C-terminal citrullinated peptide alters antigen-specific APC:T cell interactions leading to breach of immune tolerance.

In rheumatoid arthritis, the emergence of anti-citrullinated autoimmunity is associated with HLA-antigen-T cell receptor complexes. The precise mechanisms underpinning this breach of tolerance are not well understood. Porphyromonas gingivalis expresses an enzyme capable of non-endogenous C-terminal citrullination with potential to generate citrullinated autoantigens. Here we document how C-terminal citrullination of ovalbumin peptide323-339 alters the interaction between antigen-presenting cells and OTII T cells to induce functional changes in responding T cells. These data reveal that C-terminal citrullination is sufficient to breach T cell peripheral tolerance in vivo and reveal the potential of C-terminal citrullination to lower the threshold for T cell activation. Finally, we demonstrate a role for the IL-2/STAT5/CD25 signalling axis in breach of tolerance. Together, our data identify a tractable mechanism and targetable pathways underpinning breach of tolerance in rheumatoid arthritis and provide new conceptual insight into the origins of anti-citrullinated autoimmunity.

Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

The effectiveness of cognitive behavioural therapy for individuals with an intellectual disability and anxiety: a systematic review.

INTRODUCTION: Individuals with intellectual disability (ID) are at higher risk of experiencing difficulties with anxiety than the general population. However, there are major barriers for individuals to receive appropriate services. There is a growing understanding of the importance of developing appropriate psychological interventions for this group. The objective of the current review was to systematically evaluate the findings of studies investigating the effectiveness of cognitive behavioural therapy (CBT) for individuals with ID and anxiety. Another aim was to explore which adaptions to CBT and treatment components were currently being utilised within the field. METHOD: The electronic databases of CINAHL, EMBASE, Medline, PsycINFO, Psychology and Behavioural Sciences Collection and Scopus were searched to identify relevant studies. The methodological quality of these studies was assessed using established quality assessment tools by the National Institutes of Health for pre and post studies and case series. RESULTS: Nine studies were included in this systematic review, all of which reported improvements in anxiety severity for some participants (25%-100%; N = 60) following CBT. Only three studies reported moderate effect sizes for CBT interventions on anxiety for individuals with ID. DISCUSSION AND CONCLUSIONS: There is emerging literature supporting the effectiveness of CBT for individuals with mild ID. Findings highlight that CBT for individuals with anxiety and mild ID, including cognitive components, may be feasible and tolerable. While the field is gradually receiving more attention, there are significant methodological flaws present, which limit the conclusions that can be drawn regarding the effectiveness of CBT for individuals with ID. However, there is emerging evidence for techniques such as cognitive restructuring and thought replacement and modifications such as visual aids, modelling and smaller groups based on this review. Future research is warranted to investigate whether individuals with more severe ID can benefit from CBT, as well as further exploring what are the necessary components and modifications.

Nivolumab-induced localized genital bullous pemphigoid in a 60-year-old male.

A 60-year-old man with metastatic renal cell carcinoma presented with a 6-month history of a pruritic, exquisitely painful genital eruption appearing 3 months after initiation of nivolumab. Examination demonstrated a poorly defined, lichenified scrotal plaque studded with erosions, yellow crust, and tense vesicles. There was no other lesion on the body or mucosae. Histopathology revealed a subepidermal blister with a mixed lymphocytic, neutrophilic, and eosinophilic infiltrate. Direct immunofluorescence of perilesional skin demonstrated subclinical blister and linear/fibrillary patchy IgG and IgA along the dermoepidermal junction. Bullous pemphigoid (BP) serologies revealed normal IgG BP230 antibodies and minimally elevated IgG BP180 antibodies. Indirect immunofluorescence revealed positive IgG at the basement membrane ("epidermal pattern") in human split skin and monkey esophagus substrates; no IgA antibodies were detected. The patient was diagnosed with nivolumab-induced localized genital BP (LGBP). BP is a reported adverse effect of immune checkpoint inhibitors including nivolumab; however, cases are typically generalized. LGBP is a rare BP variant typically presenting in children and females; there are few reports of LGBP in adult males. We report a novel case of nivolumab-induced LGBP with unique histopathologic and clinical challenges. LGBP should be considered in patients on immune checkpoint inhibitor therapy with bullous genital eruptions.

