title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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(2-Nitroethyl)benzene: a major flower scent from the Japanese loquat Eriobotrya japonica [Rosales: Rosaceae]. | (2-Nitroethyl)benzene was identified as a major component of the flower scent of the Japanese loquat Eriobotrya japonica [Rosales: Rosaceae], together with p-methoxybenzaldehyde and methyl p-methoxybenzoate. The corresponding volatiles from chopped leaves did not contain these three compounds. This is the first time that 1-nitro-2-phenyl-ethane has been demonstrated to be a natural product among Japanese plants, although two Japanese millipedes are known to possess the same aromatics. | 25,130,732 | [
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Bisphenol A exerts estrogenic effects by modulating CDK1/2 and p38 MAP kinase activity. | Bisphenol A (BPA) is considered to be an endocrine disruptor, but the mechanisms by which it disrupts endocrine functions are poorly understood. Here, we have shown that BPA binds both estrogen receptor (ER)-α and ER-beta (ER-β) using a fluorescence polarization competitive binding assay. In addition, we found that BPA induced cell proliferation by modulating cell cycle-related genes in the MCF-7 human mammary cancer cell line. Moreover, using a BG1 luciferase ER transactivation assay, we found that BPA has estrogenic activity. Modulating the MAPK pathway by using an ERK inhibitor (PD98059) or a JNK inhibitor (SP600125) had no effect on the ability of BPA to induce estrogenic activity. However, the antiestrogen, ICI 182,780, and the p38 inhibitor, PD 169316 successfully blocked BPA-induced estrogenic activity. Our findings suggest that BPA mimics ER-dependent estrogenic activity by targeting proteins that regulate the cell cycle and p38 MAPK. | 25,130,739 | [
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Ethanol stress impairs protein folding in the endoplasmic reticulum and activates Ire1 in Saccharomyces cerevisiae. | Impaired protein folding in the endoplasmic reticulum (ER) evokes the unfolded protein response (UPR), which is triggered in budding yeast, Saccharomyces cerevisiae, by the ER-located transmembrane protein Ire1. Here, we report that ethanol stress damages protein folding in the ER, causing activation of Ire1 in yeast cells. The UPR likely contributes to the ethanol tolerance of yeast cells. | 25,130,742 | [
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Sleep duration, sleep quality, and obesity risk among older adults from six middle-income countries: findings from the study on global AGEing and adult health (SAGE). | Changes in sleep patterns often occur in older adults. Previous studies have documented associations between sleep duration, sleep quality, and obesity risk in older individuals, yet few studies have examined these trends in lower-income countries. The present cross-sectional study uses nationally representative datasets from six countries to examine these relationships. Two hypotheses related to obesity risk and sleep patterns were tested using data from the first wave of the World Health Organization's Study on global AGEing and adult health (SAGE). This longitudinal study draws on samples of older adults (>50 years old) in six middle-income countries (China, Ghana, India, Mexico, Russian Federation, and South Africa). Self-report data were used to measure sleep duration, sleep quality, lifestyle and sociodemographic information, while anthropometric measurements were collected to assess body mass index (BMI) and waist circumference (WC). Multiple linear regressions were used to examine the relationship between sleep patterns and obesity risk while controlling for lifestyle factors. Shorter sleep durations in both men and women were significantly associated with higher BMI and WC measures (P < 0.05). Low sleep quality did not significantly contribute to increased obesity risk. Surprisingly, high sleep quality was significantly associated with increased male BMI and WC in China and India (P < 0.01). This study documented an association between short sleep duration and increased obesity risk, which is important given the global increase of obesity-related diseases. | 25,130,760 | [
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6-Bromoindirubin-3'oxime (BIO) decreases proliferation and migration of canine melanoma cell lines. | Despite recent therapeutic advances, malignant melanoma is an aggressive tumor in dogs and is associated with a poor outcome. Novel, targeted agents are necessary to improve survival. In this study, 6-bromoindirubin-3'-oxime (BIO), a serine/threonine kinase inhibitor with reported specificity for glycogen synthase kinase-3 beta (GSK-3β) inhibition, was evaluated in vitro in three canine melanoma cell lines (CML-10C2, UCDK9M2, and UCDK9M3) for β-catenin-mediated transcriptional activity, Axin2 gene and protein expression levels, cell proliferation, chemotoxicity, migration and invasion assays. BIO treatment of canine malignant melanoma cell lines at 5 µM for 72 h enhanced β-catenin-mediated transcriptional activity, suggesting GSK-3β inhibition, and reduced cell proliferation and migration. There were no significant effects on invasion, chemotoxicity, or apoptosis. The results suggest that serine/threonine kinases may be viable therapeutic targets for the treatment of canine malignant melanoma. | 25,130,776 | [
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An exploratory study of evoked facial affect in adolescent females with anorexia nervosa. | The aim of this exploratory study was to investigate facial affect in adolescent females with anorexia nervosa (AN). Evoked facial affect was recorded whilst AN and control participants (n=34) viewed emotional films. Significantly less facial affect was found in AN adolescents, despite reporting no differences in subjective emotion experience. These findings correspond with previous studies in adults with AN. Altered facial affect may impair interpersonal functioning and contribute to illness maintenance. | 25,130,780 | [
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Functional dyspepsia: outcome of focus groups for the development of a questionnaire for symptom assessment in patients suffering from postprandial distress syndrome (PDS). | To date, no patient reported outcomes (PRO) instrument is available for evaluation of treatment efficacy in functional dyspepsia (FD)/postprandial distress syndrome (PDS). The aim of our study was to perform focus group interviews for the development of a new questionnaire for assessing symptom pattern and severity in PDS. Random ambulatory patients diagnosed with FD/PDS based on Rome III criteria and no predominant gastro-esophageal reflux disease (GERD) symptoms were invited to participate. Focus group sessions were organized where patients reported and discussed their symptoms, facilitated by an experienced physician. After reaching saturation of identified symptom items, questions for a pilot PRO instrument were drafted and evaluated in cognitive interviews for relevance, clarity, and consistency. Of 225 screened patients, 26 patients were diagnosed with PDS without overlapping GERD as single final diagnosis. Fifteen of these (87% female, 48 ± 3.2 years) participated in one of three focus groups. All (100%) confirmed experiencing symptoms that were triggered or aggravated by ingestion of a meal, corresponding to early satiation (100%), and postprandial fullness (100%). In addition reported gastroduodenal symptoms were nausea (40%, postprandial in all, interprandial in 20%), upper abdominal bloating (33%), excessive belching (27%), and vomiting (13%). Epigastric pain and burning were present in respectively 20% and 13%. Non-gastroduodenal symptoms that patients reported included heartburn (33%, but mostly sporadic), weight loss (93%, on average 5.0 ± 1.7 kg), and fatigue (67%). Questions evaluating these symptoms were validated in 15 cognitive interviews. This focus group study confirms symptoms corresponding to postprandial fullness and early satiation as the key items for developing a PRO for PDS. | 25,130,784 | [
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Footprints of cardiac mechanical activity as expressed in lung Doppler signals. | To determine the diagnostic information contained in cardiac pulsatile pressure waves as expressed in the Doppler signals recorded over the right lung. The pulsatile characteristics of the pulmonary vascular system were studied by means of the novel pulse Doppler technology in 38 control volunteers, 31 patients with atrial fibrillation (AF) and 7 patients with atrial flutter. The Doppler velocity waveforms recorded were interpreted in relation to the cardiac cycle mechanical events that generate them: Ventricular systole (S), diastole (D) and presystolic left atrial contraction (A). It was demonstrated that in all cases of AF, wave-A was absent. With longer diastole a high frequency velocity waves were visible. It is assumed that they represent the atrial mechanical fibrillation. In the patients with atrial flutter, the single A-wave was replaced by a waveform termed F, the frequency of which exactly matched that of the flutter wave on the ECG. The F-wave had both a positive and negative component. The lung Doppler signals contain distinct signatures typical of arrhythmias such as AF and atrial flutter that can be used for both diagnosis and to gain insight into the nature of the phenomena. | 25,130,794 | [
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[Anti-leukemia mechanism of miR-17 and miR-20a silencing mediated by miRNA sponge]. | This study was aimed to quantitatively detect the expression levels of pre-miR-17 and pre-miR-20a in acute leukemia patients and eight kinds of leukemia cell lines, and to investigate the anti-leukemia mechanism of miR-17 and miR-20a silence mediated by miRNA Sponge. Quantitative real-time PCR was used to detect the mRNA expression levels of pre-miR-17 and pre-miR-20a in patients with various types of leukemia and leukemia cell lines. The Jurkat cells over-expressing miR-17 and miR-20a were transfected with recombinant lentivirus-transfecting units targeted at miR-17 and miR-20a plus 6 µg/ml of polybrene. Then the proliferation ability and cell cycle of Jurkat cells was evaluated by CCK-8 and flow cytometry respectively. The results showed that the expression level of pre-miR-17 and pre-miR-20a in all leukemia patients was significantly higher than that in normal group(P < 0.05), the expression of pre-miR-17 and pre-miR-20a in acute lymphoid leukemia was significantly higher than that in acute myeloid leukemia(P < 0.05), and the pre-miR-17 and pre-miR-20a expression level did not correlate significantly with high white blood cell count>20.0×10(9)/L(P > 0.05). The miR-17 and miR-20a silencing mediated by miRNA Sponge led to a significant decrease of cell growth, restored G1 accumulation and increase of cell apoptosis. It is concluded that the expression of miR-17 and miR-20a is upregulated in leukemia patients, which may contribute to leukemogenesis. Over-expressed miR-17 and miR-20a promote cell growth and cell cycle progression, and inhibit apoptosis through negatively-regulating P21 and E2F1 after-transcriptionally. | 25,130,806 | [
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[Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's lymphoma]. | The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism. | 25,130,814 | [
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[Comparative analysis of collecting mononuclear cells from peripheral blood by using Fenwal CS-3000 plus, haemonetics MCS plus and COBE spectra separators]. | This study was aimed to compare the collection efficiency of mononuclear cells (MNC) from peripheral blood as well as the changes of blood-related indices in patient by using 3 cell separators. MNC were collected from 94 tumor patients by using Fenwal CS-3000plus, Haemonetics MCSplus and COBE spectra separators. Routine blood test was performed before and after MNC collection to detect the potential effects of cell separators on blood-related indices in the patients. MNC count was performed. The percentages of CD3(+), CD4(+) and CD8(+) in peripheral blood cells were determined. The results showed that the MNC counts were (3.08 ± 0.79)×10(9), (3.21 ± 1.12)×10(9), and (3.22 ± 1.84)×10(9) per bag by CS-3000plus, MCSplus and COBE spectra, respectively. And the corresponding decrease of platelet percentage was (6.86 ± 5.70)%, (8.05 ± 5.14)% and (5.89 ± 4.48)%, respectively. The CD3, CD4 and CD8 ratios in peripheral blood of patients before and after treatment were significantly statistical different (P < 0.001). It is concluded that the MNC collection can be performed successfully with CS-3000plus, MCSplus and COBE spectra, and their collections can meet the needs in clinic. | 25,130,837 | [
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[Research advances on roles of ADAMTS-13 in thrombotic diseases]. | ADAMTS-13 is a plasma metalloprotease that cleaves von willebrand factor (vWF).At the present,it has been made great progresses on its structure, biological characteristics and function. ADAMTS-13 plays an important role in artery and venous thrombosis,besides controlling the cleaving of vWF, and the activity of the ADAMTS-13 can be effected by ion concentration and thrombin signal transduction pathway,but how the mechanism of ADAMTS-13 controlled is still not clear. This article reviews ADAMTS-13 changes,relevant mechanism and influencing factors of the enzyme regulation. | 25,130,850 | [
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Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia. | Inevitably fatal some 40 years, acute promyelocytic leukemia (APL) can now be cured in more than 95% of cases. This clinical success story is tightly linked to tremendous progress in our understanding of retinoic acid (RA) signaling. The discovery of retinoic acid receptor alpha (RARA) was followed by the cloning of the chromosomal translocations driving APL, all of which involve RARA. Since then, new findings on the biology of nuclear receptors have progressively enlightened the basis for the clinical efficacy of RA in APL. Reciprocally, the disease offered a range of angles to approach the cellular and molecular mechanisms of RA action. This virtuous circle contributed to make APL one of the best-understood cancers from both clinical and biological standpoints. Yet, some important questions remain unanswered including how lessons learnt from RA-triggered APL cure can help design new therapies for other malignancies. | 25,130,873 | [
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The promise of telemedicine. | We have developed an extraordinary capability to capture and transmit digital ocular imaging, enabling remote interpretation of every aspect of the eye. The issues regarding telemedicine were primarily technical and procedural when this journal first reviewed the topic in 1999. Fourteen years later, telemedicine presents strikingly different challenges-legal, ethical, and professional. Some "tele-ophthalmology" applications have now become a reliable part of daily practice. Although it offers improved health care at lower cost to more people, telemedicine could also radically transform the traditional doctor-patient interaction. | 25,130,894 | [
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The cultural dimension of tightness-looseness: An analysis of situational constraint in Estonia and Greece. | The importance of tightness-looseness as a dimension that explains a considerable amount of variance between cultures was demonstrated by Gelfand et al. (2011). Tight nations have many strong norms and a low tolerance of deviant behaviour, whereas loose nations have weak social norms and a high tolerance of deviant behaviour. The main aim of the current studies was to examine situational constraint in Estonia and Greece: that is, how the cultural dimension of tightness-looseness is manifested in everyday situations in those two countries. The findings of a questionnaire study (Study 1) suggested that, in general, there is higher constraint across everyday situations in Greece than in Estonia, but situational constraint in Greece is especially strong in school and organisational settings where people have hierarchically structured roles. The results of an observational study (Study 2) revealed a relatively high agreement between appropriateness of certain behaviours as judged by the respondents in Study 1 and the frequencies of observed behaviours in the two countries. Our findings suggest that the strength of situations may substantially vary both within and across cultures, and that the attitudes of the members about situational strength in their respective cultures are in concordance with observations of situations by neutral observers in how people in general behave in their culture. | 25,130,924 | [
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Individual factors enhance poor health-related quality of life outcome in multiple sclerosis patients. Significance of predictive determinants. | Individual factors in multiple sclerosis (MS) patients may modify the reliability of health-related quality of life (HRQOL) assessment. Knowledge of these effects may enable physicians to identify patients at risk for poor perceived health. To investigate what individual factors may interact with MS symptoms and their severity to modify the reliability of HRQOL assessment; to explore the predictive values of the significant variables identified. HRQOL was assessed in 57 patients by the 36-Item Short Form Health Survey (SF-36). The Physical Component Summary and Mental Component Summary were dichotomized and applied as dependent variables for logistic regression analysis. The Functional Independence Measure (FIM), Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Cognitive Behavioral Assessment (CBA) and specific individual factors were tested as independent variables. Two-way contingency tables were used to calculate the predictive values. Unemployment, smoking, and night waking were the most significant individual factors. Introversion, physical pain and difficulty falling asleep were also significant. EDSS-total ≥2, EDSS-pyramidal ≥2, FIM ≤123, FSS ≥5, depressive manifestations and bowel/bladder dysfunction were significant MS-related determinants. Sensitivity and specificity differed widely for each variable. Individual factors have relevance in HRQOL assessment. Their identification may help physicians construct the patient's risk profile. Sensitivity and specificity add weight to the significance of variables. | 25,130,927 | [
