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Methane (CH4) emissions from natural landscapes constitute roughly half of global CH4 contributions to the atmosphere, yet large uncertainties remain in the absolute magnitude and the seasonality of emission quantities and drivers. Eddy covariance (EC) measurements of CH4 flux are ideal for constraining ecosystem-scale CH4 emissions due to quasi-continuous and high-temporal-resolution CH4 flux measurements, coincident carbon dioxide, water, and energy flux measurements, lack of ecosystem disturbance, and increased availability of datasets over the last decade. Here, we (1) describe the newly published dataset, FLUXNET-CH4 Version 1.0, the first open-source global dataset of CH4 EC measurements (available at https://fluxnet.org/data/fluxnet-ch4-community-product/, last access: 7 April 2021). FLUXNET-CH4 includes half-hourly and daily gap-filled and non-gap-filled aggregated CH4 fluxes and meteorological data from 79 sites globally: 42 freshwater wetlands, 6 brackish and saline wetlands, 7 formerly drained ecosystems, 7 rice paddy sites, 2 lakes, and 15 uplands. Then, we (2) evaluate FLUXNET-CH4 representativeness for freshwater wetland coverage globally because the majority of sites in FLUXNET-CH4 Version 1.0 are freshwater wetlands which are a substantial source of total atmospheric CH4 emissions; and (3) we provide the first global estimates of the seasonal variability and seasonality predictors of freshwater wetland CH4 fluxes. Our representativeness analysis suggests that the freshwater wetland sites in the dataset cover global wetland bioclimatic attributes (encompassing energy, moisture, and vegetation-related parameters) in arctic, boreal, and temperate regions but only sparsely cover humid tropical regions. Seasonality metrics of wetland CH4 emissions vary considerably across latitudinal bands. In freshwater wetlands (except those between 20∘ S to 20∘ N) the spring onset of elevated CH4 emissions starts 3 d earlier, and the CH4 emission season lasts 4 d longer, for each degree Celsius increase in mean annual air temperature. On average, the spring onset of increasing CH4 emissions lags behind soil warming by 1 month, with very few sites experiencing increased CH4 emissions prior to the onset of soil warming. In contrast, roughly half of these sites experience the spring onset of rising CH4 emissions prior to the spring increase in gross primary productivity (GPP). The timing of peak summer CH4 emissions does not correlate with the timing for either peak summer temperature or peak GPP. Our results provide seasonality parameters for CH4 modeling and highlight seasonality metrics that cannot be predicted by temperature or GPP (i.e., seasonality of CH4 peak). FLUXNET-CH4 is a powerful new resource for diagnosing and understanding the role of terrestrial ecosystems and climate drivers in the global CH4 cycle, and future additions of sites in tropical ecosystems and site years of data collection will provide added value to this database. All seasonality parameters are available at https://doi.org/10.5281/zenodo.4672601 (Delwiche et al., 2021). Additionally, raw FLUXNET-CH4 data used to extract seasonality parameters can be downloaded from https://fluxnet.org/data/fluxnet-ch4-community-product/ (last access: 7 April 2021), and a complete list of the 79 individual site data DOIs is provided in Table 2 of this paper.

While wetlands are the largest natural source of methane (CH4 ) to the atmosphere, they represent a large source of uncertainty in the global CH4 budget due to the complex biogeochemical controls on CH4 dynamics. Here we present, to our knowledge, the first multi-site synthesis of how predictors of CH4 fluxes (FCH4) in freshwater wetlands vary across wetland types at diel, multiday (synoptic), and seasonal time scales. We used several statistical approaches (correlation analysis, generalized additive modeling, mutual information, and random forests) in a wavelet-based multi-resolution framework to assess the importance of environmental predictors, nonlinearities and lags on FCH4 across 23 eddy covariance sites. Seasonally, soil and air temperature were dominant predictors of FCH4 at sites with smaller seasonal variation in water table depth (WTD). In contrast, WTD was the dominant predictor for wetlands with smaller variations in temperature (e.g., seasonal tropical/subtropical wetlands). Changes in seasonal FCH4 lagged fluctuations in WTD by ~17±11days, and lagged air and soil temperature by median values of 8±16 and 5±15days, respectively. Temperature and WTD were also dominant predictors at the multiday scale. Atmospheric pressure (PA) was another important multiday scale predictor for peat-dominated sites, with drops in PA coinciding with synchronous releases of CH4 . At the diel scale, synchronous relationships with latent heat flux and vapor pressure deficit suggest that physical processes controlling evaporation and boundary layer mixing exert similar controls on CH4 volatilization, and suggest the influence of pressurized ventilation in aerenchymatous vegetation. In addition, 1- to 4-h lagged relationships with ecosystem photosynthesis indicate recent carbon substrates, such as root exudates, may also control FCH4. By addressing issues of scale, asynchrony, and nonlinearity, this work improves understanding of the predictors and timing of wetland FCH4 that can inform future studies and models, and help constrain wetland CH4 emissions.

Objective\ud \ud The coronavirus pandemic has led to a dramatically different way of working for many therapists working with eating disorders, where telehealth has suddenly become the norm. However, many clinicians feel ill equipped to deliver therapy via telehealth, while adhering to evidence‐based interventions. This article draws together clinician experiences of the issues that should be attended to, and how to address them within a telehealth framework.\ud \ud \ud \ud Method\ud \ud Seventy clinical colleagues of the authors were emailed and invited to share their concerns online about how to deliver cognitive‐behavioral therapy for eating disorders (CBT‐ED) via telehealth, and how to adapt clinical practice to deal with the problems that they and others had encountered. After 96 hr, all the suggestions that had been shared by 22 clinicians were collated to provide timely advice for other clinicians.\ud \ud \ud \ud Results\ud \ud A range of themes emerged from the online discussion. A large proportion were general clinical and practical domains (patient and therapist concerns about telehealth; technical issues in implementing telehealth; changes in the environment), but there were also specific considerations and clinical recommendations about the delivery of CBT‐ED methods.\ud \ud \ud \ud Discussion\ud \ud Through interaction and sharing of ideas, clinicians across the world produced a substantial number of recommendations about how to use telehealth to work with people with eating disorders while remaining on track with evidence‐based practice. These are shared to assist clinicians over the period of changed practice.

Genome-wide studies provide increasing evidence of association of genetic variants with different behaviors. However, there is a growing need for replication and subsequent characterization of specific findings. In this sense, the CHRNA5 gene has been associated with nicotine (with genome-wide significance), alcohol and cocaine addictions. So far, this gene has not been evaluated in smoked (crack) cocaine. We aimed to analyze the influence of CHRNA5 variants in crack addiction susceptibility and severity. The sample includes 300 crack-addicted patients and 769 non-addicted individuals. The CHRNA5 SNPs evaluated were rs588765, rs16969968, and rs514743. Homozygosity for rs16969968 and rs588765 major alleles was nominally associated with a risk to crack addiction (GG, P = 0.032; CC, P = 0.036, respectively). Haplotype analyses reveal significant associations (rs588765|rs16969968|rs514743 pglobal-corrected = 7.66 × 10–5) and suggest a substantial role for rs16969968. These findings corroborate previous reports in cocaine addiction—in line with the expected effects of cocaine in the cholinergic system—and in the opposite direction of significant GWAS findings for nicotine addiction susceptibility. These results are strengthened by the first report of an association of rs588765 with crack addiction and by the haplotype findings. In summary, our study highlights the relevance of the α5 subunit on crack cocaine addiction, replicating previous results relating CHRNA5 with the genetics and pathophysiology of addiction of different drugs.

