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pubmed_800_23372
Langerhans cells are the most potent antigen-presenting cells in the skin and play a critical role in the induction of contact allergy. Research on the phenotypical and functional changes of LCs occurring after application of skin sensitizers indicated their use as an in vitro model for the screening of chemicals. In the present investigations, LCs from human skin explants served as the test system. The application of this cell system has been aggravated by the difficulty in isolating sufficient numbers of live LCs from skin. This disadvantage was overcome by the culture of immature dendritic cells from peripheral mononuclear blood cells. These cells can serve as a replacement for LCs as they bind haptens and show phenotypical and functional changes similar to LCs. The sensitizers NiSO(4), dinitrochlorobenzene, 2,4,6-trinitrobenzene sulfonic acid, alpha-hexylcinnamaldehyde and eugenol were applied. Both the expression of surface markers and the induction of intracellular interleukin-1 beta (IL-1 beta) were analyzed. No clear-cut results could be established for intracellular cytokine production, only NiSO(4) induced a remarkable number of IL-1 beta-positive cells. However, all skin sensitizers caused an up-regulation of the co-stimulatory molecule CD86, of intercellular adhesion molecule CD54 and of the HLA-DR antigen. The irritant sodium dodecyl sulfate (SDS) and the vehicle dimethyl sulfoxide (DMSO) had no effect.
10.1016/s0887-2333(01)00030-3
pubmed_826_4688
STUDY OBJECTIVE Oxytocin may play a role in pain modulation. The analgesic effects of breastfeeding with its associated endogenous oxytocin release have not been well investigated. To determine the impact of breastfeeding on incisional, perineal, and cramping pain after cesarean and vaginal delivery. DESIGN Institutional review board-approved prospective observational study. SETTING Labor and delivery and maternity wards. PATIENTS Healthy (American Society of Anesthesiology physical statuses 1 and 2) multiparous women who had cesarean (n = 40) and vaginal (n = 43) deliveries of singleton term infants and who were breastfeeding were enrolled. INTERVENTIONS Women completed diaries to record incisional, perineal, or cramping pain scores 5 minutes before, during, and 5 minutes after breastfeeding. MEASUREMENTS Demographic, obstetric, and neonatal variables, as well as analgesic use, were recorded. MAIN RESULTS There was no difference in incisional pain before, during, and after breastfeeding in women post-cesarean delivery. Cramping pain was significantly increased during, as compared with before or after breastfeeding in both the vaginal (P < .001) and cesarean (P < .001) delivery cohorts. CONCLUSIONS There was no analgesic effect on incisional pain during breastfeeding, indicating that endogenous oxytocin associated with breastfeeding may not play a significant role in postpartum cesarean wound pain modulation. Breastfeeding increased cramping pain after vaginal and cesarean delivery. The increase in cramping pain is most likely due to the breastfeeding-associated oxytocin surge increasing uterine tone.
pubmed_826_4688
pubmed_890_5853
In recent years, genome-wide profiling approaches have begun to uncover the molecular programs that drive developmental processes. In particular, technical advances that enable genome-wide profiling of thousands of individual cells have provided the tantalizing prospect of cataloging cell type diversity and developmental dynamics in a quantitative and comprehensive manner. Here, we review how single-cell RNA sequencing has provided key insights into mammalian developmental and stem cell biology, emphasizing the analytical approaches that are specific to studying gene expression in single cells.
10.1242/dev.133058
pubmed_611_15968
A small-scale preliminary cross-over study was conducted to investigate the effects of supercritical CO(2)-extracted sea buckthorn berry oil (SBO) on some risk factors of cardiovascular disease. Special features of the oil are high proportions of palmitic (16:0), oleic (18:1n-9), palmitoleic (16:1n-7), linoleic (18:2n-6), and alpha-linolenic (18:3n-3) acids as well as vitamin E, carotenoids, and sterols. Twelve healthy normolipidemic men were recruited and each volunteer consumed SBO and fractionated coconut oil (control) 5 g per day for a period of 4 weeks in a random order (wash-out 4-8 weeks). Phospholipid fatty acids, plasma lipids, and glucose were unaffected by SBO supplementation. Instead, a clear decrease in the rate of adenosine-5'-diphosphate-induced platelet aggregation and maximum aggregation were found. This suggested the beneficial effects of SBO on blood clotting, but further studies on the dose-response effects are needed to assess the practical use of SBO supplements.
10.1016/s0955-2863(00)00105-4
pubmed_440_9575
BACKGROUND Globally, the colorectal cancers rank the third in terms of cancer incidence and rank the fourth in cancer-associated deaths. S100A4, an important member of the S100 protein family, serves to promote tumor progression and metastasis. By conducting this study, we aim to examine the role of S100A4 in the prognosis of colon cancer and to demonstrate its prognostic significance. METHODS Tissue samples of colon cancer from 148 patients who underwent colon resection due to colon cancer were analyzed by immunohistochemical staining to determine the protein expression levels of S100A4. The protein expression levels of S100A4 in tumor tissue were matched with the clinicopathologic factors including patient survival. RESULTS Cytoplasmic expression of S100A4 protein was demonstrated in the tumor tissue of 132 patients (89.2%) out of a total of 148 study patients. Statistically, the expression levels of the cytoplasmic S100A4 protein correlated significantly with the TNM stages and patient survival. The distribution of the S100A4 protein staining in the tumor tissue was associated with the age groups, tumor localization, TNM staging, and patient survival with statistical significance. The levels of S100A4 protein expression were found to be an independent prognostic factor for TNM staging and poor survival. CONCLUSION Expression of the S100A4 protein in colon cancers may be an indicator of tumor progression and lymph node metastasis and may be useful for predicting the overall survival of the patients with colon cancer. In patients with colon cancer, it may be used as an indicator of poor prognosis.
10.1155/2018/1828791
pubmed_426_9149
The urinary tract is resistant to ascending infection due to Candida albicans. Host and microbial factors that may alter such resistance were evaluated in the rat after inoculating C. albicans into the urinary tract. Diuresis, diabetes, candidal germ-tube formation, and vaginal Candida colonization (alone or in concert) failed to promote ascending urinary tract infection with two vaginal isolates of C. albicans capable of producing renal infection by the hematogenous route. Both germinated and ungerminated Candida adhered poorly to bladder mucosa. Unlike prior urinary tract infection due to an enterococcus that failed to agglutinate Candida in vitro, prior urinary tract infection with a mannose-binding strain of Escherichia coli that agglutinated C. albicans in vitro enhanced adherence of C. albicans to bladder mucosa and increased susceptibility to ascending C. albicans urinary tract infection. Thus, resistance to Candida ascending urinary tract infection is likely to be due to poor adherence of C. albicans to normal bladder mucosa.
10.1093/infdis/155.5.841
pubmed_1014_5937
Triple-negative breast cancers (TNBCs) have poor clinical outcomes owing to a lack of targeted therapies. Activation of the MEK/MAPK pathway in TNBC has been associated with resistance to conventional chemotherapy and biologic agents and has a significant role in poor clinical outcomes. NV1066, a replication-competent herpes virus, infected, replicated in and killed all TNBC cell lines (MDA-MB-231, HCC1806, HCC38, HCC1937, HCC1143) tested. Greater than 90% cell kill was achieved in more-sensitive lines (MDA-MB-231, HCC1806, HCC38) by day 6 at a multiplicity of infection (MOI) of 0.1. In less-sensitive lines (HCC1937, HCC1143), NV1066 still achieved >70% cell kill by day 7 (MOI 1.0). In vivo, mean volume of flank tumors 14 days after treatment with NV1066 was 57 versus 438 mm(3) in controls (P=0.002). NV1066 significantly downregulated p-MAPK activation by 48 h in all cell lines in vitro and in MDA-MB-231 xenografts in vivo. NV1066 demonstrated synergistic effects with a MEK inhibitor, PD98059 in vitro. We demonstrate that oncolytic viral therapy (NV1066) effectively treats TNBC with correlation to decreased MEK/MAPK signaling. These findings merit future studies investigating the potential role of NV1066 as a sensitizing agent for conventional chemotherapeutic and biologic agents by downregulating the MAPK signaling pathway.
10.1038/cgt.2014.28
pubmed_476_21647
ETHNOPHARMACOLOGICAL RELEVANCE The natural extract glaucocalyxin A (GLA), purified from the aboveground sections of the Chinese traditional medicinal herb Rabdosia japonica (Burm. f.) Hara var. glaucocalyx (Maxim.) Hara, has various pharmacological benefits, such as anti-bacterial, anti-coagulative, anti-neoplastic, and anti-inflammatory activities. Although GLA has shown anti-tumor activity against various cancers, the therapeutic potential and biological mechanisms of GLA remain to be further explored in oral squamous cell carcinoma (OSCC). AIM OF THE STUDY This study aimed to elucidate the therapeutic potential and regulatory mechanisms of GLA in OSCC. MATERIALS AND METHODS The cell proliferation and apoptosis effects of GLA were analyzed by CCK-8, clone formation, Annexin V/PI staining, and apoptotic protein expression in vitro. An OSCC xenograft model was applied to confirm the anti-neoplastic effect in vivo. Furthermore, the changes of reactive oxygen species (ROS) were determined by DCFH-DA probe and GSH/GSSG assay, and inhibited by the pan-caspase inhibitor Z-VAD(OMe)-FMK and the ROS scavenger N-acetylcysteine (NAC). The modulation of GLA on mitochondria and ER-dependent apoptosis pathways was analyzed by JC-1 probe, quantitative real-time PCR, and Western blot. Finally, public databases, clinical samples, and transfection cells were analyzed to explore the importance of GLA's indirect targeting molecule CHAC1 in OSCC. RESULTS GLA significantly inhibited cell proliferation and induced apoptosis in vitro and in vivo. GLA perturbed the redox homeostasis, and cell apoptosis was totally rescued by Z-VAD(OMe)-FMK and NAC. Furthermore, GLA activated the mitochondrial apoptosis pathway. Simultaneously, the overexpression and knockdown of CHAC1 dramatically affected GLA-mediated apoptosis. The endoplasmic reticulum stress-associated ATF4/CHOP signal was identified to participate in GLA-upregulated CHAC1 expression. Finally, we found that CHAC1 expression was lower in OSCC compared with normal tissues and positively correlated with 4-Hydroxynonenal (4-HNE) level. High CHAC1 expression also indicated better overall survival. Moreover, CHAC1 selectively regulated the viability of oral cancer cells. CONCLUSION GLA is a promising therapeutic agent that activates the ROS-mediated ATF4/CHOP/CHAC1 axis in OSCC patients.
10.1016/j.jep.2022.115100
pubmed_1073_25465
Borderline personality disorder is a prevalent psychopathology; thus, most graduate students in psychology, residents in psychiatry, and early career clinicians will encounter patients with this disorder in the course of their training or initial professional practice. This paper provides clear and concise guidelines for conducting treatment geared toward the clinician's developmental level. It builds upon the knowledge and skills that are typically acquired during graduate education and training to provide an accessible framework for undertaking psychotherapy with patients who have borderline personality disorder. This paper draws upon common psychotherapeutic factors and existing evidence-based treatments for the disorder to identify principals and interventions that are likely to contribute to therapeutic action. It uses behavioral, cognitive, and psychodynamic interventions to address the patient's multidimensional psychopathology. This approach offers a coherent and integrated treatment framework for the beginning psychotherapy practitioner.
10.1176/appi.psychotherapy.2015.69.3.241
pubmed_1022_1387
OBJECTIVES To know the incidence of bacterial meningitis in children below five years of age. To compare conventional culture and antigen detection methods (Latex agglutination test). MATERIALS AND METHODS 100 CSF samples of clinically suspected meningitis cases in children below 5 years of age were included. The samples were subjected to cell count, Gram stain, culture and LAT. The organisms isolated in the study were characterized according to standard procedures. RESULTS Of the 100 cases studied, 31 cases were diagnosed as ABM by Gram stain, culture and latex agglutination test as per WHO criteria. The hospital frequency of ABM was 1.7%. 15 (48.38) cases were culture positive. Gram stain was positive in 22(70.96) cases and LAT in 17(54.83) cases. Haemophilus influenzae was the most common causative agent of acute bacterial meningitis followed by S.pneumoniae. Case fatality rate was 45.16%. The sensitivity and specificity of LAT was 66.66% and 87.91% respectively. CONCLUSION Bacterial meningitis is a medical emergency and early diagnosis and treatment is life saving and reduces chronic morbidity. LAT was more sensitive compared to conventional Gram stain and Culture technique in identifying the fastidious organisms like H.influenzae, S.pneumoniae and Group B Streptococcus. However, the combination of Gram stain, Culture and LAT proved to be more productive than any of the single tests alone.