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Increased proinflammatory cytokines in sera of patients with multifocal motor neuropathy. | Multifocal motor neuropathy (MMN) is characterized by clinical improvement with intravenous immunoglobulin and the frequent detection of anti-ganglioside antibodies. However, the immunological background of the neuronal damage in MMN is still unclear. The aim of this study is to investigate abnormalities in the cytokine and chemokine profiles of MMN patients. Sera from 16 patients with MMN, 16 patients with sporadic amyotrophic lateral sclerosis (ALS), and 15 patients with other non-inflammatory neurological diseases (ONDs) were analyzed for 27 cytokines and chemokines using a multiplex bead array. We also checked whether the altered cytokine/chemokine profile in the MMN group differed significantly in the presence or absence of abnormal electrophysiological findings. Serum IL-1Ra, IL-2, G-CSF, TNF-α, and TNFR1 levels were significantly higher in the MMN group than in the ONDs group. Of these, G-CSF and TNF-α also showed significant increases compared to the ALS group. Serum G-CSF and TNF-α levels were significantly higher in MMN patients presenting with focal demyelination including conduction block than in patients without any focal demyelination. Proinflammatory cytokines may contribute to peripheral nerve demyelination in MMN. | 25,130,929 | [
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Plantar pressure characteristics in hallux valgus feet. | Due to the pathoanatomical changes in hallux valgus feet, the plantar flexion moment of the first metatarsophalangeal joint is reduced. Therefore, load bearing of the hallux is decreased during push-off. We assessed loading parameters in hallux valgus feet. Based on dorsal-plantar weight bearing radiographs of 61 feet, the intermetatarsal-, hallux valgus-, distal metatarsal articulation-angle, and sesamoid position were evaluated. Plantar pressure assessment was performed with the emed® system during level walking. We found negative correlations between hallux valgus angle and peak pressure in the great toe (r=-0.301, p<0.023), the maximum force of the hallux (r=-0.481, p<0.001), and contact time of the great toe (r=-0.448, p<0.001), and positive correlations for force time integral (r=0.348, p<0.001), contact area (r=0.307, p<0.020), maximum force (r=0.430, p<0.001), and peak pressure (r=0.361, p<0.006) of the fifth metatarsal head. A positive correlation between the sesamoid and the metatarsal subluxation regarding maximum force (r=0.294, p<0.034), and a negative correlation between the contact area of the hallux (r=-0.232, p<0.020) was shown. Depending on the severity, hallux valgus angle, and sesamoid subluxation, load shows significant lateral transmission in hallux valgus feet. | 25,130,961 | [
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Surgical management of thymic epithelial tumors in children: lessons from the French Society of Pediatric Oncology and review of the literature. | We report the results of a French multicenter retrospective study based on a period of more than 30 years and a review of the literature in order to more clearly define the surgical approach and specific pediatric risk factors. Clinical data of children comprising all histologic subtypes of thymic epithelial tumors (TET) treated between 1979 and 2009 in French pediatric oncology centers were retrospectively analyzed and discussed in the light of a review of all pediatric cases reported in the literature. Nine cases were identified, corresponding to five females and four males with a median age of 13 years (range: 7.5-17). Histologic subtypes were type AB (n = 1), type B (n = 5) and type C (n = 3). Treatment consisted of tumor resection (4 R0, 4 R1, 1 R2) via right anterior thoracotomy, posterolateral thoracotomy, left thoracoscopy, sternotomy and cervicosternotomy, and/or chemotherapy, mainly cyclophosphamide-doxorubicin-cisplatin (CAP; n = 5), and/or radiotherapy (n = 4). Two patients with TET type C died. All other patients are alive with a median follow-up of 4 years (range: 1.5-20). Review of a total of 93 pediatric cases reported in the literature showed statistically significant associations between less favorable histologic subtypes and male gender (P = 0.012), advanced Masaoka stage (P < 0.001) and quality of resection (P < 0.001) respectively. A review of the literature and our series identified several risk factors to take into account in the therapeutically decision. Complete resection through a sternotomy is highly recommended. | 25,130,986 | [
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How accurate is sperm morphology as an indicator of sperm function? | Sperm morphology has been consistently correlated with fertilisation success or failure. The clinical relevance of the percentage normal spermatozoa has been a widely discussed topic amongst infertility specialists and scientists. This study aimed to evaluate the role of sperm morphology as an indicator of additional sperm functions among 114 andrology referrals. The sperm functions that were investigated included chromatin packaging quality (CMA3 test (n = 109), zona-induced acrosome reaction (ZIAR test; n = 36), hemizona assay (HZI; n = 36) and progressive motility (n = 47). Chromatin packaging quality had a negative and significant (P = 0.0001, r = -0.74) correlation with the percentage normal spermatozoa, while progressive motility had a significant and positive correlation (P = 0.0001, 0.59). Accurate sperm morphology scoring as described by the WHO 2010 manual can therefore be used as an indicator of specific sperm functions. | 25,130,990 | [
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Waiting for a kidney transplant: association with anxiety and stress. | The pretransplantation period is characterized by many stressful events that can result in symptoms of anxiety and stress and ultimately can have a negative impact on graft outcome. Our objective was to evaluate the association between symptoms of anxiety and stress in patients awaiting kidney transplantation. This was a transversal study describing 50 randomly selected patients undergoing hemodialysis and waitlisted for kidney transplantation. We collected social and demographic data, and adopted the Beck Anxiety Inventory and the Lipp Stress Symptoms for Adults Inventory to respectively evaluate anxiety and stress. The mean age was 50.2 ± 11.7 years, 54% of patients were female, time on dialysis was 6.5 ± 4.5 years, and transplant waitlist time was 5.9 ± 4.4 years. Forty-six percent of patients were married or had a stable relationship, 50% were illiterate or had only finished primary school, and 64% were pensioners. Stress was documented in 60% of patients, of which 30% had severe stress, whereas 56% of patients showed symptoms of anxiety. The presence of stress was associated with longer waitlist time (P = .006) and longer time on dialysis (P = .052). Less severe stress was associated with higher education level (P = .031), whereas patients in more advanced phases of stress showed higher levels of anxiety. After a multivariate analysis, stress was 3.6 times (CI 1.34 to 9.89) more frequent among individuals with anxiety. Stress and anxiety were prevalent in patients on a waitlist and were associated with social and chronic kidney disease-related patterns. This observation can stimulate the adoption of strategies for the prevention of stress and anxiety, avoiding posttransplantation complications, such as nonadherence to treatment. | 25,131,015 | [
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Grade IV fibrosis interferes in biliary drainage after Kasai procedure. | Biliary atresia (BA) is the most common cause of liver transplantation in children. The earlier the treatment is done, the better the prognosis. The aim is to evaluate the impact of late diagnosis in children with BA, including the histopathological findings and success rate of biliary drainage in patients submitted to hepatic portoenterostomy (HPE). A retrospective study of cases of BA in the Department of Pediatric Surgery, Federal University of São Paulo (UNIFESP) between 1998-2011. We found 63 cases of BA; of these, 42 underwent HPE and 21 were referred for liver transplantation. Clinic and pathologic data were evaluated. The HPE was performed with a mean age of 86.5 days, with 16.6% having the operation at 60 days or earlier; 59.2% between 61 and 90 days; and 23.8% after 90 days. Successful biliary drainage occurred in 31% of surgeries, Mean days when HPE drained was 69.1 days, and 94.3 days when the surgery did not drain (P = .05). All patients who were successfully drained, did not have grade IV fibrosis on histology. In cases in which surgery was performed after 60 days that had not drained, 25% had grade IV fibrosis on biopsy (P = .0469). The age of HPE relates to better prognosis of the disease. It was found that the rate of grade IV fibrosis is higher in no drainage patients. All patients with grade IV fibrosis had no biliary drainage. | 25,131,036 | [
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Surface electromyography for respiratory assessment of liver transplant candidates, healthy subjects and after chevron post-operative incision. | Surface electromyography is a noninvasive technique for detecting the activity of skeletal muscles and especially the muscles for respiratory compliance; namely, the diaphragm and rectus abdominis. This study compares these muscles in healthy individuals, liver disease patients, and after abdominal surgery. To study muscle activity by surface electromyography of the right diaphragm muscles and right rectus abdominis (root means square, RMS), and the manovacuometry muscle strength (maximal inspiratory pressure, MIP; and maximal expiratory pressure, MEP). We evaluated 246 subjects who were divided into 3 groups: healthy (65), liver disease (171), and post-surgery (10). In liver disease group the BMI was higher significantly for ascites (P = .001), and was increase in RMS rectum (P = .0001), RMS diaphragm (P = .030), and a decreased inspiratory and expiratory indices (P = .0001) pressure in the post-surgery group. A multivariate analysis showed tendency to an increased BMI in liver disease and in the post-surgery groups correlated with an increased RMS rectum and the lower MIP/MEP (P = .11). The receiver operating characteristic curve showed that RMS rectus was capable of discriminating liver disease and post-surgery patients from healthy subjects (area = 0.63; 95% CI 0.549-0.725). The muscle activity of normal individuals is lower than in subjects with deficit muscles because less effort is necessary to overcome the same resistance, observed by surface electromyography and muscle strength. | 25,131,032 | [
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Portal versus systemic venous drainage of the pancreatic graft: the effect on glucose metabolism in pancreas and kidney transplant recipients. | Two different methods of graft venous drainage are used in pancreas transplantation: portal (PVD) and systemic (SVD). PVD is considered to be more physiologic due to its similarity to venous outflow of the native pancreas. The aim of our study was to compare glucose metabolism in Type 1 diabetic recipients of kidney and pancreatic grafts with PVD versus SVD by intravenous glucose tolerance test (IVGTT). We examined 28 insulin-independent patients after simultaneous pancreas and kidney transplantation: 14 recipients with PVD of the pancreatic graft and 14 with SVD after a mean post-transplant period of 1 year. All recipients had stable good function of the kidney graft. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA1c), and standard IVGTT with coefficient of glucose assimilation (KG) calculation were assessed. Insulin sensitivity and production were evaluated using the homeostasis model assessment (homeostasis model assessment of insulin resistance [HOMA-IR], homeostasis model assessment of B-cell function [HOMA-B]). Total C-peptide and insulin secretions were calculated as areas under the curves (AUCs) from the serum levels during the IVGTT. PVD and SVD groups did not differ in age, body mass index (BMI) and duration of post-transplantation period (P ≥ .05). We did not find any significant difference in fasting glycemia, HbA1c, KG, HOMA-IR, parameters of C-peptide level, fasting insulin level, and response during IVGTT. HOMA-B and AUC of insulin level were higher in the SVD group (45.1 ± 35.1 versus 19.8 ± 15.5, P =.03 and 1075 ± 612 versus 1799 ± 954 mIU/L/60 minutes, P < .03, respectively). In the PVD group, 1 patient had an abnormal response to the glucose stimulus, 8 patients had an impaired glucose tolerance, and 5 patients had a normal glucose tolerance. In the SVD group, an abnormal response was present in none, impaired glucose tolerance in 4, and normal glucose tolerance in 10 recipients. Athough this was not a prospectively randomized trial, we conclude that the change of surgical technique from SVD to PVD did not lead to any substantial change in terms of glucose tolerance. | 25,131,068 | [
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A novel screening test for detecting graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography with sonazoid. | Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in addition to Doppler ultrasonography. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow from the horizontal region to the peripheral region of the splenic vein in the pancreatic graft, and only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. Results from CEUS with Sonazoid showed the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, despite the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation. | 25,131,070 | [
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Islet oxygen consumption rate dose predicts insulin independence for first clinical islet allotransplants. | Human islet allotransplantation for the treatment of type 1 diabetes is in phase III clinical trials in the U.S. and is the standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose-stimulated insulin release, and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following 1 transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this article we report on the assessment of clinical islet allograft preparations using OCR dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. OCR dose was most predictive of CTO. IE dose was also highly predictive, while glucoses stimulated insulin release and membrane integrity stains were not. OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical human islet allotransplantation. | 25,131,089 | [
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Human islet viability and function is maintained during high-density shipment in silicone rubber membrane vessels. | The shipment of human islets (IE) from processing centers to distant laboratories is beneficial for both research and clinical applications. The maintenance of islet viability and function in transit is critically important. Gas-permeable silicone rubber membrane (SRM) vessels reduce the risk of hypoxia-induced death or dysfunction during high-density islet culture or shipment. SRM vessels may offer additional advantages: they are cost-effective (fewer flasks, less labor needed), safer (lower contamination risk), and simpler (culture vessel can also be used for shipment). IE were isolated from two manufacturing centers and shipped in 10-cm(2) surface area SRM vessels in temperature- and pressure-controlled containers to a distant center after at least 2 days of culture (n = 6). Three conditions were examined: low density (LD), high density (HD), and a microcentrifuge tube negative control (NC). LD was designed to mimic the standard culture density for IE preparations (200 IE/cm(2)), while HD was designed to have a 20-fold higher tissue density, which would enable the culture of an entire human isolation in 1-3 vessels. Upon receipt, islets were assessed for viability (measured by oxygen consumption rate normalized to DNA content [OCR/DNA)]), quantity (measured by DNA), and, when possible, potency and function (measured by dynamic glucose-stimulated insulin secretion measurements and transplants in immunodeficient B6 Rag(+/-) mice). Postshipment OCR/DNA was not reduced in HD vs LD and was substantially reduced in the NC condition. HD islets exhibited normal function postshipment. Based on the data, we conclude that entire islet isolations (up to 400,000 IE) may be shipped using a single, larger SRM vessel with no negative effect on viability and ex vivo and in vivo function. | 25,131,090 | [
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Xenograft of microencapsulated Sertoli cells for the cell therapy of type 2 diabetes mellitus in spontaneously diabetic nonhuman primates: preliminary data. | Insulin resistance in type 2 diabetes mellitus (T2DM) may be due to a chronic inflammation of the visceral adipose tissue (VAT) leading to local and systemic increases in proinflammatory cytokines. Microencapsulated porcine Sertoli cells (MC-pSC), by provision of immunomodulatory and trophic factors, have been successfully used to reduce such inflammation in rodent animal models of type 1 diabetes with no complications or deleterious side effects. Herein, we have begun to investigate this novel and safe therapeutic approach in the spontaneously obese nonhuman primate with spontaneous, insulin-dependent T2DM. After MC-pSC intraperitoneal injection we have evaluated, throughout a 6-month follow-up period, daily ad libitum fed glucose levels, daily exogenous insulin supplementation, biweekly body weight measurements, periodic fasting blood glucose concentrations, glycated hemoglobin (HbA1c) levels, glucose tolerance tests (GTT), and fluorescence-activated cell sorting cytometry (FACS) assessment of peripheral blood mononuclear cells. Very preliminarily, we have observed a slight reduction in fasting (FPG) and mean nonfasting (NF) plasma glucose levels. We found minimal changes, only in 1 animal, in daily exogenous insulin requirements and HbA1c levels. Flow cytometric analysis was associated with decrease in CD8(+) cells only in 1 recipient with a reduction in mean regulatory T Cells (Treg), whereas interestingly, decrease of B lymphocytes was observed in both animals. These results may suggest that this novel MC-SC-based transplantation protocol might possibly impact the metabolic status of T2DM in higher mammals that are close to humans. | 25,131,093 | [
