Trends and determinants of anemia in children 6-59 months and women of reproductive age in Chad from 2016 to 2021.

BACKGROUND: Hemoglobin assessments in children and women have been conducted annually in Chad since 2016 through the Standardized Monitoring and Assessment of Relief and Transitions (SMART) cross-sectional surveys. This analysis aims to characterize national and sub-national trends in anemia among children under five and women of reproductive age from 2016 to 2021 and to compare risk factors for anemia before and during the COVID-19 pandemic. METHODS: Hemoglobin concentrations were measured in approximately half of the 12,000 to 15,000 included households each year, except for 2020 when hemoglobin tests were omitted. For children 6 to 59 months of age, anemia was defined as hemoglobin less than 11.0 g/dL. Anemia was defined as hemoglobin less than 11.0 g/dL and 12.0 g/dL for pregnant women and non-pregnant women, respectively. Trends were stratified by agroecological zone, and tests of proportions were used to assess statistical significance. Simple and multivariate logistic regression models were conducted for 2019 and 2021 to identify risk factors for anemia. RESULTS: Reductions in anemia over the 6-year period were significant among women (47.6-30.8%, p = 0.000) and children (68.6-59.6%, p = 0.000). The Sudanian zone had consistently higher rates, particularly in children, compared to the Sahelian and Saharan zones. Significant declines in women's anemia were observed in all zones from 2019 to 2021, but this global decline was not observed among children, where rates in the Saharan zone significantly increased. In 2019, only minimum dietary diversity significantly reduced the odds of anemia in children (AOR: 0.65, 95%CI: 0.46-0.92), whereas in 2021, improvements in all diet indicators were associated with lower odds of anemia. Improved household socio-economic factors, including head of household literacy, were associated with lower odds of anemia in children (2019 AOR: 0.76, 95%CI: 0.67, 0.88) and women (2019 AOR: 0.75, 95%CI: 0.65, 0.87; 2021 AOR: 0.81, 95%CI: 0.70, 0.93). CONCLUSIONS: Anemia declined significantly in Chad among women of reproductive age and children from 2016 to 2021, but the national prevalence of 60% among children remains unacceptably high. Sub-national differences in anemia rates underline the need to identify and address regional causes of anemia while strengthening national level programs.

Trends and Determinants of Children's Wasting and Women's Thinness in Chad, 2015 to 2021.

BACKGROUND: Cross-sectional surveys using the Standardized Monitoring and Assessment of Relief and Transitions methodology have been conducted annually in Chad since 2015 to evaluate population-level nutritional status. OBJECTIVE: This analysis characterizes national and subnational trends in child wasting and women's thinness from 2015 to 2021 in Chad and identifies risk factors during the COVID-19 pandemic. METHODS: Annual survey data with 12,000 to 15,000 households were included. Wasting was estimated for children 6 to 59 months using the WHO child growth standards, and among women 15 to 49 years, thinness was defined as mid-upper arm circumference <23 cm. Trends were stratified by agroecological zone, and chi-square tests used to assess statistical significance. Simple and multivariate logistic regression models were conducted for 2020 and 2021 to identify risk factors of wasting and thinness. RESULTS: About 11,958 to 17,897 children and 9883 to 15,535 women contributed values each year. National wasting and thinness rates did not significantly decrease over the 7-year period (wasting: 14.1% to 12.1%, P = .43; thinness: 15.2% to 13.4%, P = .51) and wasting rose from 2020 to 2021. The Saharan and Sahelian zones had consistently higher rates compared to the Sudanian zone. Younger age, male sex, inadequate infant and young child feeding practices, and poorer household socio-economic factors were associated with greater odds of child wasting. For women, younger age, lack of nutrition knowledge, and poorer household socio-economic factors increased the odds of thinness. CONCLUSIONS: Undernutrition in Chad has not improved since 2015, and the COVID-19 pandemic likely exacerbated the crisis among children nationally and among women subnationally. Multisectoral approaches and regional targeting of interventions are recommended.

Cancer patient and provider responses to companion scales assessing experiences with LGBTQI-affirming healthcare.

