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Objectives: This study aimed to evaluate the evidence of validity and accuracy for the Mindful Self-Care Scale-Brief (B-MSCS) in Brazil among family caregivers of people with cancer., Methods: This was a cross-sectional study with a sample of 203 family caregivers of people with cancer. The instruments used in this study were the following: B-MSCS, Brief Resilience Scale, and Brief Scale for Spiritual/Religious Coping. Exploratory factor analysis was carried out using the principal axis factoring method and direct oblimin oblique rotation, and confirmatory factor analysis using the robust weighted least squares means and variance adjusted estimation method and GEOMIM oblique rotation. The internal consistency of the latent factors was measured using Cronbach's alpha coefficients., Results: The 6-factor model showed good fit to the data, with satisfactory reliability indices and adequate representation of the scale's internal structure. The results that can support arguments in favor of validity evidence based on internal structure for the B-MSCS-Brazilian version (BR) relate to a 19-item version which, grouped into 6 latent factors, explained 46.47% of the variance. The factor solution reproduced 79.2% of the theoretically expected structure and 5 items were excluded. The Cronbach's alpha coefficient of the factors in the B-MSCS-BR ranged from 0.58 to 0.84. Positive religious/spiritual coping had a direct association with the B-MSCS-BR factors, with the exception of the Physical Care factor ( r = 0.033, p = 0.635). Negative spiritual/religious coping was inversely associated with the Mindful Relaxation ( r = -0.160, p = 0.023), Supportive Relationships ( r = -0.142, p = 0.043), and Mindful Awareness factors ( r = -0.140, p = 0.045). There were no associations between the B-MSCS-BR factors and resilience., Significance of Results: The findings reveal that the B-MSCS (19-item) is a valid, reliable, and culturally-appropriate instrument to examine the practice of mindful self-care by family caregivers of people with cancer in Brazil.

This study evaluated the psychometric properties of the Spiritual Well-Being Scale (SWBS) in a Brazilian sample. We analyzed spiritual well-being, defined as existential well-being (EWB) and religious well-being (RWB), among individuals with varying religious and spiritual experiences, both users and non-users of psychedelics. The online cross-sectional survey was conducted in Brazil, from April to June 2022. The psychometric analyses demonstrated reliability and validity based on the internal structure and the relationship with satisfactory external variables concerning the RWB and EWB factors of the SWBS. Validity evidence was shown for both factors (RWB, EWB) with adequate reliability ratings. However, the RWB factor, which was entirely replicated, demonstrated the best group differentiation and internal consistency. Although both factors showed validity, the RWB factor exhibited superior psychometric indices for validity, group discrimination, and reliability. Regarding psychedelics, the association with RWB and EWB demonstrates a U-shaped pattern, as participants who never use these substances typically exhibit higher RWB and EWB indices, succeeded by frequent users. This finding underscores the need for additional studies to further explore the intricate interplay between psychedelics and spiritual well-being.

Purpose: To identify associations of common, low-frequency, and rare variants with advanced age-related macular degeneration (AMD) using whole genome sequencing (WGS)., Methods: WGS data were obtained for 2123 advanced AMD patients (participants of clinical trials for advanced AMD) and 2704 controls (participants of clinical trials for asthma [N = 2518] and Alzheimer's disease [N = 186]), and joint genotype calling was performed, followed by quality control of the dataset. Single variant association analyses were performed for all identified common, low-frequency, and rare variants. Gene-based tests were executed for rare and low-frequency variants using SKAT-O and three groups of variants based on putative impact information: (1) all variants, (2) modifier impact variants, and (3) high- and moderate-impact variants. To ascertain independence of the identified associations from previously reported AMD and asthma loci, conditional analyses were performed., Results: Previously identified AMD variants at the CFH, ARMS2/HTRA1, APOE, and C3 loci were associated with AMD at a genome-wide significance level. We identified new single variant associations for common variants near the PARK7 gene and in the long non-coding RNA AC103876.1, and for a rare variant near the TENM3 gene. In addition, gene-based association analyses identified a burden of modifier variants in eight intergenic and gene-spanning regions and of high- and moderate-impact variants in the C3, CFHR5, SLC16A8, and CFI genes., Conclusions: We describe the largest WGS study in AMD to date. We confirmed previously identified associations and identified several novel associations that are worth exploring in further follow-up studies.

Although bioderived flame retardants are environmentally sustainable and less toxic, their impact on the thermal stability and flammability of polymers remains poorly understood. In this study, we assessed the influence of mycelium on the thermal stability and flame spread characteristics of epoxy through thermogravimetric analysis, Fourier transform infrared spectroscopy, the UL94 flammability test, and scanning electron microscopy. We observed a decrease in the maximum mass loss rate temperature when mycelium was incorporated into epoxy, indicating an earlier onset of thermal degradation. The inclusion of mycelium increased char yields above 418 °C due to mycelium's inherent char-forming ability. However, mycelium did not alter the thermal degradation pathway of epoxy. Furthermore, according to the UL94 test results, the incorporation of mycelium reduced the flame spread rate compared to that of neat epoxy. These findings contribute to our understanding of the interaction between bioderived flame retardants and polymers paving the way for the development of more sustainable fireproofing materials., (© 2023. Springer Nature Limited.)

Reflectance hyperspectroscopy is recognised for its potential to elucidate biochemical changes, thereby enhancing the understanding of plant biochemistry. This study used the UV-VIS-NIR-SWIR spectral range to identify the different biochemical constituents in Hibiscus and Geranium plants. Hyperspectral vegetation indices (HVIs), principal component analysis (PCA), and correlation matrices provided in-depth insights into spectral differences. Through the application of advanced algorithms-such as PLS, VIP, i PLS-VIP, GA, RF, and CARS-the most responsive wavelengths were discerned. PLSR models consistently achieved R 2 values above 0.75, presenting noteworthy predictions of 0.86 for DPPH and 0.89 for lignin. The red-edge and SWIR bands displayed strong associations with pivotal plant pigments and structural molecules, thus expanding the perspectives on leaf spectral dynamics. These findings highlight the efficacy of spectroscopy coupled with multivariate analysis in evaluating the management of biochemical compounds. A technique was introduced to measure the photosynthetic pigments and structural compounds via hyperspectroscopy across UV-VIS-NIR-SWIR, underpinned by rapid multivariate PLSR. Collectively, our results underscore the burgeoning potential of hyperspectroscopy in precision agriculture. This indicates a promising paradigm shift in plant phenotyping and biochemical evaluation.