10.4103/0972-2327.120491
pubmed_147_3646
OBJECTIVE To investigate the impact of interferon-stimulated exonuclease 20 kDa (ISG20) on replication of genotype 2a hepatitis C virus (HCV) subgenomic replicon RNA and infectivity of the cell culture-derived HCV strain JFH1 to determine the potential of exogenously expressed ISG20 as an anti-viral therapy of chronic hepatitis C. METHODS Plasma vectors containing wild-type (WT) ISG20 or a catalytically-inactive mutant ISG20m were transiently transfected into Huh7, Huh7.5 and HEK293 cells, and the replication of a monocistronic subgenomic JFH1 RNA replicon, SGRm-JFH1BlaRL, was measured. Huh7.5 cells stably expressing ISG20, ISG20m, or the control vector were established by transducing replication incompetent pCX4-Bsr-myc retroviruses encoding WT ISG20, D94G mutant ISG20, or the empty vector, respectively, and selecting with 5 mug/mL of blasticidin for approximately three weeks. The stable Huh7.5 cells were then transfected with HCV replicon RNA and infected with cell culture-derived HCV to investigate inhibition capacity of ISG20 against HCV. RESULTS Huh7.5-ISG20, Huh7.5-ISG20m, and Huh7.5-Bsr controls cells stably expressing ISG20, ISG20m, or the control vector, respectively, were constructed successfully; the ectopically expressed ISG20 and ISG20m were distributed in both nucleus and cytoplasm, as detected by immuno uorescence. SGRm-JFH1BlaRL replicated efficiently and with similar kinetics in the Huh7.5-Bsr and Huh7.5-ISG20m cells, with expression levels plateauing at 48-96 h post-transfection. In contrast, at all time points examined, SGRm-JFH1BlaRL replication was 9.1% to 16.7% in the Huh7.5-ISG20 cells. The Huh7, Huh7.5 and HEK293 cells transiently expressing ISG20 also showed 16.7% to 25.0% of HCV replication that the respective controls. In addition, the amount of infectious progeny JFH1 virus released in culture supernatants was 9.1% to 12.5% from the Huh7.5-ISG20 cells than from the Huh7.5-Bsr and Huh7.5-ISG20m cells at 48-72 h post-infection, and the latter two cultures produced similar JFH1 virus yields. Finally, the expression of HCV core protein was also lower in the Huh7.5-ISG20 cells, as detected by immunoblot analysis. CONCLUSION Exogenous expression of ISG20, either in a transient or stable manner, suppresses not only replication of genotype 2a HCV RNA replicons but also JFH1 virus propagation in cultured hepatocytes. The exonuclease activity of ISG20 is required for its antiviral activities against HCV.
pubmed_147_3646
others_215_10046
The pH monitoring of the tumor microenvironment in vivo seems to be in fact complicated and technically quite challenging nowadays. Also the strategy of measuring urine pH of a little amount is not fully solved. Thus, the aim of our study was to monitor pH of urine samples (< 0.1 ml) and of tumor microenvironment of anesthetized rats in a minimal invasive way. The small urine volumes of rats or mice make pH measurements difficult, as standard pH electrodes usually need a minimal volume of several milliliters to function. The manual micromanipulator together with a needle-type housed pH microsensor offers a simple and effective way to do so. Our results show that pH of urine and tumor microenvironment was lower in tumor bearing rats compared to healthy subjects. The unique technology of pH microsensors could be a promising way to monitor the pH in many experimental designs and clinical praxis. © 2015 Lifescience Global
10.6000/1927-7229.2015.04.04.3
pubmed_1135_16587
PURPOSE To investigate the longitudinal brain regional homogeneity (ReHo) changes in nonhuman primate after spinal cord injury (SCI) by resting-state functional magnetic resonance imaging (fMRI). METHODS Three adult female rhesus monkeys underwent unilateral thoracic cord injury. A resting-state fMRI examination was performed in the healthy stage and 4, 8, and 12 weeks after the injury. The ReHo value of each voxel in the monkey brain was calculated and compared between pre- and post-SCI monkeys with paired t test. The regions of interest (ROIs) in the significantly changed ReHo regions were set. The correlations between the ReHo change and the time after injury were also determined. RESULTS Compared with those in healthy period, the ReHo values of the left premotor cortex and the anterior cingulate cortex (ACC) in post-SCI rhesus monkeys significantly increased in 4-week follow-up examinations. The ReHo values of posterior cingulate cortex, left precuneus, left temporal parietooccipital area, and bilateral superior parietal lobules decreased at 8-week follow-up examinations. In 12-week follow-up examinations, the ReHo values of the left postcentral gyrus, right caudate nucleus, and superior temporal gyrus increased. Correlation analysis showed positive correlations between left ACC and the postoperative time. CONCLUSION SCI can change the regional synchronism of brain activity in sensorimotor system and the default mode network. These findings may help us to understand the potential pathophysiological changes in the central nervous system after SCI.
10.1016/j.mri.2015.06.011
pubmed_671_509
Leucocyte migration-inhibitory activity was found in the sera (cord blood) of 15/28 (53%) healthy, fullterm newborn infants as opposed to only 3/28 (10,7%) control children under three years of age (P less than 0,005). It is postulated that the migration-inhibitory activity may be related to lymphokine-dependent mechanisms.
pubmed_671_509
pubmed_248_13836
BACKGROUND Most national suicide prevention strategies set improved detection and management of depression in primary health care into a central position. However, suicidal behaviour among primary-care patients with depressive disorders has been seldom investigated. METHOD In the Vantaa Primary Care Depression Study, a total of 1119 primary-care patients in the City of Vantaa, Finland, aged 20 to 69 years, were screened for depression with the Primary Care Evaluation of Mental Disorders (PRIME-MD) questionnaire. Depressive disorders were diagnosed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and the 137 patients with depressive disorder were included in the study. Suicidal behaviour was investigated cross-sectionally and retrospectively in three time-frames: current, current depressive episode, and lifetime. Current suicidal ideation was measured with the Scale for Suicidal Ideation (SSI), and previous ideation and suicide attempts were evaluated based on interviews plus medical and psychiatric records. RESULTS Within their lifetimes, 37% (51/137) of the patients had seriously considered suicide and 17% (23/137) attempted it. Lifetime suicidal behaviour was independently and strongly predicted by psychiatric treatment history and co-morbid personality disorder, and suicidal behaviour within the current episode was predicted most effectively by severity of depression. CONCLUSIONS Based on these findings and their convergence with studies of completed suicides, prevention of suicidal behaviour in primary care should probably focus more on high-risk subgroups of depressed patients, including those with moderate to severe major depressive disorder, personality disorder or a history of psychiatric care. Recognition of suicidal behaviour should be improved. The complex psychopathology of these patients in primary care needs to be considered in targeting preventive efforts.
10.1017/S0033291705006550
pubmed_140_18383
Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Therefore, the present study designed to investigate the probable protective role of melatonin against VPA-induced liver toxicity. For that purpose, 28 Wistar rats were randomly selected and divided into four groups, namely the Group C (vehicle), VPA (500 mg/kg/day VPA), MEL + VPA (10 mg/kg/day melatonin + 500 mg/kg/day VPA) and MEL (10 mg/kg/day melatonin). The agents were given by oral gavage for 14 days. Blood and liver tissue samples from all the rats were harvested on the 15th day of experiment. Biochemical analyses were conducted on the blood samples. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), alpha glutathione S-transferases (α-GST), nuclear factor-κB (NF-κB), myeloperoxidase (MPO) and changes in gene expression were examined in the liver tissues. Also, liver histopathological analyses were conducted. VPA administration significantly increased the levels of α-GST, MDA, NF-κB and of IL-1β, TNF-α gene expression in the liver compared to Group C. Moreover, vacuolization, hydropic degeneration, inflammatory cell infiltration, and sinusoidal congestion were commonly detected in the VPA-treated group along with the highest apoptotic index (TUNEL staining) values. Melatonin administration was revealed to exhibit powerful protective properties at cellular, inflammatory and oxidative level activities against VPA-induced liver toxicity. Therefore, melatonin administration may be used as an adjuvant therapy against to VPA-induced liver toxicity.
10.1007/s11033-019-05134-6
pubmed_700_19708
Radiotherapy causes both epithelial and endothelial damage acutely with the subsequent development of interstitial and perivascular fibrosis. These effects may lead to decreased blood flow, delayed wound healing, and a delay in achieving normal wound tensile strength. In a retrospective study of wound infections that developed in 23 of 354 patients (6%) accrued in a series of prospective, randomized antibiotic trials, the incidence of wound infection in patients receiving prior radiotherapy (7.6%) was not statistically different from the incidence of wound infection observed in patients who had had no prior radiotherapy (6.3%). Wound infection that developed in patients after radiotherapy tended to be associated with increased hospitalization, an increased rate of fistulization, and more frequently required secondary surgical repair. It is concluded that major head and neck procedures can be accomplished without an absolute increase in the incidence of wound infection. However, when postoperative complications occur, it may result in a significant increase in morbidity.
10.1002/hed.2880110206
pubmed_1041_4755
In this article, we review the existing empirical research on the topic of therapeutic alliance ruptures in psychotherapy. Ruptures in the therapeutic alliance are defined as episodes of tension or breakdown in the collaborative relationship between patient and therapist. Two meta-analyses were conducted. The first reviewed studies examining the relation between rupture-repair episodes and treatment outcome (r = .24, z = 3.06, 95% CI [.09, .39], p = .002, k = 3, N = 148). The second meta-analysis reviewed the research examining the impact on treatment outcome of training therapists in the use of alliance rupture intervention principles (prepost r = .65, z = 5.56, 95% CI [.46, .78], p < .001, k = 8, N = 376). Both meta-analyses provided promising evidence regarding the relevance of alliance rupture-repair processes to therapeutic outcome. The limitations of the research reviewed are discussed as well as practice implications for repairing the inevitable alliance ruptures in psychotherapy.
10.1037/a0022140
pubmed_151_13628
Previous studies have discussed the association between apolipoprotein A5 (APOA5) gene rs2075291 polymorphism and lipid levels, but the results were inconsistent. The meta-analysis was performed to evaluate the reported effects of rs2075291 polymorphism on blood lipid levels, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in Asians. A literature search was performed in six databases from January 1, 2001 to March 1, 2017. A standardized mean difference (SMD) with 95% confidence interval (95% CI) was computed to estimate the effect value. Overall, 10 articles with 19 reports were included and most of them were from Chinese institutions. Pooled results indicated significant effects of rs2075291 on lipid levels in Asians; the carriers of T allele had higher TC and TG levels but lower HDL-C level than the non-carriers, and the corresponding SMD (95% CI) were 0.20 (0.04-0.36), 0.74 (0.54-0.94), and -0.17 (-0.33 to -0.00), respectively. No significant difference was found for the LDL-C level: P = .172. Although results from the meta-analysis suggest that the T allele of the APOA5 rs2075291 is associated with higher TC and TG levels and lower HDL-C levels, large-scale studies considering the gene-gene and gene-environment interaction are needed to further explore the effects of rs2075291 polymorphism on blood lipid levels in different ethnicities.
10.1016/j.nutres.2018.03.018
pubmed_125_15411
A broiler chicken study was conducted for 42 D to evaluate their responses to 3 commercially available microbial phytases. Growth performance, nutrient digestibility, and bone mineralization at days 21 and 42 posthatching were used as parameters of evaluation. The study was a randomized complete block design with 12 treatments, 8 replicate pens, and 25 birds per pen. Treatments included a positive control (PC), a negative control (NC) with crude protein (CP), nonphytate phosphorus (P), and calcium (Ca) reduced by 18, 1.5, and 1.8 g/kg, respectively; the NC + 4 levels of phytase A (250, 500, 750, 1,000 FTU/kg), 3 levels of phytase B (250, 500, 750 FTU/kg), and 3 levels of phytase C (500, 750, 1,000 FTU/kg). Broilers fed the NC diet had reduced (P < 0.05) performance and digestibility measures at days 21 and 42 relative to the PC. All phytase enzymes improved (P < 0.05) BW, gain, feed efficiency, and tibia ash weight and percent. Inclusion of phytase at the highest levels improved (P < 0.05) tibia ash weight by an average of 18.5 and 22% at days 21 and 42, respectively, over the NC. Phytase A linearly improved (P < 0.05) the apparent ileal digestibility (AID) of DM, Ca, P, copper, and sodium at day 21, and the AID of energy, nitrogen, and all amino acid (AA) digestibility at day 42 posthatching. Phytase B linearly (P < 0.05) improved BW gain and feed efficiency of birds at day 21 and quadratically improved (P < 0.05) the AID of nitrogen and all AA in birds at day 42. Supplementation of birds fed the NC with phytase C linearly improved (P < 0.05) the BW gain, feed intake, feed efficiency, and AID of DM, energy, nitrogen, all AA, and all minerals except manganese at day 42. In conclusion, all 3 phytase products improved the growth performance, nutrient and mineral digestibility, and bone mineralization of birds fed diets deficient in nitrogen, Ca, and P similar to or more than birds fed diet adequate in P and CP.
10.1016/j.psj.2020.05.008
pubmed_892_5799
Natural and mutant alkaline phosphatases with amino acid substitutions in the processing site and N-terminal domain of the mature polypeptide chain Val for Ala(-1), Gln for Glu (+4) and simultaneously Gln for Glu (+4) and Ala for Arg (+1) have been isolated from the periplasm and cultural fluid of E. coli. It has been found that these substitutions have little effect on the dependence of the enzyme activity on pH, ionic strength and temperature but influence its isoenzymic spectrum and decrease (almost twofold) the maximal rate of the enzyme-catalyzed reaction. Extracellular enzymes display, in contrast with periplasmic ones, other catalytic properties (Vmax) and binding activity (Km). After translocation through the outer membrane all the enzymes display decreased Vmax and increased Km. These changes are especially well-pronounced in case of the mutant protein PhoA46 which contains an uncleaved signal peptide due to the impossibility of processing resulting from the substitution of Val for Ala(-1). The Vmax for this protein is decreased 20 times, while the Km is increased 4-fold. The protein also shows a higher (in comparison with other proteins) sensitivity towards proteolytic enzymes and is less resistant upon storage. The experimental data suggest that the changes in the N-end of alkaline phosphatase located at a long distance from its active center influence the enzyme function.
pubmed_892_5799
pubmed_634_1887
OBJECTIVE To identify the barriers to evidence-based decision-making regarding chronic noncommunicable diseases perceived by health administrators from the state of Paraná, Brazil. METHODS Telephone interviews were performed with 20 health region directors using a semi-structured script. The interviews were performed in 2015 and had a mean duration of 23 minutes. After transcription of the interview, the contents were analyzed for identification of subject categories. RESULTS Two categories were identified: organizational and personal barriers. The most frequent organizational barriers were "poor planning or management" and "regional and cultural characteristics of the population." The most frequent personal barriers were "lack of incentive and difficulty to work with scientific evidence" and "lack of training and professional qualification." CONCLUSION Support to health professionals should be enhanced through technical training courses linked to political and scientific efforts that address the health needs of the community.
10.26633/RPSP.2017.147
pubmed_505_7172
The death of insulin-secreting beta-cells that causes type I diabetes mellitus (DM) occurs in part by apoptosis, and apoptosis also contributes to progressive beta-cell dysfunction in type II DM. Recent reports indicate that ER stress-induced apoptosis contributes to beta-cell loss in diabetes. Agents that deplete ER calcium levels induce beta-cell apoptosis by a process that is independent of increases in [Ca(2+)](i). Here we report that the SERCA inhibitor thapsigargin induces apoptosis in INS-1 insulinoma cells and that this is inhibited by a bromoenol lactone (BEL) inhibitor of group VIA calcium-independent phospholipase A(2) (iPLA(2)beta). Overexpression of iPLA(2)beta amplifies thapsigargin-induced apoptosis of INS-1 cells, and this is also suppressed by BEL. The magnitude of thapsigargin-induced INS-1 cell apoptosis correlates with the level of iPLA(2)beta expression in various cell lines, and apoptosis is associated with stimulation of iPLA(2)beta activity, perinuclear accumulation of iPLA(2)beta protein and activity, and caspase-3-catalyzed cleavage of full-length 84 kDa iPLA(2)beta to a 62 kDa product that associates with nuclei. Thapsigargin also induces ceramide accumulation in INS-1 cells, and this response is amplified in cells that overexpress iPLA(2)beta. These findings indicate that iPLA(2)beta participates in ER stress-induced apoptosis, a pathway that promotes beta-cell death in diabetes.