Background Vitamin K antagonists (VKA) are indicated for the prevention of thromboembolic events and reduction of mortality in patients with atrial fibrillation and patients with valvular prostheses. However, their use is associated with bleeding complications and hospitalizations. Predictors of hospital admission for bleeding in these patients are poorly known. Objectives To define the predictors for hospitalization of VKA users who seek emergency care due to bleeding. Methods Single-center, cross-sectional study, with retrospective analysis of electronic medical records from 03/01/2012 to 02/27/2017. Clinical and laboratory variables were compared between patients who were hospitalized and those who were not. A logistic regression model as used, in which the variables were included using the Backward stepwise method, with a p value of 0.05 as the input criterion, a removal value of 0.20 and a confidence interval of 95%. The p-value was considered statistically significant when

Introduction Changes in brain-derived neurotrophic factor (BDNF) have been linked to the neuroadaptative consequences of chronic alcohol use and associated with disease severity and prognosis. Few studies have evaluated the influence of drug withdrawal and clinical and sociodemographic data on BDNF levels in severe alcohol users. Objectives Our goals were (1) to evaluate variation in BDNF levels during alcohol withdrawal and, (2) to assess the influence of putative confounding factors on BDNF levels. Methods Our sample consists of 62 men with alcohol use disorder undergoing a detoxification process. Serum BDNF levels were measured using a commercial sandwich-ELISA kit, at two points: before and after the detoxification period. Results We found an increase in BDNF levels during alcohol withdrawal (25.4±9.6 at admission vs. 29.8±10.2 ng/ml at discharge; p < 0.001), even after controlling for potential confounders (positive family history, number of days between blood sample collections, and age) (Generalized Estimating Equation: coefficient = -4.37, 95% confidence interval [95%CI] -6.3; -2.4; p < 0.001). Moreover, individuals who had first-degree relative with alcohol dependence had smaller increases in BDNF levels than individuals with no family history (14.8 [95%CI -5.3; 35.6] vs. 35.3 [95%CI 15.4; 74.8]; p = 0.005). Conclusions In summary, variation in BDNF levels seems to be influenced by withdrawal in severe alcohol users. A positive family history of alcohol dependence could also be a factor that influences variation in this biomarker.

To perform a medical analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Reunion Island, a French overseas territory.A multicenter retrospective observational study was conducted for an 8-year period, before and after introduction of sialendoscopy (2011-2014 and 2015-2018), following STROBE guidelines.To compare populations treated before (period A) and after (period B) the introduction of sialendoscopy in terms of clinical characteristics, and analyze the characteristics of patients treated by sialendoscopy.Two hundred and sixty-five patients were included: 74 in 2011-2014 and 191 in 2015-2018; 139 had sialendoscopy. Populations A and B were comparable except for the proportion of parotids treated (9% vs. 31%, respectively; P0.0001), and smaller stones (11mm vs. 7.4mm, respectively; P=0.003). One hundred and ten pure sialendoscopies and 29 combined routes (20.8%) were performed: 63% submandibular and 37% parotid. Median age was 46 years. The M/F sex ratio was 0.96. Thirty-seven patients presented stenosis. There were 10 cases of papillary catheterization failure (7.1%), and 16 false routes or creation of false channels (11.5%), including 9 during the learning period. The rate of crossover to gland resection decreased: 10.45% for 2015-2016 and 5.56% for 2017-2018.Although follow-up ranged between 12 and 55months (median, 30months), sialendoscopy appeared to be a useful and reliable technique, with a role in therapeutic strategy for the management of non-tumoral salivary pathologies in Reunion Island.

Goals Cost analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Reunion Island, a French overseas territory. Objectives Calculation and comparison of median pricing (i.e., median payment to the healthcare establishment) per patient before and after the introduction of sialendoscopy, in the only regional establishment practicing sialendoscopy and in the whole of Reunion Island. Material and method A multicenter retrospective cost study was conducted over an 8-year period, before and after the introduction of sialendoscopy (period A: 2011–2014 and period B: 2015–2018), according to the CHEERS guidelines for economic studies, and included inpatients with non-tumoral pathology of the main salivary glands, whether treated by sialendoscopy or not. Results Two hundred sixty-five patients were included, 139 of whom were treated by sialendoscopy: 74 in 2011–2014 and 191 in 2015–2018. Between the two periods, median pricing in the only center practicing sialendoscopy did not vary significantly: €3468 vs. €3368 (i.e., +2.9% (P = 0.1)). In the Island as a whole, pricing increased significantly: €598 vs. €2332, (i.e., +390% (P Conclusion Sialendoscopy is cost-effective in France in the public healthcare sector if outpatient management is optimal, but significantly increases the public health budget. It makes it possible to recruit and manage previously untreated patients (small stones, salivary strictures, etc.).

Mosaic trisomy 8 is a condition characterized by a great phenotypic and cytogenetic variability whose incidence ranges around 1 in 25,000 to 50,000 live births. Here, we report a mosaic trisomy 8 patient presenting laryngotracheomalacia, an uncommon finding, analyzing its possible role over morbidity, and mortality. The patient was a boy who, after birth, had tachypnea and paleness. He presented periods of respiratory dysfunction with need of ventilatory support. Respiratory syncytial virus test was positive. Naso fibrobronchoscopy showed moderate laryngotracheomalacia. He also had recurrent episodes of pneumonia and difficulty in withdrawing continuous positive airway pressure. The patient also presented leucoma, abnormal and low-set ears, pectus excavatum, clenched fists with overlapping fingers, cryptorchidism, clubfeet, and deep longitudinal plantar creases. G-bands by Trypsin using giemsa (GTG-banding) karyotype from a peripheral blood sample revealed a mosaic trisomy 8: mos 47,XY, + 8[15]/46,XY[7]. At 4 months, the patient developed respiratory failure, and a chest computed tomography scan showed areas of atelectasis and gross fibroatelectatic striae. He ended up presenting clinical worsening and died at 4 months and 8 days. In our literature review, we found some reports describing patients with mosaic trisomy 8 and laryngotracheomalacia. However, we cannot rule out the possibility that this association could be casual, since laryngotracheomalacia is a relatively common finding in children. Therefore, more studies are still necessary to understand the possible relation between both conditions and the role of laryngotracheomalacia over morbidity and prognosis of mosaic trisomy 8 patients.

Objectives: to calculate the prevalence and rate per 1,000 live births of sexually transmitted infections (STI) in pregnant women at a public maternity hospital in Salvador. Methods: this descriptive, cross-sectional study retrospectively collected data from compulsory notifications and medical records of pregnant women with STI seen at a maternity hospital in northeastern Brazil between 2014 and 2017 (n = 520). Prevalence and rate per 1,000 live births were estimated for hepatitis B, hepatitis C, HIV, and syphilis. Associations between STI and other clinical and sociodemographic variables were investigated. Results: most pregnant women were born and resided in Salvador, presented a mean age of 26.4 years, self-reported mixed-race and had unplanned pregnancies. Prevalence and rates per 1,000 live births were, respectively: 0.26% and 3.39 for hepatitis B, 0.06% and 0.79 for hepatitis C, 0.47% and 6.23 for HIV, and 2.46% and 32.2 for syphilis. Conclusion: higher prevalence and rates of infection per 1,000 live births were seen at the maternity hospital in northeastern Brazil compared to official data provided by the Brazilian government, notably with regard to HIV and syphilis. The appropriate epidemiological notification of STI, especially in pregnant women, enables the elaboration of effective preventive strategies incorporating specific sociodemographic and clinical characteristics. Resumo Objetivos: calcular a prevalência e as taxas por 1000 nascidos vivos de infecções sexualmente transmissíveis (IST) em gestantes de uma maternidade pública de Salvador. Métodos: estudo transversal, descritivo, com dados coletados retrospectivamente a partir das fichas de notificação dos agravos e dos prontuários de todas as gestantes com IST atendidas na maternidade, entre os anos de 2014 e 2017 (n=520). Foram calculadas as prevalências e as taxas por 1000 nascidos vivos de hepatite B, hepatite C, HIV e sífilis para a população de gestantes da maternidade. Associações entre as IST e demais variáveis clínicas e sociodemográficas também foram investigadas. Resultados: a maioria das gestantes era natural e residente de Salvador, pardas, com idade média de 26,4 anos e que não planejaram a gravidez. As prevalências e as taxas por 1000 nascidos vivos foram respectivamente: 0,26% e 3,39 para hepatite B, 0,06% e 0,79 para hepatite C, 0,47% e 6,23 para HIV e 2,46% e 32,2 para sífilis. Conclusão: a maternidade apresenta prevalências e taxas por 1000 nascidos vivos superiores aos dados oficiais do governo brasileiro, especialmente para HIV e sífilis. A correta notificação epidemiológica desses agravos, especialmente em gestantes, permite o desenvolvimento de estratégias preventivas mais eficientes e com enfoque nas características sociodemográficas e clínicas das pacientes.