The study of the coping strategies used by humans to cope with their finitude has been the center of attention of several researchers throughout the history of psychology. The present study aimed to translate, culturally adapt, and validate the Death Transcendence Scale (DTS) for the Brazilian context. This was a cross-sectional study with a sample of 517 Brazilians. The European Organisation for Research and Treatment of Cancer - Quality of Life Group Translation Procedure protocol was used for the translation and the cultural adaptation process. The results of parallel analyses indicated the relevance of extracting up to five factors, which explained 58.23% of the scale's total variance. The Brazilian version of the DTS, with validity evidence, consisted of 21 items, considering that items 13, 17, 20, and 21 were excluded according to exploratory factor analysis. As far as we know, the version of the DTS developed in this study is the only instrument available in the Brazilian context that allows the measurement of a theory dedicated to understanding how humans cope with their finitude, beyond death denial., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To establish the incidence of pancreatic trauma in North Queensland to the region's only tertiary paediatric referral centre, and to determine the patient's outcomes based on their management., Methods: A single centre, retrospective cohort study of patients < 18 years with pancreatic trauma from 2009 to 2020 was performed. There were no exclusion criteria., Results: Between 2009 and 2020 there were 145 intra-abdominal trauma cases, 37% from motor vehicle accidents (MVA), 18.6% motorbike or quadbike, and 12.4% bicycle or scooter accidents. There were 19 cases of pancreatic trauma (13%), all from blunt trauma and with associated injuries. There were 5 AAST grade I, 3 grade II, 3 grade III, 3 grade IV injuries, and 4 with traumatic pancreatitis. Twelve patients were managed conservatively, 2 were managed operatively for another reason, and 5 were managed operatively for the pancreatic injury. Only 1 patient with a high grade AAST injury was successfully managed non-operatively. Complications included pancreatic pseudocyst (n = 4/19; 3 post-op), pancreatitis (n = 2/19; 1 post op), and post-operative pancreatic fistula (POPF) (n = 1/19)., Conclusion: Due to North Queensland's geography, diagnosis and management of traumatic pancreatic injury is often delayed. Pancreatic injuries requiring surgery are at high risk for complications, prolonged length of stay, and further interventions., (© 2023. Crown.)

The paper critically analyzed different interfacial enhancing methods used in thermoplastic composites. Although the absence of cross-linked polymer chains and chemical bonds on solidification enables the thermoplastics to be remelted, it creates weak interfacial adhesion between fibre reinforcements and the thermoplastic matrix. The weak fibre-matrix interface bonding reduces the efficiency with which the applied load can be transferred between these composite constituents, causing the composite to fail prematurely. Their need for high-temperature processing, poor compatibility with other polymer matrices, and relatively high viscosity render thermoplastics challenging when used to manufacture composite laminates. Therefore, various methods, including nanoparticles, changing the polarity of the fibre surface by plasma etching, chemical treatment with ozone, or an oxidative attack at the fibre surface, have been applied to improve the fibre/matrix bonding in thermoplastic composites. The fabrication steps followed in these techniques, their progress in research, and the associated toughening mechanisms are comprehensively discussed in this paper. The effect of different fibre-matrix interfacial enhancement methods on the mechanical properties of thermoplastic composites is also deliberated.

Silicone elastomers are widely recognised as artificial skins for medical prosthesis and cranial injury assessment. Since silicone is not an ideal skin simulant due to the lack of mechanical stiffness and a fibrous structure, the present study aimed to tailor the mechanical and structural characteristics of silicone by integrating biocompatible reinforcements (namely, short polyethylene fibres and bioglass particles) to develop suitable bio-integrative skin simulant candidates. The influences of short polyethylene fibres and bioglass particles in the selected platinum silicone on the mechanical properties of silicone-based composite skin simulants were investigated with various factors, including filler concentration, KMnO 4 surface treatment of the polyethylene fibre, and particle size. A comprehensive assessment of the tensile, compressive, and hardness properties of the examined composites was conducted, and they were compared with the properties of human biological skin. The results exhibited that the elastic moduli and the hardness of all composites increased with the concentration of both reinforcements. While integrating only the bioglass particles had the advantage of an insignificant effect on the hardness change of the silicone matrix, the composite with polyethylene fibres possessed superior tensile elastic modulus and tensile strength compared to those of the bioglass reinforced composite. The composites with 5% untreated polyethylene fibres, KMnO 4 surface-treated fibres, and bioglass reinforcements enhanced the tensile elastic moduli from the pure silicone up to 32%, 44%, and 22%, respectively. It reflected that the surface treatment of the fibres promotes better interfacial adhesion between the silicone matrix and the fibres. Moreover, the smaller bioglass particle had a greater mechanical contribution than the larger glass particle. Systematically characterised for the first time, the developed composite skin simulants demonstrated essential mechanical properties within the range of the human skin and constituted better skin alternatives than pure silicone for various biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to translate, culturally adapt, and validate the Mindful Self-Care Scale (MSCS, 33-item) in a Brazilian hospice and palliative care context., Method: This was a cross-sectional study with a sample of 336 Brazilian hospice and palliative care providers. The European Organisation for Research and Treatment of Cancer - Quality of Life Group Translation Procedure protocol was used for the translation and the cultural adaptation process. Psychometric properties supporting the use of the MSCS were examined through confirmatory factor analysis (CFA) and correlation analysis with other instruments to assess congruence to related constructs (resilience and self-compassion). The reliability of the Brazilian-Portuguese version of the MSCS was assessed using Cronbach's α and composite reliability coefficients., Results: The six-factor (33-item) model showed a good fit to the data, with satisfactory reliability indices and adequate representation of the scale's internal structure. Further validity is evidenced in the significant, positive correlations found between the MSCS, and similar well-being constructs, namely the Self-Compassion and Resilience scales., Significance of Results: The findings reveal that the MSCS (33-item) is a valid, reliable, and culturally appropriate instrument to examine the practice of mindful self-care by hospice and palliative care providers in Brazil. More broadly, it represents a promising instrument for future research into self-care practices and well-being among Brazilian healthcare providers.

Mycelium fungal species exhibit fire retardant characteristics. The influence of the growth media on the fungal growth rates, biochemical composition, and microstructural characteristics and their relationship to thermal properties is poorly understood. In this paper, we demonstrate that molasses can support the growth of non-pathogenic Basidiomycota phylum fungal species producing bio-derived materials with potential fire retardation characteristics. Scanning electron microscopy and Fourier transform infrared (FTIR) spectrometry were used to interrogate the microstructural and biochemical properties of the molasses-grown mycelia species. Thermal decomposition of molasses-fed mycelia was evaluated via thermogravimetric analysis interfaced with FTIR for real-time evolved gas analysis. The morphological and microstructural characteristics of the residual char post-thermal exposure were also evaluated. The material characterization enabled the establishment of a relationship between the microstructural, biochemical properties, and thermal properties of molasses-fed mycelia. This paper presents a comprehensive exploration of the mechanisms governing the thermal degradation of three mycelial species grown in molasses. These research findings advance the knowledge of critical parameters controlling fungal growth rates and yields as well as how the microstructural and biochemical properties influence the thermal response of mycelia., (© 2022. The Author(s).)

Objective: To analyze the association between team climate, team characteristics and satisfaction at work in teams of the Estratégia Saúde da Família com Saúde Bucal (Family Health Strategy with Oral Health) (ESF with SB)., Methods: Cross-sectional correlational study with ESF teams with SB in the municipality of São Paulo. Universe of 1,328 teams and random sample of 124 teams with 1,231 professionals. Applied questionnaire with data teams' characterization, team climate scale, and satisfaction at work. Analysis of validity, of climate and satisfaction scores through mean among professionals in each team, cluster analysis, association between variables by Pearson's correlation and Chi-square, and tested linear regression model for the two factors of satisfaction at work., Results: There was a directly proportional association between team climate and satisfaction at work. The better the climate with regard to team goals, the greater the intrinsic satisfaction at work and with the physical environment. The better the climate with regard to team goals and task orientation, the greater the satisfaction with hierarchical relations. The group with best team climate reported higher percentage of teams ranked with better satisfaction at work, and in the group with the worst team climate there was higher percentage of teams with the lowest satisfaction at work., Conclusions: The study provides consistent although moderate evidence of association between favorable teamwork climate and job satisfaction in ESF with SB. It emphasizes the dimensions of climate, common goals and task orientation, and may serve as subsidy for management and permanent education of teams, aiming at the quality of care to the health needs of users, family and community in APS.