10.1021/bi035536m
pubmed_294_19857
PURPOSE This report determines the incidence of pathologic complete response in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with mitomycin, vinca alkaloid, and high-dose cisplatin (MVP) chemotherapy, and estimates the effect of MVP on survival. PATIENTS AND METHODS We have identified and reviewed the course of 21 patients with advanced NSCLC who achieved a pathologic complete response following a median of three preoperative MVP combination chemotherapy courses including vinblastine or vindesine, cisplatin (120 mg/m2), and mitomycin (n = 19). RESULTS All patients had a major objective response following preoperative chemotherapy and nine (43%) had a clinical complete response. Nine patients with pathologic complete responses were among 73 entered on a preoperative chemotherapy program, yielding an incidence estimate of 12% (95% confidence interval, 6% to 22%). The median survival duration for all 21 patients has not been reached. The median follow-up duration is now 68 months (range, 17 to 109). Survival estimates are 90% at 1 year, 62% at 3 years, and 54% at 5 years. Nine patients have relapsed with initial sites of recurrence as follows: brain (n = 5), other systemic sites (n = 3), and locoregional (n = 1). One patient died in the postoperative period. Eleven patients remain disease-free and all have excellent functional status. CONCLUSION We have observed pathologic complete responses in approximately 12% of advanced NSCLC patients treated with preoperative MVP chemotherapy. These pathologically determined responses were seen only in patients with major objective responses clinically. Pathologic complete response predicts excellent survival and functional level and should be considered a major end point in the evaluation of preoperative chemotherapy programs.
10.1200/JCO.1993.11.9.1757
others_314_121215
When competition between males for mates is intense it is common to find that some males will adopt alternative tactics for acquiring fertilisations, often involving the use of sneak tactics whereby males avoid contests. These alternative tactics are sometimes associated with discrete differences in male morphology, with sneak males investing less in weaponry but more in traits such as testes which will give an advantage in sperm competition. In some cases it appears that males develop into more than two morphs, with a number of examples of tri- and even tetramorphic arthropod species being described. Here we analyse the scaling relations of the dung beetle species Proagoderus watanabei, which expresses two distinct weapon traits: paired head horns and a pronotal horn. We find that males of this species are trimorphic, with alpha males expressing long head horns and a pronotal horn, beta males with long head horns but no pronotal horn, and gamma males with short head horns only. We also find that alpha males invest less in testes than do beta or gamma males, indicating that beta and gamma males in this species probably experience higher risks of sperm competition than do alphas
10.1101/2021.05.09.443318
pubmed_761_14446
Hecker, KA, Carlson, LA, and Lawrence, MA. Effects of the safety squat bar on trunk and lower-body mechanics during a back squat. J Strength Cond Res 33(7S): S45-S51, 2019-The purpose of this study was to determine whether the safety squat bar (SSB) alters the mechanics and muscle activity of a back squat compared with a standard barbell (ST). Motion and muscle activation of the trunk and lower extremity were measured while 12 competitive powerlifters (8 males, 4 females, age 31.5 ± 6.3 years, body mass 88.1 ± 20.7 kg, competitive lifting experience 3.3 ± 2.8 years) squatted 3 sets of 5 repetitions at 75% of their 3 repetition maximum (3RM). Mean muscle activity and peak joint flexion angles were measured for the trunk and one lower extremity. A repeated-measures analysis of variance (p = 0.05) revealed an 11.3% decrease in 3RM when using the SSB. When using the SSB, there was a decrease in trunk and hip flexion (7.3 and 5.7° respectively) and a 50.3% increase in lower trapezius activation. However, using the SSB decreased activation of the rectus abdominis (46.3%), medial hamstring (17.1%), lateral hamstring (15.1%), vastus lateralis (9.3%), and medial gastrocnemius (18.8%). Squatting with the SSB resulted in a more upright trunk angle, which places less stress on the lower back, a commonly injured area when squatting. Decreases in lower-extremity muscle activation are likely due to the decreased load used, suggesting that the SSB may not be as effective as a standard bar to increase lower-extremity strength. However, the increase in the lower trapezius with the lighter load suggests that midback musculature may be challenged more by the SSB than a standard barbell.
10.1519/JSC.0000000000002912
pubmed_950_13437
BACKGROUND Duraplasty is one of the most critical issues in neurosurgical procedures because the defect of dura matter will cause many complications. Electrospinning can mimic the 3D structure of the natural extracellular matrix whose structure is similar to that of dura matter. Poly(L-lactic acid) (PLLA) has been used to fabricate dura matter substitutes and showed compatibility to dural tissue. However, the mechanical properties of the PLLA substitute cannot match the mechanical properties of the human dura mater. METHODS AND RESULTS We prepared stereocomplex nanofiber membranes based on enantiomeric poly(lactic acid) and poly(D-lactic acid)-grafted tetracalcium phosphate via electrospinning. X-ray diffraction results showed the formation of stereocomplex crystallites (SC) in the composite nanofiber membranes. Scanning electron microscope observation images showed that composites nanofibers with higher SC formation can keep its original morphologies after heat treatment, suggesting the heat resistance of composite nanofiber membranes. Differential scanning calorimeter tests confirmed that the melting temperature of composite nanofiber membranes was approximately 222°C, higher than that of PLLA. Tensile testing indicated that the ultimate tensile strength and the elongation break of the stereocomplex nanofiber membranes were close to human dura matter. In vitro cytotoxicity studies proved that the stereocomplex nanofiber membranes were non-toxic. The neuron-like differentiation of marrow stem cells on the stereocomplex nanofiber membranes indicated its neuron compatibility. CONCLUSION The stereocomplex nanofiber membranes have the potential to serve as a dura mater substitute.
10.2147/IJN.S248998
pubmed_156_5100
Ctenomys is the most numerous genus of South American subterranean rodents and one of the most karyotypically diverse clades of mammals known. Ctenomys magellanicus is the southernmost species of the group and the only one living in Isla Grande de Tierra del Fuego (Argentina). This species presents two chromosomal forms, i.e. 2n=34, and 2n=36 (FN=68). Recent studies suggest that genetic divergence between both karyotypic forms resulted from a chromosomal speciation process. In order to identify the chromosomal rearrangement involved in the process of karyotype evolution in this species, we used chromosome banding techniques and fluorescence in situ hybridization with a telomeric probe to metaphase chromosomes of the two chromosomal forms of Ctenomys magellanicus. Chromosome analysis of Giemsa-stained and G-banding preparations showed that Cm34 and Cm36 karyotypes differ in one rearrangement involving chromosomes A9 from Cm34 and B12 and B17 from Cm36. In addition FISH analysis showed that all of the chromosomes from both chromosomal forms exhibit a telomeric-only distribution pattern of the (TTAGGG)n sequence, indicating that none of the chromosomal forms of Ctenomys magellanicus has true telocentric chromosomes. Our results suggest that a chromosome fission event would have occurred during the process of karyotype evolution in this species.
10.1111/j.1601-5223.2003.01696.x
pubmed_244_12597
Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by 'the EMT International Association' (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.
10.1038/s41580-020-0237-9
others_201_8070
CAD/CAM-manufactured implants are increasingly becoming the standard in current therapy. The question of whether the manufacturing-related rougher surface of selective laser fusion plates compared to milled, smoother reconstruction plates leads to increased postoperative complications such as infections, plate exposure, and fistulas has not yet been determined. A retrospective analysis of 98 patients who underwent surgical treatment with either a selective laser fusion plate or a milled reconstruction plate at our hospital was performed. The only significant predictors of the revision risk were the operation time and use of antiresorptive medication. In the KLS Martin® group, the risk of revision decreased by approximately 20% for each additional hour by which the operation time was increased (OR = 0.81). In the Depuy Synthes® group, the risk of revision increased by approximately 11% with each additional hour of operative time (OR = 0.81 × 1.37 = 1.11). Both groups showed no significant differences in the number of necessary revision surgeries as well as inpatient complications. In summary, we can say that the assumption that additively manufactured reconstruction plates have a rougher surface due to selective laser melting and thus make plaque accumulation and revisions more likely has not been confirmed. Overall, it seems imperative to select further studies regarding the clinical outcome depending on the selected plate system. © 2023 by the authors
10.3390/jpm13040648
pubmed_529_8842
BACKGROUND The optimal treatment strategy for stage I-II glottic squamous cell carcinoma (SCC) is not well-defined. This study analyzed treatment results and prognostic factors. PATIENTS AND METHODS This is a single-institution retrospective analysis of 244 patients with T1-2 glottic SCC who underwent normofractionated radiotherapy (RT) and/or surgery between 1990 and 2013. The primary endpoint was relapse-free survival (RFS). RESULTS Median age was 65 years (range: 36-92 years), the majority (82%) having stage I disease. Definitive RT was used in 82% (median dose: 68 Gy, 2 Gy per fraction). Median follow-up was 59 months. The 5‑year RFS rates were 83 and 75% (p = 0.05) for stage I and 62 and 50% (p = 0.47) for stage II in the RT and surgery groups, respectively. Multivariate analyses indicate T1 vs. T2 and RT vs. surgery as independent prognostic factors for RFS, with hazard ratios of 0.38 (95% confidence interval, CI: 0.21-0.72) and 0.53 (95% CI: 0.30-0.99), respectively (p < 0.05). The 5‑year overall and cause-specific survival rates in the whole cohort were 92 and 96%, respectively, with no significant differences between treatment groups. Anterior commissure involvement was neither a prognostic nor a predictive factor. The incidence of secondary malignancies was not significantly different between patients treated with and without RT (22 vs. 9% at 10 years, respectively, p = 0.18). CONCLUSION Despite a possible selection bias, our series demonstrates improved RFS with RT over surgery in stage I glottic SCC.
10.1007/s00066-017-1139-4
pubmed_1086_10698
Four hundred and eighty Chinese subjects with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were enrolled in a multicenter, double-blind, randomized, placebo-controlled study of adefovir dipivoxil (ADV) 10 mg once daily. There was a significant difference in reduction of serum hepatitis B virus (HBV) DNA after 12 weeks between subjects who received ADV and those who received the placebo (3.4 and 0.1 log10 copies/mL, respectively, P < .001). Further reductions in serum HBV DNA and increases in the proportion of subjects with an HBV DNA level of at most 10(5) copies/mL, with HBV DNA undetectable, and with ALT normalization were observed in ADV-treated subjects at week 52 (median HBV DNA reduction of 4.5 log(10) copies/mL, 67% with HBV DNA <or= 10(5) copies/mL, 28% with HBV DNA undetectable, and 79% with ALT normalization). Subjects who initially received ADV lost some treatment benefit after being rerandomized to the placebo in week 40. Subjects with YMDD mutant HBV at baseline had virological, biochemical, and serological responses to treatment that were similar to those of subjects with wild-type HBV. The incidence of clinically adverse events was similar in nature and severity between the treatment groups, and there was no evidence of renal toxicity. No adefovir-related HBV mutations were identified. In conclusion, treatment with ADV 10 mg daily over 52 weeks was safe and effective in Chinese subjects with HBeAg-positive CHB and did not lead to the emergence of drug resistance. The study is continuing for an additional 4 years with all subjects on open-label ADV 10 mg daily.
10.1002/hep.21225
pubmed_728_4281
Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.
10.1161/01.res.38.4.250
pubmed_157_9902
Quality of life (QoL) is a multidimensional concept regarding self-assessment of patients' situation. Quality of life has not been clearly defined up to date, although it is clear that it is a subjective self-assessment that to a significant extent is determined by individual needs, beliefs, values, attitudes, which are changing with time. Health-related QoL comprises basic dimensions such as patients' performance status, physical, emotional, and social functioning, symptoms of the disease and adverse effects of treatment, spiritual (God and existential) and other dimensions. In women, the ovary, cervical, corpus uterus, vagina and vulva cancers deteriorate QoL by disease progression and consequences of treatment, also in cancer survivors. Common symptoms include the genito-urinary system, the lower gastrointestinal tract and peripheral neuropathies induced by chemotherapy. In young women, QoL is impaired by infertility, sexual problems and menopause symptoms. An overview of QoL questionnaires used in oncology with special regard to patients with gynecological tumors was conducted. A screening tool for psychological state assessment of oncology patients (distress thermometer), the Edmonton Symptom Assessment System (ESAS) and modular approach of QoL assessment recommended by the EORTC (European Organization for the Research and Treatment of Cancer) were presented. Practical guidelines were proposed to assess appropriately QoL in patients with gynecological cancers who stay at in-patient gynecology units and those treated at home and in an ambulatory care setting.
10.5114/pm.2015.56539
pubmed_147_25458
The aim of the study was to explore whether G-Protein-Coupled Receptor 30 (GPR30) was expressed in rat testicular Sertoli cells and to assess the impact of monobutyl phthalate (MBP) on the expression of GPR30 in Sertoli cells. By using RT-PCR, Western-Blot and immunofluorescent microscopy, the expression of GPR30 in rat Sertoli cells was found at both gene and protein level. Cultures of Sertoli cells were exposed to MBP (10- -1000 mM) or a vehicle. The results indicated that the expression of GPR30 increased at gene and protein levels in Sertoli cells following administration of MBP even at a relatively low concentration. We suggest that changes of GPR30 expression may play an important role in the effects of the xenoestrogen MBP on Sertoli cell function. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 18-24).
10.5603/FHC.2013.003
pubmed_126_9454
The general practitioner's (GP's) doctor's bag is exposed to extreme temperatures that may affect the stability of the drugs it contains. Adrenaline (1:1000 solution) is more stable than previous studies would suggest. GPs carry out-of-date drugs despite stating that they regularly check expiry dates.
pubmed_126_9454
pubmed_165_11735
Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with neurotrophic activity on midbrain dopaminergic neurons and on developing and mature motoneurons of the brainstem and spinal cord. To investigate the extent of GDNF dependency of central and peripheral nervous structures during development, we have performed an immunohistochemical analysis of sections from the whole head including brain, peripheral ganglia, developing teeth and tongue, as well as intestines, in mutant mice lacking a part of the third exon that encodes the GDNF protein. As described previously, these null-mutated mice lack most of the enteric nerve plexus and are subject to agenesis or severe dysgenesis of the kidneys. In the present communication, we examined the development of vibrissae and incisor and molar teeth, as well as the innervation of these structures, and found no differences between null-mutated and control mice. A decrease in the immunohistochemical labeling intensity with tyrosine hydroxylase was observed in the superior cervical ganglion (SCG), as well as in the pontine nucleus locus coeruleus, and the sympathetic innervation of blood vessels and glands in the head was significantly decreased. None of the brain nuclei studied exhibited any significant decreases in the total number of neurons, but the packing density of neurons in the nucleus locus coeruleus was decreased. These data indicate that GDNF might be one neurotrophic factor that contributes to the development of central and peripheral noradrenergic neurons.
pubmed_165_11735
pubmed_332_9209
In order to assess their destination memory, sixteen patients with probable mild Alzheimer Disease (AD), sixteen older adults and 16 young adults were asked to tell facts to pictures. On a subsequent task, they were asked to remember whether they had previously told that fact to that face or not. AD patients showed poorer destination recall than the older adults, and the older adults showed poorer destination recall than the young adults. Our results suggest that destination memory is highly impaired in AD.