Objectives The purpose of this study is to compare the risks of novel postoperative curcumin infusion in patients with increased proliferative vitreoretinal retinopathy (PVR) after retinal detachment with steroid infusion or no treatment. Methods This was a prospective, non-randomized pilot study of 15 eyes of 15 patients (mean age 68 ± 7 years) with retinal detachment, macula off, and flare >15 pc/ms. Postoperatively, the patients received either curcumin-HSA (human serum albumin) infusion (C, n=5), prednisolone infusion (P, n=5), or no therapy (N, n=5) for three days. The outcome measures included postoperative PVR rate, the number of vitreoretinal surgeries (VRS) required, epiretinal membrane development, and visual acuity (VA). Results All patients had a preoperative VA of hand movements, macula-off detachment situation, and two quadrants rhegmatogenous retinal detachment. Patients underwent VRS at a mean time of 5.6 ± 1.5 (C), 4.9 ± 2.0 (P), 4.7 ± 1.2 (N) days after first recognized symptoms. Postoperative PVR developed just in one eye (P) after 16 days and required VRS due to PVR retinal detachment. The remaining 14 patients of group C and N did not develop PVR. BCVA improved six months post surgery to 0.56 ± 0.31 (P), 0.53 ± 0.19 (D), 0.53 ± 0.17 (N) logMAR. There were no side effects nor complications related to the postoperative infusions. Conclusions In this pilot study, we demonstrated that a postoperative application of curcumin infusion is a safe option in patients with an increased risk of PVR. Whether or not PVR can be reduced by curcumin infusion would require to be investigated in larger, randomized clinical trials.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Objective To know situations of vulnerabilities experienced by children and adolescents with cancer and their implications on health rights. Method A qualitative study, developed from 2017 to 2018, in two Santa Catarina hospitals. The interviewees were 11 family members of children/adolescents with cancer, a prevalent chronic disease identified in hospitalizations in 2017. A descriptive and thematic analysis was carried out based on the vulnerability and human rights framework. Results Among the chronic diseases, cancer was prevalent. Vulnerability situations were discussed considering the trajectories in the health care network, the challenges facing the care routine and the support networks for the exercise of the right to health. Final considerations Chronic diseases such as cancer require timely, decisive and effective responses from the health system with a view to maintaining human rights. RESUMEN Objetivo Conocer las situaciones de vulnerabilidad experimentadas por niños y adolescentes con cáncer y sus implicaciones para el derecho a la salud. Método Estudio cuantitativo, desarrollado de 2017 a 2018, en dos hospitales de Santa Catarina. Se entrevistó a 11 familiares de niños/adolescentes con cáncer. Se realizó un análisis descriptivo y temático basado en el marco de vulnerabilidad y derechos humanos. Resultados Entre las enfermedades crónicas, hubo prevalencia de cáncer. Se discutieron las situaciones de vulnerabilidad considerando las trayectorias en la red de atención de la salud, los desafíos en la rutina de atención y las redes de apoyo para el ejercicio del derecho a la salud. Consideraciones finales Las enfermedades crónicas como el cáncer requieren respuestas oportunas, decisivas y efectivas por parte del sistema de salud con miras a mantener los derechos humanos. RESUMO Objetivo Conhecer as situações de vulnerabilidades vivenciadas por crianças e adolescentes com câncer e suas implicações no direito à saúde. Método Estudo qualitativo, desenvolvido de 2017 a 2018, em dois hospitais de Santa Catarina. Foram entrevistados 11 familiares de crianças/adolescentes com câncer, doença crônica prevalente identificada nas internações de 2017. Realizou-se análise descritiva e temática ancorada no referencial da vulnerabilidade e dos direitos humanos. Resultados As situações de vulnerabilidades foram discutidas considerando as trajetórias na rede de atenção à saúde, os desafios frente à rotina de cuidado e as redes de apoio para o exercício do direito à saúde. Considerações finais Doenças crônicas como o câncer infanto-juvenil exigem respostas pontuais, resolutivas e efetivas pelo sistema de saúde com vistas a mitigar as situações de vulnerabilidades e promover os direitos à saúde.

Chronic subdural hematoma (CSDH) is a common neurosurgical condition, especially among elderly patients. Here we have analyzed our institutional experience with surgical management of CSDH. We aimed at identifying predictors of hematoma recurrence and cure, and the respective time course.Pertinent data were collected from all 208 patients (136 males; median age, 78 years) treated for unilateral CSDH in our department from 2014 to 2016 after exclusion of cases with CSDH following previous head surgery or missing postoperative imaging. Pre- and postoperative neuroimaging studies were subjected to computer-assisted volumetric analyses. CSDH composition and anatomy were assessed using a modified Nakaguchi classification.A total of 67.8% of the patients presented with neurologic deficits, and 51.4% were at least on 1 anticoagulant agent. Burr hole trephinations were performed in 94.7%. The median residual hematoma volume was 35.0 mL (44.1 mL including air). Surgical recurrences were seen in 17.8%. The median time to repeat surgery was 17 days, and 91.9% of recurrences occurred within 60 days. Recurrence rates varied between 36.4% (separated or trabecular subtypes and postoperative CSDH volume ≥35.0 mL) and 3.7% (all other subtypes and postoperative CSDH volume35.0 mL). A neuroimaging proven cure could be documented in an estimated 90% of cases at 145 days after first surgery.Postoperative CSDH volume and the Nakaguchi classification subtypes proved the most powerful predictors of recurrence, cure, and the time to recurrence and cure. Although our results demonstrate the important impact of CSDH volume, composition, and anatomy, they also show that other so far unknown factors play a significant role as well.

Intestinal malformations are common disorders in newborn and favorable outcomes have been reported for such conditions. Although, if the patient is treated in a not experienced center, misinterpretation of the clinical and radiological findings may lead to errors in treatment and possible complications in adulthood. We report a case of a congenital megaduodenum which was misinterpreted as an intestinal malrotation resulting in late complications. The patient underwent a successful surgical resection of the duodenum with improvement of his clinical symptoms and nutritional status.This case report emphasizes the importance of considering megaduodenum in the differential diagnosis of patients with feeding impairment, even during adulthood. Early diagnosis and treatment may improve patients’ outcome and reduce morbidity. Keywords: Duodenum, Congenital Malformation, Multislice computed tomography

Host resistance to Mycobacterium tuberculosis infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis are incompletely understood. Here we uncover an unexpected association between eosinophils and Mtb infection. In humans, eosinophils are decreased in the blood but enriched in resected human tuberculosis lung lesions and autopsy granulomas. Influx of eosinophils is also evident in infected zebrafish, mice, and nonhuman primate granulomas, where they are functionally activated and degranulate. Importantly, employing complementary genetic models of eosinophil deficiency, we demonstrate that, in mice, eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings uncover an unexpected recruitment of eosinophils to the infected lung tissue and a protective role for these cells in the control of Mtb infection in mice.