Age-related macular degeneration (AMD) is a major cause of vision loss among the elderly in the Western world. The complement system has been identified as one of the main AMD disease pathways. We performed a comprehensive expression analysis of 32 complement proteins in plasma samples of 255 AMD patients and 221 control individuals using mass spectrometry-based semi-quantitative multiplex profiling. We detected significant associations of complement protein levels with age, sex and body-mass index (BMI), and potential associations of C-reactive protein, factor H related-2 (FHR-2) and collectin-11 with AMD. In addition, we confirmed previously described associations and identified new associations of AMD variants with complement levels. New associations include increased C4 levels for rs181705462 at the C2 / CFB locus, decreased vitronectin (VTN) levels for rs11080055 at the TMEM97 / VTN locus and decreased factor I levels for rs10033900 at the CFI locus. Finally, we detected significant associations between AMD-associated metabolites and complement proteins in plasma. The most significant complement-metabolite associations included increased high density lipoprotein (HDL) subparticle levels with decreased C3, factor H (FH) and VTN levels. The results of our study indicate that demographic factors, genetic variants and circulating metabolites are associated with complement protein components. We suggest that these factors should be considered to design personalized treatment approaches and to increase the success of clinical trials targeting the complement system.

Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy occurring in 30% of the 6 million infected with the protozoan Trypanosoma cruzi in Latin America. Survival is significantly lower in CCC than ischemic (IC) and idiopathic dilated cardiomyopathy (DCM). Previous studies disclosed a selective decrease in mitochondrial ATP synthase alpha expression and creatine kinase activity in CCC myocardium as compared to IDC and IC, as well as decreased in vivo myocardial ATP production. Aiming to identify additional constraints in energy metabolism specific to CCC, we performed a proteomic study in myocardial tissue samples from CCC, IC and DCM obtained at transplantation, in comparison with control myocardial tissue samples from organ donors. Left ventricle free wall myocardial samples were subject to two-dimensional electrophoresis with fluorescent labeling (2D-DIGE) and protein identification by mass spectrometry. We found altered expression of proteins related to mitochondrial energy metabolism, cardiac remodeling, and oxidative stress in the 3 patient groups. Pathways analysis of proteins differentially expressed in CCC disclosed mitochondrial dysfunction, fatty acid metabolism and transmembrane potential of mitochondria. CCC patients' myocardium displayed reduced expression of 22 mitochondrial proteins belonging to energy metabolism pathways, as compared to 17 in DCM and 3 in IC. Significantly, 6 beta-oxidation enzymes were reduced in CCC, while only 2 of them were down-regulated in DCM and 1 in IC. We also observed that the cytokine IFN-gamma, previously described with increased levels in CCC, reduces mitochondrial membrane potential in cardiomyocytes. Results suggest a major reduction of mitochondrial energy metabolism and mitochondrial dysfunction in CCC myocardium which may be in part linked to IFN-gamma. This may partially explain the worse prognosis of CCC as compared to DCM or IC., Competing Interests: PT, AD, and EN are current employees of F. Hoffmann-La Roche Ltd and may own company stock. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Teixeira, Ducret, Langen, Nogoceke, Santos, Silva Nunes, Benvenuti, Levy, Bydlowski, Bocchi, Kuramoto Takara, Fiorelli, Stolf, Pomeranzeff, Chevillard, Kalil and Cunha-Neto.)

Polymer matrix composite materials have the capacity to aid the indirect transmission of viral diseases. Published research shows that respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19), can attach to polymer substrata as a result of being contacted by airborne droplets resulting from infected people sneezing or coughing in close proximity. Polymer matrix composites are used to produce a wide range of products that are "high-touch" surfaces, such as sporting goods, laptop computers and household fittings, and these surfaces can be readily contaminated by pathogens. This article reviews published research on the retention of SARS-CoV-2 and other virus types on plastics. The factors controlling the viral retention time on plastic surfaces are examined and the implications for viral retention on polymer composite materials are discussed. Potential strategies that can be used to impart antiviral properties to polymer composite surfaces are evaluated. These strategies include modification of the surface composition with biocidal agents (e.g., antiviral polymers and nanoparticles) and surface nanotexturing. The potential application of these surface modification strategies in the creation of antiviral polymer composite surfaces is discussed, which opens up an exciting new field of research for composite materials., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Nano Select published by Wiley‐VCH GmbH.)

Age-related macular degeneration (AMD) is the principal cause of blindness in the elderly population. A strong effect on AMD risk has been reported for genetic variants at the CFH locus, encompassing complement factor H (CFH) and the complement-factor-H-related (CFHR) genes, but the underlying mechanisms are not fully understood. We aimed to dissect the role of factor H (FH) and FH-related (FHR) proteins in AMD in a cohort of 202 controls and 216 individuals with AMD. We detected elevated systemic levels of FHR-1 (p = 1.84 × 10 -6 ), FHR-2 (p = 1.47 × 10 -4 ), FHR-3 (p = 1.05 × 10 -5 ) and FHR-4A (p = 1.22 × 10 -2 ) in AMD, whereas FH concentrations remained unchanged. Common AMD genetic variants and haplotypes at the CFH locus strongly associated with FHR protein concentrations (e.g., FH p.Tyr402His and FHR-2 concentrations, p = 3.68 × 10 -17 ), whereas the association with FH concentrations was limited. Furthermore, in an International AMD Genomics Consortium cohort of 17,596 controls and 15,894 individuals with AMD, we found that low-frequency and rare protein-altering CFHR2 and CFHR5 variants associated with AMD independently of all previously reported genome-wide association study (GWAS) signals (p = 5.03 × 10 -3 and p = 2.81 × 10 -6 , respectively). Low-frequency variants in CFHR2 and CFHR5 led to reduced or absent FHR-2 and FHR-5 concentrations (e.g., p.Cys72Tyr in CFHR2 and FHR-2, p = 2.46 × 10 -16 ). Finally, we showed localization of FHR-2 and FHR-5 in the choriocapillaris and in drusen. Our study identifies FHR proteins as key proteins in the AMD disease mechanism. Consequently, therapies that modulate FHR proteins might be effective for treating or preventing progression of AMD. Such therapies could target specific individuals with AMD on the basis of their genotypes at the CFH locus., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

This paper reports on a cross-sectional study performed with 370 students and graduates from 15 undergraduate health courses in a public university in Rio Grande do Sul, Brazil. The objective was to identify interprofessional education (IPE) curricular experiences and to evaluate the readiness for IPE among students and graduates who have attended a practical experience of IPE (Integrative Module) compared with undergraduate students who did not. The dimensionality and reliability of the Portuguese-validated expanded version of the Readiness for Interprofessional Learning Scale (RIPLS) with 40-items were also evaluated. This version of RIPLS was validated with 32 items. Cronbach's alpha values of the three factors of the scale were: Factor 1 α = 0.89, Factor 2 α = 0.47 and Factor 3 α = 0.83. IPE initiatives were identified in the undergraduate curricula mainly in the practical experience (Integrative Module) (47.5%), curricular placements (29.8%) and extracurricular activities (29.5%). Students and graduates who participated in the Integrative Module demonstrated greater readiness for IPE than students who did not attend. This study suggested that shared experiences among different undergraduate courses are associated with positive attitudes and greater availability of students and graduates for interprofessional learning and work. Future studies including the psychometric analysis of the Portuguese-validated expanded RIPLS are recommended.