Effectiveness of intervention focused on vocational course vocabulary in post-16 students with (developmental) language disorder.

BACKGROUND: People with language disorders (including developmental language disorder-DLD) often struggle to learn new words and, for young adults, this could affect their success in future work. Therefore, it is crucial to support their learning of career-specific vocabulary. However, little published evidence exists regarding the effectiveness of speech and language intervention for older adolescents and young adults with (developmental) language disorder (D)LD within a post-16 provision. AIMS: To investigate whether for students with (D)LD in a post-16 environment, the addition of direct individual intervention from a speech and language therapist (SLT) teaching course-specific vocabulary leads to more progress than just in-course teaching on bespoke vocabulary measures. METHODS & PROCEDURES: A total of 28 college-aged students (11 female and 17 male) with (D)LD (aged 16.0-19.9) participated in a within-participant study comparing progress with explicit vocabulary intervention plus in-course teaching versus in-course teaching alone. The participants were assessed at four time points (3 months pre-intervention, immediately pre- and post-intervention, 3.5 months after intervention) using bespoke vocabulary assessments with an equal number of nouns, verbs and adjectives. All participants received one-to-one vocabulary intervention from their usual SLT for 30 min per week for 9 weeks. The intervention had four main components: (1) to identify intervention focus, (2) to recap previously taught terms (using an online flashcard program), (3) to explicitly teach new words using word maps to help with: creating definition and pictorial representation, identification of word class and investigation of phonological and morphological properties, and (4) to add new words, with their definition and pictorial representation to online flashcard program. OUTCOMES & RESULTS: The results showed a stable baseline, then during the intervention term significant progress on words targeted only in lessons and significantly greater progress on words targeted both in lessons and SLT sessions. Progress was maintained for 14 weeks. Individuals with initially lower scores showed smaller intervention effects. In general, performance was higher on verbs and on the definition recognition task and lower on the production tasks, but all tasks improved with intervention. CONCLUSIONS & IMPLICATIONS: Direct one-to-one vocabulary intervention with an SLT can lead to significant gains in knowledge of course-specific terminology for college-aged students with (D)LD. The effectiveness of speech and language therapy services for this age group in a wider range of areas of language and social communication should also be investigated. WHAT THIS PAPER ADDS: What is already known on this subject Very few services exist for young adults with DLD, despite their persisting language difficulties and the detrimental impact of these on their academic attainment and employment prospects. Most careers involve specific vocabulary which is crucial to executing a role successfully and these need to be learned by those looking to move into these careers. However, children, adolescents and adults with DLD struggle to learn new words and may need help in this area. What this study adds to existing knowledge The young adults with (D)LD received 9 weeks of intervention targeting individualized course-specific vocabulary (nouns, verbs and adjectives), using word maps to focus on word forms, definitions, morphologically related words and syntactic information such as word class and how to use the word in a sentence. An online learning tool provided regular spaced retrieval practice of previously taught words and their definitions. The participants showed significant progress with learning course-specific vocabulary from attending lessons. However, they made significantly greater progress on those words which were also targeted in individual SLT sessions, regardless of word class. Progress was maintained over 14 weeks. What are the potential or actual clinical implications of this work? Direct one-to-one vocabulary intervention with an SLT can lead to significantly greater gains in the acquisition of targeted course-specific terminology for young adults with (D)LD than the vocabulary teaching available in lessons. Individual intervention delivered by SLTs should therefore be offered to this age group of students with (D)LD to maximize their ability to access the academic curriculum and their future careers. Indeed, the broader role of SLTs in helping these young adults to access the world of work and independent living should be further investigated and supported.

Clinical characteristics and successful treatment outcomes of children and adolescents with Kaposi sarcoma in Southwestern Tanzania.

