Human versus Artificial Intelligence: Validation of a Deep Learning Model for Retinal Layer and Fluid Segmentation in Optical Coherence Tomography Images from Patients with Age-Related Macular Degeneration.

Artificial intelligence (AI) models have received considerable attention in recent years for their ability to identify optical coherence tomography (OCT) biomarkers with clinical diagnostic potential and predict disease progression. This study aims to externally validate a deep learning (DL) algorithm by comparing its segmentation of retinal layers and fluid with a gold-standard method for manually adjusting the automatic segmentation of the Heidelberg Spectralis HRA + OCT software Version 6.16.8.0. A total of sixty OCT images of healthy subjects and patients with intermediate and exudative age-related macular degeneration (AMD) were included. A quantitative analysis of the retinal thickness and fluid area was performed, and the discrepancy between these methods was investigated. The results showed a moderate-to-strong correlation between the metrics extracted by both software types, in all the groups, and an overall near-perfect area overlap was observed, except for in the inner segment ellipsoid (ISE) layer. The DL system detected a significant difference in the outer retinal thickness across disease stages and accurately identified fluid in exudative cases. In more diseased eyes, there was significantly more disagreement between these methods. This DL system appears to be a reliable method for accessing important OCT biomarkers in AMD. However, further accuracy testing should be conducted to confirm its validity in real-world settings to ultimately aid ophthalmologists in OCT imaging management and guide timely treatment approaches.

Dose-response and efficacy of 904 nm photobiomodulation on diabetic foot ulcers healing: a randomized controlled trial.

PURPOSE: This study aimed to examine the impact of a 904 nm photobiomodulation (PBM) on diabetic ulcers using varying dosages. METHODS: The study was a randomized, double-blind, placebo-controlled clinical trial that compared treatments using PBM (GaAs 904 nm 30w) with three different energy densities (4 J/cm2; 8 J/cm2; 10 J/cm2) in the healing process of non-infected diabetic foot ulcers. Eighty volunteers (48.75% female; 58.5 ± 11.1 years) were randomized into three intervention groups treated with PBM and one control group (PBM placebo). Volunteers performed up 20 interventions with PBM, either placebo or actual, in conjunction with conventional therapy, which involved dressing the wound with Helianthus annuus vegetable oil. The primary variable was the ulcer size reduction rate. RESULTS: GaAs 904 nm PBM yielded a clinically and significant ulcer size rate reduction of diabetic foot ulcers, independently of energy density range (p < 0.05). However, 10 J/cm² had 60% of completely healed ulcers and the highest proportion of patients reaching 50% of ulcer reduction rate after 5 weeks of treatment. In addition, only 10 J/cm² showed a significant difference between control group after a 10-week follow-up (p < 0.05). CONCLUSION: GaAs 904 nm PBM was effective in treating diabetic foot ulcers in this study and a dosage of 10 J/cm², after a 10-week follow-up, proved to be the most effective compared to the other groups. CLINICAL TRIAL REGISTRATION NUMBER: NCT04246814.

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study.

Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects.

PREVAIT after modern open surgery and endothermal ablation: a systematic review.