Objective: to assess the evidence of validity and reliability of the academic motivation scale (AMS) based on the internal structure., Method: this is a methodological study with 205 undergraduate nursing students. Dimensionality/internal structure of the AMS was assessed using factor analysis in the context of exploratory structural equation modeling (ESEM) and reliability of the factors was assessed by Cronbach's alpha (α) coefficient and composite reliability (CR) coefficient., Results: acceptable fit indexes were obtained (CFI = 0.92; RMSEA = 0.07; SRMR = 0.06) for a three-dimensional model: intrinsic motivation (10 items; α = 0.84; CR = 0.86); extrinsic motivation (8 items; α = 0.84; CR = 0.90); and demotivation (4 items; α = 0.84; CR = 0.88). A significant correlational pattern was found for the motivation continuum., Conclusion: the dimensionality analysis for the AMS presented a model with three factors: intrinsic motivation, extrinsic motivation and demotivation, and was considered a reduced alternative to the original version of seven factors. This study helped assess the validity of the measurement instrument and its theory refinement; further studies should be conducted to assess its invariance property.

Background: To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status., Methods/design: This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change in physical performance using the Short Physical Performance Battery, handgrip strength, fatigue, gait speed, dual-task gait speed, depressive symptoms, FRAIL-BR and SARC-F scores, and quality of life at the 12-week period of intervention and after 3 months of follow-up., Discussion: We expect a reduction in inflammatory interleukins or an increase in anti-inflammatory mediators in those who performed the VIVIFRAIL© protocol. The results of the study will imply in a better knowledge about the effect of a low-cost intervention that could be easily replicated in outpatient care for the prevention and treatment of frailty, especially regarding the inflammatory and anti-inflammatory pathways involved in its pathophysiology., Trial Registration: Brazilian Registry of Clinical Trials (RBR-9n5jbw; 01/24/2020). Registred January 2020. http://www.ensaiosclinicos.gov.br/rg/RBR-9n5jbw/ .

Objectives: The aim of this study was to translate, culturally adapt, and psychometrically evaluate the Brazilian version of the "End-of-Life Professional Caregiver Survey" (BR-EPCS)., Method: This is an observational cross-sectional study. The sample was composed of 285 Brazilian healthcare professionals who work or worked in the palliative care area. A minimum number of 280 participants were established, following the recommendation of 10 subjects for each instrument item. The European Organisation for Research and Treatment of Cancer - Quality of Life Group Translation Procedure protocol was used for the translation and the cultural adaptation. For the precise/reliable evaluation of factors measured by the BR-EPCS, Cronbach's alpha (α) and composite reliability coefficients were used. The factorial analyses were made by means of the exploratory structural equation modeling methods and confirmatory factor analysis. We have conducted a multiple linear regression analysis to evaluate the sociodemographic variables' capabilities in the result prediction measured by BR-EPCS factors., Results: The factorial analysis showed the relevance of two factors: Factor 1 - "Given care effectiveness" (18 items; Cronbach's α = 0.94; Composite Reliability = 0.95) and Factor 2 - "Mourning and ethical and cultural values" (10 items; Cronbach's α = 0.89; Composite Reliability = 0.88). Multiple linear regression analyses revealed that the working time, sex, palliative care training, and its own advance directives are predictors of the constructs assessed by the BR-EPCS., Significance of Results: The BR-EPCS is a reliable, valid, and culturally appropriate tool to identify the educational needs of healthcare professionals who work with palliative care. This instrument can be used for educational and research reasons.

Despite annual climate variability threats, traditional farming in semi-arid Zimbabwe remains entrenched in unproductive, rain-fed agricultural practices. Adaptation strategies by farmers are seemingly failing to mitigate climate impacts, as evidenced by annual crop and livestock losses. Matabeleland South Province was a thriving livestock and small grain-producing province in the 1970s. Today, the province relies heavily on humanitarian assistance from government and humanitarian agencies. Through literature review, observations and focus group discussions with 129 farmers, the qualitative study established the perceptions of farmers around climate variability impacts in the past 20 years in Mangwe, Matobo and Gwanda districts in Zimbabwe. The study (1) analysed changes in climate and weather patterns in the past 20 years; (2) analysed climate impacts on traditional farming systems in the past 20 years in Gwanda, Mangwe and Matobo districts in Zimbabwe; and (3) established farmers' perceptions, experiences and their climate adaptive strategies. The findings showed that the farmers experienced annual heat waves, protracted droughts, chaotic rain seasons, frost and floods, which led to environmental degradation. Traditional farming systems or practices have been abandoned in favour of buying and selling and gold panning, among other alternative livelihood options, because of climate-related threats and misconceptions around the subject of climate change. Farmers fail to access timely and comprehensive weather forecasts, resulting in annual crop and livestock losses, as decision-making is compromised. Given that the smallholder farming system sustains the bulk of the population in Matabeleland South Province in Zimbabwe, climate education and capital investment is needed to change traditional farmer perceptions about climate change impacts on the farming practices. Increased climate awareness initiatives, establishment of village-based weather stations and the marrying of traditional farming climate knowledge to modern practices are highly recommended to enhance resilience to climate., Competing Interests: The authors have declared that no competing interests exist., (© 2020. The Authors.)

Importance: Faricimab, the first bispecific antibody designed for intraocular use, simultaneously and independently binds and neutralizes angiopoietin 2 (Ang-2) and vascular endothelial growth factor A (VEGF-A)., Objective: To assess the efficacy and safety of different doses and regimens of faricimab vs ranibizumab in patients with neovascular age-related macular degeneration (nAMD)., Design, Setting, and Participants: AVENUE was a 36-week, multiple-dose-regimen, active comparator-controlled, double-masked, phase 2 randomized clinical study performed at 58 sites in the United States. Eligible participants were anti-VEGF treatment naive with choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 73 (Snellen equivalent, 20/40) to 24 (Snellen equivalent, 20/320). Data were collected from August 11, 2015, to January 12, 2017, with the final patient visit completed September 26, 2017. Data were analyzed from August 11, 2015, to October 4, 2019., Interventions: Patients were randomized 3:2:2:2:3 to receive ranibizumab, 0.5 mg every 4 weeks (arm A [n = 68]); faricimab, 1.5 mg every 4 weeks (arm B [n = 47]); faricimab, 6.0 mg every 4 weeks (arm C [n = 42]); faricimab, 6.0 mg every 4 weeks until week 12, then faricimab, 6.0 mg every 8 weeks (arm D [n = 47]); and ranibizumab, 0.5 mg every 4 weeks until week 8, then faricimab, 6.0 mg every 4 weeks (arm E [n = 69])., Main Outcomes and Measures: Mean change in BCVA from baseline to week 36, proportion of participants gaining at least 15 letters, BCVA of 20/40 or better or 20/200 or worse, and ocular coherence tomographic outcomes in anti-VEGF treatment-naive participants (arms A, B, C, D) and from weeks 12 to 36 in those with incomplete response (participants in arms A and E with week 12 BCVA ETDRS letter score of ≤68 [Snellen equivalent, 20/50 or worse])., Results: A total of 263 participants were included in the analysis (172 [65.4%] female; 258 [98.1%] white; mean [SD] age, 78.3 [8.7] years). At week 36, adjusted mean change in BCVA vs ranibizumab was 1.6 (80% CI, -1.6 to 4.7) letters for arm B (P = .52), -1.6 (80% CI, -4.9 to 1.7) letters for arm C (P = .53), and -1.5 (80% CI, -4.6 to 1.6) letters for arm D (P = .53). For arm E, adjusted mean change from week 12 was -1.7 (80% CI, -3.8 to 0.4) letters (P = .30)., Conclusions and Relevance: AVENUE did not meet its primary end point of superiority of faricimab over ranibizumab in BCVA at week 36. Although not superior to monthly ranibizumab as given in this trial, overall visual and anatomical gains noted with faricimab support pursuing phase 3 trials for a potential alternative to monthly anti-VEGF therapy. Faricimab showed no new or unexpected safety signals., Trial Registration: ClinicalTrials.gov Identifier: NCT02484690.