The HIV/AIDS epidemic has driven the rise in cases of Kaposi sarcoma (KS) among children and adolescents living with HIV in countries with high Human gammaherpesvirus 8 (HHV-8) seroprevalence, such as Tanzania, where specialized oncology programs are sparse. Consequently, descriptions of successful treatment of KS in children and adolescents by general pediatricians are important. A retrospective analysis was performed of children and adolescents diagnosed with KS and treated with chemotherapy and combination antiretroviral therapy (cART) at the Baylor College of Medicine Children's Foundation Tanzania Center of Excellence - Mbeya between 2011 and 2017. Sixty-one patients were diagnosed with KS with a median age of 12.6 years (interquartile range (IQR) 9.4 - 15.5). Diagnosis was confirmed by histopathology in 36% (22/61). Among HIV positive patients (59/61), 78% (46/59) were on cART at KS diagnosis. Severe immunosuppression was present in 63% (35/56) of those with CD4 data and 44% (27/61) had SAM. Advanced-stage T1 disease was present in 64% (39/61), including 28% (17/61) with visceral/disseminated KS. Two-year estimated overall survival (OS) was 72% (95% Confidence Interval (CI): 58%-82%) and median follow up for survivors was 25.7 months (IQR 14.2-53.8). No patients were lost to follow up. Two-year OS was 63% (95% CI: 44%-77%) in patients with severe immune suppression and 60% (95% CI: 37%-76%) in patients with SAM. Among patients with visceral/disseminated KS, 53% (9/17) survived. This retrospective analysis demonstrated favorable outcomes in a complex cohort of children and adolescents with KS treated with chemotherapy by general pediatricians in Tanzania.

Bone mineral density, kidney function, weight gain and insulin resistance in women who switch from TDF/FTC/NNRTI to ABC/3TC/DTG.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). METHODS: We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual-energy X-ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. RESULTS: In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479-800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new-onset metabolic syndrome. CONCLUSIONS: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.

Toward a complete and comprehensive cross section database for electron scattering from NO using machine learning.

We review experimental and theoretical cross sections for electron scattering in nitric oxide (NO) and form a comprehensive set of plausible cross sections. To assess the accuracy and self-consistency of our set, we also review electron swarm transport coefficients in pure NO and admixtures of NO in Ar, for which we perform a multi-term Boltzmann equation analysis. We address observed discrepancies with these experimental measurements by training an artificial neural network to solve the inverse problem of unfolding the underlying electron-NO cross sections while using our initial cross section set as a base for this refinement. In this way, we refine a suitable quasielastic momentum transfer cross section, a dissociative electron attachment cross section, and a neutral dissociation cross section. We confirm that the resulting refined cross section set has an improved agreement with the experimental swarm data over that achieved with our initial set. We also use our refined database to calculate electron transport coefficients in NO, across a large range of density-reduced electric fields from 0.003 to 10 000 Td.

Estimated glomerular filtration rate slopes on tenofovir alafenamide.

OBJECTIVES: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. METHODS: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements. RESULTS: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). CONCLUSIONS: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial.

OBJECTIVES: The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF). METHODS: Individuals with a history of TDF-associated PRT and currently suppressed HIV infection on a tenofovir-sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol-binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016-003345-29. RESULTS: We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (ß 19.6; 95% confidence interval -35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed. CONCLUSIONS: In people with a history of proximal renal tubulopathy while on TDF, 12-week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long-term safety of TAF in this group of patients.

The histopathological features of the nail plate in pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) is a rare autosomal dominant disorder of keratinization mediated by genetic mutations in KRT6A, KRT6B, KRT6C, KRT16, or KRT17. While nail dystrophy in PC has a significant impact on quality of life, the histopathological features of the nail plate in PC have not been previously reported. We report the histopathological features of nail plates provided by 19 patients with genetically confirmed PC. METHODS: Nineteen patients with genetically confirmed PC provided a total of 56 nail plates for histopathologic examination. The nail plates were examined for the presence of hyphae, yeast, bacteria, neutrophils, parakeratosis, plasma globules, and hemorrhage. Specimens with onychomycosis (three patients) were excluded from the analysis. RESULTS: No specific histopathological feature was identified in PC nails. Parakeratosis and plasma globules were the most prominent features in both clinically affected and unaffected PC nails. There was a significant association between clinical dystrophy of all 20 nails and KRT6A mutations, and a lack of dystrophy of all 20 nails in KRT6B mutations. CONCLUSIONS: Parakeratosis and plasma globules in the absence of other inflammatory disorders should raise PC in the histopathologic differential diagnosis. The presence of onychomycosis in a nail plate does not exclude a diagnosis of PC.