INTRODUCTION: Presence of varices after operative treatment (PREVAIT) is a common finding after varicose vein surgery, and has been shown to significantly reduce the quality of life of those it affects. As such, long-term results after varicose vein interventions have to be taken into account when choosing a technique. This study aims to systematically review current evidence on the recurrence of varicose veins after three different techniques: conventional surgery (HLS), endovenous laser ablation (EVLA) and radiofrequency ablation (RFA). EVIDENCE ACQUISITION: A literature search was performed on the PubMed and Web of Science databases, which returned 546 studies. Fourteen studies were included. Data were extracted using predefined forms. EVIDENCE SYNTHESIS: A total of 2795 patients were included, for a total of 3056 legs treated. 503 legs (16.5%) were treated by HLS, 1791 (58.6%) by EVLA and 762 (25.0%) by RFA. PREVAIT was reported in 34.4% for patients treated by HLS, for a mean follow-up comprised between 18 months and 5 years; 16.6% by EVLA, for a mean follow-up between 112 days and 5 years and 6.7% of those treated by RFA, for a mean follow-up between 106 days and 5 years. Regarding patterns of recurrence, the development of new varicose veins was the most commonly reported mechanism of recurrence after HLS (range: 29.8-91%) and EVLA (range: 40-81.6%), but not RFA, where recanalization of the occluded saphenous trunk accounted for up to 67.0% of the cases. Only one study reported quality of life related recurrence, and included patients treated by HLS and EVLA, but not RFA. Aberdeen Varicose Vein Questionnaire (AVVQ) score, physical functioning domains of the SF-36 score and patient satisfaction were significantly worse in patients with clinical recurrence. Re-intervention rates after recurrence were reported in 5 studies, ranging between 7.7% and 37.7% for HLS and 0-57.0% for EVLA. Only one study reported data on re-intervention for RFA patients, which was 6.67%. CONCLUSIONS: Recurrence is a reliable indicator of long-term efficacy of a varicose vein treatment and appears to occur more frequently after HLS. Although there are several mechanisms of recurrence, the development of new varicose veins was the most commonly observed. There is clear heterogeneity among definitions of recurrence and follow-up periods in literature.

Translation and validity of the Multidimensional Individual and Interpersonal Resilience Measure.

OBJECTIVE: to translate, culturally adapt and validate the Multidimensional Individual and Interpersonal Resilience Measure to Brazilian Portuguese. METHOD: after initial translation, the pre-final version underwent rigorous cultural adaptation procedures. As a result, the final adapted version was submitted to a validity study. RESULTS: adaptation procedures provided equivalence between the pre-final and the original versions in semantic, idiomatic, experiential and conceptual terms. A total of 187 older adults were included in the validity study. Exploratory factorial analysis (EFA) generated a model of five factors ((RMSEA = 0.030; TLI = 0.959; X2 = 151.590 p> 0.05). Final version showed adequate consistency (Cronbach's α = 0.705) and test-retest reliability (ICC=0.835). No statistically significant correlation was found between resilience and sociodemographic and epidemiological variables assessed in this study. CONCLUSION: EMRII-BR is a valid and reliable instrument for measuring resilience in Brazilian older adults.

Identifying inhibitors of Trypanosoma cruzi nucleoside diphosphate kinase 1 as potential repurposed drugs for Chagas' disease.

Trypanosoma cruzi is the causative agent of Chagas' disease, an endemic and neglected disease. The treatment is limited to only two drugs, benznidazole (BZL) and nifurtimox (NFX), introduced more than fifty years ago and no new advances have been made since then. Nucleoside diphosphate kinases (NDPK) are key metabolic enzymes which have gained interest as drug targets of pathogen organisms. Taking advantage of the computer-assisted drug repurposing approaches, in the present work we initiate a search of potential T. cruzi nucleoside diphosphate kinase 1 (TcNDPK1) inhibitors over an âˆ¼ 12,000 compound structures database to find drugs targeted to this enzyme with trypanocidal activity. Four medicines were selected and evaluated in vitro, ketorolac (KET, an anti-inflamatory), dutasteride (DUT, used to treat benign prostatic hyperplasia), nebivolol and telmisartan (NEB and TEL, used to treat high blood pressure). The four compounds were weak inhibitors and presented different trypanocidal effect on epimastigotes, trypomastigotes and intracellular stages. NEB and TEL were the most active drugs with increased effect on intracellular stages, (IC50 = 2.25 µM and 13.21 µM respectively), and selectivity indexes of 13.01 and 8.59 respectively, showing comparable effect to BZL, the first line drug for Chagas' disease treatment. In addition, both presented positive interactions when combined with BZL. Finally, transgenic epimastigotes with increased expression of TcNDPK1 were more resistant to TEL and NEB, suggesting that TcNDPK1 is at least one of the molecular targets. In view of the results, NEB and TEL could be repurposed medicines for Chagas' disease therapy.