10.3233/BEN-2012-129014
pubmed_841_19132
Two cases of amoebic infection were diagnosed in a heterosexual couple. The cases, a Frenchman with previous trips to various African countries and his sexual partner, a Cameroonese woman immigrant living outside the community, were both asymptomatic; the infection had been diagnosed by chance in the man at the time of his employment in a hospital kitchen. Based on what is known of the epidemiology of amoebic infection, it may be acquired and then transmitted within a couple via the indirect faecal-oral route or, in greater likelihood, by sexual practices. Both amoebic isolates were characterised by isoenzyme electrophoresis as non-pathogenic Entamoeba dispar, zymodemel. Other diagnostic tools, such as ELISA direct stool antigen detection tests and serological assays were employed, confirming the diagnosis of E. dispar infection. Given there are a number of asymptomatic cyst passers of Entamoeba histolytica, besides human carriers of saprophyte E. dispar, we stress the importance of applying, when possible, advanced protocols of diagnosis to distinguish the microscopically identical pathogenic species from the non-pathogenic one.
pubmed_841_19132
pubmed_391_20890
The sensitivity and resistance of six human melanoma cell lines to gamma-interferon (gamma-IFN) and tumour necrosis factor-alpha (TNF-alpha) have been examined. Amelanotic cell lines were more sensitive to gamma-IFN and TNF-alpha than melanotic cells. The cytotoxicity of gamma-IFN and TNF-alpha could be reversed in all cells by the addition of L- or D-tryptophan to the culture medium. Melanoma cells resistant to gamma-IFN excrete calcium activated neutral protease (CANP) and as a consequence, make L-tryptophan available by the hydrolysis of serum proteins in the culture medium. Resistance to gamma-IFN could be reversed by the addition of specific CANP inhibitor, whereas gamma-IFN-sensitive strains became more resistant with the addition of CANP to the culture medium. It has been confirmed that gamma-IFN induces indoleamine 2,3-dioxygenase in melanoma cells. This enzyme utilizes the superoxide anion (O2-) as a substrate for the oxidation of either L- or D-tryptophan to N-formylkynurenic acid leading to cell death. The induction of this degradative pathway for L-tryptophan kills cells by starvation of this essential and relatively scarce amino acid. TNF-alpha induces manganese-containing superoxide dismutase (MnSOD) which also uses O2- to produce cytotoxic concentrations of hydrogen peroxide. Therefore, it can be concluded that the cytotoxicity of both gamma-IFN and TNF-alpha depends on the availability of L-tryptophan as the substrate for the removal of O2- via indoleamine 2,3-dioxygenase.
pubmed_391_20890
pubmed_173_24659
BACKGROUND Both omeprazole and its S enantiomer (esomeprazole) have been available and used to treat symptoms of gastroesophageal reflux disease (GERD) and conditions associated with excessive stomach acid secretion for more than a decade. Controversy exists over improved efficacy of S enantiomer (esomeprazole) over parent racemate (omeprazole). However, a comparison of the clinical outcomes of these products may reveal the rationale for switching from the racemate to single enantiomer. Since enantiomers of omeprazole are equipotent, we compared the outcomes of equal doses of each product to see if both actually differ in their efficacy's or the reported superiority of S enantiomer is just a dose effect. METHODS A web search was carried out for randomized controlled trials with head-to-head comparisons of omeprazole and S-omeprazole. The data were abstracted and after calculating the odd ratios (OR) for the outcomes reported in each study, the combined overall odd ratios (OR') were estimated. The random effect inverse variance method with omeprazole as the reference (OR" = 1) was used. RESULTS Out of 1171 studies, 14 were deemed eligible. There was no significant difference in the therapeutic success between omeprazole and S-omeprazole as a part of triple therapy for the treatment of H. pylori in both intention-to-treat (OR', 1.06; CI, 0.83, 1.36; p = 0.63) as well as per-protocol analysis (OR', 1.07; CI, 0.84, 1.36; p = 0.57). For the treatment of gastro-oesophageal reflux disease, S-omeprazole was significantly but marginally superior to the racemate (OR', 1.18; CI, 1.01, 1.38; p = 0.04). The two products were equipotent in all metrics used to assess intragastric pH except for the % patients maintaining a 24 h gastric pH above 4 (1.57; CI, 1.04, 2.381; p = 0.03). CONCLUSION The therapeutic benefit of chiral switch of omeprazole is questionable considering the substantially greater economic burden involved.
10.1186/s40199-015-0133-6
pubmed_923_8205
Two young drug addicts received in the course of their treatment a 10-fold overdose of methadone by error. One person died, the other was severely intoxicated but survived. The cause for the mistreatment was the unawareness of the medical personnel, that did not realize the change in concentration of the methadone stock solution from 0.1% to 1.0%, provided by the pharmacy. To prevent such mistakes in the future a change in labelling of the bottle giving directions for correct dosing is suggested.
pubmed_923_8205
pubmed_271_22032
The risks and benefits of fish from markets in Chinese cities have not previously been fully evaluated. In the present study, 24 common fish species with more than 400 individual samples were collected from markets from five big Chinese cities in 2007. The main nutrients and contaminants were measured and the risk-benefit was evaluated based on recommended nutrient intakes and risk level criteria set by relevant authorities. The comprehensive effects of nutrients and contaminants in marine oily fish were also evaluated using the data of two related human dietary intervention trials performed in dyslipidemic Chinese men and women in 2008 and 2010, respectively. The results showed that concentrations of contaminants analyzed including DDT, PCB(7), arsenic and cadmium were much lower than their corresponding maximum limits with the exception of the mercury concentration in common carp. Concentrations of POPs and n-3 LCPUFA, mainly EPA and DHA, were positively associated with the lipid content of the fish. With a daily intake of 80-100g marine oily fish, the persistent organic pollutants in fish would not counteract the beneficial effects of n-3 LCPUFA in reducing cardiovascular disease (CVD) risk markers. Marine oily fish provided more effective protection against CVD than lean fish, particularly for the dyslipidemic populations. The risk-benefit assessment based on the present daily aquatic product intake in Chinese urban residents (44.9 and 62.3g for the average values for all cities and big cities, respectively) indicated that fish, particularly marine oily fish, can be regularly consumed to achieve optimal nutritional benefits from n-3 LCPUFA, without causing significant contaminant-related health risks. However, the potential health threat from contaminants in fish should still be emphasized for the populations consuming large quantities of fish, particularly wild fish.
10.1016/j.scitotenv.2011.12.020
pubmed_43_14787
BACKGROUND Visceral leishmaniasis is a disease caused by disseminated Leishmania donovani infection which affects almost half a million people annually. Most of the patients are reported from the Indian sub-continent, Eastern Africa and Brazil. In this study, we aimed to determine the levels of antibodies and cytokines in visceral leishmaniasis patients and to examine associations of parasitemia with the clinical states of patients. A prospective study was carried out, enrolling a total of 48 active VL patients who were evaluated before, during different time points and, three months after treatment. Serum cytokine concentrations, antibody levels, parasitemia, laboratory (hematologic and biochemical) measurements, and clinical parameters were assessed. RESULTS Counts of WBC and platelets, and measurements of hemoglobin (Hb) increased during treatment (P ≤ 0.05). Elevated levels of circulating IL-10, IFN-γ, and TGF-β1 were measured before treatment. The observed increase in serum IL-10 remarkably declined within 7 days after the start of treatment. Anti-leishmanial antibody index (AI) was high in all VL patients irrespective of spleen aspirate parasite grade before treatment and at different times during treatment. However, a significant (P ≤ 0.05) decrease of AI was observed 120 days post-treatment. IL-2 serum levels were below the detection limit at all sampling points. CONCLUSIONS The present results suggest that IL-10, IFN-γ, and TGF-β1 can be used as markers of active visceral leishmaniasis. In addition, measuring circulating cytokines concentrations, particularly IL-10, in combination with other clinical evaluations, could be used as criteria for the cure. The observation that a high serum concentration of IFN-gamma at baseline was associated with low parasitemia deserves further investigations.
10.1371/journal.pntd.0009632
pubmed_719_6031
Leaf senescence is a highly-programmed developmental process regulated by an array of multiple signaling pathways. Our group previously reported that overexpression of the protein phosphatase-encoding gene SSPP led to delayed leaf senescence and significantly enhanced cytokinin responses. However, it is still unclear how the delayed leaf senescence phenotype is associated with the enhanced cytokinin responses. In this study, we introduced a cytokinin receptor AHK3 knockout into the 35S:SSPP background. The phenotypic analysis of double mutant revealed that AHK3 loss-of-function reversed the delayed leaf senescence induced by SSPP. Moreover, we found the hypersensitivity of 35S:SSPP to exogenous cytokinin treatment disappeared due to the introduction of AHK3 knockout. Collectively, our results demonstrated that AHK3-mediated cytokinin signaling is required for the delayed leaf senescence caused by SSPP overexpression and the detailed mechanism remains to be further elucidated.
10.3390/ijms20082043
pubmed_857_3046
From December 1989 to March 1992, 50 (32%) of 156 patients with hepatobiliary and pancreatic ascariasis underwent various endoscopic interventional procedures. Endoscopic intervention was performed when patients did not respond to energetic symptomatic treatment within the first few days of hospitalization (n = 45) or when worms had not moved out of the ducts into the duodenum at 3 weeks (n = 5). Worm extraction was successful in all 18 patients from the ampullary orifice and in 34 (89.5%) of 38 patients from the bile or pancreatic duct. In five patients with pyogenic cholangitis, endoscopic nasobiliary drainage was performed to decompress the bile ducts. After worm extraction/nasobiliary drainage, 41 (91%) of the 45 patients with biliary disease (n = 42) or acute pancreatitis (n = 3) had rapid relief of symptoms. Three patients developed complications related to endoscopy, including cholangitis (n = 2) and hypotension (n = 1).
10.1016/s0016-5107(93)70222-9
pubmed_939_13688
This study examined the klotho (KL) longevity gene polymorphism rs9315202 and psychopathology, including posttraumatic stress disorder (PTSD), depression, and alcohol-use disorders, in association with advanced epigenetic age in three postmortem cortical tissue regions: dorsolateral and ventromedial prefrontal cortices and motor cortex. Using data from the VA National PTSD Brain Bank (n = 117), we found that rs9315202 interacted with PTSD to predict advanced epigenetic age in motor cortex among the subset of relatively older (>=45 years), white non-Hispanic decedents (corrected p = 0.014, n = 42). An evaluation of 211 additional common KL variants revealed that only variants in linkage disequilibrium with rs9315202 showed similarly high levels of significance. Alcohol abuse was nominally associated with advanced epigenetic age in motor cortex (p = 0.039, n = 114). The rs9315202 SNP interacted with PTSD to predict decreased KL expression via DNAm age residuals in motor cortex among older white non-Hispanics decedents (indirect β = -0.198, p = 0.027). Finally, in dual-luciferase enhancer reporter system experiments, we found that inserting the minor allele of rs9315202 in a human kidney cell line HK-2 genomic DNA resulted in a change in KL transcriptional activities, likely operating via long noncoding RNA in this region. This was the first study to examine multiple forms of psychopathology in association with advanced DNA methylation age across several brain regions, to extend work concerning the association between rs9315202 and advanced epigenetic to brain tissue, and to identify the effects of rs9315202 on KL gene expression. KL augmentation holds promise as a therapeutic intervention to slow the pace of cellular aging, disease onset, and neuropathology, particularly in older, stressed populations.
10.1038/s41386-020-00884-5
pubmed_880_18782
OBJECTIVES To describe the characteristics and outcomes after resection of incidentally discovered, nonfunctioning pancreatic endocrine tumors (PETs). DESIGN Case series. SETTING Academic hospital. PATIENTS Consecutive patients with an incidentally identified, nonfunctioning PET resected from May 1, 1977, through July 31, 2009. MAIN OUTCOME MEASURES Operative morbidity and survival after resection. RESULTS A total of 139 patients with median age of 56 years (range, 21-85 years) underwent resection; tumor size ranged from 0.4 to 17.0 cm, with median size of 3.0 cm. No perioperative deaths were reported. Sixty-one patients (43.9%) experienced a perioperative complication. Twenty-six tumors (18.7%) were classified as benign, 39 (28.1%) as malignant, and 72 (51.8%) as uncertain. We were unable to confidently classify 2 tumors due to lack of information regarding mitotic rate in the pathology report. Complete follow-up was available for 112 patients (80.6%) (median, 34.2 months). Five-year actuarial survival rates were 88.8% for patients with benign disease, 92.5% for patients with tumors of uncertain biology, and 49.8% for those with malignant tumors (P = .01). Late metastasis, tumor recurrence, or disease progression were seen in 1 patient (3.8%) with tumors initially classified as benign, 8 patients (11.1%) with uncertain tumors, and 15 patients (38.5%) with tumors classified as malignant (P < .001). Of the 39 patients with tumors 2 cm or smaller, 3 (7.7%) had late metastases or recurrence. When compared with patients with symptomatic, nonfunctioning PETs, no large difference was observed in tumor size, patient age, disease, or survival. CONCLUSIONS Incidentally detected, nonfunctioning PETs can display aggressive behavior, even when small. Although patients with malignant disease had diminished survival and increased rates of recurrence, benign histologic findings did not eliminate the possibility of progression. Patients with incidentally discovered, nonfunctioning PETs should undergo tumor resection and careful postoperative surveillance, even if surgical pathologic findings suggest benign disease.
10.1001/archsurg.2011.102
pubmed_496_13041
Infarction of prolactin-secreting or growth hormone-secreting pituitary adenomas is not unusual. However, Infarction of ACTH-secreting adenomas has rarely been reported. Cyclical course of Cushing's syndrome alternating with adrenal insufficiency due to recurrent infarction of an ACTH-secreting pituitary adenoma has not been reported. We report here a 20-year-old lady who presented with florid signs of Cushing's syndrome but was found to have adrenal insufficiency on biochemical evaluation. Magnetic resonance imaging (MRI) of the pituitary gland showed that she had infarction of an ACTH-secreting macroadenoma. Over the next 6 years, her disease ran a cyclical course characterized by periods of hypercortisolism alternating with adrenal insufficiency due to repeated episodes of infarctions of the ACTH-secreting pituitary macroadenoma with corresponding changes in the pituitary adenoma on serial MRIs. The case alerts clinicians to this possibility when a patient presents with clinical picture of Cushing's syndrome but has adrenal insufficiency on biochemical testing. It also suggests that silent or subclinical infarction of pituitary adenomas is not uncommon and is probably under diagnosed.