Validation of Image Quality and Diagnostic Accuracy Using a Mobile Phone Camera Microscope Adaptor Compared With Glass Slide Review in Teledermatopathology.

New modalities of evaluating histopathology, such as whole-slide imaging, have been validated in the field of dermatopathology but are often unfeasible and unavailable in developing countries. Widely available across the globe, mobile phone camera technology represents a potential simple and inexpensive method of imaging histologic slides through the use of a mobile phone camera microscope adaptor. This study aims to validate the use of a commercially available adaptor in the diagnosis of inflammatory and infectious conditions in dermatopathology. Representative images were taken of slides for fifty-four cases using the adaptor and shared through a cloud-based platform with five dermatopathologists who rendered diagnoses and judged the quality of the images. After a washout period of 8 weeks, the same cases were assessed by the same dermatopathologists using the original glass slides. The intraobserver concordance rate was 93.3%, and the quality of the mobile phone images was rated as "excellent" or "diagnostic" in 94.4% of the cases. This study validates the use of this low-tech and low-cost adaptor as a reliable tool in teledermatopathology. Limitations of the study include those inherent to use of the adaptor and the limited panel of diagnoses. The primary value of this device may be in developing countries, but its practicality and ease of use lend itself to use in academic and consultative settings in the developed world as well.

Frequency modulated free electron laser.

It is shown that the output frequency of a free electron laser may be modulated to generate a series of modes that span a bandwidth of at least an order of magnitude greater than the normal FEL bandwidth. This new method of frequency modulated FEL operation has close analogies to frequency modulation in conventional cavity lasers. The FM-FEL is analysed and described in the linear regime by a summation over the exponentially amplified frequency modes. Simulations using a 3D, broad bandwidth, numerical code also demonstrate FM-FEL operation for parameters typical of FEL facilities currently under construction. Harmonic bunching methods are used to seed the FM-FEL modes to generate a temporally correlated frequency modulated output over a large bandwidth. This new, FM-FEL mode of operation scales well for X-ray generation, offering users a significantly new form of high-power, short wavelength FEL output.

Protocol of a two arm randomised, multi-centre, 12-month controlled trial: evaluating the impact of a Cognitive Behavioural Therapy (CBT)-based intervention Supporting UPtake and Adherence to antiretrovirals (SUPA) in adults with HIV.

BACKGROUND: Delay to start antiretroviral therapy (ART) and nonadherence compromise the health and wellbeing of people living with HIV (PLWH), raise the cost of care and increase risk of transmission to sexual partners. To date, interventions to improve adherence to ART have had limited success, perhaps because they have failed to systematically elicit and address both perceptual and practical barriers to adherence. The primary aim of this study is to determine the efficacy of the Supporting UPtake and Adherence (SUPA) intervention. METHODS: This study comprises 2 phases. Phase 1 is an observational cohort study, in which PLWH who are ART naïve and recommended to take ART by their clinician complete a questionnaire assessing their beliefs about ART over 12 months. Phase 2 is a randomised controlled trial (RCT) nested within the observational cohort study to investigate the effectiveness of the SUPA intervention on adherence to ART. PLWH at risk of nonadherence (based on their beliefs about ART) will be recruited and randomised 1:1 to the intervention (SUPA intervention + usual care) and control (usual care) arms. The SUPA intervention involves 4 tailored treatment support sessions delivered by a Research Nurse utilising a collaborative Cognitive Behavioural Therapy (CBT) and Motivational Interviewing (MI) approach. Sessions are tailored to individual needs and preferences based on the individual patient's perceptions and practical barriers to ART. An animation series and intervention manual have been developed to communicate a rationale for the personal necessity for ART and illustrate concerns and potential solutions. The primary outcome is adherence to ART measured using Medication Event Monitoring System (MEMS). Three hundred seventy-two patients will be sufficient to detect a 15% difference in adherence with 80% power and an alpha of 0.05. Costs will be compared between intervention and control groups. Costs will be combined with the primary outcome in cost-effectiveness analyses. Quality adjusted life-years (QALYs) will also be estimated over the follow-up period and used in the analyses. DISCUSSION: The findings will enable patients, healthcare providers and policy makers to make informed decisions about the value of the SUPA intervention. TRIAL REGISTRATION: The trial was retrospectively registered 21/02/2014, ISRCTN35514212 .