Variation in Early Pediatric Intensive Care Management Strategies and Duration of Invasive Mechanical Ventilation for Acute Viral Bronchiolitis in the United Kingdom: A Retrospective Multicenter Cohort Study.

OBJECTIVES: Management of mechanically ventilated patients with bronchiolitis is not standardized and duration of mechanical ventilation has been shown to vary widely between centers. The aim of this study was to examine practice in a large number of U.K. PICUs with a view to identify if early management choices relating to fluid prescription, sedative agent use, and endotracheal tube (ETT) placement were associated with differences in duration of invasive mechanical ventilation (IMV). DESIGN: Retrospective multicenter cohort study. Primary outcome was duration of IMV. A hierarchical gamma generalized linear model was used to test for associations between practice variables (sedative and neuromuscular blocking agents, route of endotracheal intubation at 24 hr and fluid balance at 48 hr) and duration of IMV after adjustment for known confounders. SETTING: Thirteen U.K. PICUs. Duration of 2 months between November and December 2019. PATIENTS: Three hundred fifty infants receiving IMV for bronchiolitis. Excluded were patients receiving long-term ventilation, extracorporeal life support, or who died before separation from IMV. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjustment for confounders, several variables were associated with an increase in the geometric mean duration of IMV (expressed as a percentage) including: nasal ETT use, 16% (95% CI, 1-32%); neuromuscular blockade use, 39% (95% CI, 21-61%); and fluid balance at 48 hr, 13% per 100 mL/kg positive fluid balance (95% CI, -1% to 28%). The association of sedative use varied with class of agent. The use of an alpha-2 agonist alone was associated with a reduction in duration of IMV by 19% in relation to no sedative agent (95% CI, -31 to -5%), whereas benzodiazepine uses alone or with alpha-2 agonist in combination were similar to using neither agent. CONCLUSIONS: Early management strategies for bronchiolitis were associated with the duration of IMV across U.K. centers after adjustment for confounders. Future work should prospectively assess the impact of fluid restriction, route of endotracheal intubation, and alpha-2 agonist use on duration of IMV in infants with bronchiolitis, with the aim of reducing seasonal bed pressure.

Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy.

Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the intestinal mucosa of diet-induced obese mice and found that they exhibited increased gut permeability and reduced Treg cells frequency. Upon oral treatment with ovalbumin (OVA), obese mice failed to develop oral tolerance. However, hyperglycemia treatment improved intestinal permeability and oral tolerance induction in mice. Furthermore, we observed that obese mice exhibited a more severe food allergy to OVA, and this allergy was alleviated after treatment with a hypoglycemic drug. Importantly, our findings were translated to obese humans. Individuals with T2D had higher serum IgE levels and downregulated genes related to gut homeostasis. Taken together, our results suggest that obesity-induced hyperglycemia can lead to a failure in oral tolerance and to exacerbation of food allergy. These findings shed light on the mechanisms underlying the relationship among obesity, T2D, and gut mucosal immunity, which could inform the development of new therapeutic approaches.

Pediatric Sepsis: a Summary of Current Definitions and Management Recommendations.

Purpose of Review: Pediatric sepsis remains an important cause of morbidity and mortality in children. This review will summarize the main aspects of the definition, the current evidence base for interventions discuss some controversial themes and point towards possible areas of improvement. Recent Findings: Controversy remains regarding the accurate definition, resuscitation fluid volume and type, choice of vasoactive/inotropic agents, and antibiotic depending upon specific infection risks. Many adjunctive therapies have been suggested with theoretical benefits, although definitive recommendations are not yet supported by data. We describe best practice recommendations based on international guidelines, a review of primary literature, and a discussion of ongoing clinical trials and the nuances of therapeutic choices. Summary: Early diagnosis and timely intervention with antibiotics, fluid resuscitation, and vasoactive medications are the most important interventions in sepsis. The implementation of protocols, resource-adjusted sepsis bundles, and advanced technologies will have an impact on reducing sepsis mortality.

Potential Biomarkers of impulsivity in mild traumatic brain injury: A pilot study.