Introduction: Thoracic ultrasound is frequently used in the emergency department (ED) to determine the etiology of dyspnea, yet its use is not widespread in the prehospital setting. We sought to investigate the feasibility and diagnostic performance of paramedic acquisition and assessment of thoracic ultrasound images in the prehospital environment, specifically for the detection of B-lines in congestive heart failure (CHF). Methods: This was a prospective observational study of a convenience sample of adult patients with a chief complaint of dyspnea. Paramedics participated in a didactic and hands-on session instructing them how to use a portable ultrasound device. Paramedics assessed patients for the presence of B-lines. Sensitivity and specificity for the presence of bilateral B-lines and any B-lines were calculated based on discharge diagnosis. Clips archived to the ultrasound units were reviewed and paramedic interpretations were compared to expert sonologist interpretations. Results: A total of 63 paramedics completed both didactic and hands-on training, and 22 performed ultrasounds in the field. There were 65 patients with B-line findings recorded and a discharge diagnosis for analysis. The presence of bilateral B-lines for diagnosis of CHF yielded a sensitivity of 80.0% (95% confidence interval [CI], 51.4–94.7%) and specificity of 72.0% (95% CI, 57.3–83.3), while presence of any B-lines was 93.3% sensitive (95% CI, 66.0–99.7%), and 50% specific (95% CI, 35.7–64.2%) for CHF. Paramedics archived 117 ultrasound clips of which 63% were determined to be adequate for interpretation. Comparison of paramedic and expert sonologist interpretation of images showed good inter-rater agreement for detection of any B-lines (k = 0.60; 95% CI, 0.36–0.84). Conclusion: This observational pilot study suggests that prehospital lung ultrasound for B-lines may aid in identifying or excluding CHF as a cause of dyspnea. The presence of bilateral B-lines as determined by paramedics is reasonably sensitive and specific for the diagnosis of CHF and pulmonary edema, while the absence of B lines is likely to exclude significant decompensated heart failure. The study was limited by being a convenience sample and highlighted some of the difficulties related to prehospital research. Larger funded trials will be needed to provide more definitive data.

Anxiety and eating disorders (EDs) often co-occur, prompting calls to explore anxiety-related maintenance processes in ED samples. Safety behaviors, which function to prevent a feared outcome from occurring or to reduce anxiety associated with a feared stimulus, are observed across anxiety disorders and, along with overt avoidance behaviors, are an important target in treatment. Data suggest that individuals with EDs also engage in safety behaviors. However, no existing assessments provide a comprehensive measure of eating-disorder-specific overt avoidance and safety behaviors. The goal of this Stage 1 Registered Report is to develop a comprehensive self-report measure of ED-specific safety behaviors. In Study 1, we will recruit 50 women with EDs to complete the scale and provide feedback on the response scale. Feedback from these participants will be used to refine the measure. In Study 2, we will evaluate the psychometric properties of the measure in a large sample of women with EDs (n dependent on the size of measurement) and a community sample without current or a history of ED symptoms. We will explore the measure factor structure, known-groups validity by comparing scores from women with EDs to healthy controls, internal consistency, and convergent and divergent validity with other psychological instruments.

Andrea C. Bohrer (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Ehydel Castro (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Zhidong Hu (Fudan University. Shanghai Public Health Clinical Center. Department of Scientific Research. Shanghai, China / Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China.); Artur T. L. Queiroz (The KAB Group / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundacao Oswaldo Cruz. Instituto Goncalo Moniz. Salvador, BA, Brasil.); Claire E. Tocheny (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Maike Assmann (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Shunsuke Sakai (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Christine Nelson (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Paul J. Baker (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.); Hui Ma (Fudan University. Shanghai Public Health Clinical Center. Department of Scientific Research. Shanghai, China / Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China.); Lin Wang (Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China / Fudan University. Shanghai Public Health Clinical Center. Department of Thoracic Surgery. Shanghai, China.); Wen Zilu (Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China / Fudan University. Shanghai Public Health Clinical Center. Department of Thoracic Surgery. Shanghai, China.); Elsa du Bruyn (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa.); Catherine Riou (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa.); Keith D. Kauffman (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Tuberculosis Imaging Program (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of Intramural Research. Tuberculosis Imaging Program. Bethesda, MD, United States of America.); Ian N. Moore (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Comparative Medicine Branch. Infectious Disease Pathogenesis Section. Bethesda, MD, United States of America.); Franca Del Nonno (Istituto Di Ricovero e Cura a Carattere Scientifico. National Institute for Infectious Diseases "L. Spallanzani". Pathology Unit. Rome, Italy.); Linda Petrone (Istituto Di Ricovero e Cura a Carattere Scientifico. Department of Epidemiology and Preclinical Research National Institute for Infectious Diseases. Translational Research Unit. Rome, Italy.); Delia Goletti (Istituto Di Ricovero e Cura a Carattere Scientifico. Department of Epidemiology and Preclinical Research National Institute for Infectious Diseases. Translational Research Unit. Rome, Italy.); Adrian R. Martineau (University College London. Institute of Immunity and Transplantation. London, United Kingdom.); David M. Lowe (University College London. Institute of Immunity and Transplantation. London, United Kingdom.); Mark R. Cronan (Max Planck Institute for Infection Biology. In Vivo Cell Biology of Infection Unit. Berlin, Germany / Duke University School of Medicine. Department of Molecular Genetics and Microbiology. Durham, NC, United States of America.); Robert J. Wilkinson (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa / Imperial College London. Department of Infectious Diseases. London, United Kingdom.); Clifton E. Barry, III (University of Cape Town. Institute of Infectious Disease and Molecular Medicine. Wellcome Centre for Infectious Diseases Research in Africa. Cape Town, South Africa / National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Tuberculosis Research Section. Bethesda, MD, United States of America.); Laura E. Via (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Division of Intramural Research. Tuberculosis Imaging Program. Bethesda, MD, United States of America / National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Tuberculosis Research Section. Bethesda, MD, United States of America.); Daniel L. Barber (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. T Lymphocyte Biology Section. Bethesda, MD, United States of America.); Amy D. Klion (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Human Eosinophil Section. Bethesda, MD, United States of America.); Bruno B. Andrade (The KAB Group / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil / Fundacao Oswaldo Cruz. Instituto Goncalo Moniz. Salvador, BA, Brasil.); Yanzheng Song (Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China / Fudan University. Shanghai Public Health Clinical Center. Department of Thoracic Surgery. Shanghai, China.); Ka-Wing Wong (Fudan University. Shanghai Public Health Clinical Center. Department of Scientific Research. Shanghai, China / Fudan University. Shanghai Emerging and Re-emerging Infectious Disease Institute. Tuberculosis Center. Shanghai, China.); Katrin D. Mayer-Barber (National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Immunology and Microbiology. Inflammation and Innate Immunity Unit. Bethesda, MD, United States of America.).