Objective: To identify the social reproduction characteristics of nursing undergraduates., Method: A quantitative descriptive cross-sectional study conducted in two undergraduate degree courses in nursing, one public and one private, in the state of São Paulo., Results: There were 285 students who participated, with 195 from the public university and 90 from the private one, who answered a questionnaire to classify social reproduction profiles. Four groups with different social conditions were identified. Although most families had stable living conditions, the percentage of families with poor working and living conditions was not negligible., Conclusion: The analysis on the social reproduction of the families of undergraduate students of the two courses exposed stability gradients which are compatible with intermediate social strata.

Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field., Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized., Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year., Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method., Competing Interests: None

Purpose: To identify whether the colon mucosa is affected by ten days of gastric restriction in an animal model., Methods: An experimental model of gastric restriction was devised using rats. The animals were submitted to surgical gastrostomy, and a cylindrical loofah was inserted into the stomach. We studied 30 adult male Wistar rats divided into three groups: the stomach restriction group (R10); the sham group (S10), which underwent the same procedure except for the loofah insertion; and the control group (C10). The expression of neutral and acid mucins was evaluated using histochemical techniques. Goblet cells and protein content were compared between groups using generalized estimation equations (GEEs). Bonferroni's multiple comparison was applied to identify differences between the groups. All tests considered a 5% significance level., Results: There was an increased expression of neutral mucins, acid mucins and goblet cells in the R10 group. Collagen was also enhanced in the R10 group., Conclusion: The colon mucosa is affected by ten days of gastric restriction in an animal model, increasing neutral mucins, acid mucins and collagen content with trophic maintenance.

Purpose: The phase 2 BOULEVARD trial compared safety and efficacy of faricimab, a novel bispecific antibody targeting angiopoietin-2 and vascular endothelial growth factor-A (VEGF-A), with ranibizumab in patients with diabetic macular edema (DME)., Design: The BOULEVARD trial (ClinicalTrials.gov identifier, NCT02699450) was a prospective, randomized, active comparator-controlled, double-masked, multicenter, phase 2 study conducted at 59 sites in the United States., Participants: The trial enrolled patients 18 years of age or older with center-involving DME, best-corrected visual acuity (BCVA) of 73 to 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and central subfield thickness (CST) of 325 μm or more., Methods: Anti-VEGF treatment-naïve patients were randomized 1:1:1 to intravitreal 6.0 mg faricimab, 1.5 mg faricimab, or 0.3 mg ranibizumab, and patients previously treated with anti-VEGF were randomized 1:1 to 6.0 mg faricimab or 0.3 mg ranibizumab. Patients were dosed monthly for 20 weeks, followed by an observation period up to week 36 to assess durability., Main Outcome Measures: The prespecified primary outcome measure was mean change in BCVA from baseline at week 24 for faricimab versus ranibizumab in treatment-naïve patients. Key secondary and exploratory outcome measures included CST, Diabetic Retinopathy Severity Scale (DRSS) score, and durability as assessed by time to re-treatment., Results: The trial enrolled 229 patients (168 treatment-naïve and 61 previously treated with anti-VEGF). In treatment-naïve patients, 6.0 mg faricimab, 1.5 mg faricimab, and 0.3 mg ranibizumab resulted in mean improvements of 13.9, 11.7, and 10.3 ETDRS letters from baseline, respectively. The 6.0-mg faricimab dose demonstrated a statistically significant gain of 3.6 letters over ranibizumab (P = 0.03). In both patient populations, faricimab resulted in dose-dependent reductions in CST, improvements in DRSS score, and longer time to re-treatment during the observation period compared with ranibizumab. Faricimab showed no new or unexpected safety signals., Conclusions: The BOULEVARD trial met its primary end point; faricimab demonstrated statistically superior visual acuity gains versus ranibizumab at week 24 in treatment-naïve patients. Central subfield thickness reduction, DRSS score improvement, and extended durability outcomes support the primary outcome. These findings suggest the benefit of simultaneous inhibition of angiopoietin-2 and VEGF-A with faricimab for patients with DME., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: Novel bifunctional VEGF-A neutralizing therapies are being developed for the treatment of retinal vascular diseases such as age-related macular degeneration and diabetic retinopathy. In developing new therapeutic drugs, only small aqueous humor sample volumes are available for analyzing several parameters. Highly sensitive detection methods must be applied in analyzing VEGF-A levels in ocular fluids in order to demonstrate VEGF-A suppression following drug administration. Experimental: A highly sensitive immunoassay for VEGF-A was developed on the single molecule array (Simoa) platform, and validated before being used for the analysis of clinical aqueous humor samples from patients treated with anti-VEGF-A therapeutics. Results: This highly sensitive immunoassay allows the detection of baseline VEGF-A levels and suppression effects after drug administration, even in sample volumes as low as 12 μl. Conclusion: The Simoa VEGF-A assay is a valuable tool for the reliable monitoring of VEGF-A suppression after intravitreal administration of anti-VEGF-A drugs.

Mycelium and mycelium-biomass composites are emerging as new sustainable materials with useful flame-retardant potentials. Here we report a detailed characterisation of the thermal degradation and fire properties of fungal mycelium and mycelium-biomass composites. Measurements and analyses are carried out on key parameters such as decomposition temperatures, residual char, and gases evolved during pyrolysis. Pyrolysis flow combustion calorimetry (PCFC) evaluations reveal that the corresponding combustion propensity of mycelium is significantly lower compared to poly(methyl methacrylate) (PMMA) and polylactic acid (PLA), indicating that they are noticeably less prone to ignition and flaming combustion, and therefore safer to use. The hyphal diameters of mycelium decrease following pyrolysis. Cone calorimetry testing results show that the presence of mycelium has a positive influence on the fire reaction properties of wheat grains. This improvement is attributable to the relatively higher charring tendency of mycelium compared to wheat grain, which reduces the heat release rate (HRR) by acting as a thermal insulator and by limiting the supply of combustible gases to the flame front. The mycelium growth time has been found to yield no significant improvements in the fire properties of mycelium-wheat grain composites.