Very few studies have investigated cognition and impulsivity following mild traumatic brain injury (mTBI) in the general population. Furthermore, the neurobiological mechanisms underlying post-TBI neurobehavioral syndromes are complex and remain to be fully clarified. Herein, we took advantage of machine learning based-modeling to investigate potential biomarkers of mTBI-associated impulsivity. Twenty-one mTBI patients were assessed within one-month post-TBI and their data were compared to 19 healthy controls on measures of impulsivity (Barratt Impulsiveness Scale - BIS), executive functioning, episodic memory, self-report cognitive failures and blood biomarkers of inflammation, vascular and neuronal damage. mTBI patients were significantly more impulsive than controls in BIS total and subscales. Serum levels of sCD40L, Cathepsin D, IL-4, Neuropilin-1, IFN-α2, and Copeptin were associated with impulsivity in mTBI patients. Besides showing that mTBI are associated with impulsivity in non-military people, we unveiled different pathophysiological pathways potentially implicated in mTBI-related impulsivity.

Hsp65-producing Lactococcus lactis inhibits experimental autoimmune encephalomyelitis by preventing cell migration into spinal cord.

Multiple sclerosis is an autoimmune disease that affects the central nervous system. Because of its complexity and the difficulty to treat, searching for immunoregulatory responses that reduce the clinical signs of disease by non-aggressive mechanisms and without adverse effects is a scientific challenge. Herein we propose a protocol of oral tolerance induction that prevented and controlled MOG-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The genetically modified strain HSP65-producing Lactococcus lactis was orally administered for 5 consecutive days either before or during disease development in mice. Both protocols of feeding HSP65 resulted in significant reduction in the clinical score of EAE. Frequencies of LAP+CD4+Foxp3- regulatory T cells were higher in spleens and inguinal lymph nodes of fed mice. In addition, intravital microscopy showed that adherence of leukocytes to venules in the spinal cord was reduced in orally treated mice. Oral treatment with HSP65-producing L.lactis prevented leukocytes to leave the secondary lymphoid organs, therefore they could not reach the central nervous system. Despite the inhibition of pathological immune response that drive EAE development, activated T cells were at normal frequencies suggesting that oral tolerance did not induce general immunosuppression, but it led to specific control of pathogenic T cells. Our results indicate a novel therapeutic strategy to prevent and control autoimmune diseases such as multiple sclerosis.

[Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests by the SPCPTGI]. / Orientações de Consenso para a Abordagem dos Resultados Alterados nos Testes de Rastreio do Cancro do Colo do Útero pela SPCPTGI.

Cervical cancer is one of the most common types of cancer in women. Cervical cancer screening is needed for the detection and treatment of cervical neoplastic lesions that can evolve to neoplasia and to reduce the incidence of cervical cancer. Recently, changes were made to increase the efficiency of the screening process such as employing the human papilloma virus detection test as the gold standard for cervical cancer screening and acknowledging the importance of adapting clinical practice to consider the risk of developing this neoplasia. Considering this paradigm shift, new clinical practice guidelines are now needed. For this purpose, a group of experts analyzed and discussed the most recent literature, defining recommendations and proposing clinical practice guidelines that focus on risk stratification, diagnostic evaluation, and on the therapeutical approach and follow-up of women with altered screening results. The aim of this article is to guide clinical practice regarding actions to take in face of altered results of cervical cancer screening and, consequently, to improve the secondary prevention of this condition.

O cancro do colo do útero (CCU) é globalmente um dos tipos de cancro mais comum em mulheres. O rastreio do CCU é indispensável para a deteção e tratamento de lesões neoplásicas cervicais que possam evoluir para neoplasia, com o objectivo de reduzir a incidência deste cancro. Nos últimos anos, têm ocorrido alterações que visam o aumento da eficácia do rastreio. Nomeadamente, o uso de teste de deteção do vírus do papiloma humano como método de rastreio primário do CCU e a valorização da importância de adaptar a prática clínica em função do risco de desenvolvimento do CCU. Desta forma, são necessárias novas normas de atuação clínica, que contemplem esta mudança de paradigma. Assim, um grupo de especialistas analisou e discutiu a literatura mais recente, definindo recomendações e propondo normas de prática clínica que se focam na estratificação de risco, avaliação diagnóstica, e na conduta terapêutica e de seguimento de mulheres com resultados dos testes de rastreio alterados. Este trabalho tem como objetivo facilitar a prática clínica em resposta a resultados alterados nos testes e, consequentemente, melhorar a prevenção secundária do CCU.