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Donor organ shortage crisis: a case study review of a financial incentive-based system. | Current organ supply system depends on altruistic noncoercive donation, which has failed to meet the demand of organ transplantation. Providing financial incentives to donors is one of several approaches to address organ shortage. However, its feasibility is debatable as it relates to medical, ethical, and economic dimensions. An incentive-based procurement system (IBPS) applied by the Mobile Donor Action Team (MDAT) was instituted in Riyadh, Saudi Arabia, resulting in a 3-fold increase in donation rate. The goal of this study was to provide a qualitative review of a 7-year experience with IBPS. A qualitative approach was used. Documents were reviewed to create a chronological audit and shape interview questions. Sampling was purposeful and inclusive of MDAT members. Semi-structured interviews were conducted, and findings were subjected to thematic analysis. Documents reflected the evolution of MDAT. The essence of MDAT is field work and liberal use of financial incentives, which resulted in a 3-fold increase in the donation rate. MDAT members believed that IBPS is the main reason behind this increase. Moreover, IBPS is viewed as acceptable from a moral, ethical, and religious standpoint, with a high degree of professional satisfaction. Theoretical assumptions doubted the feasibility of IBPS. This real-life experience with IBPS proved the contrary. The findings may be applicable only to the setting in Riyadh, Saudi Arabia, however; further research is thus needed to explore its transferability to other settings. IBPS may be an alternative to altruistic noncoercive donation and should be piloted in different settings. | 25,131,100 | [
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Successful management of a ruptured mycotic pseudoaneurysm following pancreas transplantation using bovine pericardial patch: a case report. | Arterial mycotic pseudoaneurysms are a rare complication of pancreas transplantation. Rupture results in catastrophic hemorrhage with a high risk of mortality. Definitive management is complicated by an extensive arterial defect within a contaminated surgical field. Synthetic vascular grafts often fail due to subsequent graft infection whereas primary repair often results in arterial stenosis. Arterial ligation may be required to prevent exsanguination. A 41-year-old man, type 1 diabetic with associated renal failure, underwent successful simultaneous pancreas and kidney transplantation. He presented, 9 months following transplantation, with life-threatening rectal bleeding secondary to a ruptured mycotic pseudoaneurysm. This was successfully managed with a bovine pericardial patch (BPP) repair of the arterial defect and enteric diversion following graft pancreatectomy. He remains well with no vascular insufficiency 18 months following the procedure. A ruptured mycotic pseudoaneurysm following transplantation carries a significant risk of mortality and represents a surgical challenge as conventional techniques using synthetic materials often fail due to the contaminated field. A BPP offers good handling characteristics, excellent hemostatic properties and a favorable profile of infection risk in comparison with synthetic grafts. This case highlights its use as a treatment for a post-transplantation ruptured mycotic pseudoaneurysm. | 25,131,098 | [
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Histologic evaluation of organ preservation injury and correlation with cold ischemia time in 13 intestinal grafts. | Lesions produced in the graft mucosa due to harvesting, storage, and implantation must be graduated to assess the subsequent protocolized biopsy specimens. The aim is to identify type and intensity of graft mucosal lesions observed immediately after implantation. Congestion, hemorrhage, microthrombi, neutrophilic infiltrates, shortening of villi, epithelial detachment, erosion, and crypt loss were separately evaluated by two pathologists in mucosal biopsy specimens from 13 grafts. Each change was assessed as normal, mild, moderate, or severe and by splintering the summation of points a global score was designed. Cold ischemia time was registered. Correlation between the pathologists' evaluations and between final preservation injury degree and cold ischemia time was determined using the "index of correlation rho (ρ)" (Spearman's test). The same changes were assessed in 19 biopsy specimens from day 2 to day 6 (3.6 ± 1.1) to determine their evolution. Congestion was found in 7 biopsy specimens, microthrombi in 2, hemorrhage in 4, neutrophils in 6, villous atrophy in 8, epithelial detachment in 9, erosions in 2 and/or crypt loss in 2. The maximum degree of preservation injury was expressed as intense congestion and hemorrhage associated with epithelial detachment and villous atrophy. The global preservation score was grade 3 in 2 cases, grade 2 in 5, grade 1 in 2, and grade 0 in 4. There was positive correlation (ρ = 0.915) in the evaluation between pathologists (P < .01), total agreement in 9 biopsy specimens, and partial agreement (only 1 point disagreement) in 4. Mean cold ischemia time was 327 ± 101 min. (135-480). There was positive correlation (ρ = 0.694) between preservation score and cold ischemia time (P < .01). In the follow-up biopsy procedures, histological injury decreased by at least one grade in every case. Additionally, karyorrhexis was observed in 3 grafts and very occasional apoptosis in 2 others. This scale achieves good reproducibility and allows graduate preservation injury in intestinal transplantation. | 25,131,115 | [
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Impact of intestinal transplantation for intestinal failure in Japan. | The prognosis of intestinal failure has improved dramatically in the past few decades with the development of parenteral nutrition (PN). However, PN-dependent patients still have numerous complications. Intestinal transplantation can significantly improve their prognosis and quality of life. We report on the impact of intestinal transplantation for intestinal failure in Japan. Intestinal transplantations have been performed in Japan since 1996. Standardized forms were sent to all known intestinal transplantation programs, asking for information on intestinal transplantations performed between 1996 and June 31, 2012. All programs responded. Patient and graft survival estimates were obtained using the Kaplan-Meier method and analyzed with the Wilcoxon statistic. Five institutions provided data on 24 grafts in 21 patients. There were 12 cadaveric and 12 living related donor transplants. Causes of intestinal failure included short gut syndrome (n = 9), intestinal motility function disorders (n = 11), retransplantation (n = 3), and other (n = 1). The overall 1- and 5-year patient survival rates were 86% and 68%, respectively. In cases (n = 15) after 2006, the 1-year patient survival rate was 92%, and the 5-year survival rate was 83%. One- and five-year graft survival rates were 87% and 78%, respectively. More than 80% of all current survivors discontinued PN. Intestinal transplantation has become an effective therapy for patients with intestinal failure who cannot tolerate PN. After 2006, patient and graft survival rates approached rates associated with standard treatment for end-stage intestinal failure. Further improvements are expected with early referral due to suitable donor organ and pretransplant management. | 25,131,121 | [
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Psychiatric disorders in patients undergoing intestinal transplantation. | Psychiatric disorders are common in chronic disease states; intestinal transplantation recipients may therefore be at high risk for psychiatric disorder (PD). We sought to investigate the frequency and type of PD in our cohort of patients undergoing transplantation between 2007 and 2012. The notes of 25 patients who had undergone transplantations since 2007 were available for analysis. Five of 25 patients had died at the time of data collection. Pretransplantation, 14 of 25 patients had a history of a single psychiatric disorder (SPD) (depression). Two of 25 had double psychiatric diagnoses (DPD; depression with anxiety), and 1 had three PDs. Three of 25 patients suffered from chronic pain syndrome and 1 patient had this as an isolated diagnosis without any other PD. Post-transplantation, 10 of 14 patients still had an SPD; however, 3 of 14 had acquired a second diagnosis (DPD; anxiety with depression) with suicidal ideation in 2 cases. Those with DPD preoperatively did not improve. Depression resolved in 1 of 14 after transplantation. One patient without a history of psychiatric issues developed DPD during the postoperative course. Only 3 of 25 surviving patients are free of any psychological diagnosis post-transplantation. The presence of other problems in the cohort such as chronic pain syndrome in 4 of 25, medical noncompliance in 3 of 25, cyclizine dependency in 2 of 25, and recreational drug use suspected in 1 were also identified. Problems with body image relating to the stoma were experienced by 2 of 25 patients. The incidence of psychiatric disorder in patients embarking on transplantation is high and relates to their history of chronic illness. The additional stress of the transplantation operation and the long in-hospital rehabilitation period takes its toll on patients' emotional health and many acquire further psychiatric diagnoses. Managing the psychiatric health of patients is important for successful rehabilitation and their long-term health and wellbeing. | 25,131,124 | [
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Early histopathological changes in new-onset diabetes after kidney transplantation. | New-onset diabetes after transplantation (NODAT) is one of the most common complications after kidney transplantation. Patients were randomly assigned to receive cyclosporine A-based or tacrolimus-based immunosuppression. Fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following 3 groups, on the basis of the results: normal, impaired fasting glucose/impaired glucose tolerance, or NODAT. NODAT developed in 14% of patients receiving cyclosporine A-based immunosuppression and in 26% of patients taking tacrolimus (P = .0002). Albumin levels were similar, but uric acid level (P = .002) and the age of the recipient (P = .003) were significantly different between the diabetic and the normal groups. Evaluation of tissue samples revealed that acute cellular rejection and interstitial fibrosis/tubular atrophy were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis and interstitial inflammation (P = .05). The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before the development of any sign of functional impairment. | 25,131,129 | [
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Three-year longitudinal clinical trial of arterial function assessed by a oscillometric non-invasive method in comparison with carotid sclerosis and transferrin kidney-transplanted patients. | Chronic kidney disease remains one of the main risk factors of cardiovascular disease. However, patients with kidney transplantation have better life expectancy and better quality of life compared with patients on dialysis. In patients with a well-functioning graft, the main cause of death is cardiovascular in origin. Metabolic pathways have complex effects on arterial function that can be monitored by conventional ultrasonography and with the assessment of arterial stiffness by oscillometric non-invasive technique. Forty-one primer cadaver kidney-transplanted patient were involved in a 3-year longitudinal clinical trial (21 female, 20 male; average age, 40.16 ± 12.56 years). Arterial stiffness parameters referring to rigidity of the arterial wall (pulse wave velocity [PWV], augmentation index, and pulse pressure) were investigated. Correlation between stiffness, and laboratory parameters (serum creatinine, urea, hemoglobin, albumin, cholesterine, triglycerides, transferrin, uric acid, glomerular filtration rate, and C-reactive protein) were analyzed. A non-invasive oscillometric method--Tensiomed Arteriograph--was applied to assess the arterial stiffness parameters. Statistical analysis was performed with the use of Statistica for Windows, version 8.0. A value of P < .05 was considered statistically significant for all statistical tests. We found a positive correlation between PWV and left ventricular wall thickness and a negative correlation between PWV and ejection fraction. We also found a positive significant correlation between serum level of transferrin and PWV. There was simultaneous significant progression concerning PWV and carotid artery sclerosis in a 3-year follow-up. There was no fatal cardiovascular event during the study period among our patients. All of our patients involved in this study are still alive. Our findings suggest that arterial stiffness monitoring is a reliable method to assess global cardiovascular risk among kidney-transplanted patients. The oscillometric method is convenient, fast, painless technique to monitor arterial function, which, in the case of pathological findings, proposes more frequent cardiovascular control. | 25,131,132 | [
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Psychogenic nonepileptic seizures: should we use response to AEDS as a red flag for the diagnosis? | Lack of response to anti-epileptic drugs (AEDS) is considered a "red flag" pointing to a diagnosis of Psychogenic Nonepileptic Seizures (PNES). On the other hand, placebo effects are relevant in any medical condition with a complex psychosocial component. We aimed to evaluate the presence and frequency of a placebo response in patients with sole PNES and explore its impact on diagnostic delay. We reviewed the medical records of 102 patients referred for video EEG monitoring and diagnosed with PNES. Patients with PNES and epilepsy were excluded. The response to AEDs was analyzed according to patients' reports and medical records. Patients were classified, according to the response to AEDs, in two groups: responders (patients achieving remission) and non-responders. Then, we compared the diagnostic delay from the first event to the final diagnosis between these groups. Forty-seven patients (79.7%) with sole PNES who were using AEDs were identified. Twenty-two patients (46.8%) had reported complete or partial remission of PNES with mean response duration of 7.2 months (SD+9.6 months). The time delay of the diagnosis in the AED responder group was 10.6 years; the delay in non-responders was 5.6 years (p=0.035). Patients with sole PNES receiving AEDs can go into PNES remission. A favorable response to AEDs is likely to be interpreted as supporting a diagnosis of epilepsy and is associated with diagnostic delay. Physicians should bear in mind that patients with PNES may be particularly vulnerable to placebo effects. | 25,131,161 | [
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A new target for the old regulator: H-NS suppress T6SS secretory protein EvpP, the major virulence factor in the fish pathogen Edwardsiella tarda. | The evpP gene in fish pathogen Edwardsiella tarda, coding the T6SS secretory protein EvpP and carrying an evpA-evpO independent promoter region, was crucial for host cell invasion. The transcription of evpP was positively regulated by either the two-component system EsrA-EsrB or iron concentration, and its overexpression was known to enhance the invasion ability in our previous study. This work demonstrated that the H-NS protein, a pleiotropic regulator of gene expression, was a new transcriptional modulator of evpP gene. The results showed that in vivo the transcriptional level of evpP was downregulated by H-NS and in vitro this global regulator interacted directly with evpP promoter region. Moreover, DNase I footprinting experiments mapping the interaction regions of H-NS and evpP revealed that this global regulator bound to evpP promoter and neighbouring areas at multiple sites. We provided a new insight into evpP regulation network and demonstrated the repression of H-NS to the transcription of evpP gene. Recently, the devastating fish disease edwardsiellosis caused by Edwardsiella tarda has been widely concerned. The xenogeneic silencing of the classic regulator H-NS to the T6SS secretory protein EvpP, which played an important role in the virulence of Edw. tarda, was firstly reported in this study. It raised a better understanding of the virulence regulation of EvpP and provided more information about the complex infection mechanism of this pathogen. Our findings would contribute to the development of live attenuated vaccines against edwardsiellosis thus reducing the economic losses caused by this bacterium. | 25,131,176 | [
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Surface confined heteroleptic copper(II)-polypyridyl complexes for photonuclease activity. | Heteroleptic copper(II)-polypyridyl complexes with extended π-conjugated, aromatic terminal units were immobilized on glass/Si substrates to intercalate DNA and cleave it upon photoexposure. Photonuclease activity is shown to be high, well reproducible and non-destructible towards the assembled complexes. | 25,131,185 | [