Diagnosis provides means of communication, may serve to validate a person’s experience, and can inform treatment. It is imperative for clinicians to utilize appropriate diagnostic tools and best practices when diagnosing eating disorders. There are several considerations to take into account when assessing and diagnosing eating disorders in boys and men. Recent years have seen an increase in studies examining eating disorder symptoms among boys and men, and the notion that these issues do not affect this population has been unequivocally dismissed. However, the effects of this historical gender disparity in the eating disorder field persist, and researchers are just beginning to more fully understand the sometimes distinct nature of eating disorders among boys and men.

Sexual minority individuals are at greater risk for the development of eating-disorder (ED) psychopathology. Despite the importance of understanding ED symptoms in sexual minority men, most ED measures were developed and validated in heterosexual, young adult, white women. The psychometric properties of ED measures in diverse populations remain largely unknown. The purpose of this study was to test: 1) whether the eight-factor structure of the Eating Pathology Symptoms Inventory (EPSI) replicated in sexual minority men and 2) group-level mean differences between gay and bisexual men on the eight EPSI scales. International participants (N = 722 sexual minority men from 20 countries) were recruited via the Grindr smartphone application. Confirmatory factor analysis (CFA) was completed using a weighted least square mean and variance adjusted estimator. Group differences in eating pathology between gay and bisexual men were tested using independent samples t-tests. The CFA model fit was good on all fit indices (CFI/TLI > 0.90, RMSEA

Objective: to understand the experience of pregnancy and motherhood by adolescents/young people who were born infected with HIV. Method: we carried out a qualitative study specialized in HIV service in Porto Alegre (RS/Brazil). Ten adolescents/young people were interviewed from June 2017 to March 2018. Thematic analysis was performed, using a vulnerability framework to reflect about unplanned pregnancy and its implications for care. Results: four categories were highlighted: Discovery of the ongoing pregnancy: ambivalent feelings towards seropositivity; Breaking the news of the pregnancy to partner, family and health professionals; Experience of childbirth and prophylaxis of vertical transmission of HIV; and Experience of motherhood: implications for life stories and future projects. Final considerations: the study contributes to addressing situations of vulnerability to the occurrence of unplanned pregnancy, showing the need for dialogical proposals that respect human rights in the production of comprehensive care and reproductive planning. RESUMEN Objetivo: comprender la experiencia del embarazo y la maternidad de adolescentes/jóvenes que nacieron infectados con VIH. Métodos: estudio cualitativo, realizado en un servicio especializado en VIH en Porto Alegre (RS/Brasil). Se entrevistó a 10 adolescentes / jóvenes, de junio de 2017 a marzo de 2018. Se realizó un análisis temático, utilizando un marco de vulnerabilidad para reflexionar sobre el embarazo no planificado y sus implicaciones para la atención. Resultados: se destacaron cuatro categorías: descubrimiento del embarazo en curso: sentimientos ambivalentes hacia la seropositividad; Divulgación de noticias de embarazo a socios, familiares y profesionales de la salud; Experiencia de parto y profilaxis de la transmisión vertical del VIH; y Experiencia de la maternidad: implicaciones para historias de vida y proyectos futuros. Consideraciones finales: el estudio contribuye a enfrentar situaciones de vulnerabilidad a la ocurrencia de embarazo sin planificación, señalando la necesidad de propuestas dialógicas que respeten los derechos humanos en la producción de atención integral y planificación reproductiva. RESUMO Objetivo: compreender a vivência da gestação e da maternidade por adolescentes/jovens que nasceram infectadas pelo HIV. Método: estudo qualitativo, realizado em serviço especializado em HIV de Porto Alegre (RS/Brasil). Entrevistaram-se 10 adolescentes/jovens, de junho de 2017 a março de 2018. Realizou-se análise temática, utilizando referencial de vulnerabilidade para refletir sobre a gestação sem planejamento e suas implicações no cuidado. Resultados: evidenciaram-se quatro categorias: Descoberta da gravidez em curso: sentimentos ambivalentes diante da soropositividade; Revelação da notícia da gestação ao parceiro, familiares e profissionais de saúde; Vivência do parto e da profilaxia da transmissão vertical do HIV; e Vivência da maternidade: implicações nas histórias de vida e projetos futuros. Considerações finais: o estudo contribui ao enfrentamento das situações de vulnerabilidades à ocorrência da gestação sem planejamento, apontando a necessidade de propostas dialógicas que respeitem os direitos humanos na produção do cuidado integral e planejamento reprodutivo.

Background: Lung cancer causes impairment of health-related quality of life (QoL), but little is known about gender aspects in QoL and symptom burden of lung cancer patients. The aim of this study was to investigate gender differences in QoL as assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the updated lung cancer module. Methods: In a prospective, international, cross-cultural, multicenter study that was undertaken to update the lung cancer-specific module EORTC QLQ-LC13, patients filled in the core questionnaire EORTC QLQ-C30 and the updated lung cancer module. Gender differences were calculated for all QoL scores using ANCOVAs that controlled for known and suspected confounders. Comparisons with historic data were drawn. Results: A total of 200 patients (82 female and 118 male, median age 65 years) were recruited. With the exception of coughing (estimated marginal means: women 33.86 and men 43.52, P=0.022) and diarrhea (estimated marginal means: women 26.01 and men 17.93, P=0.038) there were no significant QoL gender differences. Fatigue was the most pronounced symptom in both, men and women, outpacing typical respiratory symptoms. Quite generally, our sample of lung cancer patients showed considerably worse QoL in all scores when compared to EORTC reference data (lung cancer and combined cancer diagnoses, mean differences up to 13.70 and 21.54 score points, respectively) and to a German norm reference sample (up to 35.37 score points). Conclusions: This study adds to the literature in showing that the typical QoL gender difference effect (women doing worse than men) may not be generalizable across all patient samples.

Proper assessment and diagnosis of eating disorders (EDs) are critical to determine to whom prevention and treatment efforts should be targeted, the extent to which treatment is working, and when an individual has recovered. Although existing ED diagnostic interviews have numerous strengths, they also have certain limitations, including poor internal consistency, low discriminant validity, and poor factor-structure replicability. The purpose of the current study was to address problems of past ED diagnostic interviews through the creation of a new clinician-rated interview-the Eating Pathology Symptoms Inventory-Clinician-Rated Version (EPSI-CRV). The EPSI-CRV was designed to measure dimensional constructs assessed in the self-report version of the EPSI and generate current Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) diagnoses. Participants were community-recruited adults with a DSM-5 ED (N = 257). Participants completed self-report and interview-based measures of eating, mood, and anxiety disorders and self-report measures of psychiatric impairment. The EPSI-CRV demonstrated evidence for interrater reliability, convergent and discriminant validity, and a good-fitting factor structure. EPSI-CRV dimensions showed concurrent validity for distinguishing among ED diagnoses. Baseline EPSI-CRV dimensions significantly predicted psychiatric impairment at baseline but not at 1-year follow-up. Although some scales had lower internal consistency than ideal, internal consistency values were similar to those of other established diagnostic measures. The EPSI-CRV appears to represent a promising new interview that can be used across a variety of clinical and research settings. Interested readers can access the EPSI-CRV and relevant training materials here: https://kuscholarworks.ku.edu/handle/1808/29616. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. Methods: In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. Results: We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. Conclusions: This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.

Kenny-Caffey syndrome (KCS) is a rare genetic condition characterized by growth retardation, bone abnormalities, and hypoparathyroidism. Herein, we report an unusual case of a 10-year-old girl with Kenny-Caffey syndrome type 2 (KCS2) presenting with vision impairment-suspected maculopathy and intellectual disability. Endocrine evaluation showed low calcium and high phosphorus plasma levels. Radiographic evaluation revealed short metacarpal bones and delayed bone age. Sequencing analysis showed a missense variant in FAM111A (R569H), unidentified in her parents. Better understanding of potential neurological and ophthalmological findings in KCS2 patients is important to improve quality of life of these patients as usually they exhibit long survival.

