these arrays exhibited tailorable magnetic anisotropy that can be used to switch magnetic nanowires easily and unconventional temperature-dependent coercivity with much better thermal stability.
|
10.1039/c8cc02294a
|
pubmed_964_7873
|
Recently, a pulsatile, basal oxytocin blood level has been described in human adults. To investigate if such a hormone profile exists already during the neonatal period, we collected blood samples continuously with 20-s fractions for 4 min in 1-day-old infants (n = 26). Plasma oxytocin concentrations were determined by a specific radioimmunoassay. The values were further analysed by the pulse detection program PULSAR. We found that 42% of the infants presented one peak in the oxytocin level during a 4-min period. The peak constituted a 111 +/- 66% (mean +/- SD) increment of the baseline value. It is suggested that the release of oxytocin during basal conditions occurs in a pulsatile way in newborn infants and that these hormone pulses reflect fluctuations in the activity of the hypothalamic neurosecretory cells.
|
10.1071/rd9960163
|
pubmed_137_14044
|
Sarcopenia (loss of muscle mass and/or strength) frequently complicates liver cirrhosis and adversely affects the quality of life; cirrhosis related liver decompensation and significantly decreases wait-list and post-liver transplantation survival. The main therapeutic strategies to improve or reverse sarcopenia include dietary interventions (supplemental calorie and protein intake), increased physical activity (supervised resistance and endurance exercises), hormonal therapy (testosterone), and ammonia lowering agents (L-ornithine L-aspartate, branch chain amino acids) as well as mechanistic approaches that target underlying molecular and metabolic abnormalities. Besides other factors, hyperammonemia has recently gained attention and increase sarcopenia by various mechanisms including increased expression of myostatin, increased phosphorylation of eukaryotic initiation factor 2a, cataplerosis of α ketoglutarate, mitochondrial dysfunction, increased reactive oxygen species that decrease protein synthesis and increased autophagy-mediated proteolysis. Sarcopenia contributes to frailty and increases the risk of minimal and overt hepatic encephalopathy.
|
10.3350/cmh.2019.0015
|
pubmed_1122_9869
|
We present a 73 year-old Japanese woman with localized scleroderma involving the right side of the scalp accompanied by continuous tingling pain, who developed insidiously progressive left hemiparesis. In magnetic resonance imaging of the brain, an infarct first appeared in the watershed region of the right middle cerebral artery territory and subsequently extended to deep white matter accompanied by scattered hemorrhages. Focal stenosis in the M2 portion of the right middle cerebral artery was revealed on magnetic resonance angiography, and the distal vessels were only shown faintly. A biopsy specimen from the sclerotic scalp lesion showed obvious thickening of vessel walls and mild mononuclear cell infiltration. We believe that the progressing ischemic stroke was caused by hemodynamic disturbances from localized sclerotic obstruction of the middle cerebral artery, with an autoimmune pathogenesis.
|
10.1016/s0022-510x(98)00267-6
|
pubmed_195_24043
|
Although quetiapine is routinely used in the treatment of schizophrenia and bipolar disorders, the precise mechanism of its antidepressant activity is poorly understood. Since quetiapine binds with sigma receptor, the possibility exists that antidepressant action of quetiapine may be mediated through interaction with sigma receptors. In the present study, quetiapine [40-80 μg/mouse, intracerebroventricular (i.c.v.) and 40 mg/kg, intraperitoneal (i.p.)], sigma1 receptor agonist, (+)-pentazocine (120 μg/mouse, i.c.v.) and sigma2 receptor agonist, PB-28 [1-Cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalenyl)propyl]piperazine] (20 μg/mouse, i.c.v.) significantly decreased immobility time in forced swim test. In combination studies, the antiimmobility effect of quetiapine (20 μg/mouse, i.c.v.) was significantly potentiated by pretreatment with (+)-pentazocine (30 and 60 μg/mouse, i.c.v.) or PB-28 (5 and 10 μg/mouse, i.c.v.). Conversely, prior administration of sigma1 receptor antagonist, BD-1063 [1-[2-(3,4-Dichlorophenyl)ethyl]-4-methylpiperazine] and sigma2 receptor antagonists, SM-21 [(±)-Tropanyl 2-(4-chlorophenoxy)butanoate] antagonized the antiimmobility effect induced by quetiapine and its synergistic combination with sigma receptor agonists. These results demonstrated the involvement of sigma receptors in the antidepressant like effect of quetiapine and suggest that sigma receptors can be explored as a potential therapeutic target for the treatment of depressive disorders.
|
pubmed_195_24043
|
pubmed_740_10722
|
Benzothiazole (BT) and its derivates are commonly used as vulcanization accelerators in rubber production. Information on the occurrence of BTs in road dust (RD) and on human exposure to these compounds is very limited. BT and its six derivates in tire wear particles (TWPs) and RD were determined in this study. Samples were extracted using solid-liquid extraction, purified by a HLB SPE column, and determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All seven BTs were found in 17 TWPs samples from different tire brands. The mass fractions of all seven BTs (∑BTs) in TWPs ranged from 46.93 to 215 μg/g with an average concentration of 99.32 μg/g. Benzothiazole and 2-hydroxybenzothiazole (2-OH-BT) were the two major compounds, accounting for 56%-89% of the total. The seven BTs were also found in all 36 sets of RD samples (each set included one sample of TSP (particles < 75 μm in diameter), PM10 (particles < 10 μm in diameter) and PM2.5 (particles < 2.5 μm in diameter)) fractions of RD. The median ∑BTs concentration was highest in PM2.5 (26.62 μg/g), followed by PM10 (22.03 μg/g), and TSP (0.68 μg/g). Of the seven BTs, BT, 2-aminobenzothiazole (2-NH2-BT), 2-mercaptobenzothiazole (MBT), and 2-(methylthio)benzothiazole (MTBT) were distributed in PM2.5 and 2-OH-BT was distributed in PM2.5-10 of RD. Based on the mass fractions of BTs in the TSP, PM10, and PM2.5 fractions of RD, human exposure via ingestion, inhalation and dermal absorption were evaluated. Ingestion was found to be the main exposure pathway in humans, and daily intake of BTs in PM2.5 was highest, followed by PM10 and TSP, respectively. Children may suffer more health risks than adults when exposed to RD.
|
10.1016/j.chemosphere.2018.03.007
|
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