Background: Sexual and gender minority (SGM) persons are at a higher risk for some cancers and may have poorer health outcomes as a result of ongoing minority stress, social stigma, and cisnormative, heteronormative healthcare environments. This study compared patient and provider experiences of affirming environmental and behavioral cues and also examined provider-reported knowledge, attitudes, behaviors, and clinical preparedness in caring for SGM patients among a convenience sample. Methods: National convenience samples of oncology providers (n = 107) and patients (n = 88) were recruited separately via snowball sampling. No incentives were provided. After reverse coding of appropriate items for unidirectional analysis, lower scores on items indicated greater knowledge, more affirming attitudes or behaviors, and greater confidence in clinical preparedness to care for SGM patients. Pearson chi-square tests compared dichotomous variables and independent samples t-tests compared continuous variables. Other results were reported using descriptive frequencies. Results: Both patient and provider samples were predominantly female sex assigned at birth, cisgender, and heterosexual. Providers were more likely than patients to report affirming cues in clinic, as well as the ability for patients to easily document their name in use and pronouns. Providers were more likely to report asking about patient values and preferences of care versus patients' recollection of being asked. Patients were more likely to report understanding why they were asked about both sex assigned at birth and gender identity compared to providers' perceptions that patients would understand being asked about both. Patients were also more likely to report comfort with providers asking about sex assigned at birth and gender identity compared to providers' perceptions of patient comfort. SGM providers had greater knowledge of SGM patient social determinants of health and cancer risks; felt more prepared to care for gay patients; were more likely to endorse the importance of knowing patient sexual orientation and gender identity; and were more likely to indicate a responsibility to learn about SGM patient needs and champion positive system changes for SGM patients compared to heterosexual/cisgender peers. Overall, providers wished for more SGM-specific training. Conclusion: Differences between patient and provider reports of affirming environments as well as differences between SGM and heterosexual/cisgender provider care support the need for expanded professional training specific to SGM cancer care.

Exploring HPV vaccine hesitant parents' perspectives on decision-making and motivators for vaccination.

Introduction: The human papillomavirus (HPV) vaccine is highly effective at preventing HPV-associated cancers in both males and females, yet vaccination rates remain sub-optimal in part due to vaccine hesitancy. This study sought to assess which strategies vaccine-hesitant parents perceive as most likely to motivate them to vaccinate their children against HPV. Methods: In 2021, we recruited parents with children ages 10-17 years old who were not vaccinated against HPV and who felt unsure or hesitant about their decision to vaccinate their child. Participants were recruited through an online patient portal within a single institution. A screening survey assessed for vaccine hesitancy. Semi-structured interviews focused on HPV vaccine decision-making, motivators, and potential strategies to improve vaccination rates in hesitant parents. Audio recordings were transcribed and analyzed via a combination of deductive and inductive codes. Results and Discussion: A total of twenty-two vaccine-hesitant parents were interviewed. The major themes identified were a lack of confidence in vaccine decision-making, a desire for more information, and dissatisfaction with provider encounters. Parents reported that their hesitancy was driven by concerns about safety and necessity, often based on negative anecdotal reports. Although pediatricians were the most often cited source of vaccine information, many parents were dissatisfied with the encounters they had regarding the vaccine. Parents expressed a desire for detailed information on both the benefits and risks of the vaccine, and resources that allowed them to actively participate in vaccine discussions with providers. Suggested modes of delivery for this information included in-depth pediatrician discussions, written materials provided by pediatricians, and facilitation tools, such as a list of questions to help parents prepare for pediatrician visits. Thus, strategies that empower parents to feel informed and confident in their decision to vaccinate their children could be useful in motivating vaccine-hesitant parents to vaccinate their children against HPV.

Translating Virtual Reality Cue Exposure Therapy for Binge Eating into a Real-World Setting: An Uncontrolled Pilot Study.

