Validation of the Persian version of the attitudes toward intellectual disability.

BACKGROUND: Attitudes toward individuals with intellectual disability (ID) are the most important factor affecting their social integration and can cause them to experience a sense of achievement or discrimination. The present study aimed to evaluate the latent factor structure and validity of the Persian version of the Attitudes toward Intellectual Disability (ATTID) Short-Form questionnaire. METHODS: The latent factor structure of the Persian version of the ATTID Short-Form was established in a convenient sample of the general population (N = 280) in Iran. The structural validity and temporal reliability, internal consistency and confirmatory factor analysis were evaluated. Data analysis was done with SPSS v23 Windows edition and R v4.2.1. RESULTS: The Persian version of the ATTID Short-Form was shown to have a five-factor structure: discomfort, knowledge of capacity, interaction, sensitivity and knowledge of cause. The structure was appropriately fit according to the fit indices (χ2(485) = 530.12), (P-value = 0.077). All the subscales had good temporal reliability. CONCLUSIONS: Findings suggest that the Persian version of the Short-Form of ATTID is a brief, valid and reliable measure that can be used in research and clinical practice.

Temporal and institutional trends in robotic surgery.

Robotic surgery has become increasingly prevalent in general surgery practice. While previous studies have shown the safety and efficacy of robotic assistance in laparoscopic general surgery procedures, few studies have evaluated the temporal and regional trends in implementation. In our retrospective population-based study, we aim to evaluate the national trends in robotic surgery. National Inpatient Database (NIS 2009-2014) was used to identify adults who underwent robotic assisted surgery (ICD 9 codes 17.41 to 17.49). Robotic procedures related to seven abdominal organ systems were compared against the trends of Urology, Gynaecologic, and Orthopedic robotic procedures. Discharge weights were applied to calculate National temporal trends separated by hospital size, teaching status and US geographic region. 894,163 patients received a robotic assisted procedure between 2009 and 2014 with 64% increase in utilization. The largest percent change was witnessed in biliary robotic procedures with 2984% change in utilization, followed by hernia (1376%). Lowest percent change was witnessed in esophageal procedures with 114% increase. Medium sized hospitals had the largest change in robotic utilization (41%), with large institutions seeing 18% decrease. Gastric procedures were the most common robotic procedure performed at small institutions (7917 total cases; 316%). Large institutions saw an overall decrease in gastric (- 47%), esophageal (- 17%), small and large intestinal (-16%), and hepatic (- 7%) robotic procedures. Rural non-teaching hospitals saw the largest increase in robotic surgery (274%). Urban non-teaching hospitals saw a decrease of 29%. While urban teaching institutions saw a 20% and 6% increase in gynecological and urological procedures, an overall decrease was seen in esophageal (- 10%), gastric (- 12%), intestinal (- 11%), hepatic (- 17%), biliary (- 10%), pancreatic (- 11%) and hernia procedures (- 14%). Biliary procedures saw the largest increase in rural institutions (740 cases; 392%), followed by hernia (144% increase). South region of the nation had the largest increase in robotic procedures (23%). No change was seen in the use of robotic surgery in the northeast region with the midwest and west seeing an overall decrease (- 4% and - 22%, respectively). Our study highlights the increase in use of robotics for both general and specialty surgery, with an increase in utilization over time. Increased incidence of robotic surgery in smaller, rural institutions with overall decrease in larger, urban teaching hospitals suggests increasing comfort in robotic surgery in the community setting. Further studies are necessary to evaluate the factors associated with increased utilization in smaller institutions.

A survey of patients with facial angiofibromas associated with tuberous sclerosis complex: Short-, medium- and long-term efficacy and safety of topical rapamycin.

AIMS: Topical rapamycin is used to reduce facial angiofibromas in patients with tuberous sclerosis (TSC). In the absence of a commercially available preparation, numerous formulations have been tested clinically, although only in the short term. METHODS: The pharmacy at Angers University Hospital (France) produced a cream formulation that was administered to people presenting this genetic disease. We conducted a questionnaire-based survey among 79 patients with TSC about their perceptions regarding the short-, medium- and long-term efficacy and safety of a topical rapamycin preparation in relation to facial angiofibromas. RESULTS: This formulation was very well tolerated and its efficacy was sustained over the long term with a mean treatment duration of 33 months (extremes 1-60). Efficacy was rated ≥ 8/10 by 67.1% of patients while safety was rated ≥ 8/10 by 84.8% of patients. CONCLUSION: This survey supports the safety and efficacy of topical rapamycin in the short-, medium- and long-term in the treatment of facial angiofibromas in a cohort of 79 patients with TSC.