Translation and validity of the Multidimensional Individual and Interpersonal Resilience Measure / Tradução e validação do Multidimensional Individual and Interpersonal Resilience Measure / Traducción y validación del Multidimensional Individual and Interpersonal Resilience Measure

ABSTRACT Objective: to translate, culturally adapt and validate the Multidimensional Individual and Interpersonal Resilience Measure to Brazilian Portuguese. Method: after initial translation, the pre-final version underwent rigorous cultural adaptation procedures. As a result, the final adapted version was submitted to a validity study. Results: adaptation procedures provided equivalence between the pre-final and the original versions in semantic, idiomatic, experiential and conceptual terms. A total of 187 older adults were included in the validity study. Exploratory factorial analysis (EFA) generated a model of five factors ((RMSEA = 0.030; TLI = 0.959; X2 = 151.590 p> 0.05). Final version showed adequate consistency (Cronbach's α = 0.705) and test-retest reliability (ICC=0.835). No statistically significant correlation was found between resilience and sociodemographic and epidemiological variables assessed in this study. Conclusion: EMRII-BR is a valid and reliable instrument for measuring resilience in Brazilian older adults.

RESUMO Objetivo: traduzir, adaptar culturalmente e validar o Multidimensional Individual and Interpersonal Resilience Measure para o português brasileiro. Método: após a tradução inicial, a versão pré-final passou por rigorosos procedimentos de adaptação cultural. Como resultado, a versão final adaptada foi submetida a um estudo de validade. Resultados: os procedimentos de adaptação proporcionaram equivalência entre as versões pré-final e original em termos semânticos, idiomáticos, experienciais e conceituais. Um total de 187 idosos foram incluídos no estudo de validade. A análise fatorial exploratória (AFE) gerou um modelo de cinco fatores ((RMSEA = 0,030; TLI = 0,959; X2 = 151,590 p> 0,05). A versão final apresentou consistência adequada (α de Cronbach = 0,705) e confiabilidade teste-reteste (ICC=0,835). Não foi encontrada correlação estatisticamente significativa entre a resiliência e as variáveis sociodemográficas e epidemiológicas avaliadas neste estudo. Conclusão: o EMRII-BR é um instrumento válido e confiável para mensurar a resiliência em idosos brasileiros.

RESUMEN Objetivo: traducir, adaptar culturalmente y validar el Multidimensional Individual and Interpersonal Resilience Measure para el portugués brasileño. Método: después de la traducción inicial, la versión pre-final pasó por rigurosos procedimientos de adaptación cultural. Como resultado, la versión final adaptada fue sometida a un estudio de validez. Resultados: los procedimientos de adaptación proporcionaron equivalencia entre las versiones pre-final y original en términos semánticos, idiomáticos, experienciales y conceptuales. Un total de 187 ancianos fueron incluidos en el estudio de validez. El análisis factorial exploratorio (AFE) generó un modelo de cinco factores ((RMSEA = 0,030; TLI = 0,959; X2 = 151,590 p> 0,05). La versión final mostró adecuada consistencia (α de Cronbach = 0,705) y confiabilidad prueba-reprueba (ICC=0,835). No se encontró correlación estadísticamente significativa entre la resiliencia y las variables sociodemográficas y epidemiológicas evaluadas en este estudio. Conclusión: EMRII-BR es un instrumento válido y confiable para medir la resiliencia en ancianos brasileños.

Crime Stereotypicality and Severity Database (CriSSD): Subjective norms for 63 crimes.