10.1007/s11102-005-2961-8
pubmed_568_9561
RATIONALE Mucous membrane pemphigoid (MMP) is a rare, autoimmune bullous disease that affects mucosal surfaces and skin. Early and aggressive treatment initiation may be warranted due to the risks of serious complications. However, it can be challenging to make an initial diagnosis. Viral infection such as hepatitis B virus (HBV) infection has been found to be associated with the formation of autoimmune bullous diseases. PATIENT CONCERNS The patient was a 43-year-old male with gingivitis and recurrent swelling over the neck, cheeks, lips, and eyelids. The patient presented at oral medicine, otolaryngology, plastic surgery, and ophthalmology sequentially, and was later referred to the rheumatology, dermatology, and family medicine departments. Recurrent hemorrhagic bullae on oral mucosa and skin scarring occurred 2 years after the onset of the initial symptoms. DIAGNOSIS Skin biopsy with direct immunofluorescence was performed under the suspicion of MMP. Lesional hematoxylin and eosin stain and perilesional direct immunofluorescence were consistent with MMP. INTERVENTIONS Systemic Prednisolone and topical corticosteroid were used to control the disease. OUTCOMES A flare-up of hepatitis B developed as a result of systemic prednisolone use. The disease went through relapses and remissions. The patient is on low-dose prednisolone (5 mg/day) with a monthly outpatient visit in the family medicine department. LESSONS It would be useful for medical practitioners in different specialties to be alert of the heterogeneous presentations of MMP. Chronic HBV infection might be a risk factor for MMP. In patients with chronic HBV infection, treatment of MMP must be closely monitored for the risk of reactivation of HBV.
10.1097/MD.0000000000025955
pubmed_1082_7574
This review examines recent studies on the effects of exercise on tendons in animal models. Although tendon adaptation to exercise has been described using histology, morphometry, ultrasonography and molecular biology, precise measurements of excess tendon loading during exercise protocols have not been reported. Only a few studies have attempted to evaluate the mechanical strength of exercised tendons. The long term effect of exercise on tendons appears to be positive, but researchers have suggested that periods of mechanical weakness occur in tendons during adaptation to loading conditions. Studies documenting changes associated with the terminal state of pathological tendons are also summarised. Unfortunately, there are no descriptions of tendon tissue in the early stages of overuse injury. Since blood flow is commonly implicated in the emergence of tendinitis, the final section covers recent work on blood flow and tendon physiology. Related research identifying cellular mediators (hyperthermia, hypoxia, and oxidative stress) involved in the development of tendinitis is also presented. Suggestions for further research into exercise loading and the development of tendon overuse injuries are made.
10.2165/00007256-199520020-00003
pubmed_935_6895
Cerebrospinal fluid (CSF) protein abnormalities in 2 hydrocephalic children are described. 1 of the cases presented a degenerative pattern in lumbar CSF protein electrophoresis in spite of high total protein content. This is thought to be due to an excess of tissue proteins as a result of abnormal conditions of circulation and absorption of CSF in hydrocephalus. The other case makes clear the role of inflammation on CSF protein electrophoretic patterns.
10.1159/000119897
pubmed_494_10620
PURPOSE The treatment of celiac disease is a strict gluten-free diet for life. This diet is assumed to be more expensive, although no studies confirm this assumption. In the current study, the prices of gluten-free foods and regular (gluten-containing) foods were compared to determine if and to what extent gluten-free products are more expensive. METHODS Prices were compared for all food products labelled "gluten-free" and comparable gluten-containing food items in the same group available at two large-chain general grocery stores. The unit cost of each food, calculated as the price in dollars per 100 grams of each product, was calculated for purposes of comparison. RESULTS All 56 gluten-free products were more expensive than regular products. The mean (+/- standard deviation) unit price for gluten-free products was $1.71 (+/- 0.93) compared with $0.61 (+/- 0.38) for regular products (p<0.0001). On average, gluten-free products were 242% more expensive than regular products (+/- 212; range, 5% to 1,000%). CONCLUSIONS All the commercially available products labelled gluten-free were significantly more expensive than comparable products. This information will be useful to dietitians who counsel individuals and families with celiac disease, and to celiac advocacy groups for lobbying the government about financial compensation.
10.3148/69.3.2008.147
pubmed_719_11216
An operationally simple one-jar one-step mechanochemical Reformatsky reaction using in situ generated organozinc intermediates under neat grinding conditions has been developed. Notable features of this reaction protocol are that it requires no solvent, no inert gases, and no pre-activation of the bulk zinc source. The developed process is demonstrated to have good substrate scope (39-82 % yield) and is effective irrespective of the initial morphology of the zinc source.
10.1002/cssc.201900886
pubmed_953_16354
BACKGROUND Australian federal and jurisdictional governments are implementing ambitious policy initiatives intended to improve health care access and outcomes for Aboriginal and Torres Strait Islander people. In this qualitative study we explored Aboriginal Medical Service (AMS) staff views on factors needed to improve chronic care systems and assessed their relevance to the new policy environment. METHODS Two theories informed the study: (1) 'candidacy', which explores "the ways in which people's eligibility for care is jointly negotiated between individuals and health services"; and (2) kanyini or 'holding', a Central Australian philosophy which describes the principle and obligations of nurturing and protecting others. A structured health systems assessment, locally adapted from Chronic Care Model domains, was administered via group interviews with 37 health staff in six AMSs and one government Indigenous-led health service. Data were thematically analysed. RESULTS Staff emphasised AMS health care was different to private general practices. Consistent with kanyini, community governance and leadership, community representation among staff, and commitment to community development were important organisational features to retain and nurture both staff and patients. This was undermined, however, by constant fear of government funding for AMSs being withheld. Staff resourcing, information systems and high-level leadership were perceived to be key drivers of health care quality. On-site specialist services, managed by AMS staff, were considered an enabling strategy to increase specialist access. Candidacy theory suggests the above factors influence whether a service is 'tractable' and 'navigable' to its users. Staff also described entrenched patient discrimination in hospitals and the need to expend considerable effort to reinstate care. This suggests that Aboriginal and Torres Strait Islander people are still constructed as 'non-ideal users' and are denied from being 'held' by hospital staff. CONCLUSIONS Some new policy initiatives (workforce capacity strengthening, improving chronic care delivery systems and increasing specialist access) have potential to address barriers highlighted in this study. Few of these initiatives, however, capitalise on the unique mechanisms by which AMSs 'hold' their users and enhance their candidacy to health care. Kanyini and candidacy are promising and complementary theories for conceptualising health care access and provide a potential framework for improving systems of care.
10.1186/1472-6963-12-369
pubmed_756_11933
γ-Aminobutyric acid (GABA) has been shown to inhibit apoptosis of rodent β-cells in vitro. In this study, we show that activation of GABAA receptors (GABAA-Rs) or GABAB-Rs significantly inhibits oxidative stress-related β-cell apoptosis and preserves pancreatic β-cells in streptozotocin-rendered hyperglycemic mice. Moreover, treatment with GABA, or a GABAA-R- or GABAB-R-specific agonist, inhibited human β-cell apoptosis following islet transplantation into NOD/scid mice. Accordingly, activation of GABAA-Rs and/or GABAB-Rs may be a useful adjunct therapy for human islet transplantation. GABA-R agonists also promoted β-cell replication in hyperglycemic mice. While a number of agents can promote rodent β-cell replication, most fail to provide similar activities with human β-cells. In this study, we show that GABA administration promotes β-cell replication and functional recovery in human islets following implantation into NOD/scid mice. Human β-cell replication was induced by both GABAA-R and GABAB-R activation. Hence, GABA regulates both the survival and replication of human β-cells. These actions, together with the anti-inflammatory properties of GABA, suggest that modulation of peripheral GABA-Rs may represent a promising new therapeutic strategy for improving β-cell survival following human islet transplantation and increasing β-cells in patients with diabetes.
10.2337/db13-0931
pubmed_1119_14805
We report the use of color Doppler imaging in the diagnosis of four arteriovenous fistulas in the neck region: two had a traumatic origin and two were spontaneous. A perivascular color artifact was the most common initial finding on color images to indicate the underlying abnormality. In all four cases, a low-resistance flow with high systolic and diastolic velocities was observed in the feeding artery. Although angiography remains essential before therapeutic embolization, color Doppler sonography may be an important tool for screening and follow-up of cervical arteriovenous fistulas.
10.7863/jum.1995.14.3.233
pubmed_82_8762
PURPOSE The purpose of this study was to describe and compare the experiences, needs, priorities, and concerns reported by black and white nursing home residents during the living-dying interval. The living-dying interval is defined as the time between the knowledge of one's impending death and death itself. DESIGN This qualitative study was part of a larger ethnographic project. Residents participated in from one to four individual, in-depth, semi-structured, audiotaped interviews. SETTING Residents lived in two large county-financed nursing homes that have historically provided care to indigent black and white older adults. PARTICIPANTS Purposive sampling was used to identify eight black and five white residents with terminal cancer diagnoses who could serve as rich resources about the experience of living-dying in a nursing home. MEASURES Residents were asked open-ended questions about how things have been and what would make things better; what comforts them and would make them more comfortable; what dying means to them; and what things are important for nursing staff to know. RESULTS Verbatim transcripts of the interviews were coded using QRS NUD-IST software. Codes were placed in categories, categories were reviewed for common and different concepts, themes, and patterns, and a conceptual model was developed. The model identified six care needs: (1) day-to-day living; (2) inadequate pain relief for black residents; (3) difficulty chewing and swallowing; (4) importance of religious activities; (5) giving care to others; and (6) appreciation of respectful and prompt care. Residents validated all components of the conceptual model. CONCLUSION Black and white terminally ill residents focused on the quality of living rather than on dying, and black residents may be undertreated for pain. Important care needs for pain and religion are not routinely addressed by the Minimum Data Set (MDS) and Resident Assessment Protocol (RAP) triggers.
10.1111/j.1532-5415.1998.tb06646.x
pubmed_288_20620
We explore the variability that animals display in their movement choices as they forage in a finite-sized food patch with a uniform food distribution, and present a framework for how these choices may be adjusted to optimize foraging efficiency. Inspired by experimental studies of the zooplankton Daphnia, we model foraging animals as "agents" moving in two dimensions in repeated and successive sequences of hops, pauses, and turns. For Daphnia and other species, critical movement parameters such as hop lengths, pause times, and turning angles are typically reported as probability density functions. Similarly, the agents in our simulations choose their movement parameters at random from such distributions. Each distribution is defined by a characteristic width, which we interpret as a "noise width," available to be tuned for increased foraging efficiency. We investigate the sensitivity of the system by measuring the food gathered by the agents as the turning angle and hop length noise widths are varied. In all cases, we find a maximum in food gathered at some particular value of the noise width in question, suggesting that these results can be considered robust examples of natural stochastic resonance.
10.1016/j.jtbi.2008.01.026
pubmed_881_3806
The authors analysed retrospectively seven patients who underwent reoperation for recurrent thymoma. Patients have been categorised according to the classification of thymic epithelial tumours proposed by Masaoka et al. (29). In addition, patients have been subgrouped according to pleural invasion as defined by Haniuda et al. (15). Thus three substages were proposed as follows: p0-no adhesion to the mediastinal pleura; p1-patients with fibrous adhesion to the mediastinal pleura without microscopic invasion; p2-patients with microscopic invasion into the mediastinal pleura. At the initial operation, two patients were in Stage I, four Stage II, and one in Stage III. All Stage I patients were classified as p1, and of the four patients in Stage II one was classified as p0 and three patients as p2. One Stage III patient was classified as p2. Disease-free survival ranged from two years and four months to 20 years and two months. All patients underwent reoperation without preoperative treatment. Recurrent disease was aggressively resected from the pleura in six patients, mediastinum in four patients, lung in three patients, and diaphragm in three patients. Two patients refused further postoperative treatment. Adjuvant radiotherapy was administered to five patients; chemotherapy was added to the postoperative treatment of three patients with more advanced recurrent disease. Five patients were alive, free from any detectable tumour recurrence, one year and nine months to five years and four months after reoperation. In two patients with exacerbation of myasthenia gravis, reoperation was followed by complete remission of myasthenic symptoms. One patient died of post-radiation pulmonary fibrosis 13 months after reoperation, and one patient died of disease two years and two months after the second operation. Our findings indicate that an aggressive surgical approach to recurrent thymoma is justified and can be followed by prolonged disease-free survival.
pubmed_881_3806
others_78_10977
Introduction: This study reports a case of bevacizumab administered to treat choroidal neovascularisation in a woman later discovered to be pregnant. Clinical Picture: A 25-year-old pregnant woman developed myopic choroidal neovascularisation in both eyes. Treatment: Both eyes were treated with a total of 3 intravitreal injections of bevacizumab sequentially. Outcome: Vision improved signifi cantly in both eyes. There were no evident pregnancy-related complications at 1 year postpartum. Conclusion: Although anti-vascular endothelial growth factor (VEGF) therapy did not result in any detectable short-term adverse event in this mother and baby, the potential toxicity of these agents must be carefully considered in pregnant patients
others_78_10977
pubmed_99_2082
Leucocyte sodium efflux was measured in control leucocytes pre-incubated for 90 min with serum from patients with advanced liver cirrhosis. Serum from patients with advanced alcoholic liver cirrhosis was inhibitory to sodium transport in control leucocytes. The degree of inhibition was similar to that seen in the patients' own leucocytes; the defect induced by patient serum was primarily inhibition of ouabain-insensitive sodium efflux, whereas in the patients' own leucocytes, inhibition was seen in both ouabain-sensitive and -insensitive sodium efflux, as shown previously. The results suggest that a circulating factor, present in patients with advanced cirrhosis, is capable of inhibiting sodium transport in leucocytes.