Evaluation of the impact of pharmaceutical trainings and tools on the proper use of medicines in pediatrics.

Introduction: After six years of medication errors' (MEs) collection and analysis in a pediatric unit of a French University Hospital, the number of MEs was no longer decreasing. We then decided to set up pharmaceutical training and tools and evaluate their impact on the occurrence of ME. Materials and methods: This monocentric prospective study was carried out in the form of audits of prescriptions, preparations, and administrations before and after intervention (A1 and A2). After the analysis of A1 results, feedback was given to the teams, some tools for the proper use of medication (PUM) were distributed, and A2 was conducted. Finally, A1 and A2 results were compared. Results: Each audit included 202 observations. A total of 120 MEs were identified during A1 and 54 for A2 (p < 0.0001). The observation rate with at least 1 ME decreased from 39.11% to 21.29% (p < 0.0001), and no observation had more than two MEs during A2 in contrast to A1 (n = 12). Human factors were responsible for the majority of MEs. The audit feedback allowed professionals to feel concerned about ME. The PUM tools received an average satisfaction rating of 9/10. The staff had never participated in this type of training, and all felt it was useful to apply PUM. Conclusion: This study showed a significant impact of pharmaceutical training and tools on the pediatric PUM. Clinical pharmaceutic actions allowed us to reach our objectives and satisfied all the staff. They must, therefore, be continued to limit human factors' impact and thus contribute to the safety of drug management in pediatrics.

Soil bacterial community dynamics in plots managed with cover crops and no-till farming in the Lower Mississippi Alluvial Valley, USA.

AIMS: Assess bacterial community changes over time in soybean (Glycine max) crop fields following cover crop (CC) and no-till (NT) implementation under natural abiotic stressors. METHOD AND RESULTS: Soil bacterial community composition was obtained by amplifying, sequencing, and analysing the V4 region of the 16S rRNA gene. Generalized linear mixed models were used to assess the effects of tillage, CC, and time on bacterial community response. The most abundant phyla present were Acidobacteria, Actinobacteria, Bacteroidetes, and Verrucomicrobia. Bacterial diversity increased in periods with abundant water. Reduced tillage (RT) increased overall bacterial diversity, but NT with a CC was not significantly different than RT treatments under drought conditions. CCs shifted abundances of Firmicutes and Bacteroidetes depending on abiotic conditions. CONCLUSIONS: In the Lower Mississippi Alluvial Valley (LMAV), USA, NT practices lower diversity and influence long-term community changes while cover crops enact a seasonal response to environmental conditions. NT and RT management affect soil bacterial communities differently than found in other regions of the country.

Comparative study of open, laparoscopic and endoscopic treatments of intermediate grade vesicoureteral reflux in children.

BACKGROUND: Low-grade vesicoureteral-reflux (VUR) are rather treated by endoscopic injection, whereas open or laparoscopic procedures are mainly performed for high-grade VURs. Management of intermediate grades is controversial and no study focused on grade III to date. This study aims to compare the results of open, laparoscopic, and endoscopic approaches in children with grade III VUR. METHODS: A multicenter comparative retrospective study included children with grade III VUR operated for febrile urinary tract infections (UTIs) from 2007 to 2016. Children without UTI, with reflux of other grades, neurological bladder, duplex system, posterior urethral valves, and bladder exstrophy were excluded. Success was defined as no recurrence of febrile UTI and was presented as event-free survival curves. RESULTS: Out of 806 children operated of VUR, 171 met the inclusion criteria (114 females). Seventy-seven children (45%) underwent an open Cohen procedure, 35 (21%) a laparoscopic Lich-Gregoir and 59 (34%) a submucosal endoscopic injection according to the centers' preference. The mean follow-up was 64 months (24-132). Groups were not different for age, sex, and circumcision status. Compared to Cohen procedure, recurrences of febrile UTI were more frequent after laparoscopic treatment (p = 0,02, 8/35) and endoscopic treatment (p = 0.001, 16/59). Redosurgery was also more frequent after laparoscopy (n = 2) and endoscopic injection (n = 14) than after open surgery (n = 0, p < 0.001). CONCLUSION: Recurrent febrile UTIs and redosurgery are more frequent after endoscopic and laparoscopic procedures in grade III VUR than open reimplantation. Whether the lower morbidity of laparoscopic or endoscopic approaches balances the risk of recurrent febrile UTI remains to be determined for intermediate grade reflux.