Binge-eating disorder (BED) and bulimia nervosa (BN) have adverse psychological and medical consequences. Innovative interventions, like the integration of virtual reality (VR) with cue-exposure therapy (VR-CET), enhance outcomes for refractory patients compared to cognitive behavior therapy (CBT). Little is known about the feasibility and acceptability of translating VR-CET into real-world settings. To investigate this question, adults previously treated for BED or BN with at least one objective or subjective binge episode/week were recruited from an outpatient university eating disorder clinic to receive up to eight weekly one-hour VR-CET sessions. Eleven of 16 (68.8%) eligible patients were enrolled; nine (82%) completed treatment; and 82% (9/11) provided follow-up data 7.1 (SD = 2.12) months post-treatment. Overall, participant and therapist acceptability of VR-CET was high. Intent-to-treat objective binge episodes (OBEs) decreased significantly from 3.3 to 0.9/week (p < 0.001). Post-treatment OBE 7-day abstinence rate for completers was 56%, with 22% abstinent for 28 days at follow-up. Among participants purging at baseline, episodes decreased from a mean of one to zero/week, with 100% abstinence maintained at follow-up. The adoption of VR-CET into real-world clinic settings appears feasible and acceptable, with a preliminary signal of effectiveness. Findings, including some loss of treatment gains during follow-up may inform future treatment development.

Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study.

BACKGROUND: Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study. OBJECTIVE: To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity. METHODS: This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed. EXPECTED OUTCOMES: Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation. DISCUSSION: This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.

Bringing Virtual Reality From Clinical Trials to Clinical Practice for the Treatment of Eating Disorders: An Example Using Virtual Reality Cue Exposure Therapy.

Novel treatment options for eating disorders (EDs) are critically needed to enhance treatment outcomes and reduce the rates of treatment dropouts. On average, only 50% of individuals receiving evidence-based care remit, whereas 24% drop out before treatment completion. One particularly promising direction involves integrating virtual reality (VR) with existing evidence-based treatments (EBTs) such as cue exposure therapy (CET). Across psychiatric disorders, VR-based interventions are demonstrating at least preliminary efficacy and noninferiority to traditional treatments. Furthermore, VR technology has become increasingly portable, resulting in improved acceptance, increased access, and reductions in cost. However, more efficient research processes may be needed to uncover the potential benefits of these rapid technological advances. This viewpoint paper reviews existing empirical support for integrating VR with EBTs (with a focus on its use with EDs) and proposes key next steps to more rapidly bring this innovative technology-based intervention into real-world clinic settings, as warranted. VR-CET for EDs is used to illustrate a suggested process for developing such treatment enhancements. We recommend following a deployment-focused model of intervention development and testing to enable rapid implementation of robust, practice-ready treatments. In addition, our review highlights the need for a comprehensive clinical protocol that supports clinicians and researchers in the implementation and testing of VR-CET and identifies key missing protocol components with rationale for their inclusion. Ultimately, this work may lead to a more complete understanding of the full potential of the applications and integrations of VR into mental health care globally.

A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa.

OBJECTIVE: Open trials suggest phentermine/topiramate ER (PHEN/TPM-ER), food and drug administration (FDA) approved for obesity, has utility for binge eating. With no randomized controlled trials (RCTs) yet performed, this trial aimed to evaluate PHEN/TPM-ERs efficacy and safety in a crossover RCT for patients with binge-eating disorder (BED) or bulimia nervosa (BN). METHOD: Participants were randomized to 12-weeks PHEN/TPM-ER (3.75 mg/23 mg-15 mg/92 mg) or placebo followed by 2-weeks drug washout, then 12-week crossover. Demographics, vitals, eating disorder behaviors, mood, and side effects were measured. Primary outcome was objective binge-eating (OBE) days/4-weeks; secondary outcomes included binge abstinence. Mixed-effect models estimated treatment effects, with fixed effects adjusting for treatment, study period, and diagnosis. RESULTS: The 22 adults (BED = 18, BN = 4) were female (96%), Caucasian (55%), aged 42.9 (SD = 10.1) years with body mass index = 31.1 (SD = 6.2) kg/m2 . Baseline OBE days/4-weeks decreased from 16.2 (SD = 7.8) to 4.2 (SD = 8.4) after PHEN/TPM-ER versus 13.2 (SD = 9.1) after placebo (p < .0001), with abstinence rates = 63.6% on PHEN/TPM-ER versus 9.1% on placebo (p < .0001). Weight changes = -5.8 kg on PHEN/ TPM-ER versus +0.4 kg on placebo. Drop-out = 2 (9%) on PHEN/TPM-ER and 2 (9%) on placebo, with few side effects. Vital sign changes with PHEN/TPM-ER were minimal and similar to placebo. Responses were not significantly different for BED versus BN. DISCUSSION: This first RCT to evaluate the efficacy and safety of PHEN/TPM-ER for BED/BN found this drug combination significantly more effective at reducing binge eating than placebo and well tolerated. However, with only four participants with BN, findings regarding the safety of PHEN/TPM-ER in patients with BN must be taken with caution. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.