10.1042/cs0660741
pubmed_636_13332
INTRODUCTION Respiratory disturbances are important element of congestive heart failure. In systolic left ventricle (LV) dysfunction some of ventilation parameters are impaired at early stage of the disease. The knowledge on ventilation disturbances in diastolic LV dysfunction is, however, poor. The aim of the study was to assess ventilation disturbances (using spirometry) in systolic and diastolic LV failure, and to evaluate correlation between spirometric parameters and echocardiographic as well as clinical data in studied groups. MATERIAL AND METHODS The study was carried out in 56 patients with stable angina, including 17 with no LV dysfunction (I), 18 with diastolic LV dysfunction (II) and 21 systolic and diastolic dysfunction (III). In each patients NYHA class, echocardiographic parameters of systolic and diastolic LV function and spirometry parameters were assessed. Results were expresses as mean +/- standard deviation. RESULTS In patients with diastolic dysfunction spirometric indices of obstruction were decreased compared to group I (FEV1% 91.97 +/- 13.54 vs 96.2 +/- 10.43 p < 0.05; FEV1/ FVC 0.72 +/- 0.06 vs 0.78 +/- 0.04, p < 0.05), but higher than in group III (FEV1% 91.97 +/- 13.54 vs 85.78 + 16.41 p < 0.05). Vital capacity was not impaired in either subgroup. MEF75--a spirometric parameter that depends on effort--was impaired in group III compared to I (67.72 +/- 19.7 vs 83.7 +/- 22.73, p < 0.05), while in group II it was similar to group I. No correlation was found between ventilation parameters and NYHA class or echocardiographic indices of LV dysfunction. CONCLUSIONS Ventilation disturbances in patients with diastolic LV dysfunction are less advanced than in patients with systolic heart failure, but more pronounced than in patients with no LV function impairment. In both systolic and diastolic dysfunction groups patients presented with obstructive pattern in spirometry. In systolic dysfunction obstructon was more pronounced, with significantly impaired effort-dependent phase of ventilation. No correlation was found between ventilation parameters and NYHA class or echocardiographic indices of LV dysfunction
pubmed_636_13332
pubmed_1103_12502
We have cloned the nap locus encoding the periplasmic nitrate reductase in Rhodobacter sphaeroides f. sp. denitrificans IL106. A mutant with this enzyme deleted is unable to grow under denitrifying conditions. Biochemical analysis of this mutant shows that in contrast to the wild-type strain, the level of synthesis of the nitrite and N(2)O reductases is not increased by the addition of nitrate. Growth under denitrifying conditions and induction of N oxide reductase synthesis are both restored by the presence of a plasmid containing the genes encoding the nitrate reductase. This demonstrates that R. sphaeroides f. sp. denitrificans IL106 does not possess an efficient membrane-bound nitrate reductase and that nitrate is not the direct inducer for the nitrite and N(2)O reductases in this species. In contrast, we show that nitrite induces the synthesis of the nitrate reductase.
10.1128/JB.181.19.6028-6032.1999
pubmed_65_18888
Risk managers should consider misidentifications as causes of otherwise unexplained diagnostic and process errors. Genetic tests are powerful tools that can resolve problem cases and indicate ways to improve patient-sample identification. Genetic typing, especially for DNA markers, has provided evidence of patient or sample identity in 21 of 22 hospital and laboratory cases of accidental or intentional patient misidentification, specimen mislabeling, and sample contamination. Identity is established with very high probability if infrequent genetic markers are observed in both unknown and reference specimens. The odds of a match of markers express both the infrequency of finding the match by chance (in specified populations) and the adequacy of testing. Genetic tests establish nonidentity with virtual certainty.
10.1002/jhrm.5600190107
pubmed_339_11702
On 10 April last, the Dutch Senat accepted a new bill concerning voluntary active euthanasia and physician assisted suicide. This bill legally embodies a ground for exemption from punishment for physicians who conducted voluntary active euthanasia or physician assisted suicide and who complied with certain requirements. Hence, the old policy of tolerance has been transformed into a legal system of acceptance of certain forms of voluntary active euthanasia and physician assisted suicide. This contribution describes these legal changes as the final stage of a process of integration of voluntary active euthanasia and physician assisted suicide in Dutch society. In this way, it endeavours to contribute to a constructive debate.
10.1055/s-2001-18472
pubmed_723_1374
PURPOSE OF REVIEW In the context of a resurgence of syphilis worldwide, it can be anticipated that a rise in cases of ocular, otic, and neurosyphilis will also be seen. This article reviews the current epidemiology, manifestations, and approach to management and treatment. RECENT FINDINGS Although studies continue investigating alternate approaches and new diagnostic tests for ocular and neurosyphilis, few data exist to change current diagnostic algorithms and approaches to diagnosis, management, or follow up. SUMMARY The diagnosis of neurologic and eye/ear involvement with syphilis may be delayed because of a lack of specificity of findings, low suspicion for syphilis, fluctuation in symptoms, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis and re-education about the protean manifestations of syphilis by all clinicians is required provide timely diagnosis and management of ocular, otic, and neurosyphilis.
10.1097/QCO.0000000000000617
pubmed_767_2114
BACKGROUND Fibrosis in patients with Crohn's disease (CD) results from an imbalance toward excessive fibrous tissue formation driven by fibroblasts. Activation of fibroblasts is linked to the B-cell lymphoma 2 (BCL2) family, which is involved in the induction of apoptosis. We investigated the impact of BCL2 repression on fibrogenesis. METHODS The model of dextran sodium sulfate (DSS)-induced chronic colitis and the heterotopic transplantation model of fibrosis were used. Following the administration of the BCL2 antagonist (ABT-737, 50 mg/kg/d), collagen layer thickness and hydroxyproline (HYP) content were determined. Fibroblasts were stimulated with the BCL2 antagonist (0.01-100 µM). BCL2, alpha smooth muscle actin (αSMA), and collagen I (COL1A1) were determined by quantitative polymerase chain reaction (qPCR), immunofluorescence microscopy (IF), and western blot (WB). mRNA expression pattern was determined by next-generation sequencing (NGS). RESULTS Collagen layer thickness was significantly decreased in both DSS-induced chronic colitis and the transplantation model of fibrosis upon BCL2 antagonist administration compared with vehicle. Decreased HYP content confirmed the preventive effects of the BCL2 antagonist on fibrosis. In vitro, a significant increase in PI+/annexin V+ human colonic fibroblasts was determined by fluorescence-activated cell sorting upon treatment with high-dose BCL2 antagonist; at a lower dose, αSMA, COL1A1, and TGF were decreased. NGS, IF, and qPCR revealed decreased expression and nuclear translocation of GATA6 and SOX9, known for reprogramming fibroblasts. CONCLUSION BCL2 antagonist administration partially prevented fibrogenesis in both fibrosis models. The BCL2 antagonist reduced the expression of TGFβ-induced factors involved in differentiation of myofibroblasts, and therefore might represent a potential treatment option against CD-associated fibrosis.
10.1093/ibd/izy147
pubmed_171_10781
There is growing evidence that endothelial dysfunction, which is often defined as the decreased endothelial-derived nitric oxide (NO) bioavailability, is a crucial factor leading to vascular disease states such as hypertension, diabetes, atherosclerosis, heart failure and cigarette smoking. This is due to the fact that the lack of NO in endothelium-dependent vascular disorders contributes to impaired vascular relaxation, platelet aggregation, increased vascular smooth muscle proliferation, and enhanced leukocyte adhesion to the endothelium. During the last several years, it has become clear that reduction of NO bioavailability in the endothelium-impaired function disorders is associated with an increase in endothelial production of superoxide (O(2)(*-)). Because O(2)(*-) rapidly scavenges NO within the endothelium, a reduction of bioactive NO might occur despite an increased NO generation. Among many enzymatic systems that are capable of producing O(2)(*-), NAD(P)H oxidase and uncoupled endothelial NO synthase (eNOS) apparently are the main sources of O(2)(*-) in the endothelial cells. It seems that O(2)(*-) generated by NAD(P)H oxidase may trigger eNOS uncoupling and contribute to the endothelial balance between NO and O(2)(*-). That is maintained at diverse levels.
035001459
pubmed_1131_23903
Riparian ecosystems are threatened worldwide, necessitating conservation strategies. Numerical models tailored for specific geographic areas have been developed as management support tools. However, few models are suitable for multiple river conditions, and developing these models or evaluating their suitability has become an emerging topic. The dynamic riparian vegetation model (DRIPVEM) is a numerical model developed for steep and gravelly Japanese rivers, where it has been successfully tested. Our objective was to assess the performance of DRIPVEM in a river with a low slope and fine sediment, similar to the characteristics of continental rivers. A reach of the Hii River was selected for testing the model's ability to predict the distribution of Salix spp. (willow) and herbs, as well as herb biomass and tree age. The model was calibrated based on field investigations of a selected river section. Simulation of the studied reach was carried out for the past five decades, depending on data availability. Non-parametric tests were used to compare the simulated and observed results. The simulated and observed vegetation distribution maps agreed fairly well and the sensitivity of the model for simulation of trees, herbs and bare areas was greater than 0.6. The kappa coefficients of agreement values were 0.48 and 0.49, indicating fair agreement. Moreover, the simulated biomass and tree age agreed well with observation. We conclude that the DRIPVEM simulated the observed conditions in the Hii River well, indicating that the model is applicable to rivers characterized by low slope and fine sediment grain size.
10.1080/09593330.2016.1199600
pubmed_637_4379
Species of Ophraella, a North American genus of leaf beetles (Chrysomelidae), feed variously on eight genera in four tribes of Asteraceae. A phylogenetic analysis, based on morphological features and allozymes, was undertaken to deduce the history of host affiliation within the genus. The two data sets are combined to arrive at a provisional phylogeny of the species, onto which host associations are parsimoniously mapped. Among and within the 12 species studied, at least two shifts are postulated to have occurred among congeneric plant species, five between genera in the same tribe, and four between different tribes of Asteraceae. The phylogeny of Ophraella appears not to be congruent with that of its hosts. This and other evidence indicates that many host shifts in Ophraella postdate the divergence of the host plants, a conclusion that may apply commonly to phytophagous insects. A phenetic analysis of the plants' secondary compounds provides modest support for the hypothesis that host shifts are facilitated by commonalities in plant chemistry. A possible trend in host shifts is evident, from chemically simpler to chemically more forbidding plants. The chemical barriers to host shifts in Ophraella appear to require adaptation in both behavior and in physiological attributes. There is no evidence that the host associations of these insects or the divergence in secondary chemistry of their hosts can be attributed to coevolution.
10.1111/j.1558-5646.1990.tb04298.x
pubmed_371_619
Previous studies have reported that the inhalation of the alpha 2-agonist clonidine decreases airways reactivity. Other studies have shown that oral doses of clonidine acutely increase airways reactivity to histamine, but not to methacholine. Recently, a transdermal clonidine delivery system (TTS) has been approved for use, and there is an increasing interest in using this system for management of postmenopausal and smoking cessation symptoms. To our knowledge, the effects of TTS on airways function in asthmatics have not been reported. The purpose of this study was to determine if use of TTS would alter airways reactivity. Six asymptomatic asthmatic subjects underwent a baseline methacholine challenge (M). In a double-blinded randomized crossover fashion, either a placebo or a TTS patch (TTS-1, 0.1 mg/day), was applied to the arm. Four days later, the challenge was repeated. After two to three days of washout, the alternate patch was applied, and a second challenge was performed. Several days later, a second baseline challenge was repeated. This sequence was then repeated using histamine (H). The patch was well tolerated by all subjects. There was no significant change in resting pulse or blood pressure, and for the group no change in airways reactivity to either M or H was noted. In conclusion, while use of TTS-1 does not improve airways function, its short-term use in asthmatics is not associated with an increase in airways reactivity.
10.1378/chest.100.4.1035
pubmed_291_12631
Three-dimensional ultrasound images (3DUS), having two spatial and one temporal dimension, were taken of the brachial artery during baseline conditions, in the transverse and longitudinal planes. The transverse images were analyzed by three different techniques used to quantify flow-mediated dilation (FMD): (1) measuring vessel area manually (TIMA), (2) measuring vessel area semi-automatically (TISA) and (3) measuring vessel diameter (TID). The inter- and intra-observer variability and transducer repositioning variability of each method were compared to each other and to the variability of measurements taken using the traditional method of measuring vessel FMD through measuring vessel diameter on longitudinal images (LID). The percent coefficient-of-variation describing the inter-observer variability (COV(inter)) was similar for the methods, indicating that each method was equally reproducible by the different observers. The percent coefficient-of-variation describing the intra-observer variability (COV(intra)) and the smallest detectable percent change in diameter (Δd(intra)) for each method indicated that TID was the most precise at measuring vessel diameter, and could measure the smallest changes in diameter between successive measurements (COV(intra) = 0.31%, Δd(intra) = 0.87%). LID performed the poorest (COV(intra) = 0.57%, Δd(intra) = 1.59%). The percent coefficient-of-variation describing transducer repositioning (COV(rep)) and the smallest detectable percent change in FMD over time (ΔFMD) for each method indicated that TIMA was the most reproducible method (COV(rep) = 2.35%, ΔFMD = 6.52%) closely followed by TISA. TID performed the poorest (COV(rep) = 5.37%, ΔFMD = 14.89%). TIMA and TISA were found not to be statistically different so we suggest TISA as the method of choice to maximize reproducibility between measurements over time, as it is faster and simpler to perform. In each experiment it was clear that transverse imaging introduced equal or less variability into diameter measurements as compared to longitudinal imaging and we suggest this imaging plane be used in all assessments of FMD.
10.1088/0031-9155/55/21/011
pubmed_162_13909
The adhesion and friction between two Al2O3 nanowires (NWs) was characterized by the use of optical microscopy based nanomanipulation, with which peeling, shearing and sliding was performed. The elastically deformed shape of the NWs during peeling and shearing was used to calculate the adhesion and frictional forces; force sensing was not required. The obtained adhesion stress between two Al2O3 NWs varied from 0.14 to 0.25 MPa, lower than that observed for carbon nanotube junctions, and was attributed to van der Waals attraction. Stick-slip was observed during the shearing and sliding of two NWs, and was the consequence of discrete contact between surface asperities. The obtained static and kinetic frictional stresses varied from 0.7 to 1.3 MPa and 0.4 to 0.8 MPa, respectively; significantly greater than the obtained adhesion stress.
10.1088/1361-6528/aab3a5
pubmed_306_13075
It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Ménière's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns.
10.1159/000355283
pubmed_637_1758
The transcription factor p53 is at the core of a built-in tumor suppression system that responds to varying degrees of stress input and is deregulated in most human cancers. Befitting its role in maintaining cellular fitness and fidelity, p53 regulates an appropriate set of target genes in response to cellular stresses. However, a comprehensive understanding of this scheme has not been accomplished. We show that argininosuccinate synthase 1 (ASS1), a citrulline-aspartate ligase in de novo arginine synthesis pathway, was directly transactivated by p53 in response to genotoxic stress, resulting in the rearrangement of arginine metabolism. Furthermore, we found that x-ray irradiation promoted the systemic induction of Ass1 and concomitantly increased plasma arginine levels in p53+/+ mice but not in p53-/- mice. Notably, Ass1+/- mice exhibited hypersensitivity to whole-body irradiation owing to increased apoptosis in the small intestinal crypts. Analyses of ASS1-deficient cells generated using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated 9) system revealed that ASS1 plays a pivotal role in limiting Akt phosphorylation. In addition, aberrant activation of Akt resulting from ASS1 loss disrupted Akt-mediated cell survival signaling activity under genotoxic stress. Building on these results, we demonstrated that p53 induced an intrinsic Akt repressor, ASS1, and the perturbation of ASS1 expression rendered cells susceptible to genotoxic stress. Our findings uncover a new function of p53 in the regulation of Akt signaling and reveal how p53, ASS1, and Akt are interrelated to each other.