Outbreak of hemolytic uremic syndrome with unusually severe clinical presentation caused by Shiga toxin-producing Escherichia coli O26:H11 in France.

BACKGROUND: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Santé publique France in connection with microbiological investigations at the national reference center for STEC promptly identified a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. METHOD: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Santé publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. RESULTS: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/1.73m2 and four had hypertension. One patient had neurological sequelae. CONCLUSION: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at-risk foods by young children as key preventive measures against STEC infections.

Population physiologically based modeling of pirlimycin milk concentrations in dairy cows.

Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs.

Development and psychometric properties of the Attitudes Toward Intellectual Disability Questionnaire - Short Form.

BACKGROUND: Understanding public attitudes towards people with intellectual disability (ID) can help orient activities to promote the social inclusion of this group. The ATTitudes toward Intellectual Disability (ATTID) questionnaire is a validated 67-item tool used to assess attitudes towards people with ID from a multidimensional perspective. It is based on a five-factor model tapping into cognitive, emotional and behavioural components of attitudes. In order to facilitate international research, the goal of this study was to develop a short version that would retain the long form's psychometric properties. METHODS: Analyses were conducted on a sample of 1608 respondents who completed the full-length ATTID. A four-step test refinement procedure was used to reduce the number of items. The first two steps involved a Cronbach's alpha analysis. Items retained were then reviewed to assess face validity. Correlations between factors were calculated, and a factor analysis was performed to compare the original and short forms. RESULTS: The number of items in the ATTID was reduced from 67 to 35. The short form maintained good overall reliability. The correlational pattern between factors in both the long and short form is generally the same. The factor analysis of the short form showed a similar five-factor structure with some loss of variance. CONCLUSIONS: We recommend the short form be used when administration time is an issue, particularly in a research context. Replication studies with new samples are needed to further assess the psychometric properties of the ATTID-Short Form.

Attitudes of health care professionals toward people with intellectual disability: a comparison with the general population.

BACKGROUND: Few studies have examined attitudes that may promote the social inclusion of persons with an intellectual disability (ID) among health care providers (HCPs). Yet these attitudes could impact the accessibility and quality of services provided to this population, as well as the general attitudes of HCPs. The objectives of this study were to (1) examine HCPs' pro-inclusion attitudes toward people with ID, (2) compare these to the general population's attitudes and (3) examine how HCPs' attitudes vary as a function of their socio-demographic characteristics. METHOD: The Attitudes Toward Intellectual Disability Questionnaire was administered to 367 HCPs and a representative sample of the Québec population (N = 1605). RESULTS: Results indicated that at least half of HCPs displayed positive attitudes, that is, attitudes that are compatible with notions of social inclusion and equal rights, toward individuals with ID. Positive attitudes were less frequently observed for the Interaction and the Sensitivity or tenderness factors measured by the Attitudes Toward Intellectual Disability Questionnaire. In comparison with the general population, HCPs exhibited more positive attitudes on the Knowledge of causes and Sensitivity or tenderness factors and less positive attitudes on the Interaction factor. HCPs who regarded themselves as more knowledgeable about ID and those who reported higher quality contacts or interactions with persons with ID expressed attitudes that were more favourable toward social inclusion. CONCLUSIONS: In addition to providing general knowledge about ID and the specific health care needs of individuals with ID, training programmes should also promote interactions with this population. Further studies are needed to document HCPs' pro-inclusion attitudes toward people with ID and to assess the impact of interventions on these attitudes.

Association of California Mastitis Test Scores with Intramammary Infection Status in Lactating Dairy Cows Admitted to a Veterinary Teaching Hospital.