Background: Pregnant women represent a vulnerable population at higher risk of complications of infectious diseases. Data regarding the consequences of the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy are scarce. Recent evidence suggests that pregnant women might be at higher risk of severe disease, while exposed fetuses and newborns could suffer from preterm birth, growth restriction and neonatal infections. Methods: We developed an international web registry to allow structured data collection. Pregnant women at any stage during gestation tested for SARS-CoV-2 infection were enrolled. Maternal, obstetrical and neonatal outcomes were recorded. Findings: 1033 pregnant women tested for SARS-CoV-2 were included, among which 926 tested positive and 107 tested negative. Positive pregnant women were at higher risk of severe maternal outcomes compared to negative women [aRR 5.6, 95% CI 1.4-22.7]. Risk factors for severe maternal outcomes among positive women were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. No difference in term of obstetrical and neonatal outcomes were observed between positive and negative women. Positive pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. A positive neonatal SARS-CoV-2 test was observed in 2.9% (n=11/384) of newborns with an available test at birth. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Preliminary data regarding obstetrical and neonatal outcomes among women with a mild disease are reassuring. Funding Statement: None. Declaration of Interests: The authors declare that we have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD-2020-00548) and the local ethics boards at each participating center.

Background: Recent evidence suggests that pregnant women might be at higher risk of severe disease associated with the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while exposed fetuses/newborns could suffer from preterm birth, growth restriction and neonatal infections. The magnitude of this increased risk and specific risk factors for severity remains unclear. Methods: We performed a case control study comparing pregnant women with severe coronavirus disease 19 (case) to pregnant women with a milder form (controls) enrolled in COVI-Preg international registry cohort between from March 24 to July 26, 2020. Risk factors for severity, obstetrical, fetal and neonatal outcomes were assessed. Findings: A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented a severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease; complications include cesarean sections, prematurity and neonatal admission to the intensive care unit. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD- 2020-00548) and the local ethics boards at each participating center.

There is evidence that dopamine receptors D2 (DRD2) and D4 (DRD4) polymorphisms may influence substance use disorders (SUD) susceptibility both individually and through their influence in the formation of DRD2-DRD4 heteromers. The dopaminergic role on the vulnerability to addiction appears to be influenced by sex. A cross-sectional study with 307 crack cocaine addicts and 770 controls was conducted. The influence of DRD2 rs2283265 and DRD4 48 bp VNTR in exon 3 variants, as well as their interaction on crack cocaine addiction susceptibility and severity were evaluated in women and men separately. An association between the DRD2 T allele and crack cocaine addiction was found in women. In this same group, interaction analysis demonstrated that the presence of DRD2-T allele and concomitant absence of DRD4-7R allele were associated with risk for crack cocaine addiction. No influence of DRD2 and DRD4 variants was observed in men regarding addiction severity. This study reinforces the role of dopaminergic genes in externalizing behaviors, especially the influence of DRD2-DRD4 interaction on SUD. This is the fourth sample that independently associated the DRD2-DRD4 interaction with SUD itself or related disorders. In addition, our findings point out to a potential difference of dopaminergic neurotransmission across sex influencing addiction susceptibility.

IL-1R1 deficiency in mice causes severe susceptibility to Mycobacterium tuberculosis. Mice and macrophage cultures lacking IL-1R1 display increased bacterial growth, suggesting that phagocytes may require IL-1R1–dependent antimicrobial signals to limit intracellular M. tuberculosis replication directly. However, the myeloid-cell–intrinsic versus –extrinsic requirements for IL-1R1 to control M. tuberculosis infection in mice have not been directly addressed. Using single-cell analysis of infected cells, competitive mixed bone marrow chimeras, and IL-1R1 conditional mutant mice, we show in this article that IL-1R1 expression by pulmonary phagocytes is uncoupled from their ability to control intracellular M. tuberculosis growth. Importantly, IL-1R1–dependent control was provided to infected cells in trans by both nonhematopoietic and hematopoietic cells. Thus, IL-1R1–mediated host resistance to M. tuberculosis infection does not involve mechanisms of cell-autonomous antimicrobicidal effector functions in phagocytes but requires the cooperation between infected cells and other cells of hematopoietic or nonhematopoietic origin to promote bacterial containment and control of infection.

Gene correction is a valuable strategy for treating inherited retinal degenerative diseases, a major cause of irreversible blindness worldwide. Single gene defects cause the majority of these retinal dystrophies. Gene augmentation holds great promise if delivered early in the course of the disease, however, many patients carry mutations in genes too large to be packaged into adeno-associated viral vectors and some, when overexpressed via heterologous promoters, induce retinal toxicity. In addition to the aforementioned challenges, some patients have sustained significant photoreceptor cell loss at the time of diagnosis, rendering gene replacement therapy insufficient to treat the disease. These patients will require cell replacement to restore useful vision. Fortunately, the advent of induced pluripotent stem cell and CRISPR-Cas9 gene editing technologies affords researchers and clinicians a powerful means by which to develop strategies to treat patients with inherited retinal dystrophies. In this review we will discuss the current developments in CRISPR-Cas9 gene editing in vivo in animal models and in vitro in patient-derived cells to study and treat inherited retinal degenerative diseases.

Lipomas medulares são tumorações benignas pouco freqüentes, sendo considerada rara sua ocorrência sem disrafismo vertebral associado. O surgimento das manifestações clínicas ocorre predominantemente por volta 2ª e 3ª década de vida, determinando, na maioria dos casos, um curso arrastado de deterioração neurológica que varia de acordo com sua localização. Descrevemos nesse relato um caso raro de lipoma medular intradural extramedular, sem associação com disrafismo; e fazemos uma breve revisão da literatura considerando a epidemiologia, tratamento e achados histológicos destas lesões.

Liver abscess due to perforation of the gastrointestinal tract by a foreign body is a rare and possibly fatal event. Diagnosing this pathology is complicated by the lack of specific symptoms and unfamiliarity of ingestion by the patient and low clinical suspicion of this disease. In the case of liver abscess unresponsive to aspiration and administration of antibiotics, this hypothesis must be made, despite its low incidence. This case report describes and illustrates a case of liver abscess secondary to fish bone ingestion with consequent piercing of the lesser gastric curvature, diagnosed by computed tomography and specific anamnesis. Laparoscopy was performed to extract the foreign body, without complications; the patient is currently asymptomatic and does not present any abnormal physical examination findings. We believe this represents the first case report of a successful laparoscopic treatment in South America for the removal of an ingested foreign body associated with pyogenic liver abscess.

The recent outbreak of the Zika virus (ZIKV) and the discovery that perinatal Zika exposure can lead to the Congenital Zika Syndrome has promoted a call for prevention measures. Due to the increased number of babies born with microcephaly, structural brain abnormalities, and neurological alterations in regions affected by ZIKV, investigations were carried out in order to better understand this process. The maternal immune system directly influences the fetal central nervous system, and complications during pregnancy have been associated with neurodevelopmental disorders. Autism spectrum disorder (ASD), a neurodevelopmental disorder commonly manifested in the first years of life, is a disease with multifactorial etiology and is manifested typically by social and communication impairments, as well as stereotyped behaviors. Brain abnormalities, including both anatomically and functionally, can be observed in this disorder, suggesting delays in neuronal maturation and altered brain connectivity. It is known that some viral congenital infections, such as rubella, and cytomegalovirus can interfere with brain development, being associated with brain calcification, microcephaly, and ASD. Here, we reviewed a range of studies evaluating the aspects concerning brain development, immunological status during pregnancy, and neuroimmunomodulation in congenital viral infections, and we discuss if the fetal brain infection caused by ZIKV could predispose to ASD. Finally, we suggest a mechanism encompassing neurological and immunological pathways that could play a role in the development of ASD in infants after ZIKV infection in pregnancy.