Interspecific differences in the bioaccumulation of arsenic of three Patagonian top predator fish: Organ distribution and arsenic speciation.

Interspecific differences in arsenic bioaccumulation and organ distribution (muscle, liver, kidney and gills) in three predator fish (creole perch, rainbow trout and brown trout) from a Patagonian lake impacted by volcanic eruptions were studied. Arsenic in fish organs were compared analyzing: 1) temporal (before and after volcanic eruption) and spatial (near and far from the volcano) influence of Puyehue-Cordón Caulle volcanic complex activity on arsenic concentrations; 2) the influence of growth (as total length), organ type and their interactions over arsenic accumulation; and 3) arsenic speciation and total arsenic relationship with carbon to nitrogen ratios (C:N), as a proxy of lipid presence, in fish muscle. In general, total arsenic concentrations in creole perch organs were 2-7 times higher than those recorded in the corresponding organs of salmonids. Arsenic was preferentially accumulated in liver and kidney in the three fish species. The influence of the volcanic activity over arsenic concentrations was more evident in creole perch: organs from creole perch captured closest to the volcano exhibited higher arsenic concentrations. Temporal variations were not so consistent. No clear relationship between arsenic and fish length was observed. Positive and linear relationship between arsenic in all pair of organs was found in creole perch, while rainbow trout showed a quadratic relationship between muscle and the remaining organs, indicating different arsenic assimilation-elimination relationships between organs and fish. The arsenic liver:muscle ratio in the three fish species was greater than 1, suggesting some level of arsenic stress. Arsenobetaine (AB) and dimethylarsinic acid (DMA) were the dominant arsenic species in muscle of these fish, having creole perch 3-4 times higher AB than rainbow trout. A positive relationship between C:N ratio and total arsenic concentrations was found, with higher C:N in creole perchs near the volcano. In terms of food safety, no inorganic arsenic compound were detected, therefore arsenic levels in fish from Lake Nahuel Huapi does not represent any health risk to consumers.

The evolving contribution of non-communicable diseases to maternal mortality in Jamaica, 1998-2015: a population-based study.

OBJECTIVE: To describe trends in indirect cause-specific pregnancy-related mortality from 1998 to 2015. DESIGN: Secondary analysis of annual, national cross-sectional database of maternal and late maternal deaths, identified through active surveillance of deaths among women aged 10-50 years. SETTING: Jamaica, a middle-income Caribbean country. POPULATION: Maternal and late maternal deaths. METHODS: Descriptive trend analyses of demographic and cause-specific maternal and pregnancy-related mortality ratios undertaken comparing the periods 1998-2003, 2004-2009 and 2010-2015. Multivariate logistic regression was used to confirm changes in risk of indirect death. MAIN OUTCOME MEASURES: Maternal, pregnancy-related, direct, indirect and cause-specific mortality ratios (deaths/100 000 live births). RESULTS: Maternal deaths from indirect conditions increased between the first two periods (P = 0.004) and stabilised in the third (P = 0.085). Associated with upward movement in cardiovascular deaths (P[trend] = 0.003), women under 25 years were at elevated risk (odds ratio 1.44, 95% CI 1.00-2.08; P = 0.052). Haematological/immunological conditions (69% sickle cell disease) ranked second but did not vary with time. Health service utilisation was similar across age, parity, health region and major cause categories (non-communicable diseases, non-obstetric infections, direct), however women with indirect conditions spent more time in hospital (median 5 days versus 3 days) and more often died after the puerperium. CONCLUSIONS: Medical conditions, especially cardiovascular disease, are increasingly associated with maternal and late maternal mortality. Middle-income countries need to simultaneously improve management of indirect conditions, while redoubling efforts to reduce direct deaths. Postpuerperal medical services should be integrated into routine infant health services to improve continuity of care during this high-risk period. TWEETABLE ABSTRACT: Maternal survival (SDG 3.1) in LMICs requires better care for women with both non-communicable diseases and obstetric conditions.