BACKGROUND: Subclinical mastitis is of concern in veterinary hospitals because contagious mastitis pathogens might be unknowingly transmitted to susceptible cows and then back to their farm of origin. OBJECTIVES: To evaluate the California mastitis test (CMT) as an indicator of intramammary infection (IMI) in lactating dairy cows admitted to a veterinary hospital. ANIMALS: A total of 139 admissions of 128 lactating dairy cows admitted to the University of Illinois Veterinary Teaching Hospital over a 2-year period. METHODS: A retrospective study with a convenience sample was conducted. Medical records of cows with CMT results and milk culture results for the day of admission were reviewed. Breed, age, season, maximum CMT score for the 4 quarters, maximum CMT score difference, and clinical diagnosis were evaluated as predictors of IMI by the chi-square test and stepwise logistic regression. RESULTS: An IMI was identified in 51% of quarters. For cows admitted without evidence of clinical mastitis, the sensitivity of a CMT score ≥trace in predicting an IMI on a quarter or cow basis was 0.45 and 0.68, respectively. The distributions of maximal quarter CMT score and the maximum difference in quarter CMT score for cows without evidence of clinical mastitis did not differ (P = 0.28, P = 0.84, respectively) for cows with and without IMI. Stepwise logistic regression did not identify significant predictors of IMI in cows without clinical mastitis. CONCLUSIONS: Lactating dairy cattle admitted to a veterinary hospital should be managed as if they have an IMI, even in the absence of clinical mastitis.

[Childhood steroid-dependent idiopathic nephrotic syndrome: Predictive factors for the need of immunosuppressive treatment]. / Syndrome néphrotique idiopathique corticodépendant de l'enfant : facteurs prédictifs de recours à un traitement immunosuppresseur.

BACKGROUND AND AIMS: More than half of the children with idiopathic nephrotic syndrome become steroid-dependent (or frequent relapsers) and will later require the use of complementary treatment aiming to reduce steroids' side effects and to limit the number of proteinuria relapses. It appears important to identify these children as early as possible in order to adapt their treatment. The aim of this study was to analyze the population of children, under 18 years of age, diagnosed between 1/01/2000 and 31/05/2015 with an idiopathic nephrotic syndrome and followed at the Montpellier University Hospital to search for criteria predictive of steroid-sparing agent use. METHODS: In this retrospective study of children with idiopathic nephrotic syndrome, the exclusion criteria were primary steroid resistance and children with no proteinuria relapse after diagnosis. RESULTS: Eighty-four children (54 boys) were included in this study. The mean follow-up duration was 5.5 years (0.75-16). The mean age at diagnosis was 4.6 years. Sixty-five children (77%) received at least one steroid-sparing agent during their follow-up, within a mean 10 months after diagnosis. In these patients, the first relapse of the disease occurred earlier when compared with the children who were maintained on steroid alone (4 months vs 7 months; P<0.001). The use of methylprednisolone pulses to obtain a remission, the cumulative dose of steroid treatment, and the number of proteinuria relapses were also significantly correlated with the use of complementary immunosuppressive therapy. CONCLUSION: We found no predictive criteria of the use of steroid-sparing agents at diagnosis in our population of children. Nevertheless, with the steroid regimen used, the time within which the first proteinuria relapse occurred appears to be a significant criterion for the secondary use of a steroid-sparing agent. These data should be taken into account when choosing the treatment regimen.

Diabetes care: Comparison of patients' and healthcare professionals' assessment using the PACIC instrument.

RATIONALE, AIMS AND OBJECTIVE: Whereas the Patient Assessment of Chronic Illness Care (PACIC) instrument measures the extent to which care received by patients is congruent with the Chronic Care Model, the 5As model emphasizes self-management and community resources, 2 key components of the Chronic Care Model. We aimed at comparing evaluation of diabetes care, as reported by patients with diabetes and healthcare professionals (HCPs), using these instruments. METHODS: Two independent samples, patients with diabetes (n = 395) and HCPs (including primary and secondary care physicians and nurses; n = 287), responded to the 20-item PACIC and the six 5As model questions. The PACIC-5A (questions scored on a 5-point scale, 1 = never to 5 = always) was adapted for HCPs (modified-PACIC-5A). In both samples, means and standard deviations for each question as well as proportions of responses to each response modality were computed, and an overall score was calculated for the 20-item PACIC. RESULTS: Patients' and HCPs' overall scores were 2.6 (SD 0.9) and 3.6 (SD 0.5), respectively, with HCPs reporting higher scores for all questions except 1. Patients' education and self-management, referral/follow-up and participation in community programs were rated as low by patients and HCPs. CONCLUSION: Healthcare professionals, particularly diabetes specialists, tended to report better PACIC scores than patients, suggesting that care was not reported similarly when received or provided. Evaluation differences might be reduced by a closer collaboration between patients and HCPs, as well as the implementation of community-based interventions considering more patients' perspectives such as patients' education and self-management.