Atypical porcine pestivirus (APPV) has been associated with congenital tremor (CT) type A-II in newborn piglets. Although the number of APPV-based studies is increasing, the associated pathologic findings in infected piglets are underreported. This study describes the histopathologic features of spontaneous APPV infection in CT-affected piglets and complements a previous report by our group. Four two-day-old piglets with CT were evaluated by histopathology, immunohistochemistry (IHC), and molecular assay. The main histopathologic findings at the brain and spinal cord included neuronal necrosis, gliosis, neuronophagia, satellitosis, demyelination, Wallerian degeneration, and Purkinje cell necrosis. An IHC assay designed to detect the proliferation of glial fibrillary acidic protein (GFAP) in affected areas of the brain and spinal cord revealed that the proliferation of GFAP + cells and fibers was predominant in APPV-infected piglets relative to asymptomatic piglets of the same age group. The RT-nested-PCR assays identified APPV RNA in the cerebrum, cerebellum, and brainstem of all piglets; other viruses known to produce similar manifestations were not detected. These results suggest that the APPV-induced histopathologic findings are predominantly degenerative and necrotic and correlate with our previous findings. Consequently, it is proposed that neuronal necrosis, gliosis, neuronophagia, and satellitosis should be considered as important histologic features of APPV-induced infection in symptomatic CT piglets., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objectives: EUS-guided biliary drainage (EUS-BD) was shown to be useful for malignant biliary obstruction (MBO). However, there is lack of consensus on how EUS-BD should be performed., Methods: This was a worldwide multi-institutional survey among members of the International Society of EUS conducted in February 2018. The survey consisted of 10 questions related to the practice of EUS-BD., Results: Forty-six endoscopists of them completed the survey. The majority of endoscopists felt that EUS-BD could replace percutaneous transhepatic biliary drainage after failure of ERCP. Among all EUS-BD methods, the rendezvous stenting technique should be the first choice. Self-expandable metal stents (SEMSs) were recommended by most endoscopists. For EUS-guided hepaticogastrostomy (HGS), superiority of partially-covered SEMS over fully-covered SEMS was not in agreement. 6-Fr cystotomes were recommended for fistula creation. During the HGS approach, longer SEMS (8 or 10 cm) was recommended. During the choledochoduodenostomy approach, 6-cm SEMS was recommended. During the intrahepatic (IH) approach, the IH segment 3 was recommended., Conclusion: This is the first worldwide survey on the practice of EUS-BD for MBO. There were wide variations in practice, and randomized studies are urgently needed to establish the best approach for the management of this condition., Competing Interests: There are no conflicts of interest

There is an urgency to find new treatment strategies that could prevent or delay the onset or progression of AMD. Different classes of lipids and lipoproteins metabolism genes have been associated with AMD in a multiple ways, but despite the ever-increasing knowledge base, we still do not understand fully how circulating lipids or local lipid metabolism contribute to AMD. It is essential to clarify whether dietary lipids, systemic or local lipoprotein metabolismtrafficking of lipids in the retina should be targeted in the disease. In this article, we critically evaluate what has been reported in the literature and identify new directions needed to bring about a significant advance in our understanding of the role for lipids in AMD. This may help to develop potential new treatment strategies through targeting the lipid homeostasis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Genome-wide association studies (GWAS) have identified numerous genetic variants in the human genome associated with diseases and traits. Nevertheless, for most loci the causative variant is still unknown. Expression quantitative trait loci (eQTL) in disease relevant tissues is an excellent approach to correlate genetic association with gene expression. While liver is the primary site of gene transcription for two pathways relevant to age-related macular degeneration (AMD), namely the complement system and cholesterol metabolism, we explored the contribution of AMD associated variants to modulate liver gene expression. We extracted publicly available data and computed the largest eQTL data set for liver tissue to date. Genotypes and expression data from all studies underwent rigorous quality control. Subsequently, Matrix eQTL was used to identify significant local eQTL. In total, liver samples from 588 individuals revealed 202,489 significant eQTL variants affecting 1,959 genes (Q-Value < 0.001). In addition, a further 101 independent eQTL signals were identified in 93 of the 1,959 eQTL genes. Importantly, our results independently reinforce the notion that high density lipoprotein metabolism plays a role in AMD pathogenesis. Taken together, our study generated a first comprehensive map reflecting the genetic regulatory landscape of gene expression in liver.

Gweru Rural district in the Midlands province of Zimbabwe has witnessed an increasing number of outward migrations of breadwinners, leaving behind a desperate environment for families. This study was motivated by the realisation that most of the sick left behind, the elderly and children would visit the health centres unaccompanied, risking taking prescribed drugs incorrectly, thus further compromising their health. The study sought to establish the socio-economic effects of international migration on family members left behind in ward 8 of Gweru Rural. The study adopted a qualitative case study approach. Focus group discussions, questionnaires and structured individual interviews were used to elicit for data. Non-probability sampling design was used because of small samples available. Convenience and purposive sampling techniques were particularly used. Data were manually analysed and presented both qualitatively and quantitatively. The study revealed that international migration particularly to South Africa, especially by non- professionals, was not yielding the much expected economic gains; instead it was characterised by more negative social effects on the emigrant's family. The study recommends that emigrants should consider migrating with their loved ones and, where it is not feasible, to put in place sound alternative caregiving arrangements. The study has provided an insight into international migration and its effects on left-behind families. However, a more comprehensive and quantitative survey remains critical to delving deeper into this migration phenomenon, particularly on how both the emigrant and left-behind spouses handle the issue of conjugal rights., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Aims/hypothesis: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique multicentre biobank of human islets and pancreas tissues from organ donors and metabolically phenotyped pancreatectomised patients (PPP)., Methods: Affymetrix microarrays were used to assess the islet transcriptome of islets isolated either by enzymatic digestion from 103 organ donors (OD), including 84 non-diabetic and 19 type 2 diabetic individuals, or by laser capture microdissection (LCM) from surgical specimens of 103 PPP, including 32 non-diabetic, 36 with type 2 diabetes, 15 with impaired glucose tolerance (IGT) and 20 with recent-onset diabetes (<1 year), conceivably secondary to the pancreatic disorder leading to surgery (type 3c diabetes). Bioinformatics tools were used to (1) compare the islet transcriptome of type 2 diabetic vs non-diabetic OD and PPP as well as vs IGT and type 3c diabetes within the PPP group; and (2) identify transcription factors driving gene co-expression modules correlated with insulin secretion ex vivo and glucose tolerance in vivo. Selected genes of interest were validated for their expression and function in beta cells., Results: Comparative transcriptomic analysis identified 19 genes differentially expressed (false discovery rate ≤0.05, fold change ≥1.5) in type 2 diabetic vs non-diabetic islets from OD and PPP. Nine out of these 19 dysregulated genes were not previously reported to be dysregulated in type 2 diabetic islets. Signature genes included TMEM37, which inhibited Ca 2+ -influx and insulin secretion in beta cells, and ARG2 and PPP1R1A, which promoted insulin secretion. Systems biology approaches identified HNF1A, PDX1 and REST as drivers of gene co-expression modules correlated with impaired insulin secretion or glucose tolerance, and 14 out of 19 differentially expressed type 2 diabetic islet signature genes were enriched in these modules. None of these signature genes was significantly dysregulated in islets of PPP with impaired glucose tolerance or type 3c diabetes., Conclusions/interpretation: These studies enabled the stringent definition of a novel transcriptomic signature of type 2 diabetic islets, regardless of islet source and isolation procedure. Lack of this signature in islets from PPP with IGT or type 3c diabetes indicates differences possibly due to peculiarities of these hyperglycaemic conditions and/or a role for duration and severity of hyperglycaemia. Alternatively, these transcriptomic changes capture, but may not precede, beta cell failure.