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No impact of endogenous prothrombotic conditions on the risk of central venous line-related thrombotic events in children: results of the KIDCAT study (KIDs with Catheter Associated Thrombosis). | Central venous lines (CVLs) are the major exogenous risk factor for deep venous thrombosis (DVT) in children. The study objective was to assess whether endogenous prothrombotic conditions contribute to the risk of CVL-related DVT in children. This was a cohort study of consecutive children with heart disease requiring CVLs for perioperative care. CVLs were inserted percutaneously in the upper venous system and patients received prophylaxis with continuous unfractionated heparin (50 u kg(-1) d(-1) ). Blood samples to test for prothrombotic conditions were collected prospectively and assayed in a blinded fashion. Outcome assessment was by screening for DVT by venography, venous ultrasound and echocardiography. The study population consisted of 90 children, median age 2.7 years (0 months-18 years). Prevalence rates of antithrombin deficiency, protein C deficiency, protein S deficiency, heterozygous factor V Leiden, prothrombin G20210A mutation, methylentetrahydrofolate C677TT genotype, hyperhomocysteinemia, lupus anticoagulant, anticardiolipin antibodies and increased levels of lipoprotein (a) were within the range reported for the general population. At least one prothrombotic condition was present in 38% of children and combined abnormalities in 8%. The incidence of DVT was 28% (25/90), and most DVTs were asymptomatic. None of the prothrombotic conditions showed a significant association with DVT. The population attributable risk (i.e. the risk of DVT in the overall population attributable to a specific condition) did not exceed 2.2%. Prothrombotic conditions did not have an important impact on the risk of DVT in children with short-term CVLs. The results of the study suggest that screening for prothrombotic conditions is not justified in this setting. | 25,131,188 | [
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Evaluation of 18S rDNA PCR assay using skin fragments as a diagnostic test for Trypanosoma caninum. | Trypanosoma caninum is a new species that has been recently identified in Brazil and infects domestic dogs. To date, no accurate diagnostic assays for this parasite have been established; thus, our aim was to evaluate more than one type of PCR for the diagnosis and molecular screening of T. caninum in 229 dogs living in Rio de Janeiro state. The tests were based on the amplification and sequencing of the 18S ribosomal DNA (rDNA) gene using healthy skin fragments. Additionally, PCR amplification of the kDNA minicircles region specific to the Leishmania genus was performed. The PCR results were compared with those of culture-based analysis performed with the same specimen. Using cultures, T. caninum and Leishmania chagasi were isolated from 11 and 12 dogs, respectively, whereas the 18S rDNA PCR assay detected parasitic infection in 35 dogs. Among these, 25 dogs showed an amplification pattern similar to T. caninum and 10 showed a pattern similar to L. chagasi; these results were confirmed by sequencing analysis. The kDNA PCR analysis showed that 14 dogs were positive for Leishmania infection. Of these, 2 dogs showed negative culture results and 12 were positive for L. chagasi, including 4 with negative 18S rDNA PCR results. Thus far, culture-based testing has been the only tool used successfully for T. caninum diagnosis. Our results demonstrate that 18S rDNA PCR-based test should be a useful diagnostic tool, particularly for distinguishing between T. caninum and L. chagasi infections in areas where these 2 parasites co-exist. | 25,131,189 | [
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Gas2l3 is essential for brain morphogenesis and development. | Growth arrest-specific 2-like 3 (Gas2l3) is a newly discovered cell cycle protein and a cytoskeleton orchestrator that binds both actin filament and microtubule networks. Studies of cultured mammalian cells established Gas2l3 as a regulator of the cell division process, in particular cytokinesis and cell abscission. Thus far, the role of Gas2l3 in vivo remains entirely unknown. In order to investigate Gas2l3 in developing vertebrates, we cloned the zebrafish gene. Spatiotemporal analysis of gas2l3 expression revealed a ubiquitous maternal transcript as well as a zygotic transcript primarily restricted to brain tissues. We next conducted a series of loss-of-function experiments, and searched for developmental anomalies at the end of the segmentation period. Our analysis revealed abnormal brain morphogenesis and ventricle formation in gas2l3 knockdown embryos. This signature phenotype could be rescued by elevated levels of gas2l3 RNA. At the tissue level, gas2l3 downregulation interferes with cell proliferation, suggesting that the cell cycle activities of Gas2l3 are essential for brain tissue homeostasis. Altogether, this study provides the first insight into the function of gas2l3 in vivo, demonstrating its essential role in brain development. | 25,131,197 | [
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Reconstruction of insulin signal flow from phosphoproteome and metabolome data. | Cellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data. | 25,131,207 | [
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Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease. | Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca(2+) signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation. | 25,131,209 | [
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Relationship between chronic diarrhea with normal colonoscopy findings and terminal ileum lesions. | The causes and mechanisms of chronic diarrhea are complex. This study aimed to explore the relationship between chronic diarrhea with normal colonoscopy findings and terminal ileum lesions. All cases were collected from January 2009 to June 2010. The 40 patients in the patient group had chronic diarrhea with normal colonoscopy findings. Those who had hyperthyroidism, diabetes, chronic pancreatitis, cirrhosis, atrophic gastritis, short bowel syndrome and connective tissue diseases had been excluded. The control group contained 40 healthy individuals without diarrhea. Endoscopy of the terminal ileum was applied in both groups, with the endoscope inserted into terminal ileum for more than 20 cm. The patients diagnosed of chronic diarrhea with terminal ileum lesions were treated with metronidazole and probiotics for 10-14 days. Before treatment there were significant differences in endoscopy findings of the terminal ileum between the two groups (P < 0.05). In the patient group, endoscopy showed congestion, edema, erosion and ulcers in 29 cases, hyperplasia and enlargement of lymphoid follicles in 10 cases with a maximal diameter of 7-8 mm, and 1 case showed normal endoscopy results. After treatment, 35 patients recovered from diarrhea, and terminal ileum lesions disappeared in 30 cases as determined by endoscopy. In the control group, endoscopy showed scattered hyperplasia of lymphoid follicles in 5 cases, and the follicles were small with the maximal diameter being 3 mm. There was no hyperemia, edema, erosion or ulcers. Chronic diarrhea patients with normal colonoscopy findings may have lesions in the terminal ileum that can be detected by endoscopy; including hyperemia, erosion, ulcers and lymphoid follicle hyperplasia. Therapeutic effect is good with metronidazole and probiotics. | 25,131,227 | [
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The small GTPases regulate HMC05-induced NQO-1 expression with an antioxidant effect in smooth muscle cells. | Recently, Banhabackchulchunmatang (HMC05) has been implicated as a preventive and/or therapeutic candidate for cardiovascular diseases due to its inhibition of atherosclerosis lesions and its reduction of neointima formation. Knowledge of the mechanism of HMC05 in smooth muscle cells (SMC) is limited. However, SMC may be a potential target for HMC05 therapy because they are supported by the HMC05-mediated preservation of medial smooth muscle cell layers in pathogenic progression. Therefore, in the present study, we hypothesized that the effect of HMC05 is associated with reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H):quinone oxidoreductase-1 (NQO-1) gene regulation, which precipitates an antioxidant effect in SMC. HMC05 significantly increased NQO-1 gene expression in a dose- and time-dependent manner. The reactive oxygen species-mediated toxicity that was generated by xanthine/xanthine oxidase was suppressed by HMC05. The knockdown of the NQO-1 gene abrogated the HMC05-mediated cytoprotection. Interestingly, pretreatment with a chemical inhibitor of geranylgeranyl transferase 1 or farnesyl transferase abolished the NQO-1 gene induction and cytoprotection by HMC05. The transfection of dominant negative RhoA or Ras suppressed HMC05-induced gene expression. Berberine and hesperidin, which are found in large quantities in HMC05, also induced NQO-1 gene expression. Taken together, this is the first study to demonstrate that HMC05 is efficacious in protection against oxidative stress through NOQ-1 gene induction via the regulation of RhoA and/or Ras, and that berberine and hesperidin are major components of NQO-1 gene induction. This study provides mechanistic targets of HMC05 in reducing atherosclerotic lesions in atherosclerosis. | 25,131,260 | [
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Uses of cancer registries for public health and clinical research in Europe: Results of the European Network of Cancer Registries survey among 161 population-based cancer registries during 2010-2012. | To provide insight into cancer registration coverage, data access and use in Europe. This contributes to data and infrastructure harmonisation and will foster a more prominent role of cancer registries (CRs) within public health, clinical policy and cancer research, whether within or outside the European Research Area. During 2010-12 an extensive survey of cancer registration practices and data use was conducted among 161 population-based CRs across Europe. Responding registries (66%) operated in 33 countries, including 23 with national coverage. Population-based oncological surveillance started during the 1940-50s in the northwest of Europe and from the 1970s to 1990s in other regions. The European Union (EU) protection regulations affected data access, especially in Germany and France, but less in the Netherlands or Belgium. Regular reports were produced by CRs on incidence rates (95%), survival (60%) and stage for selected tumours (80%). Evaluation of cancer control and quality of care remained modest except in a few dedicated CRs. Variables evaluated were support of clinical audits, monitoring adherence to clinical guidelines, improvement of cancer care and evaluation of mass cancer screening. Evaluation of diagnostic imaging tools was only occasional. Most population-based CRs are well equipped for strengthening cancer surveillance across Europe. Data quality and intensity of use depend on the role the cancer registry plays in the politico, oncomedical and public health setting within the country. Standard registration methodology could therefore not be translated to equivalent advances in cancer prevention and mass screening, quality of care, translational research of prognosis and survivorship across Europe. Further European collaboration remains essential to ensure access to data and comparability of the results. | 25,131,265 | [
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Third-grade retention and reading achievement in Texas: a nine year panel study. | The academic performance of over 38,000 Texas students who failed the state's 1994 reading test was examined through their sophomore year in high school. Propensity score matching resulted in strata with retained and promoted students of comparable observed characteristics. Reading scores were analyzed using a two-level hierarchical linear model. Same grade comparisons show that third graders failing the state-mandated reading test who repeated the grade consistently outperformed in later grades the socially promoted children who also failed the third grade test. Additional analyses indicate that alternative explanations for the findings such as omitted variables, regression to the mean, differential panel attrition and cohort effects are not supported. The results are consistent with findings from other recent studies which suggest that grade retention in third grade may help increase student achievement. | 25,131,271 | [
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Homonegativity among first and second generation migrants in Europe: the interplay of time trends, origin, destination and religion. | Previous studies reported declining disapproval of homosexuality in Europe but have simultaneously identified the decelerating effect of religiosity and the higher disapproval of homosexuality among migrants. In this paper, we address disapproval of homosexuality among first- and second-generation migrants in Europe by assessing (1) period and cohort changes, (2) origin and destination country influences and (3) the role of religiosity. We develop a specific cross-classified multilevel design enabling us to simultaneously examine these influences. We test hypotheses using a subsample of the European Social Survey (ESS), containing 19,878 first and second generation migrants. The analyses lead to three important conclusions. Firstly, disapproval of homosexuality is declining both over time and across cohorts. Secondly, migrants conform to levels of disapproval of homosexuality among natives in the destination country, and this explains the decline among migrants over time. Thirdly, religion has a multi-faceted influence on levels of disapproval of homosexuality among migrants. | 25,131,278 | [
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College quality and hourly wages: evidence from the self-revelation model, sibling models and instrumental variables. | This paper addresses the recent discussion on confounding in the returns to college quality literature using the Norwegian case. The main advantage of studying Norway is the quality of the data. Norwegian administrative data provide information on college applications, family relations and a rich set of control variables for all Norwegian citizens applying to college between 1997 and 2004 (N = 141,319) and their succeeding wages between 2003 and 2010 (676,079 person-year observations). With these data, this paper uses a subset of the models that have rendered mixed findings in the literature in order to investigate to what extent confounding biases the returns to college quality. I compare estimates obtained using standard regression models to estimates obtained using the self-revelation model of Dale and Krueger (2002), a sibling fixed effects model and the instrumental variable model used by Long (2008). Using these methods, I consistently find increasing returns to college quality over the course of students' work careers, with positive returns only later in students' work careers. I conclude that the standard regression estimate provides a reasonable estimate of the returns to college quality. | 25,131,279 | [
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Identifying predictors of survey mode preference. | To increase the likelihood of response, many survey organizations attempt to provide sample members with a mode they are thought to prefer. Mode assignment is typically based on conventional wisdom or results from mode choice studies that presented only limited options. In this paper we draw heavily on research and theory from the mode effects and the survey participation literatures to develop a framework for understanding what characteristics should predict mode preferences. We then test these characteristics using data from two different surveys. We find that measures of familiarity with and access to a mode are the strongest predictors of mode preference and measures of safety concerns, physical abilities, and normative concerns are unexpectedly weak predictors. Our findings suggest that variables that may exist on sample frames can be used to inform the assignment of "preferred" modes to sample members. | 25,131,280 | [
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When do doctors follow patients' orders? Organizational mechanisms of physician influence. | Physicians, like other professionals, are expected to draw from specialized knowledge while remaining receptive to clients' requests. Using nationally representative U.S. survey data from the Community Tracking Study, this paper examines the degree to which physicians are influenced by patients' requests, and how physicians' workplaces may mediate acquiescence rates through three mechanisms: constraints, protection, and incentives. We find that, based on physicians' reports of their responses to patients' suggestions, patient influence is rare. This influence is least likely to be felt in large workplaces, such as large private practices, hospitals, and medical schools. We find that the protection and incentives mechanisms mediate the relationship between workplace types and physician acquiescence but more prescriptive measures such as guidelines and formularies do not affect acquiescence. We discuss these findings in light of the ongoing changes in the structure of medicine. | 25,131,283 | [
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Twelve-year survey (2001-2012) of the antimicrobial susceptibility of Streptococcus pneumoniae isolates from otorhinolaryngology clinics in Miyagi Prefecture, Japan. | Streptococcus pneumoniae is one of the most common bacteria causing otorhinolaryngological infections, such as acute otitis media and upper respiratory tract infection. Our group surveyed the drug susceptibility profile of S. pneumoniae isolates from otorhinolaryngology patients. A total of 41,069 S. pneumoniae isolates were detected at Miyagi Medical Association Health Center between May 2001 and December 2012. Specimens were obtained from patients at 40 otorhinolaryngology outpatient clinics in Miyagi Prefecture, Japan. The minimum inhibitory concentrations (MICs) of 8 antimicrobial agents were measured using the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines. In children aged 0-2 years old, the MIC50 values of penicillins decreased after 2010 (PCG: 1 μg/ml (2010) to 0.06 μg/ml (2012); ABPC: 1 μg/ml (2010) to 0.25 μg/ml (2012)). The prevalence of penicillin-resistant S. pneumoniae (PRSP) decreased from 35.2% (2010) to 14.6% (2012) in rhinorrhea specimens and from 43.4% (2010) to 14.3% (2012) in otorrhea specimens. Susceptibility to cephems (ceftriaxone and cefditoren) and carbapenems (panipenem) also showed improvement after 2010. For macrolides (clarithromycin) and lincosamides (clindamycin), MIC50 values increased in all age groups during the study period, and a high level of resistance was seen until 2012. There were no marked changes of susceptibility to fluoroquinolones (LVFX) during the study period. Improvement of susceptibility of S. pneumoniae to β-lactams occurred after 2010 in Miyagi Prefecture, Japan. | 25,131,291 | [