The existence of crime-related racial stereotypes has been well documented. People tend to associate certain groups with specific crimes, which, in turn, impacts criminal-sentencing decisions through the perceptions of crime severity. This evidence calls for regular updating of rating norms combining these variables. With this objective, and given that most of the normative studies provide norms for a small number of crimes and/or with an insufficient number of participants, a new norming study was conducted. Furthermore, norms from European countries are absent, and the existing ones (mostly with USA-based populations) do not simultaneously examine crime stereotypicality and crime severity. The Crime Stereotypicality and Severity Database (CriSSD) presents normative ratings for a set of 63 crimes on three dimensions: White stereotypicality, Black stereotypicality, and crime severity. The crimes were selected according to a comprehensive procedure. A total of 340 Portuguese participants (72.6% female; Mage = 26.86, SD = 7.65) answered an online survey. Each crime was evaluated by a range of 46-60 participants. Data allowed us to identify a crime typology with three clusters. We present descriptive data (means, standard deviations, and 95% confidence intervals) for each crime. Crime evaluations were associated with sociodemographic characteristics. Additionally, this study gives input regarding the understudied link between crime stereotypes and crime severity, showing that crime severity is predicted by ratings of both Black and White stereotypicality. The CriSSD (available at osf.io/gkbrm ) provides a valuable resource for researchers in the field of social psychology to conduct studies with controlled materials on potential disparities in criminal-sentencing decisions.

Vulnerabilidade individual, social e programática na adesão ao tratamento antirretroviral em adultos / Individual, social and program-related vulnerability in adults' adherence to antiretroviral treatment / Vulnerabilidad individual, social y programática en la adherencia al tratamiento antirretroviral en adultos

Objetivo: analisar a associação da adesão à terapia antirretroviral em adultos com HIV/Aids e as dimensões das vulnerabilidades. Métodos: estudo quantitativo, com 230 pacientes de serviço especializado, por meio de questionários de avaliação da adesão ao tratamento, com dados submetidos à análise estatística inferencial. Resultados: dos pacientes, 44,3% apresentaram boa/adequada adesão com elementos da vulnerabilidade individual: apoio para conversar/desabafar sobre o problema de saúde (p=0,002); apoio para se divertir ou fazer atividade de lazer (p=0,000); e deixar de tomar a medicação devido à alteração na prescrição médica (p=0,018); social: sexo (p=0,005); nível de instrução (p=0,010); renda familiar (p=0,034); e condição empregatícia (p=0,007); e programática: acesso ao serviço (p=0,005); recebimento de informações (p=0,039); comunicação com os profissionais (p=0,024); educação em saúde (p=0,013); e deixar de tomar a medicação por não tê-la (p=0,039). Conclusão: a adesão foi classificada como boa/adequada e apontam-se elementos de vulnerabilidades que fragilizam ou potencializam a adesão.

Objective: to examine how adherence to antiretroviral therapy among adults with HIV/Aids associated with dimensions of vulnerability. Methods: this quantitative study of 230 patients in a specialized service used questionnaires to assess adherence to treatment. The resulting data were submitted to inferential analysis. Results: adherence was good/adequate in 44.3% of patients and associated with elements of vulnerability, which could be individual: support to talk or vent about the health problem (p = 0.002), support for fun or leisure activities (p = 0.000), and for not taking medication due to a change in medical prescription (p = 0.018); social: sex (p = 0.005); education level (p = 0.010), family income (p = 0.034), and employment status (p = 0.007); or program-related: access to the service (p = 0.005), receiving information (p = 0.039), communication with professionals (p = 0.024), health education (p = 0.013), and not taking medication for not having them (p = 0.039). Conclusion: Adherence was classified as good or adequate, and pointed to elements of vulnerability that weaken or strengthen adherence.