Replication and extension of dietary adherence as a predictor of suboptimal weight-loss outcomes in postbariatric patients.

BACKGROUND: Sarwer et al. found that poor dietary adherence at 6 months postoperatively predicted lower weight loss. OBJECTIVES: To replicate and extend these findings. SETTING: University bariatric clinic. METHODS: Fifty-four adults (72% female; age 51.1 ± 11.3 yr; mean body mass index [BMI] = 43.8 ± 7.4 kg/m2; 53.7% = Roux-en-Y gastric bypass, 42.6% = laparoscopic sleeve gastrectomy, and 3.7% = gastric banding) were identified as low or high dietary adherers following the method of Sarwer et al. Patients self-reported dietary adherence with a 9-point Likert scale. Splitting the group at the median, low adherers scored <7 and high dietary adherers ≥7. BMI, percentage excess weight loss (%EWL), and percentage total weight loss (%TWL) were prospectively assessed at 12, 24, and 36 months. Two-tailed independent t tests and Cohen's d effect sizes were used to compare between-group outcomes. RESULTS: BMI did not differ between low (n = 24) and high (n = 30) dietary adherers at 6 months after surgery. At 12 months, the BMI of low (n = 17) adheres was significantly higher (34.1 ± 4.61 versus 30.3 ± 3.90 kg/m2, P = .006, d = 0.90) than that of high (n = 25) adherers, with significantly less %EWL (49.0 ± 24% versus 70.7 ± 21.5%; P = .004; d = 0.95) and %TWL (20.7 ± 11.5% versus 28.9 ± 10.5, P = .02, d = 0.74). At 24 months, BMI remained significantly higher for low (n = 12) versus high (n = 10) adherers (33.7 ± 4.77 versus 29.7 ± 3.82 kg/m2, P = .045, d = 0.92), but %EWL and %TWL were not significantly different, despite large effect sizes. At 36 months, moderate effects supported continued higher BMIs and lower %EWL and %TWL for low (n = 5) versus high (n = 8) adherers. Attrition from follow-up was 22.2% (12 mo), 59.3% (24 mo), and 75.9% (36 mo). Post hoc analyses revealed no impact of baseline characteristics on low follow-up rates except younger age (at 1 yr). CONCLUSIONS: Findings that 6-month postoperative dietary adherence predicts 12-month BMI, %EWL, and %TWL were replicated. Medium to large effects suggest findings extend to 24 and 36 months, with low follow-up rates likely affecting statistical significance.

Correlates of Dietary Adherence and Maladaptive Eating Patterns Following Roux-en-Y Bariatric Surgery.