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Vmp1 regulates PtdIns3P signaling during autophagosome formation in Dictyostelium discoideum. | Generation and turnover of phosphatidylinositol 3-phosphate (PtdIns3P) signaling is essential for autophagosome formation and other membrane traffic processes. In both Dictyostelium discoideum and mammalian cells, autophagosomes are formed from specialized regions of the endoplasmic reticulum (ER), called omegasomes, which are enriched in the signaling lipid PtdIns3P. Vacuole membrane protein 1 (Vmp1) is a multispanning membrane protein localized at the ER that is required for autophagosome formation. There are conflicting reports in the literature as to whether Vmp1 is strictly required or not for autophagy-related PtdIns3P signaling and its hierarchical relationship with Atg1 and PI3K. We have now addressed these questions in the Dictyostelium model. We show that Dictyostelium cells lacking Vmp1 have elevated and aberrant PtdIns3P signaling on the ER, resulting in an increased and persistent recruitment of Atg18 and other autophagic proteins. This indicates that Vmp1 is not strictly essential for the generation of PtdIns3P signaling but rather suggests a role in the correct turnover or modulation of this signaling. Of interest, these PtdIns3P-enriched regions of the ER surround ubiquitinated protein aggregates but are unable to form functional autophagosomes. vmp1 null cells also have additional defects in macropinocytosis and growth, which are not shared by other autophagy mutants. Remarkably, we show that these defects and also the aberrant PtdIns3P distribution are largely suppressed by the concomitant loss of Atg1, indicating that aberrant autophagic signaling on the ER inhibits macropinocytosis. These results suggest that Atg1 functions upstream of Vmp1 in this signaling pathway and demonstrates a previously unappreciated link between abnormal autophagy signaling and macropinocytosis. | 25,131,297 | [
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Lateral MoS2 p-n junction formed by chemical doping for use in high-performance optoelectronics. | This paper demonstrates a technique to form a lateral homogeneous 2D MoS2 p-n junction by partially stacking 2D h-BN as a mask to p-dope MoS2. The fabricated lateral MoS2 p-n junction with asymmetric electrodes of Pd and Cr/Au displayed a highly efficient photoresponse (maximum external quantum efficiency of ∼7000%, specific detectivity of ∼5 × 10(10) Jones, and light switching ratio of ∼10(3)) and ideal rectifying behavior. The enhanced photoresponse and generation of open-circuit voltage (VOC) and short-circuit current (ISC) were understood to originate from the formation of a p-n junction after chemical doping. Due to the high photoresponse at low VD and VG attributed to its built-in potential, our MoS2 p-n diode made progress toward the realization of low-power operating photodevices. Thus, this study suggests an effective way to form a lateral p-n junction by the h-BN hard masking technique and to improve the photoresponse of MoS2 by the chemical doping process. | 25,131,298 | [
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Hybrid technique for laparoscopic incisional ventral hernia repair combining laparoscopic primary closure and mesh repair. | Incisional ventral hernia is one of the most common surgical complications after laparotomy. Laparoscopic repair of incisional ventral hernia has been conducted recently, and the advantages of this procedure have been reported. However, in large orifice cases, the recurrence rate is increased. To improve recurrence rates in large cases, a hybrid method combining laparoscopic primary closure and mesh repair can be applied. Monofilament thread was inserted into the abdominal cavity for hernia closure and pulled from the other side of the orifice. The same procedure was performed from the upper side to the lower side without closure, and all thread was placed in line. Both sides of the thread were then introduced to the midline of the incision through a subcutaneous route. This procedure was conducted with an introducer. All threads were tied, and then a mesh was placed. Hybrid techniques already combine mini-laparotomy for hernia closure and subsequent laparoscopic intraoperative onlay mesh for reinforcement, but such techniques require laparotomy. In our technique, closure of the linea alba does not require laparotomy. All procedures were performed laparoscopically. This procedure is very easy and safe, and does not require the abdominal cavity to be opened. Thus, hybrid methods are effective for treating cases of incisional hernia involving a large orifice. | 25,131,330 | [
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IFITM3-containing exosome as a novel mediator for anti-viral response in dengue virus infection. | Interferon-inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV-2 infection, we found that IFITM3 contributed to both the baseline and interferon-induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM-containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non-infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome-mediated anti-viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species. | 25,131,332 | [
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Dietary squid ink polysaccharides ameliorated the intestinal microflora dysfunction in mice undergoing chemotherapy. | Gastrointestinal mucositis and infection by chemotherapy treatment are associated with alteration of intestinal microflora and bacterial translocation due to the potential damage induced by anti-cancer drugs on the intestinal barrier and microbiota homeostasis. This study aimed to investigate the protective effect of dietary polysaccharides on chemotherapy induced intestinal microflora dysfunction. In the current contribution, with a mouse model intraperitoneally injected with 50 mg kg(-1) of cyclophosphamide (Cy) for 2 days, we revealed that polysaccharides from the ink of Ommastrephes bartrami (OBP) altered the intestinal microflora composition. OBP retarded the excessive growth of intestinal bacteria induced by cyclophosphamide, based on 16S rRNA gene (16S rDNA) quantification. The clone libraries of intestinal bacteria 16S rDNA were used to decipher the difference in bacterial community structures in different groups of mice. Followed by RFLP evaluation and OTU abundance analysis, they imply that OBP changed the intestinal microflora composition, in which the quantity of probiotic Bifidobacterium got up-regulated but Bacteroidetes decreased in mice undergoing chemotherapy. Our results may have important implications for OBP as a functional food component or nutrient against chemotherapy induced intestinal injury and potential pathogenic intestinal disorders involving inflammation and infection. | 25,131,333 | [
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Control of neural circuit formation by leucine-rich repeat proteins. | The function of neural circuits depends on the precise connectivity between populations of neurons. Increasing evidence indicates that disruptions in excitatory or inhibitory synapse formation or function lead to excitation/inhibition (E/I) imbalances and contribute to neurodevelopmental and psychiatric disorders. Leucine-rich repeat (LRR)-containing surface proteins have emerged as key organizers of excitatory and inhibitory synapses. Distinct LRR proteins are expressed in different cell types and interact with key pre- and postsynaptic proteins. These protein interaction networks allow LRR proteins to coordinate pre- and postsynaptic elements during synapse formation and differentiation, pathway-specific synapse development, and synaptic plasticity. LRR proteins, therefore, play a critical role in organizing synaptic connections into functional neural circuits, and their dysfunction may contribute to neuropsychiatric disorders. | 25,131,359 | [
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[Place and role of the pleura in non-small cell lung cancer dissemination]. | The pleural involvement (PLI) in non-small cell lung cancer (NSCLC) has a poor prognosis, even though it might be very heterogeneous. A multicentric retrospective descriptive study was performed over 2329 patients who were operated for NSCLC between 1979 and 2010. The patients with PLI were classified in P(Parietal)PLI and V(visceral)PLI and then each subdivided : VPLI to peripheric (VPLI-P) and fissural (VPLI-F) and PPLI to mediastinal (PPLI-M) and costal (PPLI-C). Characteristics and survival were compared between the subgroups as well as with patients without PLI (WPLI, n=1439). The sex-ratio was 2.8 (males: n=1713). The PLI patients were significantly younger, with a less sex-ratio, less R0 resections (96% versus 98.7%, P=0.000076), and less N0 (60% vs 70%, P<10(-6)) as their 5-year survival (45.7% vs 55.5%, P<10(-6)). The PLI was related to the size of NSCLC (P<10(-6)) and N2 involvement (P=0.0020). It was less frequent after neoadjuvant treatment (36.2% vs 39.1% P=0.03). In the VPLI-F or PPLI-M, pneumonectomies were more frequent (P<10(-6)). In VPLI-P (n=196/561), there were more pN1 and pN2 (P=0.0065) with a 5-year survival of 42.9% vs 54.4%, P=0.013. In multivariate analysis, the PLI was not an independent prognostic factor contrary to age, sex, type of resection, pT and pN. The pleura play a major role in NSCLC dissemination. Its involvement affects pN, the type of surgical resection and justifies the use of neoadjuvant treatment. | 25,131,365 | [
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[Extrapulmonary tuberculosis]. | Each year, there are more than eight million new cases of tuberculosis and 1.3 million deaths. There is a renewed interest in extrapulmonary forms of tuberculosis as its relative frequency increases. Among extrapulmonary organs, pleura and lymph nodes are the most common. Their diagnosis is often difficult and is based on clinical, radiological, bacteriological and histological findings. Extrapulmonary lesions are paucibacillary and samplings, in most cases, difficult to obtain, so diagnosis is often simply presumptive. Nucleic acid amplification tests, which are fast and specific, have greatly facilitated the diagnosis of some forms of extrapulmonary tuberculosis. However, their sensitivity is poor and a negative test does not eliminate the diagnosis. Treatment is the same as for pulmonary forms, but its duration is nine to 12 months for central nervous system and for bone tuberculosis. Corticosteroids are indicated in meningeal and pericardial localizations. Complementary surgery is used for certain complicated forms. | 25,131,362 | [
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Sustaining dignity? food insecurity in homeless young people in urban Australia. | Food insecurity is recognised as an increasing problem in disadvantaged and marginalised groups. The aim of this study was to investigate issues associated with food insecurity and nutrition in young people experiencing, or at risk of, homelessness in metropolitan Australia. Eight focus group discussions were conducted with 48 young people (aged between 15 and 25 years) in specialist homelessness services in central and south-western Sydney. Participants described daily experiences of food insecurity, persistent hunger and poverty. Structural barriers to food security and nutrition were identified and included poverty and reduced physical access to fresh foods. Participants also described a desire to save time, for convenience and to be socially connected. Despite the hardships and the chaos of youth homelessness, the groups were defined by their strength of character, resilience and hope for the future. Homeless young people within central and south-western Sydney report varying degrees of food insecurity, despite being supported by specialist youth homelessness services. SO WHAT? A collaborative, multistrategic approach with youth participation is required to further enhance the capacity of youth services to improve food security, food access and the availability of nutritious foods for homeless young people. A greater focus on advocacy and policy action is also required to bring food security and nutrition to the forefront of national efforts to improve the health and welfare of disadvantaged groups. | 25,131,381 | [
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Long-term functional outcomes and quality of life after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal cancer. | Surgery for oral or oropharyngeal cancer with free-flap reconstruction is associated with moderate but persistent functional and quality of life (QoL) problems. Patient age, tumor stage, tumor site, and radiotherapy were the main predictors of functional outcome. To evaluate long-term functional outcomes and QoL, and to determine their predictive factors in patients with oral or oropharyngeal cancer after oncologic surgery and free-flap reconstruction. Patients who underwent surgery with free-flap reconstruction for oral or oropharyngeal cancer between 2000 and 2009 who were alive at least 1 year after therapy were included in this study. Patients completed the Voice Handicap Index (VHI-10) questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QoL questionnaires QLQ-C30 and H&N35. Swallowing was evaluated using the Dysphagia Outcome and Severity Scale (DOSS) and by flexible fiberoptic laryngoscopy. Sixty-four patients were included in the study. VHI-10 mean score was 11.2 ± 9 and its predictive factors were T stage (p = 0.005) and tumor involvement of the tongue base (p = 0.01). The mean DOSS score was 4 ± 0.8. Age (p = 0.008), gender (p = 0.04), and radiotherapy (p = 0.001) were the main predictive factors of the DOSS score. | 25,131,390 | [
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Suppression of NGB and NAB/ERabp1 in tomato modifies root responses to potato cyst nematode infestation. | Plant-parasitic nematodes cause significant damage to major crops throughout the world. The small number of genes conferring natural plant resistance and the limitations of chemical control require the development of new protective strategies. RNA interference or the inducible over-expression of nematicidal genes provides an environment-friendly approach to this problem. Candidate genes include NGB, which encodes a small GTP-binding protein, and NAB/ERabp1, which encodes an auxin-binding protein, which were identified as being up-regulated in tomato roots in a transcriptome screen of potato cyst nematode (Globodera rostochiensis) feeding sites. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization confirmed the localized up-regulation of these genes in syncytia and surrounding cells following nematode infection. Gene-silencing constructs were introduced into tomato, resulting in a 20%-98% decrease in transcription levels. Nematode infection tests conducted on transgenic plants showed 57%-82% reduction in the number of G. rostochiensis females in vitro and 30%-46% reduction in pot trials. Transmission electron microscopy revealed a deterioration of cytoplasm, and degraded mitochondria and plastids, in syncytia induced in plants with reduced NAB/ERabp1 expression. Cytoplasm in syncytia induced in plants with low NGB expression was strongly electron translucent and contained very few ribosomes; however, mitochondria and plastids remained intact. Functional impairments in syncytial cytoplasm of silenced plants may result from NGB's role in ribosome biogenesis; this was confirmed by localization of yellow fluorescent protein (YFP)-labelled NGB protein in nucleoli and co-repression of NGB in plants with reduced NAB/ERabp1 expression. These results demonstrate that NGB and NAB/ERabp1 play important roles in the development of nematode-induced syncytia. | 25,131,407 | [
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High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients. | Critically ill children can develop withdrawal syndrome after prolonged analgesia and sedation in a paediatric intensive care unit (PICU), when treatment is stopped abruptly or reduced quickly. The aim of this study was to evaluate the incidence of withdrawal syndrome in patients after three or more days of analgesic or sedative drug therapy, using a validated scale. We also analysed the association between withdrawal syndrome and the patients' outcome and factors related to analgesia and sedation treatment. This prospective observational study analysed 89 periods of weaning from analgesia and sedation in 60 children between October 2010 and October 2011. Of these, 65% were less than six months old and 45% were admitted to the PICU after heart surgery. Withdrawal syndrome was assessed using the Withdrawal Assessment Tool-1 (WAT-1) scale. The incidence of withdrawal syndrome was 37%, and the only variable that predicted its presence was the highest administered dose of benzodiazepine. The duration of weaning, Sophia Observational Withdrawal Symptom scale score and nurse judgment were also associated with positive WAT-1 scores. Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms. | 25,131,427 | [
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... |
Anticonvulsants to treat post-traumatic stress disorder. | We reviewed the existing literature on the efficacy of anticonvulsants in treating post-traumatic stress disorder. We performed a literature search using PubMed, EMBASE and the Cochrane database on 30 September 2013. Randomized,controlled studies that investigated the efficacy of anticonvulsants for post-traumatic stress disorder were included in this review. Studies with retrospective designs, case reports and case series were excluded. A total of seven studies met the inclusion criteria for this review. Three studies used topiramate with negative findings regarding its efficacy. Two studies used divalproex, both of which failed to show superiority over placebo. One study used lamotrigine, with favourable results, and one study used tiagabine, with negative results. Future long-term studies with larger sample sizes are needed to investigate the clinical utility of anticonvulsants for posttraumatic stress disorder treatment. | 25,131,430 | [