Objetivo: analizar la asociación de la adherencia a la terapia antirretroviral en adultos con VIH/SIDA y las dimensiones de las vulnerabilidades. Métodos: estudio cuantitativo, junto a 230 pacientes de servicios especializados, mediante cuestionarios para evaluar la adherencia al tratamiento, cuyos datos se sometieron al análisis estadístico inferencial. Resultados: el 44,3% de los pacientes tuvo buena / adecuada adherencia con elementos de vulnerabilidad individual: apoyo para hablar o desahogarse sobre el problema de salud (p = 0,002); apoyo para divertirse o realizar actividades de ocio (p = 0,000) y no tomar medicación por cambio de prescripción médica (p = 0,018); social: sexo (p = 0,005); nivel educativo (p = 0,010); ingresos familiares (p = 0,034) y situación laboral (p = 0,007); y programática: acceso al servicio (p = 0,005); recibir información (p = 0.039); comunicación con profesionales (p = 0,024); educación en salud (p = 0,013) y no tomar medicamentos por no tenerlos (p = 0,039). Conclusión: La adherencia se clasificó como buena / adecuada y se señalan elementos de vulnerabilidades que debilitan o mejoran la adherencia.

Can aged microplastics be transport vectors for organic micropollutants? - Sorption and phytotoxicity tests.

Microplastics have been investigated over the last decade as potential transport vectors for other pollutants. However, the specific role of plastic aging, in which plastics change their characteristics over time when exposed to environmental agents, has been overlooked. Therefore, sorption experiments were herein conducted using virgin and aged (by ozone treatment or rooftop weathering) microplastic particles of LDPE - low-density polyethylene, PET - poly(ethylene terephthalate), or uPVC - unplasticized poly(vinyl chloride). The organic micropollutants (OMPs) selected as sorbates comprise a diversified group of priority substances and contaminants of emerging concern, including pharmaceutical substances (florfenicol, trimethoprim, diclofenac, tramadol, citalopram, venlafaxine) and pesticides (alachlor, clofibric acid, diuron, pentachlorophenol), analyzed at trace concentrations (each ≤100 µg L-1). Sorption kinetics and equilibrium isotherms were obtained, as well as the confirmation that the aging degree of microplastics plays a major role in their sorption capacities. The results show an increased sorption of several OMPs on aged microplastics when compared to pristine samples, i.e. the sorption capacity increasing from one or two sorbed substances (maximum 3 µg g-1 per sorbate) up to nine after aging (maximum 10 µg g-1 per sorbate). The extent of sorption depends on the OMP, polymer and the effectiveness of the aging treatment. The modifications (e.g. in the chemical structure) between virgin and aged microplastics were linked to the increased sorption capacity of certain OMPs, allowing to better understand the different affinities observed. Additionally, phytotoxicity tests were performed to evaluate the mobility of the OMPs sorbed on the microplastics and the potential effects (on germination and early growth) of the combo on two species of plants (Lepidium sativum and Sinapis alba). These tests suggest low or no phytotoxicity effect under the conditions tested but indicate a need for further research on the behavior of microplastics on soil-plant systems.

A Case of Late Diagnosis of Latent Autoimmune Diabetes in Adults.

Latent autoimmune diabetes of adults (LADA) is a type of autoimmune diabetes that begins in adulthood (usually after the age of 35 years); its main feature is the presence of diabetes-associated autoantibodies (most often autoantibody against glutamic acid decarboxylase), which leads to progressive destruction of the islets of Langerhans. This is a heterogeneous condition that presents with clinical and laboratory manifestations common to type 1 diabetes and type 2 diabetes. We report a case of a 71-year-old man diagnosed with type 2 diabetes two years ago, poorly controlled with oral antidiabetic therapy, and worsening in the third year. He had a positive family history of type 2 diabetes in two second-degree relatives (nephews). No pathologic findings at the physical examination were found. His body mass index was 23 kg/m2 and glycated hemoglobin was 10.6%. Laboratory workup revealed low basal C-peptide (<0.1 ng/mL) and positive glutamic acid decarboxylase antibodies, and the LADA diagnosis was confirmed. This case highlights the importance of being aware of this disease, especially in patients previously diagnosed with type 2 diabetes who remain uncontrolled with diet and oral hypoglycemic agents. LADA is often confused with type 2 diabetes, and therefore, the management is frequently inadequate. An early diagnosis and treatment are crucial to delaying disease progression.