BACKGROUND: Self-reported poor dietary adherence following bariatric surgery is associated with less successful weight loss outcomes. Poor dietary adherence is a global construct lacking specificity regarding its underlying, clinically targetable, maladaptive eating behaviors. METHODS: Comprehensive online survey data were obtained from a sample of 274 adults who underwent Roux-en-Y surgery in the prior 1-12 years. Correlations between dietary adherence and six eating-related behaviors were calculated, with the frequency of each behavior reported on a 7-point scale. Linear regression modeling was applied. RESULTS: All six maladaptive eating behaviors were highly correlated with dietary adherence (Pearson's r > 0.5): grazing (r = - 0.565), mindless eating (r = - 0.572), loss of control eating (r = - 0.517), eating "more than is best" after dinner (r = - 0.518), eating foods off of one's plan (r = - 0.557), and "when I eat something off-plan, I feel like I have blown it and I give up and eat more" (r = - 0.574). The estimated regression coefficients in the linear model was statistically significant, [F(5, 261) = 60.006, p < 0.001] and accounted for approximately 54% of the variance of global dietary adherence (R 2 = 0.535, adjusted R 2 = 0.526). CONCLUSION: Six maladaptive eating behaviors accounted for a highly significant portion of post-Roux-en-Y patients' poor self- reported dietary adherence. Prospective studies are needed to investigate the relationship between targetable maladaptive eating behaviors and bariatric surgery outcomes.

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa.

INTRODUCTION: Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN. METHODS: Adults with BED (n=15) or BN (n=15) are randomized 1:1 to receive 12weeks Qsymia (phentermine/topiramate ER, 3.75mg/23mg-15mg/92mg) or placebo, followed by 2-weeks washout and 12-weeks crossover, where those on Qsymia receive placebo and vice versa. Subsequently participants receive 8weeks follow-up off study medications. The primary outcome is the number of binge days/week measured by EDE. Secondary outcomes include average number of binge episodes, percentage abstinence from binge eating, and changes in weight/vitals, eating psychopathology, and mood. DISCUSSION: To our knowledge this is the first randomized, double-blind protocol investigating the safety and efficacy of phentermine/topiramate in BED and BN. We highlight the background and rationale for this study, including the advantages of a crossover design. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02553824 registered on 9/17/2015. https://clinicaltrials.gov/ct2/show/NCT02553824.

Accent modulates access to word meaning: Evidence for a speaker-model account of spoken word recognition.

Speech carries accent information relevant to determining the speaker's linguistic and social background. A series of web-based experiments demonstrate that accent cues can modulate access to word meaning. In Experiments 1-3, British participants were more likely to retrieve the American dominant meaning (e.g., hat meaning of "bonnet") in a word association task if they heard the words in an American than a British accent. In addition, results from a speeded semantic decision task (Experiment 4) and sentence comprehension task (Experiment 5) confirm that accent modulates on-line meaning retrieval such that comprehension of ambiguous words is easier when the relevant word meaning is dominant in the speaker's dialect. Critically, neutral-accent speech items, created by morphing British- and American-accented recordings, were interpreted in a similar way to accented words when embedded in a context of accented words (Experiment 2). This finding indicates that listeners do not use accent to guide meaning retrieval on a word-by-word basis; instead they use accent information to determine the dialectic identity of a speaker and then use their experience of that dialect to guide meaning access for all words spoken by that person. These results motivate a speaker-model account of spoken word recognition in which comprehenders determine key characteristics of their interlocutor and use this knowledge to guide word meaning access.

What variables are associated with successful weight loss outcomes for bariatric surgery after 1 year?

BACKGROUND: Prior evidence indicates that predictors of weight loss outcomes after gastric bypass surgery fall within 5 domains: 1) presurgical factors, 2) postsurgical psychosocial variables (e.g., support group attendance), 3) postsurgical eating patterns, 4) postsurgical physical activity, and 5) follow-up at postsurgical clinic. However, little data exist on which specific behavioral predictors are most associated with successful outcomes (e.g.,≥ 50% excess weight loss) when considering the 5 domains simultaneously. The objective of this study was to specify the behavioral variables, and their respective cutoff points, most associated with successful weight loss outcomes. METHODS: Signal detection analysis evaluated associations between 84 pre- and postsurgical behavioral variables (within the 5 domains) and successful weight loss at ≥ 1 year in 274 postgastric bypass surgery patients. RESULTS: Successful weight loss was highest (92.6%) among those reporting dietary adherence of>3 on a 9-point scale (median = 5) who grazed no more than once-per-day. Among participants reporting dietary adherence<3 and grazing daily or less, success rates more than doubled when highest lifetime body mass index was<53.7 kg/m(2). Success rates also doubled for participants with dietary adherence = 3 if attending support groups. No variables from the physical activity or postsurgical follow-up domains were significant, nor were years since surgery. The overall model's sensitivity = .62, specificity = .92. CONCLUSIONS: To our knowledge, this is the first study to simultaneously consider the relative contribution of behavioral variables within 5 domains and offer clinicians an assessment algorithm identifying cut-off points for behaviors most associated with successful postsurgical weight loss. Such data may inform prospective study designs and postsurgical interventions.

Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance.

Central tolerance can be mediated by peripheral dendritic cells (DCs) that transport innocuous antigens (Ags) to the thymus for presentation to developing T cells, but the responsible DC subsets remained poorly defined. Immature plasmacytoid DCs (pDCs) express CCR9, a chemokine receptor involved in migration of T cell precursors to the thymus. We show here that CCR9 mediated efficient thymic entry of endogenous or i.v. transfused pDCs. pDCs activated by Toll-like receptor (TLR) ligands downregulated CCR9 and lost their ability to home to the thymus. Moreover, endogenous pDCs took up subcutaneously injected fluorescent Ag and, in the absence of TLR signals, transported Ag to the thymus in a CCR9-dependent fashion. Injected, Ag-loaded pDCs effectively deleted Ag-specific thymocytes, and this thymic clonal deletion required CCR9-mediated homing and was prevented by infectious signals. Thus, peripheral pDCs can contribute to immune tolerance through CCR9-dependent transport of peripheral Ags and subsequent deletion of Ag-reactive thymocytes.

Alternatives to animal testing: current status and future perspectives.

On the occasion of the 20th anniversary of the Center for Alternative Methods to Animal Experiments (ZEBET), an international symposium was held at the German Federal Institute for Risk Assessment (BfR) in Berlin. At the same time, this symposium was meant to celebrate the 50th anniversary of the publication of the book "The Principles of Humane Experimental Technique" by Russell and Burch in 1959 in which the 3Rs principle (that is, Replacement, Reduction, and Refinement) has been coined and introduced to foster the development of alternative methods to animal testing. Another topic addressed by the symposium was the new vision on "Toxicology in the twenty-first Century", as proposed by the US-National Research Council, which aims at using human cells and tissues for toxicity testing in vitro rather than live animals. An overview of the achievements and current tasks, as well as a vision of the future to be addressed by ZEBET@BfR in the years to come is outlined in the present paper.

Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010.

The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in five toxicological areas, i.e. toxicokinetics, repeated dose toxicity, carcinogenicity, skin sensitisation, and reproductive toxicity for which the Directive foresees that the 2013 deadline could be further extended in case alternative and validated methods would not be available in time. The selected experts were asked to analyse the status and prospects of alternative methods and to provide a scientifically sound estimate of the time necessary to achieve full replacement of animal testing. In summary, the experts confirmed that it will take at least another 7-9 years for the replacement of the current in vivo animal tests used for the safety assessment of cosmetic ingredients for skin sensitisation. However, the experts were also of the opinion that alternative methods may be able to give hazard information, i.e. to differentiate between sensitisers and non-sensitisers, ahead of 2017. This would, however, not provide the complete picture of what is a safe exposure because the relative potency of a sensitiser would not be known. For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion, and even longer to integrate the methods to fully replace the animal toxicokinetic models. For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, the time horizon for full replacement could not be estimated.

A prospective assessment of psychosocial factors among bariatric versus non-bariatric surgery candidates.