Background and Aims: Endoscopic ultrasound-guided drainage (EUS-GLB) is a minimally invasive option for patients with cholecystitis who are poor surgical candidates. Compared with percutaneous drainage (PC-GLB), earlier studies have demonstrated similar efficacy with improved quality of life. We present a multicenter, international experience comparing PC-GLB and EUS-GLB in nonsurgical patients with cholecystitis., Methods: All patients who underwent either PC-GLB drainage or EUS-GLB drainage from 7 centers between January 2010 and December 2015 were included. Technical success was defined as successful placement of a catheter or stent into the gallbladder. Clinical success was defined as resolution of clinical symptoms after intervention. Adverse events, length of stay, and the need for repeat interventions and/or hospitalizations were recorded for all patients., Results: A total of 155 patients were included (mean age 74±14.24 y; range, 31 to 96; 56% male). Forty-two patients underwent EUS-GLB and 113 patients underwent PC-GLB. Technical success was achieved in 40 patients (95%) in the EUS-GLB group and 112 patients (99%) in the PC-GLB group (P=0.179). Clinical success was achieved in 40 patients (95%) in the EUS-GLB group and 97 patients (86%) in the PC-GLB group (P=0.157). There was no difference in hospital readmission rates between the 2 groups (14% vs. 24%; P=0.194). However, there was significantly higher number of patients requiring repeat interventions in the PC-GLB group (n=28, 24%) compared with the EUS-GLB group (n=4, 10%) (P=0.037). There was no difference in adverse events between the 2 groups., Conclusions: EUS-GLB is safe and efficacious, with comparable technical and clinical success rates and no difference in adverse events. In addition, EUS-GLB offers a potential cost-saving benefit and morbidity benefit by demonstrating a decreased number of repeat interventions.

Objectives: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN)., Methods: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence., Results: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one., Conclusions: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst drainage and endoscopic necrosectomy should be performed. This survey was carried out amongst members of the EUS Journal Editorial Board to describe their practices in performing this procedure. This was a worldwide multi-institutional survey amongst members of the EUS Journal Editorial Board in May 2017. The responses to a 22-question survey with respect to the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the opinion that lumen-apposing metal stents (LAMS) should be the standard of care for the creation of an endoscopic cystenterostomy in patients with pancreatic walled-off necrosis (WON); 95.5% (21/22) recommended large diameter (d=15 mm) LAMS for drainage in patients with WON; 54.5% (12/22) would not dilate LAMS after placement into the WOPN; 86.4% (19/22) would not perform endoscopic necrosectomy during the same procedure as the creation of the cystenterostomy; 45.5% (10/22) recommend that agents, such as diluted hydrogen peroxide, should be used to lavage the peri-pancreatic fluid collection (PFC) cavity in patients with WON; and 45.5% (10/22) considered a naso-cystic or other tube to be necessary for lavage of WON after initial drainage. The mean optimal interval recommended for endoscopic necrosectomy procedures after EUS-guided drainage was 6.23 days. The mean optimal interval recommended for repeat imaging in patients undergoing endoscopic necrosectomy was 12.32 days. The mean time recommended for LAMS removal was 4.59 weeks. This is the first worldwide survey on the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy. There were wide variations in practice and randomized studies are urgently needed to establish the best approach for management of this condition. There is also a pressing need to establish a best practice consensus.

AbstractCutaneous leishmaniasis (CL) by Leishmania braziliensis is associated with decreasing cure rates in Brazil. Standard treatment with pentavalent antimony (Sb v ) cures only 50-60% of the cases. The immunopathogenesis of CL ulcer is associated with high interferon-γ and tumor necrosis factor (TNF) production. Pentoxifylline, a TNF inhibitor, has been successfully used in association with Sb v in mucosal and cutaneous leishmaniasis. This randomized, double-blind, and placebo-controlled trial aimed to evaluate the efficacy and safety of oral pentoxifylline plus Sb v versus placebo plus Sb v in patients with CL in Bahia, Brazil. A total of 164 patients were randomized in two groups to receive the combination or the monotherapy. Cure rate 6 months after treatment was 45% in the pentoxifylline group and 43% in the control group. There was also no difference between the groups regarding the healing time (99.7 ± 66.2 days and 98.1 ± 72.7 days, respectively). Adverse events were more common in the pentoxifylline group (37.8%), versus 23% in the placebo group. This trial shows that Sb v combined therapy with pentoxifylline is not more effective than Sb v monotherapy in the treatment of CL caused by L. braziliensis .

Retroviral vector-mediated stem cell gene therapy is a promising approach for the treatment of hematopoietic disorders. However, genotoxic side effects from integrated vector proviruses are a significant concern for the use of retroviral vectors in the clinic. Insulated foamy viral (FV) vectors are potentially safer retroviral vectors for hematopoietic stem cell gene therapy. We evaluated two newly identified human insulators, A1 and A2, for use in FV vectors. These insulators had moderate insulating capacity and higher titers than previously developed insulated FV vectors. The A1-insulated FV vector was chosen for comparison with the previously described 650cHS4-insulated FV vector in human cord blood CD34 + repopulating cells in an immunodeficient mouse model. To maximize the effects of the insulators on the safety of FV vectors, FV vectors containing a highly genotoxic spleen focus forming virus promoter were used to elicit differences in genotoxicity. In vivo, the A1-insulated FV vector showed an approximate 50% reduction in clonal dominance compared with either the 650cHS4-insulated or control FV vectors, although the transduction efficiency of the A1-insulated vector was higher. This data suggests that the A1-insulated FV vector is promising for future preclinical and clinical studies.