Surface roughness – a key control on land-atmosphere exchanges of heat and momentum – differs between dormant and growing seasons. However, how surface roughness shifts seasonally at fine time scales (e.g., days) in response to changing canopy conditions is not well understood. This study: (1) explores how aerodynamic resistance changes seasonally; (2) investigates what drives these seasonal shifts, including the role of vegetation phenology; and (3) quantifies the importance of including seasonal changes of aerodynamic resistance in “big leaf” models of sensible heat flux (H). We evaluated aerodynamic resistance and surface roughness lengths for momentum (z0m) and heat (z0h) using the kB−1 parameter (ln(z0m/z0h)). We used AmeriFlux data to obtain surface-roughness estimates, and PhenoCam greenness data for phenology. This analysis included 23 sites and ∼190 site years from deciduous broadleaf, evergreen needleleaf, woody savanna, cropland, grassland, and shrubland plant-functional types (PFTs). Results indicated clear seasonal patterns in aerodynamic resistance to sensible heat transfer (Rah). This seasonality tracked PhenoCam-derived start-of-season green-up transitions in PFTs displaying the most significant seasonal changes in canopy structure, with Rah decreasing near green-up transitions. Conversely, in woody savanna sites and evergreen needleleaf forests, patterns in Rah were not linked to green-up. Our findings highlight that decreases in kB−1 are an important control over Rah, explaining > 50% of seasonal variation in Rah across most sites. Decreases in kB−1 during green-up are likely caused by increasing z0h in response to higher leaf area index. Accounting for seasonal variation in kB−1 is key for predicting H as well; assuming kB−1 to be constant resulted in significant biases that also exhibited strong seasonal patterns. Overall, we found that aerodynamic resistance can be sensitive to phenology in ecosystems having strong seasonality in leaf area, and this linkage is critical for understanding land-atmosphere interactions at seasonal time scales.

Background Several problems with the classification and diagnosis of eating disorders (EDs) have been identified, including proliferation of ‘other specified’ diagnoses, within-disorder heterogeneity, and frequent diagnostic migration over time. Beyond problems within EDs, past research suggested that EDs fit better in a spectrum of internalizing psychopathology (characterized by mood and anxiety disorders) than in a separate diagnostic class. Purpose To develop a transdiagnostic, hierarchical-dimensional model relevant to ED psychopathology that: 1) reduces diagnostic heterogeneity, 2) includes important dimensions of internalizing psychopathology that are often excluded from ED diagnostic models, and 3) predicts clinical impairment. Procedures Goldberg's (2006) method and exploratory structural equation modeling were used to identify a hierarchical model of internalizing in community-recruited adults with EDs ( N = 207). Findings The lowest level of the hierarchy was characterized by 15 factors that defined specific aspects of eating, mood, and anxiety disorders. At the two-factor level, Internalizing bifurcated into Distress (low well-being, body dissatisfaction, suicidality, dysphoria, ill temper, traumatic intrusions) and Fear-Avoidance (claustrophobia, social avoidance, panic symptoms, dietary restricting, excessive exercise, and compulsions). Results showed that the lowest level of the hierarchy predicted 67.7% of the variance in clinical impairment. In contrast, DSM eating, mood, and anxiety disorders combined predicted 10.6% of the variance in impairment secondary to an ED. Conclusions The current classification model represents an improvement over traditional nosologies for predicting clinically relevant outcomes for EDs.

Diffuse radiation can increase canopy light use efficiency (LUE). This creates the need to differentiate the effects of direct and diffuse radiation when simulating terrestrial gross primary production (GPP). Here, we present a novel GPP model, the diffuse-fraction-based two-leaf model (DTEC), which includes the leaf response to direct and diffuse radiation, and treats maximum LUE for shaded leaves (emsh defined as a power function of the diffuse fraction (Df)) and sunlit leaves (emsu defined as a constant) separately. An Amazonian rainforest site (KM67) was used to calibrate the model by simulating the linear relationship between monthly canopy LUE and Df . This showed a positive response of forest GPP to atmospheric diffuse radiation, and suggested that diffuse radiation was more limiting than global radiation and water availability for Amazon rainforest GPP on a monthly scale. Further evaluation at 20 independent AmeriFlux sites showed that the DTEC model, when driven by monthly meteorological data and MODIS leaf area index (LAI) products, explained 70% of the variability observed in monthly flux tower GPP. This exceeded the 51% accounted for by the MODIS 17A2 big-leaf GPP product. The DTEC model's explicit accounting for the impacts of diffuse radiation and soil water stress along with its parameterization for C4 and C3 plants was responsible for this difference. The evaluation of DTEC at Amazon rainforest sites demonstrated its potential to capture the unique seasonality of higher GPP during the diffuse radiation-dominated wet season. Our results highlight the importance of diffuse radiation in seasonal GPP simulation.

Experimental studies have demonstrated that methylphenidate (MPH) modulates the synaptic vesicle trafficking and synaptotagmin-1 (SytI) mRNA levels. SytI is a regulatory protein of the SNARE complex, a neurotransmitter exocytosis mediator. Despite this evidence, most SNARE complex-related genes have never been evaluated in attention-deficit/hyperactivity disorder (ADHD) pharmacogenetics. This study evaluates, for we believe the first time, polymorphisms on the SNARE complex-related genes STX1A (rs2228607), VAMP2 (26bp Ins/Del) and SYT1 (rs1880867 and rs2251214) on the response to immediate-release methylphenidate (IR-MPH) in a naturalistic sample of adults with ADHD. The sample comprised 433 subjects, of which 272 (62.8%) have completed the short-term IR-MPH treatment (at least 30 days). The main outcome measure was the categorical variable of short-term response to IR-MPH based on the Swanson, Nolan and Pelham Rating Scale version 4 (SNAP-IV), and on the clinical global impression-improvement scale. Additional analyses evaluated the percentage of SNAP-IV symptom reduction for each dimension as well as short- and long- (7 years) term treatment persistence. SYT1-rs2251214 was associated with the categorical short-term response to IR-MPH (P=0.006, PFDR=0.028), and with the percentage of inattention and oppositional defiant disorder symptoms reduction (P=0.007, PFDR=0.028 and P=0.017, PFDR=0.048, respectively). SYT1-rs2251214 was also associated with short-term treatment persistence (P=0.018, PFDR=0.048), and with months of treatment (P=0.002, PFDR=0.016) in the long-term protocol. Our findings suggest that SYT1-rs2251214 presents a broad influence in IR-MPH response variability in adults with ADHD, being involved with both symptom response and treatment persistence. If such findings are replicated, SytI could represent a key element in MPH pharmacodynamics in adults with ADHD.

Background: This study aims to compare allele and genotype frequencies of a 30-bp variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene, located at intron 8, between adult crack cocaine users and nonaddicted individuals. Due to its involvement in drug addiction, this gene is a good candidate for molecular studies. Methods: A cross-sectional sample of 239 current adult crack abusers or dependents from in- and outpatient clinics and 211 control individuals was collected in Brazil. They were evaluated using ASRS, ASI-6, WAIS-III, and MINI assessments. DNA samples extracted from whole blood were genotyped for the intron 8 VNTR in DAT1. Results: Logistic regression analysis was performed and controlled for gender, age, ethnicity, educational level, and comorbidities of clinical interest (generalized anxiety disorder, suicide risk, major depressive episode, and attention deficit/hyperactivity disorder). This analysis showed that the 6R6R genotype was associated with crack cocaine addiction (OR = 1.844; CI = 1.101–3.089; p = 0.020). Conclusions: Our results are consistent with the role of DAT1 in the neurobiology of drug addiction. Nevertheless, the study of other genes, environmental factors, and their interactions is also important to gain a broader understanding of this condition.