10.1126/sciadv.1603204
pubmed_13_18282
Macrophages exhibit heterogeneity and plasticity and imbalance between pro-inflammatory and anti-inflammatory macrophages plays a critical role in atherosclerosis progression. Telomerase reverse transcriptase (TERT) in macrophages can be activated by nuclear factor-kappa B (NF-κB), but the regulation of telomerase activation on macrophages polarization remains unknown. We previously identified microRNA-216a (miR-216a) to promote inflammation through directly targeting the Smad3/NF-κB pathway. The present study aimed to assess whether miR-216a can regulate telomerase activity and promote macrophages polarization during atherosclerosis progression. The results verified that TERT was highly expressed in macrophages of human carotid atherosclerotic plaques. miR-216a was found to promote telomerase activation in macrophages by 4.5-fold (P = 0.002) through the Smad3/NF-κB pathway. miR-216a also induced macrophages senescence characterized by senescence-associated-β-galactosidase activity and p53 and p16 expression. TERT overexpression promoted the transformation of M2 to M1 while this conversion was suppressed once TERT was inhibited, and the related inflammatory factors and lipid uptake ability of M1 cells were also increased by TERT. In the carotid atherosclerotic plaques from miR-216a-treated apolipoprotein E-/- mice, the numbers of M1 macrophages were increased whereas M2 cells reduced, accompanying with inhibited Smad3 expression and upregulated inflammatory markers and TERT activity. Furthermore, plasma miR-216a level was specifically higher in patients with vulnerable mixed plaques (n = 181) than those with calcified plaques (n = 73) and controls (n = 264). In summary, our findings first revealed a new molecular mechanism of macrophage polarization involving telomerase activation induced by miR-216a through the Smad3/NF-κB signaling, which might serve as a potential therapeutic target for atherosclerosis progression.
10.1016/j.bbadis.2018.06.016
pubmed_1098_12151
(1) Background: Ellagic acid (EA) acts as a product of gut microbiota transformation to prevent insulin resistance, which is limited by high-fat diet (HFD)-induced dysbiosis. The aim of this study was to investigate the synergistic effects and mechanisms of supplementation with the probiotic Weizmannia coagulans (W. coagulans) on the prevention of insulin resistance by EA; (2) Methods: C57BL/6J mice were divided into five groups (n = 10/group): low-fat-diet group, high-fat-diet group, EA intervention group, EA + W. coagulans BC77 group, and EA + W. coagulans BC2000 group; (3) Result: W. coagulans BC2000 showed a synergistic effect on EA's lowering insulin resistance index and inhibiting high-fat diet-induced endotoxemia. The combined effect of BC2000 and EA activated the autophagy pathway in the mouse liver, a urolithin-like effect. This was associated with altered β-diversity of gut microbiota and increased Eggerthellaceae, a potential EA-converting family. Ellagic acid treatment alone and the combined use of ellagic acid and W. coagulans BC77 failed to activate the hepatic autophagy pathway; (4) Conclusions: W. coagulans BC2000 can assist EA in its role of preventing insulin resistance. This study provides a basis for the development of EA-rich functional food supplemented with W. coagulans BC2000.
10.3390/nu14194206
pubmed_857_4415
The importance of changes in glucagon in the regulation of hepatic glucose production (Ra) during exercise has been questioned, as an increase in arterial immunoreactive glucagon (IRG) is not always detectable. However, IRG in the portal vein (PV) and not in the artery is most relevant, as flow through PV is approximately 80% of liver blood flow. To assess the extent that arterial IRG reflects the levels the liver is exposed to in PV, dogs (n = 5) were implanted with catheters in a carotid artery, hepatic vein (HV), and PV. Dogs were studied > or = 16 days later during rest and 150 min of moderate treadmill exercise, with indocyanine green and [3-3H]glucose infused to assess hepatic plasma flow (HPF) and hepatic Ra. IRG was 66 +/- 7, 73 +/- 8, and 81 +/- 7 pg/ml in the artery, HV, and PV at rest; it rose at 10 and 150 min of exercise to 89 +/- 9 and 127 +/- 13 pg/ml in the artery, 106 +/- 17 and 186 +/- 21 pg/ml in HV, and, by considerably more, to 153 +/- 20 and 261 +/- 25 pg/ml in PV. HPF fell by approximately 30% with exercise. The fall in HPF accounted for < 11% of the increased arterial-to-PV IRG gradient during exercise, with increased splanchnic IRG release comprising the remainder. Ra was linearly related to IRG levels in the three vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
10.1152/jappl.1993.75.2.724
pubmed_170_7145
Protein hepatocyte nuclear factor 4alpha (HNF-4alpha) is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. HNF-4alpha and Foxo1 can physically interact with each other and represent an important signal transduction pathway that regulates the synthesis of glucose in the liver. Foxo1 and HNF-4alpha interact with their own binding sites in the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) promoters, and this binding is required for their effects on those promoters. However, the effect of physical activity on the HNF-4alpha/Foxo1 pathway is currently unknown. Here, we investigate the protein levels of HNF-4alpha and the HNF-4alpha/Foxo1 pathway in the liver of leptin-deficient (ob/ob) and diet-induced obese Swiss (DIO) mice after acute exercise. The ob/ob and DIO mice swam for four 30 min periods, with 5 min rest intervals for a total swimming time of 2h. Eight hours after the acute exercise protocol, the mice were submitted to an insulin tolerance test (ITT) and determination of biochemical and molecular parameters. Acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions. These phenomena were accompanied by a reduction in the expression of gluconeogenesis genes, such as PEPCK and G6Pase. Importantly, the PI3K inhibitor LY292004 reversed the acute effect of exercise on fasting hyperglycaemia, confirming the involvement of the PI3K pathway. The present study shows that exercise acutely improves the action of insulin in the liver of animal models of obesity and diabetes, resulting in increased phosphorylation and nuclear exclusion of Foxo1, and a reduction in the Foxo1/HNF-4alpha pathway. Since nuclear localization and the association of these proteins is involved in the activation of PEPCK and G6Pase, we believe that the regulation of Foxo1 and HNF-4alpha activities are important mechanisms involved in exercise-induced improvement of glucose homeostasis in insulin resistant states.
10.1113/jphysiol.2009.183996
pubmed_1045_6524
This investigation tested the hypothesis that hypnosis can differentially modulate T-cell subsets, and that this effect is mediated by changes in hypothalamo-pituitary-adrenal (HPA) mediators. Seven healthy, highly hypnotizable volunteers participated in three one-day sessions, a baseline and two intervention sessions. Hypnosis intervention entailed a standardized induction, suggestions for ego strengthening and optimally balanced functioning of the immune and neuroendocrine systems, and post-hypnotic suggestions for stress management and continued optimal balance of bodily systems. Blood samples were drawn at five time points between 8:00 a.m. and 3:00 p.m. and were analyzed for T-cell activation and intracellular cytokine expression (Interferon (IFN)-gamma, Interleukin-2, Interleukin-4) and HPA axis mediators (ACTH, cortisol, and beta-endorphin). Following hypnosis intervention, statistically significant immunological effects were noted. Specifically, the proportion of T-cells expressing IFN-gamma (p = .0001) and IL-2 (p = .013) were lower after hypnosis. T-cell activation response to polyclonal stimulation was positively correlated with ACTH (p = .01) and beta-endorphin (p = .001) while IFN-gamma expression was correlated with levels of cortisol (p < .001). Further controlled studies utilizing hypnosis with patients in treatment are warranted in order to examine whether an altered T-cell response can be replicated in the presence of disease.
10.1080/00029157.2003.10403525
pubmed_840_11575
gamma-Hydroxybutyrate (GHB) is believed to function as a neurotransmitter in the mammalian brain by binding to a GHB-specific binding site. In addition, GHB may also indirectly enhance the neuroinhibitory actions of gamma-aminobutyric acid (GABA) by converting to GABA at neuronal synapses. The purpose of the present study was to examine the effects of representative GABA(A) and GABA(B) receptor agonists in rats treated chronically with GHB. Using a rotorod apparatus, the motor-impairing effects of GHB, the indirect GABA(A) receptor agonist, flunitrazepam, and the direct GABA(B) receptor agonist, baclofen, were examined before, during and after chronic treatment with 1000 mg/kg GHB, b.i.d. Prior to chronic treatment, all three drugs produced dose-dependent decreases in motor performance at low (8 rpm) and high (32 rpm) rotational speeds. Chronic treatment with GHB significantly decreased the potency of baclofen at both speeds, but did not alter the potency of either GHB or flunitrazepam. Following termination of chronic treatment, the potency of baclofen increased significantly at both speeds and returned to that observed prior to chronic treatment. These data indicate that chronic treatment with GHB confers tolerance to a GABA(B) receptor agonist under conditions in which tolerance is not conferred to a GABA(A) receptor agonist. These findings are consistent with the in vivo behavioral profile of GHB, which reveals a greater role for GABA(B) receptors than for GABA(A) receptors in its behavioral effects.
10.1016/j.ejphar.2006.08.080
pubmed_809_7036
Glyoxal and methylglyoxal are two important markers of oxidative stress and both are involved in the evaluation of several diseases. A new HPLC method for determining glyoxal and methylglyoxal in urine was developed. The method is based on the reaction of alpha-dialdehydes, glyoxal and methylglyoxal, with 5,6-diamino-2,4-hydroxypyrimidine sulfate in basic medium to form highly fluorescent lumazine derivatives. Creatinine was also included in the method even though it does not react with the reagent. The derivatives and creatinine are separated on a C(18) reversed-phase column with a mobile phase consisting of acetonitrile:citrate buffer, pH 6.0 (3:97 v/v). The flow rate was 1.0mLmin(-1) and the effluent was monitored photometrically at 250 nm for determination of creatinine and fluorimetrically at 500 nm (exciting at 330 nm) for determination of glyoxal and methylglyoxal derivatives. Recording time of the separation is less than 10 min. Determination of the analytes is performed in urine after incubation of the sample, with the reagent in alkaline medium, for 30 min at 60 degrees C. Urinary levels of glyoxal and methylglyoxal, expressed as glyoxal/creatinine and methylglyoxal/creatinine ratios, in healthy young women and men were determined. For women, values of 0.80+/-0.37 and 0.60+/-0.22 microg/mg of creatinine were found for glyoxal and methylglyoxal, respectively. For men, values of 0.63+/-0.15 and 0.49+/-0.05 microg/mg of creatinine were found for glyoxal and methylglyoxal, respectively. These results were also related to the body mass index of each individual.
10.1016/j.ab.2007.07.028
others_394_240
Germany's zoological collections are among the oldest, most diverse, and historically most interesting natural history collections. From the perspective of three herpetologists with particular interest in taxonomy, we recount how invaluable visits to German collections have been to our own research efforts. Not only have we been able to use our findings in multiple publications, we also list examples of how we discovered new species and rediscovered specimens long thought lost, and we see in these experiences reasons to believe that many treasures in Germany's herpetological collections remain to be discovered. We also provide a brief historical overview of how Central Europe's and Germany's political structures in the seventeenth and eighteenth centuries led to a more diverse pattern for the formation of natural history collections than elsewhere, and we comment on the effects that the Second World War had on the well-being and continuity of collections. At the beginning of the twenty-first century, German zoological collections are a nexus for zoological research and a globally important scientific treasur
10.1007/978-3-319-44321-8_2
pubmed_380_2238
The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.
10.1002/ana.10669
pubmed_99_656
The authors report two cases of temporal arteritis complicated with dissecting aneurysm of the aorta. The first one is discovered on systematical physical examination, the second is revealed by a thoracic pain. Clinical course is favourable under steroid therapy in both cases. Eleven cases of such complication with pathological control are reported in literature. Physiopathological mechanisms are discussed and active inflammatory involvement of aortic wall seem to be the main cause.
pubmed_99_656
pubmed_424_2928
Macrophages play an important role in the pathogenesis of chronic colitis. However, it remains unknown how macrophages residing in the colonic lamina propria are regulated. We characterized colonic lamina proprial CD11b-positive cells (CLPMphi). CLPMphi of wild-type mice, but not IL-10-deficient mice, displayed hyporesponsiveness to TLR stimulation in terms of cytokine production and costimulatory molecule expression. We compared CLPMphi gene expression profiles of wild-type mice with IL-10-deficient mice, and identified genes that are selectively expressed in wild-type CLPMphi. These genes included nuclear IkappaB proteins such as Bcl-3 and IkappaBNS. Because Bcl-3 has been shown to specifically inhibit LPS-induced TNF-alpha production, we analyzed the role of IkappaBNS in macrophages. Lentiviral introduction of IkappaBNS resulted in impaired LPS-induced IL-6 production, but not TNF-alpha production in the murine macrophage cell line RAW264.7. IkappaBNS expression led to constitutive and intense DNA binding of NF-kappaB p50/p50 homodimers. IkappaBNS was recruited to the IL-6 promoter, but not to the TNF-alpha promoter, together with p50. Furthermore, small interference RNA-mediated reduction in IkappaBNS expression in RAW264.7 cells resulted in increased LPS-induced production of IL-6, but not TNF-alpha. Thus, IkappaBNS selectively suppresses LPS-induced IL-6 production in macrophages. This study established that nuclear IkappaB proteins differentially regulate LPS-induced inflammatory cytokine production in macrophages.
10.4049/jimmunol.174.6.3650
pubmed_663_1032
The effects of oxidation using HNO(3) on the properties of the carbonized wheat and barley straw were investigated by measuring different properties such as specific surface area, PZC, total surface acidic groups as well as FTIR and TG-DTA. A small decrease in the specific surface area due to pore blockage was observed after oxidation. After oxidation, the acidity was increased considerably and the point of zero charge shifted from approximately pH 9 to pH 2 in both types of carbon. By the oxidation of the carbon with nitric acid, carboxylic groups were produced as shown by absorption peaks at 1750 cm(-1) in the FTIR spectra. Boehm titration results showed that the number of carboxyl groups increased by approximately 11-fold after oxidation. The oxidized carbon samples were compared with the unoxidized original carbon samples for Cr(III) adsorption. It was observed that the oxidized carbons exhibit high adsorption efficiencies for Cr(III) ions compared to the original carbonized straws and this can be correlated to the decrease in PZC which is mainly due to the increase in carboxylic functional groups in the oxidized carbonized straws and these are responsible for their cation ion exchange phenomenon.