Background and Aims: Gastric per-oral endoscopic myotomy (G-POEM) recently has been reported as minimally invasive therapy for gastroparesis. The aims of this study were to report on the first multicenter experience with G-POEM and to assess the efficacy and safety of this novel procedure for patients with gastroparesis with symptoms refractory to medical therapy., Methods: All patients with gastroparesis who underwent endoscopic pyloromyotomy (G-POEM) at 5 medical centers were included. Procedures were performed following the same principles as esophageal POEM. Clinical response was defined as improvement in gastroparetic symptoms with absence of recurrent hospitalization. Adverse events were graded according to the American Society for Gastrointestinal Endoscopy lexicon., Results: A total of 30 patients with refractory gastroparesis (11 diabetic, 12 postsurgical, 7 idiopathic) underwent G-POEM. Previous therapies included Botox injection in 12, transpyloric stenting in 3, and PEG with jejunal extension (PEGJ) in 1. Nausea/vomiting were the predominant symptoms in 25 patients. Weight loss was present in 27 patients with an average of 10% loss of body weight. G-POEM was completed successfully in all 30 (100%) patients with a mean procedure time of 72 minutes (range, 35-223 min). The mean myotomy length was 2.6 ± 2.3 cm. The mean length of hospital stay was 3.3 days (range, 1-12 days). Two adverse events occurred in 2 (6.7%) patients, including 1 capnoperitoneum and 1 prepyloric ulcer, rated as mild and severe, respectively. Clinical response was observed in 26 (86%) patients during a median follow-up of 5.5 months. Four patients (2 diabetic, 1 postsurgical, 1 idiopathic cause) did not respond to G-POEM. Repeat gastric emptying scan was obtained in 17 patients, normalized in 8 (47%), and improved in 6 (35%) patients., Conclusion: G-POEM is a technically feasible procedure. This small non-randomized study suggests the effectiveness of G-POEM for the treatment of patients with gastroparesis refractory to medical therapy. It concomitantly results in normalization of GES in a significant proportion of treated patients., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Endoscopic retrograde pancreatography (ERP) is considered first-line therapy for management of symptomatic pancreatic duct obstruction. Technical failure with ERP occurs when the main pancreatic duct cannot be cannulated. EUS-guided drainage of the pancreatic duct is a minimally invasive alternative to surgery for failed conventional ERP. We present an international, multicenter study on the safety and efficacy of EUS-guided pancreatic drainage (EUS-PD) for patients who fail conventional endoscopic therapy., Methods: Between January 2006 and December 2015, 80 patients underwent EUS-PD at 4 academic centers in 3 countries. Patient demographics, medical history, procedure data, and follow-up clinical data were collected. Technical success was defined as successful pancreatic duct drainage with stent placement. Clinical success was defined as resolution or improvement of symptoms or improvement on postprocedure imaging., Results: Eighty patients (62.5% men; mean age, 58.2 ± 15.5 years) were included. All patients had attempted ERP and/or extracorporeal lithotripsy if needed before EUS-PD. Technical success was achieved in 89% of patients (n = 71). Clinical success was achieved in 81% of patients overall (65/80) and in 92% of patients who achieved technical success (65/71). Immediate adverse events occurred in 20% of patients (n = 16) and delayed adverse events occurred in 11% of patients (n = 9)., Conclusions: With appropriate endoscopic expertise, EUS-PD offers a minimally invasive, more effective, and safer alternative to some surgical PD procedures. Prospective studies are needed to evaluate long-term outcomes. (Clinical trial registration number: NCT01522573.)., (Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze the levels of lysophosphatidic acids (LPAs) and autotaxin (ATX) in undiluted vitreous of untreated patients with retinal vein occlusion (RVO)., Methods: Sixty-four vitreous samples (40 RVO, 24 controls with idiopathic floaters) were analyzed in this retrospective case series using LC/MS for LPAs 16:0, 18:0, 18:1, 20:4, and ELISA kits or Luminex technology for ATX, angiopoetin-1 (ANG-1), interleukin-6 (IL-6), interleukin-7 (IL-7), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), pigment epithelium-derived factor (PEDF), and vascular endothelial growth factor (VEGF). LPA and ATX levels were correlated with the visual acuity, central macular thickness (CMT), average retinal thickness (AvT), vitreal cytokine levels and with each other., Results: Levels of every LPA species tested and ATX were significantly increased in the vitreous fluid from all patients with RVO (total LPAs: 968.0 ± 842.3 nM; ATX: 2.5 ± 1.02 nM) compared with controls (total LPAs: 225.2 ± 292.8 nM, P < 0.0001; ATX: 1.9 ± 1.00 nM, P = 0.005). There were strong positive correlations between the vitreal levels of IL-6, IL-8, MCP-1, VEGF and LPAs., Conclusion: Levels of LPAs and ATX were positively correlated with proinflammatory cytokines and VEGF and might thus play an important role in the development of macular edema secondary to RVO.

Anti-angiogenic therapies using biological molecules that neutralize vascular endothelial growth factor-A (VEGF-A) have revolutionized treatment of retinal vascular diseases including age-related macular degeneration (AMD). This study reports preclinical assessment of a strategy to enhance anti-VEGF-A monotherapy efficacy by targeting both VEGF-A and angiopoietin-2 (ANG-2), a factor strongly upregulated in vitreous fluids of patients with retinal vascular disease and exerting some of its activities in concert with VEGF-A. Simultaneous VEGF-A and ANG-2 inhibition was found to reduce vessel lesion number, permeability, retinal edema, and neuron loss more effectively than either agent alone in a spontaneous choroidal neovascularization (CNV) model. We describe the generation of a bispecific domain-exchanged (crossed) monoclonal antibody (CrossMAb; RG7716) capable of binding, neutralizing, and depleting VEGF-A and ANG-2. RG7716 showed greater efficacy than anti-VEGF-A alone in a non-human primate laser-induced CNV model after intravitreal delivery. Modification of RG7716's FcRn and FcγR binding sites disabled the antibodies' Fc-mediated effector functions. This resulted in increased systemic, but not ocular, clearance. These properties make RG7716 a potential next-generation therapy for neovascular indications of the eye., (© 2016 F. Hoffmann‐La Roche Ltd. Published under the terms of the CC BY 4.0 license.)

We present optical Thomson scattering results that image for the first time in a single measurement the spatial transition from collective to non-collective scattering. Data were taken in the Phoenix laser laboratory at the University of California, Los Angeles. The Raptor laser was used to ablate a carbon plasma, which was diagnosed with the frequency-doubled Phoenix laser serving as a Thomson scattering probe. Scattered light was collected from the laser plasma up to 10 cm from the target surface and up to 10 us after ablation, and imaged with high spatial and spectral resolutions. The results show a strong Thomson collective feature close to the target surface that smoothly transitions to a non-collective feature over several mm.

Although monitoring childhood obesity prevalence is critical for state public health programs to assess trends and the effectiveness of interventions, few states have comprehensive body mass index measurement systems in place. In some states, however, assorted school districts collect measurements on student height and weight as part of annual health screenings. To estimate childhood obesity prevalence in Alaska, we created a logistic regression model using such annual measurements along with public data on demographics and socioeconomic status. Our mixed-effects model-generated prevalence estimates validated well against weighted estimates, with 95% confidence intervals overlapping between methodologies among 7 of 8 participating school districts. Our methodology accounts for variation in school-level and student-level demographic factors across the state, and the approach we describe can be applied by other states that have existing nonrandom student measurement data to estimate childhood obesity prevalence.

Active participation of the girl child in development is hampered by Menstrual Hygiene Management (MHM) challenges. MHM is an important gender issue and a critical component in holistic human development. It affects about 25% of the global population aged between 15 and 49 years. Water, sanitation and hygiene (WASH) interventions in schools have not prioritised MHM, thus exposing girls and the entire school community to health related hazards. The study explored knowledge, attitudes and community practices, and investigated the impact of religious and cultural beliefs on MHM and how they impact on the girl child in Masvingo district. The survey was largely qualitative and employed methodologies of document analysis, Focus Group Discussions (FGD) and structured interviews. Participants included four churches, 13 NGOs, eight government departments and 40 women. Findings revealed deeply embedded power relations, a culture of silence around MHM, noninvolvement of men in MHM issues, limited availability in terms of information, and a girl unfriendly infrastructure, and limited access to menstrual hygiene products due to poverty and poor management and disposal practices. Resultant effects ranged from poor class participation, lack of concentration and constrained interactions with peers and teachers, low self-esteem, anxiety and the general feeling of being discriminated against. Results confirmed the need for increased awareness initiatives on MHM in a bid to tackle inherent religious and cultural beliefs that are a barrier to effective holistic implementation of WASH interventions that empower women and girls. Lobbying government to provide an appropriate policy framework, education and training, construction of girl friendly sanitary facilities, exploring and capitalisation of local production of Reusable Menstrual Pads (RUMPS), more research targeting children living with disabilities, those living in refugee and makeshift camps and Orphans and Vulnerable Children (OVC), are some of the recommendations coming out of the study., Competing Interests: The authors declare that they have no financial or personal relationships which may have inappropriately influenced them in writing this article.

Objective Conduct a cross-cultural adaptation of the expanded version of the 29-items Readiness for Interprofessional Learning Scale (RIPLS) into Brazilian Portuguese. Method Five steps were adopted: three translations, synthesis, three back-translations, assessment by an expert committee, and pre-test. Validation comprised 327 students from 13 undergraduate health courses from a public university. Parallel analyses were conducted using the R software and factor analysis using Exploratory Structural Equation Modeling. Results 1 9 12 16 10 11 17 19 21 24 25 29 Conclusion Evidences were found relating to the validity of the RIPLS version in Brazilian Portuguese in its application in the national context.