BACKGROUND: Psychological factors are considered potential contraindicators to bariatric surgery, but inconsistently predict surgical outcomes. We examined biomedical and psychosocial predictors of future bariatric candidacy in a population of veterans enrolling in a multidisciplinary weight management program. METHODS: Ninety-five obese veterans meeting bariatric surgery eligibility criteria participating in a weight control intake class from 2007 to 2008 completed the MOVE!23 questionnaire to assess biomedical, psychiatric, social, and eating behavior factors. Twenty-five patients from this cohort completed or obtained approval for bariatric surgery during the next 2 years of follow-up. RESULTS: Patients progressing to bariatric candidacy over follow-up differed from non-bariatric patients in multiple areas, including reporting significantly lower rates of depression (28% versus 48.7%, respectively; p = 0.04) and smoking (4% versus 16%; p = 0.05), better self-rated health (e.g., 28% versus 10.7% rating themselves as in excellent or very good health), and averaged 50% fewer cardiovascular risk factors (p = 0.01). Bariatric patients also rated themselves as significantly faster eaters (p = .03) and as having higher rates of obsessive compulsive disorder (OCD; 28% versus 7%; p = 0.04). Depression and OCD status predicted patients going on to bariatric candidacy independent of body mass index (BMI), biomedical status, and demographic factors. CONCLUSIONS: Our results suggest that many of the commonly cited psychosocial contraindicators to bariatric surgery are already lower in patients considered for surgery relative to BMI equivalent treatment-seeking peers not approved for surgery. These differences may help explain inconsistent relationships between psychosocial factors and bariatric surgery outcomes.

Testing potential developmental toxicants with a cytotoxicity assay based on human embryonic stem cells.

Since the differentiation of embryonic stem cells mimics early development, these cells could potentially permit the detection of embryotoxicants which interfere with this process. Although reliable tests based on murine embryonic stem cells exist, no such methods are available for human embryonic stem (hES) cells. Nonetheless, to avoid the false classification of substances due to inter-species differences, human-relevant toxicity tests are needed. We therefore developed an assay based on three human cell types, representing different degrees of developmental maturation, namely, human foreskin fibroblasts, hES cell-derived progenitor cells, and pluripotent hES cells. A set of embryotoxicants for which existing in vivo data were available, namely, all-trans retinoic acid (ATRA), 13-cis retinoic acid (13CRA), valproic acid (VPA) and dimethyl sulphoxide (DMSO), were tested. 5-fluorouracil (5-FU) was used as a positive control, and saccharin as a negative control. Two methods were compared for the assessment of cell viability -- the determination of intracellular ATP content and of resazurin reduction. In addition, the protective capacity of basic fibroblast growth factor (bFGF) against retinoid-induced toxicity was investigated. This novel assay system reliably detected the embryotoxic potentials of the test substances, 5-FU, ATRA, 13-CRA (a substance that displays inter-species differences in its effects) and VPA. This was possible due to the apparent differences in the sensitivities of the human cell types used in the assay system. Thus, our results clearly indicate the advantages and relevance of using hES cells in in vitro developmental toxicity testing.

First steps in establishing a developmental toxicity test method based on human embryonic stem cells.

The use of embryonic stem cells is currently the most promising approach to assess developmental toxicity in vitro. In addition, the possibility of using human embryonic stem (hES) cells will increase safety of consumers and patients as false classification of substances due to inter-species variations can be avoided. One validated test based on murine embryonic stem cells, the embryonic stem cell test (EST), consists of following endpoints: IC(50) values of fibroblasts and embryonic stem cells as well as the inhibition of differentiation of mES cells into cardiomyocytes. As a follow up of its successful validation study we established a cytotoxicity assay based on hES cells and human fibroblasts employing two developmental toxicants: 5-fluorouracil (5-FU) and all-trans retinoic acid (RA). The results were compared to historical data from the EST. For 5-FU, no significant differences were obtained between the different cell lines. However, for RA, both test systems produced higher IC(50) values for the fibroblasts than for the stem cells, which is a well-known effect of developmental toxicants. Moreover, the reliability and relevance of several marker genes as possible toxicological endpoints were tested. During early differentiation Oct-4, hTert and Dusp6 showed the most reliable results. Brachyury and GATA-4 were found to be best suited to monitor cardiac differentiation. The late cardiac marker gene TNNT2 demonstrated significant results until day 18. Therefore, these marker genes have the highest potential to serve as endpoints for a developmental toxicity test.