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Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report. | Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody for the treatment of various forms of lymphoma and haematological autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a molecular platform activated upon signs of cellular 'danger' to trigger the maturation of pro-inflammatory cytokines. We report the first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3 inflammasome activation in the lung. A 30-year-old male patient diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four cycles of rituximab in one month. Three weeks after last rituximab administration, he developed progressive dyspnoea associated with respiratory failure, which was diagnosed as R-ILD. The patient showed a good response to steroid treatment, and lung biopsy was performed 5 days after the treatment. Immunohistopathological studies of lung specimens showed high expressions of inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a heavy infiltration of CD19-positive cells. The levels of inflammasome-related cytokines IL-1β and IL-18 in the serum were declined during the therapy. This is the first report confirmed the role of NLRP3 inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3 inflammasome in lung by steroid treatment could reverse R-ILD and block subsequent lung fibrosis. This result could open a new sight into the pathogenesis and provide a new target for the treatment of R-ILD. | 25,131,433 | [
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APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS). | We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56 (0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis. | 25,131,445 | [
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[Characteristics of lymph node metastasis in patients undergoing radical cystectomy for bladder cancer: a retrospective single-center study of 522 cases]. | To investigate the characteristics and related influence factors of lymph node metastases in patients undergoing radical cystectomy and lymph node dissection for bladder cancer. The data of 522 patients who underwent radical cystectomy and pelvic lymph node dissection at Department of Urology, Peking University First Hospital from 1998 to 2012, were retrospectively collected, and the lymph node mapping was performed in all the patients to determine the location of metastatic lymph nodes. For the 522 patients with bladder cancer, lymph node metastasis occurred in 99 patients, and the incidence of lymph node metastasis was 19.0%. The incidence at different tumor stages was: 3.7% in T1 (6/164), 10.5% in T2 (17/160), 36.7% in T3(40/107), and 41.9% in T4 (36/86). The most common involved lymph nodes were hypogastric/obturator lymph nodes (77/99, 77.8%) and external iliac lymph nodes (35/99, 35.4%). The mean number of lymph nodes dissected was 11.6 (1-51). The lymph node density (number of lymph nodes involved/number of lymph nodes removed) was 44.1%. The incidence of lymph node metastasis was statistical related to tumor stage (P < 0.01, OR 2.71,95% CI 2.13-3.44) and tumor grade (P < 0.01, OR 3.81,95% CI 1.66-8.74), while age, gender, smoke history, and weight had no statistical significance. Lymph node metastasis is the most common metastasis route of bladder cancer. The incidence of lymph node tumor involvement is correlated with increasing tumor stage and tumor grade. The most common involved lymph nodes are hypogastric/obturator lymph nodes and external iliac lymph nodes. Radical cystectomy and bilateral pelvic lymph nodes dissection are of great significance in the treatment of bladder cancer. | 25,131,462 | [
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[Ureteral stricture following renal transplantation: risk factors and surgical management]. | To evaluate the prevalence and the risk factors of the ureteral stricture following renal transplantation and outcomes of surgical managements. By a retrospective analysis, we assessed 1 293 patients who underwent renal transplantation between January 2001 and December 2013 at our center. The patients with ureteral stricture had undergone surgical management which included neoureterocystostomy, ureteral anastomosis with the native ureter and endoscopic therapy. Ureteral stricture following renal transplantation was diagnosed in 17 cases (1.3%) including 6 males and 11 females. The mean age of the patients at the time of surgery was 44 (29 to 64) years. The median interval between ureteral stricture obstruction and kidney transplantation was 4 (1 to 120) months. The ureteral stricture was significantly correlated with multiple renal arteries, donor age and delayed graft function. The effective rate of surgical management was 65.75%. The incidence of ureteral stricture as a urologic complication after renal transplantation is low. The advanced techniques that preserve the ureteric blood supply should be applied. The surgical managements have respective advantages and disadvantages. The neoureterocystostomy shows best outcome, while ureteral anastomosis with the native ureter has poor outcome. | 25,131,468 | [
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[Diagnosis and treatment of hydrocephalus-accompanied renal calculi complicated with renal tumor: 5 case reports]. | To investigate the diagnosis and treatment of renal pelvic tumor combined with renal urinary calculi and hydronephrosis. Five patients with renal pelvic tumor who underwent relief of the upper urinary obstruction were reviewed. One of the cases lost the opportunity of surgical therapy when pelvic tumor was detected at the advanced stage, and the other 4 cases had received surgery and were followed up. As pelvic tumor progresses rapidly after the renal blood flow is improved, and renal urinary calculi with hydronephrosis relieved; the patients with renal pelvic tumor need early diagnosis, aggressive treatment and close follow-up. | 25,131,470 | [
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[Analysis for risk factors of systemic inflammatory response syndrome after one-phase treatment for apyrexic calculous pyonephrosis by percutaneous nephrolithotomy]. | To investigate the risk factors of systemic inflammatory response syndrome (SIRS) after one-phase treatment for apyrexic calculous pyonephrosis by percutaneous nephrolithotomy (PCNL). Clinical data of consecutive apyrexic calculous pyonephrosis patients who underwent one-stage PCNL from January 2008 to December 2013 were analyzed retrospectively. The data collected included white blood cells in urine analysis before surgery, midstream urine culture, preoperative renal function, using antibiotics time before surgery, operative time, the number of tracts, intraoperative irrigation peak flow, blood transfusion, and stone composition. Chi-square, t test and Logistic regression methods were used for analysis of each factor and SIRS. A total of 182 patients were enrolled in this study and 38 patients developed SIRS (20.88%). There were no statistically significant differences among white blood cells in urine analysis (P = 0.483), urine culture positive (P = 0.136), and struvite (P = 0.324) in terms of the incidence of postoperative SIRS. Multivariate Logistic regression model indicated that risk factors of SIRS for apyrexic calculous pyonephrosis after one-phase PCNL were renal insufficiency (OR = 5.41, 95% CI 1.84 to 22.64, P = 0.014), operative time (OR = 1.01, 95% CI 1.00 to 1.02, P = 0.024), operative tracts (OR = 3.37, 95% CI -1.92 to 32.55, P = 0.077), intraoperative irrigation peak flow ≥500 mL/min (OR = 45.87,95% CI 4.39 to 231.68, P = 0.007), and blood transfusion (OR = 5.98, 95% CI 1.12 to 46.66, P = 0.043). The protective factor was antibiotics use for more than 3 days (OR = 0.34, 95% CI -3.92 to 12.55, P = 0.047). The incidence of SIRS after one-phase PCNL treatment for apyrexic calculous pyonephrosis was similar to that of other patients. It is relatively safe and reliable to do this. Preoperative antibiotics should be used for more than 3 days before surgery. Careful manipulation is needed to avoid blood transfusion. It is better to shorten the operative time and to reduce multiple tracts operation. Particularly, irrigation peak flow ≥500 mL/min should be avoided in the circumstance of bleeding or turbid urine. | 25,131,472 | [
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[Relationship of genetic variants and cardiovascular risk factors with interleukin-6 and interleukin-10 secreted by monocytes]. | To examine the relationship of interleukin (IL)-6 and IL-10 genetic variants and cardiovascular factors [oxygenized low density lipoprotein (ox-LDL), lower physical activity, overweight, etc.] with IL-6 and IL-10 secreted by monocytes. In the study, 40 health persons, aged from 51 to 80 years, without stroke and myocardial infarction, were randomly sampled from a community-based population in Beijing in 2010. Their data on smoking, drinking, blood pressure, fasting glucose, and lipid were collected. The single nucleotide polymorphisms (SNPs) of IL-6 (rs1800796, rs1524107, rs2066992) and IL-10 (rs1800872, rs1554286, rs3021094) were genotyped. The human monocytes were cultivated in RPMI 1640 medium for 24 h; then divided into two equal parts, in which ox-LDL (50 mg/L) and phosphate buffer solution (PBS) were added for another 48 h. Finally, the secretions of IL-6 and IL-10 in the culture supernatants were measured with ELISA. Paired Wilcoxon tests showed that the IL-6, IL-10, and IL-6/IL-10 were significantly higher in ox-LDL medium than in PBS one (all P < 0.01). The concentrations in PBS/ox-LDL taken as repeated measurements, and adjusted for age and gender, the repeated general linear models showed: IL-10 was significantly lower for those overweight (BMI ≥ 26 kg/m(2)) than for those normal weight (P = 0.007), and IL-6/IL-10 was significantly higher in those overweight (P = 0.003). The IL-6/IL-10 was significantly higher in those with lower physical activity [metabolic equivalent of energy, METS < 166 kJ/(kg.d)] than those with higher physical activities (P = 0.046). IL-6 and IL-10 were significantly higher in alcohol drinkers (P = 0.049 and P = 0.006). IL-6 was significantly higher in those with higher high-density lipoprotein-cholesterol (HDL-c, ≥ 56.4 mg/dL, P = 0.027). There were significant interactions between IL-10 SNPs and ox-LDL on IL-10 (all P < 0.05), but no significant interactions between IL-6 gene SNPs and ox-LDL on IL-6. The ox-LDL together with lower physical activity and overweight shifts the balance of pro-inflammatory and anti-inflammatory in the direction of pro-inflammatory. The interaction between IL-10 gene and ox-LDL is intensively correlated with the secretion of the anti-inflammatory cytokine IL-10. | 25,131,477 | [
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[Clinical observation of middle cerebral artery angioplasty in treatment of subcortex cerebral watershed infarction with moderate or severe disabilities]. | To assess the safety and effectiveness of middle cerebral artery angioplasty in treatment of subcortical watershed infarcts (S-CWI) with moderate or severe disabilities. From June 2011 to May 2012, 5 S-CWI patients (six lesions) with moderate or severe disabilities combining severe stenosis in Ipsilateral middle cerebral artery received middle cerebral artery angioplasty in Interventional Radiology and Vascular Surgery Department, Peking University Third Hospital. We observed the neurological score before and after angioplasty and assessed the improvement of neurological functions. The National Institute of Health stroke scale(NIHSS) scores were decreased by 4-6 points and modified Rankin scale(mRs) scores were decreased 1 point in 7 days. In the 3 months' follow-up, 4 patients' mRs scores were 1 point, and 1 patient's was 2 points. In the 1-year follow-up, there were no new strokes and instent restenosis events. Middle cerebral artery angioplasty in treatment of S-CWI with moderate or severe disabilities is beneficial. | 25,131,480 | [
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[Balloon dilation by B ultrasound monitoring for treatment of urethral stricture: 5 case reports]. | Urethral stricture is a common urologic disease and there are many therapeutic methods for it. Here we investigated the application of balloon dilation under B-mold ultrasound monitoring in the treatment of urethral stricture. Five male patients suffering from urethral stricture were treated with balloon dilation under B-mold ultrasound monitoring.Their urination was assessed after operation. All the patients underwent the operation successfully, without serious complications. The urinary catheter was removed 3-4 weeks after operation. The patients were followed up for 8 to 15 months. Four patients were voiding well and one improved. Balloon dilation under B-mold ultrasound monitoring in the treatment of urethral stricture was intuitive, safe and effective. | 25,131,490 | [
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The role of influenza in the severity and transmission of respiratory bacterial disease. | Infections with influenza viruses and respiratory bacteria each contribute substantially to the global burden of morbidity and mortality. Simultaneous or sequential infection with these pathogens manifests in complex and difficult-to-treat disease processes that need extensive antimicrobial therapy and cause substantial excess mortality, particularly during annual influenza seasons and pandemics. At the host level, influenza viruses prime respiratory mucosal surfaces for excess bacterial acquisition and this supports increased carriage density and dissemination to the lower respiratory tract, while greatly constraining innate and adaptive antibacterial defences. Driven by virus-mediated structural modifications, aberrant immunological responses to sequential infection, and excessive immunopathological responses, co-infections are noted by short-term and long-term departures from immune homoeostasis, inhibition of appropriate pathogen recognition, loss of tolerance to tissue damage, and general increases in susceptibility to severe bacterial disease. At the population level, these effects translate into increased horizontal bacterial transmission and excess use of antimicrobial therapies. With increasing concerns about future possible influenza pandemics, the past decade has seen rapid advances in our understanding of these interactions. In this Review, we discuss the epidemiological and clinical importance of influenza and respiratory bacterial co-infections, including the foundational efforts that laid the groundwork for today's investigations, and detail the most important and current advances in our understanding of the structural and immunological mechanisms underlying the pathogenesis of co-infection. We describe and interpret what is known in sequence, from transmission and phenotypic shifts in bacterial dynamics to the immunological, cellular, and molecular modifications that underlie these processes, and propose avenues of further research that might be most valuable for prevention and treatment strategies to best mitigate excess disease during future influenza pandemics. | 25,131,494 | [
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WITHDRAWN: Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways. | This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.05.006. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. | 25,131,502 | [
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A case for the use of autoethnography in nursing research. | This paper discusses the basis for and potential usefulness of autoethnography as a research method in nursing. While qualitative research in nursing has traditionally involved the researcher taking an objective stance, autoethnography, with roots in the social sciences, is an emerging method that examines the researcher's own experience in a cultural context. Discussion paper. Data sources from 1979-2013 in the CINAHL, Medline and PsycInfo databases were drawn on including articles from nursing and social science journals on autoethnography and related narrative-based approaches. Autoethnography is based on the assumption that reality is multifaceted and the role of culture and context is crucial in understanding human experience. The reader is engaged through the evocation of emotion and the stimulation of reflection. While autoethnography has thus far been little used in the discipline of nursing, it is a methodology that offers novel insights and an opportunity to examine the impact of nurses' personal and professional cultural identity on their practice. Through the use of a subjective lens, autoethnography gives nurses the opportunity to tell stories that would otherwise not be heard. It involves a courageous laying bare of the self to gain new cultural understandings and it offers the potential for nurses to learn from the experiences and reflections of other nurses. | 25,131,503 | [
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Spontaneous coronary artery dissection. | Spontaneous coronary artery dissection (SCAD) is a rare but challenging clinical entity of unknown etiology. From a pathophysiological standpoint, SCAD may occur in patients with a coronary intimal tear (presenting with the classic angiographic "flap" and multiple lumens), but also in patients without an intimal rupture (presenting as an intramural hematoma). Until now, available information on SCAD was largely based on multiple, small case-series studies but, recently, data from relatively large registries have cast a new light on this disease. Classically, SCAD was thought to present in young females without traditional atherosclerotic risk factors but recent reports suggest a broader clinical spectrum encompassing older patients with associated coronary artery disease. In this review, we concentrate on 3 main aspects of this unique disease: (1) the value of intracoronary diagnostic techniques (intravascular ultrasound and optical coherence tomography) to complement coronary angiography and to provide novel diagnostic insights on this elusive clinical condition; (2) the growing clinical evidence suggesting an association and potential causation between fibromuscular dysplasia and SCAD; and (3) the challenges of coronary revascularization in this adverse anatomic setting, together with recent data suggesting that a initial, conservative medical management may be preferable for the majority of patients with SCAD. | 25,131,524 | [