Naphthalene cytotoxicity in microsomal epoxide hydrolase deficient mice.

Naphthalene (NA) is a ubiquitous pollutant to which humans are widely exposed. 1,2-Dihydro-1,2-dihydroxynaphthalene (NA-dihydrodiol) is a major metabolite of NA generated by microsomal epoxide hydrolase (mEH). To investigate the role of the NA-dihydrodiol and subsequent metabolites (i.e. 1,2-naphthoquinone) in cytotoxicity, we exposed both male and female wild type (WT) and mEH null mice (KO) to NA by inhalation (5, 10, 20 ppm for 4h). NA-dihydrodiol was ablated in the KO mice. High-resolution histopathology was used to study site-specific cytotoxicity, and formation of naphthalene metabolites was measured by HPLC in microdissected airways. Swollen and vacuolated airway epithelial cells were observed in the intra- and extrapulmonary airways of all mice at and below the current OSHA standard (10 ppm). Female mice may be more susceptible to this acute cytotoxicity. In the extrapulmonary airways, WT mice were more susceptible to damage than KO mice, indicating that the metabolites associated with mEH-mediated metabolism could be partially responsible for cytotoxicity at this site. The level of cytotoxicity in the mEH KO mice at all airway levels suggests that non-mEH metabolites are contributing to NA cellular damage in the lung. Our results indicate that the apparent contribution of mEH-dependent metabolites to toxicity differs by location in the lung. These studies suggest that metabolites generated through the mEH pathway may be of minor importance in distal airway toxicity and subsequent carcinogenesis from NA exposure.

One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes.

Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [± standard error of the mean (s.e.m.)] age of 39.2 (±4) years, presented with familial partial lipodystrophy (n = 11, 10 women) or congenital generalized lipodystrophy (n = 5, four women). Their mean (± s.e.m.) BMI (23.9 ± 0.7 kg/m(2) ), glycated haemoglobin levels (8.5 ± 0.4%) and serum triglycerides levels (4.6 ± 0.9 mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic-hyperinsulinaemic clamps, n = 4 and n = 12, respectively), insulin secretion during graded glucose infusion (n = 12), and acute insulin response to i.v. glucose adjusted to insulin sensitivity (disposition index, n = 12), significantly increased after 1 year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies.

[Epidemiology of diabetes in children in Languedoc-Roussillon (France)]. / Registre épidémiologique du diabète chez l'enfant en Languedoc-Roussillon.

Since 1st January 2000, the PEDIAB-LR registry has listed new cases of diabetes in children under 16 years of age in the Languedoc-Roussillon region of France, in order to assess the incidence and epidemiological characteristics of children affected by diabetes. At the end of December 2010, 745 children had been registered. The characteristics of these children included an identical proportion of girls and boys, a mean age of 8 years at diagnosis, and a family history of type 1 diabetes in 8.4% of the cases. Inaugural ketoacidosis was observed in 69.5% of the patients and was severe in 23.7% of these cases. To replace intravenous insulin, a two-injection dosing regimen (in the morning and before dinner) was prescribed in 76.5% of cases, multi-injections of basal-bolus in 16%, and subcutaneous insulin infusion (insulin pump therapy) in 7.5% of cases. Between 2000 and 2010, there was no increase in overall incidence. It is noteworthy that age at diagnosis tended to decrease, but this was not statistically significant. In conclusion, the PEDIAB-LR registry is currently the only French registry on diabetes in children, analyzing many factors related to its incidence, such as age at diagnosis and the existence of ketoacidosis.

Norms of the Attitudes Toward Intellectual Disability Questionnaire.