Surgery in ovarian cancer - Brazilian Society of Surgical Oncology consensus.

Surgical management in epithelial ovarian cancer (EOC) has a significant impact in overall survival and progression-free survival. The Brazilian Society of Surgical Oncology (BSSO) supported a taskforce of experts to reach a consensus: experienced and specialised trained surgeons, in cancer centres, provide the best EOC surgery. Laparoscopic and/or radiological staging prognosticates the possibility of complete cytoreduction (CC0) and helps to reduce unnecessary laparotomies. Surgical techniques were reviewed. Multidisciplinary input is essential for treatment planning. Quality assurance criteria are proposed and require national consensus. Genetic testing is mandatory. This consensus states the final recommendations from BSSO for management of EOC. TWEETABLE ABSTRACT: Brazilian Society of Surgical Oncology consensus for surgery in epithelial ovarian cancer patients.

Depression and anxiety symptoms during the transition to early adulthood for people with intellectual disabilities.

BACKGROUND: The transition to adulthood is a major developmental milestone; a time of self-discovery and increased independence. For young adults (YA) with intellectual disabilities (ID), however, this period is especially challenging. The increased incidence of mental health disorders in this population, such as depression and anxiety, make this transition even more difficult, increasing caregiver burden at a time when the young adult would traditionally be gaining independence. It is not clear, however, why YA with ID are more susceptible and what factors may predict mental health symptoms. METHOD: Potential risk and protective factors (demographic variables, coping styles, sense of hopelessness, unmet achievement of adulthood milestones, self-reflection and insight) of anxiety and depression symptoms were assessed in 55 YA with ID and a sample of age-matched controls. RESULTS: Insight was the strongest predictor of anxiety (with gender in the controls) for YA with and without ID, with increased insight predicting fewer anxiety symptoms. However, YA with ID had significantly less insight than their aged-matched counterparts and significantly higher levels of anxiety. They were also less likely to have achieved traditional adulthood milestones. Maladaptive coping was the strongest predictor of depression for YA with ID. In comparison, both maladaptive coping and insight predicted depression in controls. More maladaptive coping predicted increased depressive symptoms in both populations, whilst increased insight predicted fewer depressive symptoms in controls. CONCLUSIONS: Insight and maladaptive coping are potential targets in the treatment of anxiety and depression among YA with ID. Longitudinal intervention studies exploring the efficacy of such targeted programmes in reducing mental health symptoms and improving the transition to adulthood for these young people are recommended.

Mediation Effect of Physical Activity on Obesity in Black Women.

BACKGROUND AND OBJECTIVE: Sociodemographic and lifestyle factors, physical activity, diet, and nutrients are important in the understanding of obesity. The possibly direct or indirect nature of the associations among these factors and the eventual link to obesity is not well understood. In this study, we assess the indirect association between socio-demographic factors and obesity. DESIGN: A case-control study involving African American women conducted at Howard University Cancer Center. PARTICIPANTS AND METHODS: One hundred ninety eight participants gave information on anthropometric measurements, intake of dietary supplements and nutrients, socio-demographic factors (age, marital status, income and education) and physical activity. Path analysis was utilized to assess associations between socio-demographic factors and obesity through physical activity, dietary supplements and nutrients, smoking or alcohol consumption. MAIN RESULTS: The mean age of the participants was (55 ± 12 years), with 50% being obese (BMI ≥ 30 kg/m2). Obesity level decreased by approximately 7% for every one level increase in education via its prior effect on vigorous physical activity. Age had a significant positive indirect effect on obesity through vigorous physical activity - with obesity levels increasing by approximately 6% for every one year increase in age via its prior effect on vigorous physical activity. CONCLUSIONS: Vigorous physical activity mediates the association between education and age on obesity.