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[International comparative study on health condition of young people]. | The connection between physical condition, coping strategies and emotional intelligence is widely studied in the international literature, but comparative research data collected among Transylvanian and Hungarian adolescents are not available in contemporary psychological literature. The aim of the authors was to study health indicators, emotional intelligence and coping strategies among adolescents and analyse connections between these factors and physical condition as part of an international research. The physical condition, coping strategies and emotional intelligence of 390 individuals, aged between 13 and 19 years living in Debrecen (Hungary) and Érmihályfalva (Romania) were observed. adaptive (i. e. problem-focused) coping strategies used in stressful situations resulted in lower depression rates, as well as better mental well-being than the maladaptive ones such as emotional clearing, self-punishment, distraction of attention. Adolescents showing higher emotional intelligence had lower depression levels and better mental well-being. Institutionally initiated emotional intelligence and coping strategy development for young people may prove to be an important preventive interventional public health programme. This may serve as a basis to assist health-consciousness and personality formatting. | 25,131,528 | [
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Structural and mutational studies on an aldo-keto reductase AKR5C3 from Gluconobacter oxydans. | An aldo-keto reductase AKR5C3 from Gluconobacter oxydans (designated as Gox0644) is a useful enzyme with various substrates, including aldehydes, diacetyl, keto esters, and α-ketocarbonyl compounds. The crystal structures of AKR5C3 in apoform in complex with NADPH and the D53A mutant (AKR5C3(-D53A) ) in complex with NADPH are presented herein. Structure comparison and site-directed mutagenesis combined with biochemical kinetics analysis reveal that the conserved Asp53 in the AKR5C3 catalytic tetrad has a crucial role in securing active pocket conformation. The gain-of-function Asp53 to Ala mutation triggers conformational changes on the Trp30 and Trp191 side chains, improving NADPH affinity to AKR5C3, which helps increase catalytic efficiency. The highly conserved Trp30 and Trp191 residues interact with the nicotinamide moiety of NADPH and help form the NADPH-binding pocket. The AKR5C3(-W30A) and AKR5C3(-W191Y) mutants show decreased activities, confirming that both residues facilitate catalysis. Residue Trp191 is in the loop structure, and the AKR5C3(-W191Y) mutant does not react with benzaldehyde, which might also determine substrate recognition. Arg192, which is involved in the substrate binding, is another important residue. The introduction of R192G increases substrate-binding affinity by improving hydrophobicity in the substrate-binding pocket. These results not only supplement the AKRs superfamily with crystal structures but also provide useful information for understanding the catalytic properties of AKR5C3 and guiding further engineering of this enzyme. | 25,131,535 | [
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Correlates of quality of sexual life in male and female patients with Parkinson disease and their partners. | Patients with Parkinson disease (PD) and their partners may experience a worsening of their sexual life. To assess quality of sexual life (QoSL) in male and female PD patients and their partners. Medical, demographic and clinical data was collected regarding consecutive PD patients, including depression, and motor symptom rating. Partners' data included the short form-12 health questionnaire (SF-12). All patients and partners filled the 5-item QoSL questionnaire. Data from 89 PD patients (66 men) and 69 spouses (52 women) was analyzed. Male patients rejected sex significantly less than female patients and their sexual desire was higher, but female patients reported higher sexual satisfaction. Patients and partners similarly perceived their relationship which was averagely good. Analysis within couples demonstrated that better QoSL of patients could be predicted by gender (male), better QoSL of their partners and, motor severity, but not the patient's depression, age or use of l-dopa. The partner's QoSL was explained by younger age, and better motor scores of their parkinsonian partner. Treatment of the PD patient with l-dopa or dopamine agonist was associated with worse partner's QoSL. Differences in QoSL of male and female PD patients and within couples were found. These findings suggest that focusing on partner's needs may improve QoSL of patients and partners troubled by PD. | 25,131,540 | [
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Epigenetic regulatory mechanisms in stress-induced behavior. | Stress response is considered to have adaptive value for organisms faced with stressful condition. Chronic stress however adversely affects the physiology and may lead to neuropsychiatric disorders. Repeated stressful events in animal models have been shown to cause long-lasting changes in neural circuitries at molecular, cellular, and physiological level, leading to disorders of mood as well as cognition. Molecular studies in recent years have implicated diverse epigenetic mechanisms, including histone modifications, DNA methylation, and noncoding RNAs, that underlie dysregulation of genes in the affected neural circuitries in chronic stress-induced pathophysiology. A review of the myriad epigenetic regulatory mechanisms associated with neural and behavioral responses in animal models of stress-induced neuropsychiatric disorders is presented here. The review also deals with clinical evidence of the epigenetic dysregulation of genes in psychiatric disorders where chronic stress appears to underlie the etiopathology. | 25,131,544 | [
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Smart vesicle kit for in situ monitoring of intracellular telomerase activity using a telomerase-responsive probe. | A smart vesicle kit was designed for in situ imaging and detection of cytoplasmic telomerase activity. The vesicle kit contained a telomerase primer (TSP) and a Cy5-tagged molecular beacon (MB) functionalized gold nanoparticle probe, which were encapsulated in liposome for intracellular delivery. After the vesicle kit was transfected into cytoplasm, the released TSP could be extended in the presence of telomerase to produce a telomeric repeated sequence at the 3' end, which was just complementary with the loop of MB assembled on probe surface. Thus, the MB was opened upon hybridization to switch the fluorescent state from "off" to "on". The fluorescence signal depended on telomerase activity, leading to a novel strategy for in situ imaging and quantitative detection of the cytoplasmic telomerase activity. The cytoplasmic telomerase activity was estimated to be 3.2 × 10(-11), 2.4 × 10(-11), and 8.6 × 10(-13) IU in each HeLa, BEL tumor and QSG normal cell, respectively, demonstrating the capability of this approach to distinguish tumor from normal cells. The proposed method could be employed for dynamic monitoring of the cytoplasmic telomerase activity in response to a telomerase-based drug, suggesting the potential application in discovery and screening of telomerase-targeted anticancer drugs. | 25,131,551 | [
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The object of sexual desire: examining the "what" in "what do you desire?". | Over the past two decades, sexual desire and desire discrepancy have become more frequently studied as have potential pharmaceutical interventions to treat low sexual desire. However, the complexities of sexual desire-including what exactly is desired-remain poorly understood. To understand the object of men's and women's sexual desire, evaluate gender differences and similarities in the object of desire, and examine the impact of object of desire discrepancies on overall desire for partner in men and women in the context of long-term relationships. A total of 406 individuals, 203 men and 203 women in a relationship with one another, completed an online survey on sexual desire. Reports of the object of sexual desire in addition to measures of sexual desire for current partner were collected from both members of the couple. There were significant gender differences in the object of sexual desire. Men were significantly more likely to endorse desire for sexual release, orgasm, and pleasing their partner than were women. Women were significantly more likely to endorse desire for intimacy, emotional closeness, love, and feeling sexually desirable than men. Discrepancies within the couple with regard to object of desire were related to their level of sexual desire for partner, accounting for 17% of variance in men's desire and 37% of variance in women's desire. This research provides insights into the conceptualization of sexual desire in long-term relationships and the multifaceted nature of sexual desire that may aid in more focused ways to maintain desire over long-term relationships. Future research on the utility of this perspective of sexual desire and implications for clinicians working with couples struggling with low sexual desire in their relationships is discussed. | 25,131,552 | [
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Association of serum uric acid levels to inflammation biomarkers and endothelial dysfunction in obese prepubertal children. | High serum uric acid (SUA) levels are present in patients with metabolic syndrome (MetS), when the latter is associated with endothelial dysfunction, inflammation, and hypertension. This increase in SUA levels may have a key role in cardiovascular diseases. We aim to quantify the differences in inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS in obese prepubertal children compared to non-obese children, and determine if there is a relationship between uric acid levels and these variables. A cross-sectional study was carried out on obese children (6-9 yr old). The study included 43 obese children and the same number of non-obese children (control group), matched by age and sex. SUA, C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), glucose, insulin, lipid profile, and blood pressure were all measured. SUA levels, CRP, and sICAM-1 were significantly higher in obese children. In the obese group, SUA levels showed a positive correlation with body mass index (BMI), insulin, homeostasis model assessment for insulin resistance (HOMA-IR), CRP, IL-6, sICAM-1, and triglycerides (TGs), and correlated negatively with high-density lipoprotein cholesterol (HDL-C) and Apo-AI, but not with Apo-B. When adjusted for age, sex, and creatinine, it was noted that SUA levels are independent predictive factors for sICAM-1, CRP, and IL-6. Inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS are elevated in obese prepubertal children and correlate to uric acid levels. | 25,131,560 | [
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Commercial sexual exploitation and sex trafficking of children in the United States. | Child commercial sexual exploitation and sex trafficking are global health problems requiring a multidisciplinary approach by individuals, organizations, communities, and national governments. The adverse emotional, physical, and social consequences for victims are legion and in many areas of the United States and the rest of the world, victim resources are scarce. Since violence, deprivation, abuse, and infection are so integral to the exploitation experience, victims may present for care to community and academic pediatric and adolescent health care providers. It is essential that medical professionals have the knowledge, skills, and resources to recognize victims, assess their needs, and treat them appropriately, including making key referrals for community services. However, to date medical information and resources regarding commercial sexual exploitation and sex trafficking has been sparse. There are no clinically validated screening tools specifically designed to identify victims in the health care setting and since victims seldom self-identify, it is likely that the majority of victims are unrecognized. The opportunity for comprehensive assessment and intervention is lost. Further, professionals receive little training on appropriate interview techniques for this special population, and many are ill equipped to ensure safety and optimal medical evaluation during the visit. This article provides a general overview of child sex trafficking and commercial sexual exploitation (CSEC), describing the epidemiology of international and domestic exploitation, and reviewing the challenges of conducting research on this population. The five stages of trafficking are explained, as are typical physical and emotional consequences of exploitation. The medical evaluation is described, including potential indicators of CSEC and sex trafficking, common medical presentations by victims, approaches to the comprehensive medical interview, and the appropriate medical exam with diagnostic testing and treatment. Finally, a discussion of common victim needs is provided, with a description of resources and referrals. | 25,131,563 | [
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Non-small cell lung cancer metastasis to the oral cavity: a case report. | Lung cancer, including non-small cell lung cancer, remains prevalent in Australia and has a very poor survival rate. Metastases to the oral cavity are a rare occurrence that can arise from lung cancers. This case report describes the presentation of a metastatic lesion from a poorly differentiated lung adenocarcinoma on the mandibular buccal alveolar attached gingivae. The inpatient had terminal disease with known pleural, brain and liver metastases and was receiving palliative care at the time of diagnosis of the oral lesion. | 25,131,571 | [
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Quality of life in caregivers of severely disabled war survivors. | To evaluate quality of life (QOL) of caregivers of severely disabled war survivors and identify variables threatening caregivers' QOL. A cross-sectional study was performed on 532 caregivers of Iran-Iraq war related injured survivors by using Persian version of 36-item Short Form Health Survey (SF-36). Caregivers had lower QOL compared to the Iranian female population (p < .001). Caregivers of amputees had better SF-36 scores compared to caregivers of two groups of chemical warfare survivors (p ranging from .01 to <.001). Caregiving to chemical warfare and being married at the time of trauma were the independent predictors of poor QOL in both the physical component summary (OR = 5.08, 95% CI = 3.35-7.7; OR = 0.57, 95% CI = 0.37-0.89) and the mental component summary (OR = 4.12, 95% CI = 2.68-6.32; OR = 0.63, 95% CI = 0.40-0.98). Caregivers of war veterans suffer from poor QOL. Chemical warfare agents contribute to more persistent poor QOL in caregivers than the injuries caused by conventional weapons. | 25,131,566 | [
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Protein folding, misfolding and quality control: the role of molecular chaperones. | Cells have to cope with stressful conditions and adapt to changing environments. Heat stress, heavy metal ions or UV stress induce damage to cellular proteins and disturb the balanced status of the proteome. The adjusted balance between folded and folding proteins, called protein homoeostasis, is required for every aspect of cellular functionality. Protective proteins called chaperones are expressed under extreme conditions in order to prevent aggregation of cellular proteins and safeguard protein quality. These chaperones co-operate during de novo folding, refolding and disaggregation of damaged proteins and in many cases refold them to their functional state. Even under physiological conditions these machines support protein homoeostasis and maintain the balance between de novo folding and degradation. Mutations generating unstable proteins, which are observed in numerous human diseases such as Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis and cystic fibrosis, also challenge the protein quality control system. A better knowledge of how the protein homoeostasis system is regulated will lead to an improved understanding of these diseases and provide potential targets for therapy. | 25,131,586 | [
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Coprinopsis atramentaria extract, its organic acids, and synthesized glucuronated and methylated derivatives as antibacterial and antifungal agents. | Despite the available data regarding antimicrobial activity of phenolic acids, studies dealing with the effects of their metabolites or derivatives are scarce. Therefore, the antimicrobial and demelanizing activities of Coprinopsis atramentaria extract, its organic acids, and methylated and glucuronated derivatives were evaluated. The antifungal activity was stronger than the antibacterial effects. In general, individual compounds (mostly organic acids) exhibited higher activity than the extract and even higher than the standards used in the assays. Methylated derivatives presented the highest demelanizing activity toward Aspergillus niger, A. fumigatus and Penicillium verrucosum var. cyclopium. The inclusion of methyl groups in the parental compound (CoAM1, CoAM2 and CoAM3) strongly increased antibacterial and antifungal activities of CoA, while the inclusion of acetyl groups (CoAGP) increased the antifungal activity but the antibacterial properties were maintained. For HA and CA, the inclusion of methyl groups (HAM1, HAM2, HAM3 and CAM) increased the demelanizing activity, but decreased the antimicrobial properties. The present work contributes to the knowledge of the mechanisms involved in the antimicrobial properties of organic acids namely, phenolic acids, usually present in mushrooms. Organic acids, and methylated and glucuronated derivatives could be used as antimicrobial agents. | 25,131,614 | [