BACKGROUND: The Attitudes Toward Intellectual Disability Questionnaire (ATTID) has demonstrated good psychometric qualities for measuring the attitudes of different groups of adults in the general population toward intellectual disability (ID). A significant advantage of the ATTID is that it addresses the concept of attitudes using a three-dimensional model (affective, cognitive and behavioural). To our knowledge, there are no normative data published regarding attitudes toward ID on general population-based samples. METHODS: The sample of 1605 men and women was stratified to be representative of the general adult population of Quebec. The ATTID was administered by phone interview through an independent survey firm. RESULTS: Normative data are presented as percentile scores associated with the raw score of the ATTID by gender and age categories. Analysis of the variance yielded significant differences in attitude by gender and age. The directions and the strength of these associations vary according to each of the five factors used to define attitudes. CONCLUSION: These norms will provide an essential tool to compare different groups and assess the effectiveness of various public campaigns to encourage more positive attitudes towards persons with ID. These norms would also allow international comparisons.

The androgen receptor mediates antiapoptotic function in myometrial cells.

During pregnancy, myometrial phenotype is programmed into three characteristic stages referred to as the early proliferative, the midterm hypertrophic, and the late contractile stage. Increased myometrial growth in the early and midterm of pregnancy involves a complex process of cell proliferation, antiapoptosis and differentiation. We have previously demonstrated that the androgen receptor (AR) is required for myometrial cell proliferation by modulating IGF-1 signaling during early pregnancy. Here, we report that AR also exerts its antiapoptotic function in human myometrial cells. Enhanced AR expression protects, whereas AR silencing sensitizes myometrial cells to both intrinsic and extrinsic apoptotic stimuli. AR agonist inhibits, whereas AR antagonist induces myometrial cells to undergo apoptotic cell death. Gene microarray analysis confirms that the central functions of AR in myometrial cells are to regulate cell cycling and apoptosis through three major gene groups involving the epidermal growth factor (EGF) signaling, RNA splicing and DNA repair processes. AR mediates its antiapoptotic function through two distinct pathways. In the receptor-dependent pathway, AR is required for the expression of several protein factors within the EGF signaling pathway. Through the PI3K/Akt pathway, AR enhances the expression of the antiapoptotic protein Mcl-1. In the ligand-dependent pathway, AR agonist triggers the activation of Src kinase, which in turn phosphorylates STAT3 to increase Mcl-1 expression. We conclude from these results that the AR signaling exerts antiapoptotic function in myometrial cells, further supporting its key role in programming of myometrial phenotype.

The cardioprotectant 3',4'-dihydroxyflavonol inhibits opening of the mitochondrial permeability transition pore after myocardial ischemia and reperfusion in rats.

The study aimed to determine the effect of 3',4'-dihydroxyflavonol (DiOHF) on mitochondrial function, in particular opening of the mitochondrial permeability transition pore (mPTP), respiratory function and reactive oxygen species (ROS) production, in isolated cardiac mitochondria after coronary artery occlusion and reperfusion in vivo. Opening of the mPTP, oxygen consumption and ROS production (assessed by measurement of H2O2) was determined in mitochondria isolated from normal hearts or from the ischemic zone of rat hearts subjected to 30min coronary artery occlusion and 15min reperfusion. Treatment of sham rats with DiOHF (10mgkg(-1) iv) significantly increased the concentration of Ca(2+) required to stimulate mPTP opening. This was accompanied by increased state 3 oxygen consumption and decreased H2O2 release. Ischemia and reperfusion (IR) significantly decreased the concentration of Ca(2+) required to stimulate mPTP opening, decreased state 3 oxygen consumption and increased H2O2 release, when pyruvate plus malate was provided as a substrate. Treatment with DiOHF prevented IR-induced changes in mPTP opening, state 3 oxygen consumption and H2O2 release so that there was no difference compared to sham. In isolated cardiac mitochondria from normal rats DiOHF had no effect on mPTP opening or on state 3 respiration but caused a small increase in state 4 respiration and decreased the respiratory control ratio. DiOHF, administered during ischemia just before reperfusion, inhibits mPTP opening and preserves mitochondrial function through a mechanism likely to be independent of its antioxidant activity or any direct effect on the mPTP.