Stafne bone defect consists of an asymptomatic, anatomic condition of uncertain origin and rare evolvement, often discovered at random in routine radiographic examinations. It is usually consisted on mandibular salivary gland inclusion as a developmental anomaly represented by a bone concavity usually containing submandibular gland tissue. A 39-year-old woman presented a hypodense lesion in the condyle of the left side of the jaw, discovered randomly. Because of the fact that the lesion mimics a cyst of odontogenic origin, excisional biopsy and later histopathologic analysis were performed. The histologic slices revealed the presence of ectopic serous salivary glands located in the head of the left condyle, characterizing a Stafne defect. Faced with this diagnosis, the conduct was the patient´s periodic follow-up.

Background It is uncertain if whole-pelvic irradiation (WPRT) in addition to dose-escalated prostate bed irradiation (PBRT) improves biochemical progression-free survival (bPFS) after prostatectomy for locally advanced tumors. This study was initiated to analyze if WPRT is associated with bPFS in a patient cohort with dose-escalated (> 70 Gy) PBRT. Methods Patients with locally advanced, node-negative prostate carcinoma who had PBRT with or without WPRT after prostatectomy between 2009 and 2017 were retrospectively analyzed. A simultaneous integrated boost with equivalent-doses-in-2-Gy-fractions (EQD-2) of 79.29 Gy or 71.43 Gy to the prostate bed was applied in patients with margin-positive (or detectable) and margin-negative/undetectable tumors, respectively. WPRT (44 Gy) was offered to patients at an increased risk of lymph node metastases. Results Forty-three patients with PBRT/WPRT and 77 with PBRT-only were identified. Baseline imbalances included shorter surgery-radiotherapy intervals (S-RT-Intervals) and fewer resected lymph nodes in the WPRT group. WPRT was significantly associated with better bPFS in univariate (p = 0.032) and multivariate models (HR = 0.484, p = 0.015). Subgroup analysis indicated a benefit of WPRT (p = 0.029) in patients treated with rising PSA values who mostly had negative margins (74.1%); WPRT was not associated with a longer bPFS in the postoperative setting with almost exclusively positive margins (96.8%). Conclusion We observed a longer bPFS after WPRT compared to PBRT in patients with locally advanced prostate carcinoma who underwent dose-escalated radiotherapy. In subset analyses, the association was only observed in patients with rising PSA values but not in patients with non-salvage postoperative radiotherapy for positive margins. Electronic supplementary material The online version of this article (10.1186/s13014-019-1301-5) contains supplementary material, which is available to authorized users.

Background Dysregulation of the hypothalamic–pituitaryadrenal (HPA) axis has been associated with craving and early relapse among individuals with substance use disorders. However, no association has been postulated regarding treatment retention and prognosis in crack cocaine users. Objective Our aim was to investigate the association between morning salivary cortisol levels and treatment retention in crack cocaine users. Methods 44 male crack cocaine users were recruited from a detoxification unit. Saliva collection was performed in the morning of the second treatment day. Substance use profile was assessed using the Addiction Severity Index. Results The median length of stay in inpatient treatment was 7 days (IQR 3–16). Treatment retention was associated with cortisol levels (r = −0.324; p = 0.032), especially in the group with positive family history. Moreover, treatment retention was correlated with age (r = 0.333, p = 0.027), and number of days of tobacco use (r = 0.332, p = 0.028) and crack use (r = 0.327, p = 0.031). A Cox regression model was performed and showed that inpatients with above normal cortisol levels (≥0.69 µg/dL) presented a worse prognostic related to treatment retention (HR = 2.39, CI95% 1.1–5.1, p = 0.024). Conclusion Several factors could contribute to increased cortisol levels in these patients, e.g. craving, dysregulation of the HPA axis, chronic drug use, stress due to confinement, and substance abstinence. Nevertheless, our findings could guide further studies about new biomarkers in crack cocaine use disorder, since HPA axis dysregulation at the time of treatment admittance may be a prognostic marker for treatment retention.

Synaptotagmin-1 is an essential regulator of synaptic vesicle exocytosis, and its encoding gene (SYT1) is a genome and transcriptome-wide association hit in cognitive performance, personality and cocaine use disorder (CUD) studies. Additionally, in candidate gene studies the specific variant rs2251214 has been associated with attention-deficit/hyperactivity disorder (ADHD), antisocial personality disorder and other externalizing phenotypes in adults with ADHD, as well as with response to methylphenidate (MPH) treatment. In this context, we sought to evaluate, in an independent sample, the association of this variant with CUD, a phenotype that shares common biological underpinnings with the previously associated traits. We tested the association between SYT1-rs2251214 and CUD susceptibility and severity (addiction severity index) in a sample composed by 315 patients addicted to smoked cocaine and 769 non-addicted volunteers. SYT1-rs2251214 was significantly associated with susceptibility to CUD, where the G allele presented increased risk for the disorder in the genetic models tested (P = 0.0021, OR = 1.44, allelic; P = 0.0012, OR = 1.48, additive; P = 0.0127, OR = 1.41, dominant). This is the same allele that was associated with increased risk for ADHD and other externalizing behaviors, as well as poor response to MPH treatment in previous studies. These findings suggest that the neurotransmitter exocytosis pathway might play a critical role in the liability for psychiatric disorders, especially externalizing behaviors and CUD.

Rheumatoid arthritis (RA) has been associated with early senescent features. However, the effects of disease progression on senescence markers are largely unknown. Here, we evaluated key senescence markers in RA, including telomere length and T cell differentiation stages as well as cytomegalovirus (CMV) serology, previously associated with premature aging. In a cross-sectional study, 44 patients with active (Ac-RA), 26 patients with controlled (Co-RA), and 30 healthy controls were recruited. Peripheral blood was collected and differentiation stages of T cells analyzed by multi-color flow cytometry. Enzyme-linked immunosorbent assays were used to evaluate the CMV serology. The telomere length was measured by multiplex quantitative PCR. Patients with Ac-RA presented lower percentage of intermediate-differentiated T cells (CD4+CD27-CD28+ and CD8+CD27-CD28+; p

Crack cocaine use disorder (CUD) has been related to sex differences. This work aimed to compare the severity of drug use and the severity of other negative related outcomes in males and females with CUD. A total of 1344 inpatients (798 males and 546 females) with crack cocaine use disorder (CUD) were evaluated by a detailed multidimensional clinical assessment, including addiction severity and trauma exposure. Linear regression predicted higher drug use severity (β = 0.273, p < 0.001) and more problems in domains related to childcare issues (β = 0.321), criminal involvement (β = 0.108), work-related problems (β = 0.281) and social support impairments (β = 0.142) for females, all with p < 0.001. Alcohol problems were predicted to be higher in males (β = -0.206, P < 0.001). Females had higher rates of other mental disorders, particularly trauma and stress-related disorders (OR: 3.206, CI: 2.22, 4.61). Important sex differences also emerged in trauma history and HIV infection prevalence. CUD has a more severe clinical presentation among females facing early abstinence. Sex differences in the CUD course indicate the need for consideration of sex-specific interventions and research.