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In vivo quantitative NMR imaging of fruit tissues during growth using Spoiled Gradient Echo sequence. | Nondestructive studies of physiological processes in agronomic products require increasingly higher spatial and temporal resolutions. Nuclear Magnetic Resonance (NMR) imaging is a non-invasive technique providing physiological and morphological information on biological tissues. The aim of this study was to design a robust and accurate quantitative measurement method based on NMR imaging combined with contrast agent (CA) for mapping and quantifying water transport in growing cherry tomato fruits. A multiple flip-angle Spoiled Gradient Echo (SGE) imaging sequence was used to evaluate the intrinsic parameters maps M0 and T1 of the fruit tissues. Water transport and paths flow were monitored using Gd(3+)/[Fe(CN)6](3-)/D-mannitol nanoparticles as a tracer. This dynamic study was carried out using a compartmental modeling. The CA was preferentially accumulated in the surrounding tissues of columella and in the seed envelopes. The total quantities and the average volume flow of water estimated are: 198 mg, 1.76 mm(3)/h for the columella and 326 mg, 2.91 mm(3)/h for the seed envelopes. We demonstrate in this paper that the NMR imaging technique coupled with efficient and biocompatible CA in physiological medium has the potential to become a major tool in plant physiology research. | 25,131,625 | [
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Surgical repositioning of a developing maxillary central incisor. A case report. | A traumatic injury to the primary dentition can cause damage to the germ of the permanent successor. As a clinical consequence a dilaceration with root deformation, malpositioning and disturbances of eruption can occur. Surgical repositioning of such a dislocated crown of a developing tooth can be a treatment option. A four year old patient was referred to our clinic because of a mobile upper primary central incisor and a radiographically visible displaced dental crown. Her history revealed a traumatic dental injury one year ago. Radiologic examination confirmed an inflammatory root resorption on tooth 61 and a dislocation of the developing tooth 21. In order to avoid further displacement due to the inflammation, 61 was extracted at the first appointment. A radiographic image 7 months later showed no improvement in the malposition of tooth 21. Therefore tooth 21 was surgically repositioned into its correct position. Follow-up over 3 years confirmed a continued root development and a full eruption of 21 in its correct position. Early diagnosis and early treatment of a dislocated permanent tooth germ is essential to allow a favorable outcome. Surgical repositioning can be successful in avoiding later malpositioning of the permanent teeth. | 25,131,644 | [
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Membrane pathology and microglial activation of mice expressing membrane anchored or membrane released forms of Aβ and mutated human Alzheimer's precursor protein (APP). | Alzheimer's disease and the transmissible spongiform encephalopathies or prion diseases accumulate misfolded and aggregated forms of neuronal cell membrane proteins. Distinctive membrane lesions caused by the accumulation of disease-associated prion protein (PrP(d)) are found in prion disease but morphological changes of membranes are not associated with Aβ in Alzheimer's disease. Membrane changes occur in all prion diseases where PrP(d) is attached to cell membranes by a glycosyl-phosphoinositol (GPI) anchor but are absent from transgenic mice expressing anchorless PrP(d). Here we investigate whether GPI membrane attached Aβ may also cause prion-like membrane lesions. We used immunogold electron microscopy to determine the localization and pathology of Aβ accumulation in groups of transgenic mice expressing anchored or unanchored forms of Aβ or mutated human Alzheimer's precursor protein. GPI attached Aβ did not replicate the membrane lesions of PrP(d). However, as with PrP(d) in prion disease, Aβ peptides derived from each transgenic mouse line initially accumulated on morphologically normal neurite membranes, elicited rapid glial recognition and neurite Aβ was transferred to attenuated microglial and astrocytic processes. GPI attachment of misfolded membrane proteins is insufficient to cause prion-like membrane lesions. Prion disease and murine Aβ amyloidosis both accumulate misfolded monomeric or oligomeric membrane proteins that are recognized by glial processes and acquire such misfolded proteins prior to their accumulation in the extracellular space. In contrast to prion disease where glial cells efficiently endocytose PrP(d) to endolysosomes, activated microglial cells in murine Aβ amyloidosis are not as efficient phagocytes. | 25,131,655 | [
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Factors associated with receiving treatment for dental decay among Medicaid-enrolled children younger than 12 years of age in Iowa, 2010. | The Iowa Department of Public Health I-Smile program provides dental screening and care coordination to over 23,000 low-income and Medicaid-enrolled children per year. The purposes of this study were to evaluate I-Smile program effectiveness to ensure that Medicaid-enrolled children obtained dental treatment after having been screened and to determine the factors associated with failure to receive dental care after screening through the I-Smile program. Based on I-Smile program priorities, we limited our sample to children younger than 12 years of age who screened positive for decay and who linked to a paid Medicaid claim for dental treatment (n = 1,816). We conducted bivariate analyses to examine associations between children's characteristics who screened positive for decay and received treatment within 6 months of their initial screening. We also performed multivariate logistic regression to assess the association of sociodemographic characteristics with receipt of treatment among children who screened positive for decay. Eleven percent of children screened positive for decay. Nearly 24 percent of children with decay received treatment based on a Medicaid-paid claim. Being 5 years or older [adjusted odds ratio (aOR): 1.48, confidence interval (CI): 1.17, 1.88] and not having a dental home (aOR: 1.90, CI: 1.41, 2.58) were associated with higher odds of not receiving dental treatment. Children 5 years and older and without a dental home were less likely to obtain dental treatment. Opportunities exist for the I-Smile program to increase the numbers of at-risk children with dental homes and who obtain dental care after screening. | 25,131,658 | [
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Trypsinogen activation as observed in accelerated molecular dynamics simulations. | Serine proteases are involved in many fundamental physiological processes, and control of their activity mainly results from the fact that they are synthetized in an inactive form that becomes active upon cleavage. Three decades ago Martin Karplus's group performed the first molecular dynamics simulations of trypsin, the most studied member of the serine protease family, to address the transition from the zymogen to its active form. Based on the computational power available at the time, only high frequency fluctuations, but not the transition steps, could be observed. By performing accelerated molecular dynamics (aMD) simulations, an interesting approach that increases the configurational sampling of atomistic simulations, we were able to observe the N-terminal tail insertion, a crucial step of the transition mechanism. Our results also support the hypothesis that the hydrophobic effect is the main force guiding the insertion step, although substantial enthalpic contributions are important in the activation mechanism. As the N-terminal tail insertion is a conserved step in the activation of serine proteases, these results afford new perspective on the underlying thermodynamics of the transition from the zymogen to the active enzyme. | 25,131,668 | [
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Self-generated movements with "unexpected" sensory consequences. | The nervous systems of diverse species, including worms and humans, possess mechanisms for distinguishing between sensations arising from self-generated (i.e., expected) movements from those arising from other-generated (i.e., unexpected) movements [1-3]. To make this critical distinction, animals generate copies, or corollary discharges, of motor commands [4, 5]. Corollary discharge facilitates the selective gating of reafferent signals arising from self-generated movements, thereby enhancing detection of novel stimuli [6-10]. However, for a developing nervous system, such sensory gating would be counterproductive if it impedes transmission of the very activity upon which activity-dependent mechanisms depend [11]. In infant rats during active (or REM) sleep--a behavioral state that predominates in early infancy [12-16]--neural circuits within the brainstem [17, 18] trigger hundreds of thousands of myoclonic twitches each day [19]. The putative contribution of these self-generated movements to the activity-dependent development of the sensorimotor system is supported by the observation that reafference from twitching limbs reliably and substantially triggers brain activity [20-23]. In contrast, under identical testing conditions, even the most vigorous wake movements reliably fail to trigger reafferent brain activity [21-23]. One hypothesis that accounts for this paradox is that twitches, uniquely among self-generated movements, lack corollary discharge [23]. Here, we test this hypothesis in newborn rats by manipulating the degree to which self-generated movements are expected and, therefore, their presumed recruitment of corollary discharge. We show that twitches, although self-generated, are processed as if they are unexpected. | 25,131,675 | [
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The iPod binocular home-based treatment for amblyopia in adults: efficacy and compliance. | Occlusion therapy for amblyopia is predicated on the idea that amblyopia is primarily a disorder of monocular vision; however, there is growing evidence that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression. Furthermore, we have found that a dichoptic treatment intervention designed to directly target suppression can result in clinically significant improvement in both binocular and monocular visual function in adult patients with amblyopia. The fact that monocular improvement occurs in the absence of any fellow eye occlusion suggests that amblyopia is, in part, due to chronic suppression. Previously the treatment has been administered as a psychophysical task and more recently as a video game that can be played on video goggles or an iPod device equipped with a lenticular screen. The aim of this case-series study of 14 amblyopes (six strabismics, six anisometropes and two mixed) ages 13 to 50 years was to investigate: 1. whether the portable video game treatment is suitable for at-home use and 2. whether an anaglyphic version of the iPod-based video game, which is more convenient for at-home use, has comparable effects to the lenticular version. The dichoptic video game treatment was conducted at home and visual functions assessed before and after treatment. We found that at-home use for 10 to 30 hours restored simultaneous binocular perception in 13 of 14 cases along with significant improvements in acuity (0.11 ± 0.08 logMAR) and stereopsis (0.6 ± 0.5 log units). Furthermore, the anaglyph and lenticular platforms were equally effective. In addition, the iPod devices were able to record a complete and accurate picture of treatment compliance. The home-based dichoptic iPod approach represents a viable treatment for adults with amblyopia. | 25,131,694 | [
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Withdrawal of skeletal muscle cells from cell cycle progression triggers differentiation of Toxoplasma gondii towards the bradyzoite stage. | Toxoplasma gondii is a widespread intracellular parasite of mammals and birds and an important opportunistic pathogen of humans. Following primary infection, fast-replicating tachyzoites disseminate within the host and either are subsequently eliminated by the immune system or transform to latent bradyzoites which preferentially persist in brain and muscle tissues. The factors which determine the parasites' tissue distribution during chronic toxoplasmosis are unknown. Here we show that mouse skeletal muscle cells (SkMCs) after differentiation to mature, myosin heavy chain-positive, polynucleated myotubes, significantly restrict tachyzoite replication and facilitate expression of bradyzoite-specific antigens and tissue cyst formation. In contrast, proliferating mononuclear myoblasts and control fibroblasts enable vigorous T. gondii replication but do not sustain bradyzoite or tissue cyst formation. Bradyzoite formation correlates with upregulation of testis-specific Y-encoded-like protein-2 gene expression (Tspyl2) and p21(Waf1/Cip1 as well as downregulation of cyclin B1 and absence of DNA synthesis, i.e. a cell cycle arrest of syncytial myotubes. Following infection with T. gondii, myotubes but not myoblasts or fibroblasts further upregulate the negative cell cycle regulator Tspyl2. Importantly, RNA interference-mediated knock-down of Tspyl2 abrogates differentiation of SkMCs to myotubes and enables T. gondii to replicate vigorously but abolishes bradyzoite-specific gene expression and tissue cyst formation. Together, these data indicate that Tspyl2-mediated host cell cycle withdrawal is a physiological trigger of Toxoplasma stage conversion in mature SkMCs. This finding might explain the preferred distribution of T. gondii tissue cysts in vivo. | 25,131,712 | [
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... |
Assessing the feasibility of hepatitis C virus vaccine trials: results from the Hepatitis C Incidence and Transmission Study-community (HITS-c) vaccine preparedness study. | Efficacy trials of preventive hepatitis C virus (HCV) vaccine candidates raise challenging scientific and ethical issues. Based on data from the first 3 years of a community-based prospective observational study - the Hepatitis C Incidence and Transmission Study-community (HITS-c) - this paper examines the feasibility of conducting trials of candidate HCV vaccines with people who inject drugs (PWID) in Sydney, Australia. Of the 166 PWID confirmed HCV antibody negative and eligible for enrolment, 156 (94%) completed baseline procedures. Retention was high, with 89% of participants retained at 48 weeks and 76% of participants completing at least 75% of study visits within 2 weeks of schedule. The rate of primary HCV infection was 7.9/100 py (95% CI 4.9, 12.7). Of the 17 incident cases, 16 completed at least one follow-up assessment and 12 (75%) had evidence of chronic viraemia with progression to chronic HCV infection estimated to be 6/100 py. Power calculations suggest a chronic HCV infection rate of at least 12/100 py (primary HCV infection rate 16/100 py) will be required for stand-alone trials of highly efficacious candidates designed to prevent chronic infection. However, elevated primary HCV infection was observed among participants not receiving opioid substitution therapy who reported heroin as the main drug injected (26.9/100 py, 95% CI 14.5, 50.0) and those who reported unstable housing (23.5/100 py, 95% CI 7.6, 72.8), daily or more frequent injecting (22.7/100 py, 95% CI 12.2, 42.2) and receptive syringe sharing (23.6/100 py, 95% CI 9.8, 56.7) in the 6 months prior to baseline. These data suggest that it is possible to recruit and retain at-risk PWID who adhere to study protocols and that modification of eligibility criteria may identify populations with sufficiently high HCV incidence. Results support the feasibility of large multi-centre HCV vaccine trials, including in the Australian setting. | 25,131,726 | [
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0.056... |
TLR7/8 agonists activate a mild immune response in rabbits through TLR8 but not TLR7. | Toll-like receptors 7 (TLR7) and 8 (TLR8) recognize viral single-stranded RNA and small molecular weight agonists to activate anti-viral immune responses. TLR8s from different species have distinct ligand recognitions. For example, human TLR8 is responsive to ligand stimulation, but mouse and rat TLR8 are activated by small molecular weight agonists only in the presence of polyT-oligodeoxynucleotides. TLR7 and TLR8 have been reported to be absent and pseudogenized, respectively, in rabbit (Oryctolagus cuniculus). In this study, we detected the expression of rabbit (rab)TLR8 in immune-cell-associated tissues. Cell proliferation and cytokine expressions in rabbit splenocytes were induced by the TLR7/8 ligand but not by the TLR7 ligands, suggesting that rabTLR8 is functional but rabTLR7 is not. In rabbits, CL075, a TLR7/8 ligand, activated an antigen-specific antibody response, although one not as potent as aluminum salt or Freund's adjuvant. Nevertheless, CL075, alone or in combination with aluminum salt, generates fewer adverse effects than Freund's adjuvant at the injection sites. To further investigate the activation of rabTLR8, we cloned its cDNA. In cell-based assay, this rabTLR8 is activated by TLR7/8 ligand but not activated by TLR7 ligand. Upon stimulation the rabTLR8 had a lower activation compared to the activation of TLR8 from other species, except the mouse and rat TLR8s. Using different deletion and human-rabbit chimeric TLR8 expressing constructs, we showed that an extra peptide in the undefined region results in reduced activity of rabTLR8. These results provide a molecular basis for the mild activities of TLR7/8 ligands in rabbits, and suggest TLR7/8 agonists may provide safer immune stimuli in rabbits than in other non-rodent species. | 25,131,730 | [
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0.05994695,
... |
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