10.1016/j.jhazmat.2008.12.125
pubmed_933_18628
We propose and demonstrate a new fuzzy associative memory model that provides an option to control the sizes of the attraction basins in neural networks. In our optoelectronic implementation we use spatial/polarization encoding to represent the fuzzy variables. Shadow casting of the encoded patterns is employed to yield the fuzzy-absolute difference between fuzzy variables.
10.1364/ol.20.002125
others_323_482
The demand for renewable energy has led to construction of offshore wind farms with high-power turbines, and many more wind farms are being planned for the shallow waters of the world's marine habitats. The growth of offshore wind farms has raised concerns about their impact on the marine environment. Marine mammals use sound for foraging, orientation and communication and are therefore possibly susceptible to negative effects of man-made noise generated from constructing and operating large offshore wind turbines. This paper reviews the existing literature and assesses zones of impact from different noise-generating activities in conjunction with wind farms on 4 representative shallow-water species of marine mammals. Construction involves many types of activities that can generate high sound pressure levels, and pile-driving seems to be the noisiest of all. Both the literature and modeling show that pile-driving and other activities that generate intense impulses during construction are likely to disrupt the behavior of marine mammals at ranges of many kilometers, and that these activities have the potential to induce hearing impairment at close range. The reported noise levels from operating wind turbines are low, and are unlikely to impair hearing in marine mammals. The impact zones for marine mammals from operating wind turbines depend on the low-frequency hearing-abilities of the species in question, on sound-propagation conditions, and on the presence of other noise sources such as shipping. The noise impact on marine mammals is more severe during the construction of wind farms than during their opera
10.3354/meps309279
pubmed_440_13158
The genus Parapterulicium was first introduced to accommodate two Brazilian species of coralloid fungi with affinities to Pterulaceae (Agaricales). Despite the coralloid habit and the presence of skeletal hyphae, other features, notably the presence of gloeocystidia, dichophyses and papillate hyphal ends, differentiate this genus from Pterulaceaesensu stricto. Fieldwork in Brazil resulted in the rediscovery of two coralloid fungi identifiable as Parapterulicium, the first verified collections of this genus since Corner's original work in the 1950s. Molecular phylogenetic analyses of nrITS and nrLSU sequences from these modern specimens revealed affinities with the /peniophorales clade in the Russulales, rather than Pterulaceae. The presence of distinctive hyphal elements, homologous to the defining features of /peniophorales, is consistent with the phylogenetic evidence and thus clearly distinguished Parapterulicium and its type species P.subarbusculum from Pterulaceae, placing this genus within /peniophorales. Parapterulicium was also found to be polyphyletic so Baltazaria gen. nov. is proposed to accommodate P.octopodites, Scytinostromagalactinum, S.neogalactinum and S.eurasiaticogalactinum also within /peniophorales.
10.3897/mycokeys.37.26303
pubmed_116_2695
Antiphospholipid antibodies (aPL), anti-beta 2-glycoprotein I (anti-beta 2-GPI) and anti-oxidized-low-density lipoprotein (LDL) antibodies are all implicated in the pathogenesis of antiphospholipid syndrome. To investigate whether different autoantibodies or combinations thereof produced distinct effects related to their antigenic specificities, we examined the frequencies of antiphospholipid syndrome (APS)-related features in the presence of different antibodies [aPL, beta 2-GPI, anti-oxidized low density lipoprotein (LDL)] in 125 patients with APS. Median follow-up was 72 months: 58 patients were diagnosed as primary APS and 67 as APS plus systemic lupus erythematosus (SLE). Anticardiolipin antibodies (aCL), anti-beta 2-GPI and anti-oxidized LDL antibodies were determined by ELISA; lupus anticoagulant (LA) by standard coagulometric methods. Univariate analysis showed that patients positive for anti-beta 2-GPI had a higher risk of recurrent thrombotic events (OR = 3.64, 95% CI, p = 0.01) and pregnancy loss (OR = 2.99, 95% CI, p = 0.004). Patients positive for anti-oxidized LDL antibodies had a 2.24-fold increase in the risk of arterial thrombosis (2.24, 95% CI, p = 0.03) and lower risk of thrombocytopenia (OR = 0.41 95% CI, p = 0.04). Patients positive for aCL antibodies had a higher risk of pregnancy loss (OR = 4.62 95% CI, p = 0.001). When these data were tested by multivariate logistic regression, the association between anti-beta 2-GPI and pregnancy loss and the negative association between anti-oxidized LDL antibodies and thrombocytopenia disappeared.
10.1093/qjmed/91.9.619
pubmed_105_14933
Purpose The biomechanical characteristics of the trauma size and postoperative drainage of different incisions for high complex anal fistula surgery were compared by numerical simulation analysis to provide a theoretical basis for the clinical selection of minimally invasive incisions for surgery. Methods Using FLUENT finite element software, a typical incision finite element model was established to obtain incision areas, and the total mass outlet flow within 200 s was calculated to evaluate the drainage effect of each incision. Results The incisions with the largest to smallest areas were the curved, spindle, and curved plus extended groove incision, indicating that the curved plus extended groove incision caused the least damage to the perianal skin muscles. Conversely, the incisions with the largest to smallest total outlet flow were as follows: curved plus extended groove, spindle, curved, and straight incision, suggesting that the curved plus extended groove model had the best diversion effect, and the curved incision had better diversion effect than that of the straight incision. Conclusion The curved plus extended groove surgical incision had the smallest incision area, minimized damage to the perianal skin and muscle tissue, conformed to the concept of minimally invasive surgery, ensured adequate drainage of exudate, maintained the normal growth of granulation tissue on the wound surface, preserved the original form of the anus, and thus better protected the function of the anus. This improved the quality of life of patients requiring high complex anal fistulas.
10.3389/fsurg.2022.974341
pubmed_1075_20908
OBJECTIVES The measurement of language development in hearing-impaired children is an important step in assessing the appropriateness of an intervention. We proposed a set of language tests (the Assessment Package for Language Development in Japanese Hearing-Impaired Children [ALADJIN]) to evaluate the development of practical communication skills. This package consisted of communication skills (TQAID), comprehensive (PVT-R and SCTAW) and productive vocabulary (WFT), comprehensive and productive syntax (STA), and the STRAW. METHODS A total of 638 children with greater than 70-dB hearing impairment were subjected to this set of language tests. Additional tests, including the PARS, the RCPM, and parental questionnaires, were administered to assess the backgrounds of the children. RESULTS A trimodal distribution was observed among hearing-impaired children by the histogram-based analysis of each test. CONCLUSIONS The ALADJIN is a useful Japanese-language evaluation kit for hearing-impaired children.
10.1177/000348941212100401
pubmed_416_3688
Dendritic cells (DC) are extremely proficient inducers of naïve CD4+ T cell activation due to their high expression level of peptide-MHC and an array of accessory molecules involved in cell migration, adhesion and co-signaling, including PD-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2). Whether PD-L1 and PD-L2 have a stimulatory or inhibitory function is a matter of debate, and could be partially dependent on the model system used. In this study we examined the role of PD-L1 and PD-L2 expressed by DC in naïve CD4+ T cell activation in a more physiologically relevant model system, using OVA-specific T cells in combination with various levels of TCR stimulation. Overexpression of PD-L1 or PD-L2 by DC did not inhibit T cell proliferation, even when B7-1 and B7-2 mediated costimulation was absent, although IL-2 production was consistently decreased. Surprisingly, blocking PD-L1 and PD-L2 with soluble programmed death-1 (sPD-1) also inhibited T cell activation, probably via reverse signaling via PD-L1 and/or PD-L2 into DC, leading to reduced DC maturation. This study suggests a relatively minor contribution of PD-1 ligands in DC-driven CD4+ T cell activation and provides evidence for reverse signaling by PD-L1 and PD-L2 into DC, resulting in a suppressive DC phenotype.
10.1002/eji.200635978
pubmed_101_18809
In this research article, a novel and simple label-free electrochemiluminescence (ECL) immunosensor using cerium stannite (Ce2Sn2O7) nanocubes as brand-new ECL emitters has been suggested for the first time. Ce2Sn2O7 nanocubes prepared by a simple hydrothermal method displayed bright ECL emission, promising biocompatibility, low noxiousness, and perfect stability. On comparison of ECL and photoluminescence (PL) spectra, a surface-state mechanism was proposed to be involved in the ECL emission. After aminofunctionalization with 3-aminopropyltriethoxysilane (APTES), Ce2Sn2O7 could be decorated with gold nanoparticles through Au-NH2 covalent linkage, which yielded Au@Ce2Sn2O7 nanocomposites and further enhanced the ECL emission. To confirm the proposed immunosensor feasibility, carcinoembryonic antigen (CEA) was employed as an exemplary analyte. Based on the abovementioned points, our fabricated immunosensor improved the ECL performance to CEA concentrations in a linear range of 0.001-70 ng/mL with a low limit of detection of 0.53 pg/mL (S/N = 3). With outstanding stability, reproducibility, and specificity, this method is expected to be an innovative one for sensitive analyses of CEA and other biomarkers in real samples.
10.1021/acs.analchem.0c05315
others_255_117
Data clustering is a thoroughly studied data mining issue. As the amount of information being analyzed grows exponentially, there are several problems with clustering diagnostic large datasets like the monitoring, microbiology, and end results (SEER) carcinoma feature sets. These traditional clustering methods are severely constrained in terms of speed, productivity, and adaptability. This paper summarizes the most modern distributed clustering algorithms, organized according to the computing platforms used to process vast volumes of data. The purpose of this work was to offer an optimized distributed clustering strategy for reducing the algorithm's total execution time. We obtained, preprocessed, and analyzed clinical SEER data on liver cancer, respiratory cancer, human immunodeficiency virus (HIV)-related lymphoma, and lung cancer for large-scale data clustering analysis. Three major contributions and their effects were covered in this paper: To begin, three current Pyspark distributed clustering algorithms were evaluated on SEER clinical data using a simulated New York cancer dataset. Second, systemic inflammatory response syndrome (SIRS) model inference was done and described using three SEER cancer datasets. Third, employing lung cancer data, we suggested an optimized distributed bisecting k-means method. We have shown the outcomes of our suggested optimized distributed clustering technique, demonstrating the performance enhancemen
10.1142/S0218001422400067
others_237_770
Vesicoureteral reflux and urinary incontinence have previously been treated by various means including the endoscopic delivery of injectable bulking materials such as silicone micro-implants, PTFE implants, glass particles, fat and bovine collagen. These first three materials do not degrade and collagen requires frequently repeated injections in order to sustain the restored continence provided. Vesicoureteric reflux in children usually resolves independently before the age of five. Correction is required before this, because treatment by prophylactic antibiotics is frequently unsuccessful in preventing breakthrough infection. The ideal material for injection should have large particles to avoid migration, inject easily and controllably, be non-toxic and dissolve over the period of time by which time the kidney will be mature. Three different controlled-release glass (CRG) granule compositions have been prepared by Giltech Ltd, and suspended in a suitable carrier medium (in this case glycerol). The degradable glasses, which have two different size ranges of 200-300 and < 53 μm, and three different solution rates, were injected intramuscularly into the dorso-lumbar region of rats. Histological analysis of cryostat cut section after time periods of 2 d, 4 and 9 wk, and 6 mon has been performed. Histology sections were stained for neutrophils and macrophages using enzyme histochemistry. ED1 (monocytes and immature macrophages), ED2 (mature tissue macrophages), CD4 (helper:inducer T-lymphocytes and macrophages), CD8 (suppresser/cytotoxic T-lymphocytes), Interleukin-1β, IL-2 (activated T-lymphocytes), Major Histocompatibility Complex (MHC) class II (activated macrophages and activated B-lymphocytes), α-β (T-lymphocytes) and CD45RA (B lymphocytes) antibodies have beed used to stain immunohistochemically each sample. This study demonstrates that particulate, degrading glass is stimulating an inflammatory response in soft tissue at time periods up to 6 mon. It should be noted that very small particulate, fast degrading glass is leading to tissue necrosis and should not be considered further for these applications. However, larger particulate, slower degrading materials are demonstrating effective potential for stress incontinence applications
10.1023/A:1008923523428
pubmed_305_11186
BACKGROUND Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes. CASE PRESENTATION We report 3 patients who developed granulomatous/sarcoid-like lesions while being treated with immune checkpoint therapy for advanced-stage melanoma, and we provide a comprehensive review of the literature in which similar cases are described. To date, 26 patients (including the 3 from this report) have been described with a median age of 57 years who developed granulomatous/sarcoid-like lesions associated with CPIs (median onset 6 months), of which 77% of patients had melanoma as primary tumor. To manage this adverse side effect, therapy was withheld in 38% of patients and 44% of the patients were treated with systemic steroids and 8% patients with localized therapy (one patient with intralesional triamcinolone). 96% of patients demonstrated either resolution or improvement of granulomatous/sarcoid-like lesions associated with CPIs irrespective of medical intervention. Therapeutic response, stable disease, or remission of primary malignancy was observed in 71% of reported patients who developed granulomatous/sarcoid-like lesions associated with CPIs over a median follow-up of 11.5 months since initiation of treatment. CONCLUSIONS The development of granulomatous/sarcoid-like lesions associated with CPIs is a recognized manifestation with the current class of immune checkpoint therapy that may clinically and radiographically mimic disease recurrence. Awareness of this type of toxicity is important for appropriate management and possible measurement of therapeutic response in a subset of patients who manifest this type of immune-mediated reaction.
10.1186/s40425-018-0323-0
pubmed_686_19920
OBJECTIVE To assess the value of MRI in the post operative evaluation of Achilles tendon rupture. MATERIAL AND METHODS 40 patients treated for acute Achilles tendon rupture at the Pasteur Hospital of Cherbourg between 1994 and 2002 underwent postoperative MRI. The objective was to look for correlations between functional outcome and reproducible measurements from imaging data previously described in the literature. RESULTS We obtained only two positive correlations among all the combinations of comparisons: the first one between the perimeter of the calf and the surface area of the posterior muscle compartment, the second between the surface area of the operated tendon and its elongation estimated by the recalculated ratio of ankle dorsiflexion amplitude. CONCLUSION MRI plays no role in the routine follow-up of post-surgical Achilles tendons. It should consequently only be used as a specific tool in problem cases, such as evaluation of possible re-tear.
10.1016/s0221-0363(05)81522-7