Revisiting trypanosomatid nucleoside diphosphate kinases.

BACKGROUND: An increasing amount of research has led to the positioning of nucleoside diphosphate kinases (NDPK/NDK) as key metabolic enzymes among all organisms. They contribute to the maintenance the intracellular di- and tri- phosphate nucleoside homeostasis, but they also are involved in widely diverse processes such as gene regulation, apoptosis, signal transduction and many other regulatory roles. OBJETIVE: Examine in depth the NDPKs of trypanosomatid parasites responsible for devastating human diseases (e.g., Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp.) which deserve special attention. METHODS: The earliest and latest advances in the topic were explored, focusing on trypanosomatid NDPK features, multifunctionality and suitability as molecular drug targets. FINDINGS: Trypanosomatid NDPKs appear to play functions different from their host counterparts. Evidences indicate that they would perform key roles in the parasite metabolism such as nucleotide homeostasis, drug resistance, DNA damage responses and gene regulation, as well as host-parasite interactions, infection, virulence and immune evasion, placing them as attractive pharmacological targets. MAIN CONCLUSIONS: NDPKs are very interesting multifunctional enzymes. In the present review, the potential of trypanosomatid NDPKs was highlighted, raising awareness of their value not only with respect to parasite biology but also as molecular targets.

Impact of Inherited Genetic Variants on Critically Ill Septic Children.

Sepsis remains an important source of morbidity and mortality in children, despite the development of standardized care. In the last decades, there has been an increased interest in genetic and genomic approaches to early recognition and development of treatments to manipulate the host inflammatory response. This review will present a summary of the normal host response to infection and progression to sepsis, followed by highlighting studies with a focus on gene association studies, epigenetics, and genome-wide expression profiling. The susceptibility (or outcome) of sepsis in children has been associated with several polymorphisms of genes broadly involved in inflammation, immunity, and coagulation. More recently, gene expression profiling has been focused on identifying novel biomarkers, pathways and therapeutic targets, and gene expression-based subclassification. Knowledge of a patient's individual genotype may, in the not-too-remote future, be used to guide tailored treatment for sepsis. However, at present, the impact of genomics remains far from the bedside of critically ill children.

X-ray diffraction and in vivo studies reveal the quinary structure of Trypanosoma cruzi nucleoside diphosphate kinase 1: a novel helical oligomer structure.

Trypanosoma cruzi is a flagellated protozoan parasite that causes Chagas disease, which represents a serious health problem in the Americas. Nucleoside diphosphate kinases (NDPKs) are key enzymes that are implicated in cellular energy management. TcNDPK1 is the canonical isoform in the T. cruzi parasite. TcNDPK1 has a cytosolic, perinuclear and nuclear distribution. It is also found in non-membrane-bound filaments adjacent to the nucleus. In the present work, X-ray diffraction and in vivo studies of TcNDPK1 are described. The structure reveals a novel, multi-hexameric, left-handed helical oligomer structure. The results of directed mutagenesis studies led to the conclusion that the microscopic TcNDPK1 granules observed in vivo in T. cruzi parasites are made up by the association of TcNDPK1 oligomers. In the absence of experimental data, analysis of the interactions in the X-ray structure of the TcNDPK1 oligomer suggests the probable assembly and disassembly steps: dimerization, assembly of the hexamer as a trimer of dimers, hexamer association to generate the left-handed helical oligomer structure and finally oligomer association in a parallel manner to form the microscopic TcNDPK1 filaments that are observed in vivo in T. cruzi parasites. Oligomer disassembly takes place on the binding of substrate in the active site of TcNDPK1, leading to dissociation of the hexamers. This study constitutes the first report of such a protein arrangement, which has never previously been seen for any protein or NDPK. Further studies are needed to determine its physiological role. However, it may suggest a paradigm for protein storage reflecting the complex mechanism of action of TcNDPK1.