Search

Introduction Addressing childhood obesity risk factors like home environment, parental roles, excess weight, physical activity and healthy eating among Latino/Hispanic (L/H) families living in rural communities is an important priority. However, evidence supporting these interventions among L/H families living in rural communities is missing. Our trial will use cultural adaptation and implementation science frameworks to evaluate the feasibility of delivering a culturally appropriate family-based childhood obesity (FBCO) programme via an automated telephone system (interactive voice response) to L/H families in rural Nebraska.Methods and analysis A mixed-methods feasibility trial for L/H families with overweight or obese children. Aim 1 will focus on collaboratively adapting and evaluating all intervention materials to fit the rural L/H community profile better, including translation of materials to Spanish, culturally relevant content and images, and use of health communication strategies to address different levels of health literacy. In aim 2, a 6-month feasibility trial with contextual evaluation will randomise 48 dyads (parent and child) to either Family Connections (FC; n=29) or a waitlist standard-care group (n=29) to determine overall study reach, preliminary effectiveness in reducing child body mass index (BMI) z-scores, potential for programme adoption, implementation and sustainability through local health departments (RE-AIM outcomes). We will also evaluate health department perceptions of the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) constructs (innovation, context, recipient characteristics) and FC participants’ view of the intervention (ie, relative advantage, observability, trialability, complexity, compatibility). The study will answer three critical questions: (1) is a telephone-delivered FBCO programme in rural Nebraska culturally relevant, usable and acceptable by L/H families?; (2) is a telephone-delivered FBCO programme effective at reducing BMI z-scores in L/H children living in rural Nebraska? and (3) what real-world institutional and contextual factors influence the impact of the intervention and might affect its potential ability to sustainably engage a meaningful population of L/H families who stand to benefit?Ethics and dissemination This protocol was approved by the University of Nebraska Medical Center Institutional Review Board (IRB#:0745-20-EP). Dissemination of findings will occur through ClinicalTrials.gov, in scientific forums and to the local rural communities, pilot data to inform the design of a larger clinical trial.Trial registration number NCT04731506.

Objectives To map the available methodological guidelines and documents for conducting and reporting benefit–risk assessment (BRA) during health technologies’ life cycle; and to identify methodological guidelines for BRA that could serve as the basis for the development of a BRA guideline for the context of health technology assessment (HTA) in Brazil.Design Scoping review.Methods Searches were conducted in three main sources up to March 2023: (1) electronic databases; (2) grey literature (48 HTA and regulatory organisations) and (3) manual search and contacting experts. We included methodological guidelines or publications presenting methods for conducting or reporting BRA of any type of health technologies in any context of the technology’s life cycle. Selection process and data charting were conducted by independent reviewers. We provided a structured narrative synthesis of the findings.Results From the 83 eligible documents, six were produced in the HTA context, 30 in the regulatory and 35 involved guidance for BRA throughout the technology’s life cycle. We identified 129 methodological approaches for BRA in the documents. The most commonly referred to descriptive frameworks were the Problem, Objectives, Alternatives, Consequences, Trade-offs, Uncertainty, Risk and Linked decisions and the Benefit–Risk Action Team. Multicriteria decision analysis was the most commonly cited quantitative framework. We also identified the most cited metric indices, estimation and utility survey techniques that could be used for BRA.Conclusions Methods for BRA in HTA are less established. The findings of this review, however, will support and inform the elaboration of the Brazilian methodological guideline on BRA for HTA.Trial registration number https://doi.org/10.17605/OSF.IO/69T3V.

The disruption of cell membranes by tau and amylin oligomers is linked to amyloid diseases such as Alzheimer’s and diabetes, respectively. The recent studies suggest that misfolded tau and amylin can form neurotoxic hetero-oligomers that are structurally different from homo-oligomers. However, the molecular interactions of these hetero-oligomers with the neuronal membranes remain unclear. Using MD simulations, we have investigated the binding behaviors, membrane disruption, and protein folding of hetero-oligomers on a raft membrane containing phase-separated lipid nanodomains like those found in neurons. We discovered that the hetero-oligomers bind to the liquid-order and liquid-disorder phase boundaries of the raft membrane. The major lipid-binding sites of these interactions include the L16 and I26 residues of amylin and the N-terminal of tau. Strong disruptions of the raft domain size by the hetero-tetramer were detected. Furthermore, the hetero-dimer disrupted the saturated phospholipid orientational order to a greater extent than the individual tau or amylin monomer. In addition, the constituent tau more strongly promoted the alpha-helix to the beta-sheet transition of the constituent amylin within the hetero-dimer when compared with the amylin monomer alone. Our results provide new molecular insights into understanding the neurotoxicity of the hetero-oligomers associated with the cross-talk between amyloid diseases.

Intracellular tau fibrils are sources of neurotoxicity and oxidative stress in Alzheimer’s. Current drug discovery efforts have focused on molecules with tau fibril disaggregation and antioxidation functions. However, recent studies suggest that membrane-bound tau-containing oligomers (mTCOs), smaller and less ordered than tau fibrils, are neurotoxic in the early stage of Alzheimer’s. Whether tau fibril-targeting molecules are effective against mTCOs is unknown. The binding of epigallocatechin-3-gallate (EGCG), CNS-11, and BHT-CNS-11 to in silico mTCOs and experimental tau fibrils was investigated using machine learning-enhanced docking and molecular dynamics simulations. EGCG and CNS-11 have tau fibril disaggregation functions, while the proposed BHT-CNS-11 has potential tau fibril disaggregation and antioxidation functions like EGCG. Our results suggest that the three molecules studied may also bind to mTCOs. The predicted binding probability of EGCG to mTCOs increases with the protein aggregate size. In contrast, the predicted probability of CNS-11 and BHT-CNS-11 binding to the dimeric mTCOs is higher than binding to the tetrameric mTCOs for the homo tau but not for the hetero tau–amylin oligomers. Our results also support the idea that anionic lipids may promote the binding of molecules to mTCOs. We conclude that tau fibril-disaggregating and antioxidating molecules may bind to mTCOs, and that mTCOs may also be useful targets for Alzheimer’s drug design.

Abstract To recognize DNA adducts, nucleotide excision repair (NER) deploys the XPC sensor, which detects damage-induced helical distortions, followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place in chromatin where DNA is tightly wrapped around histones. Here, we describe how the histone methyltransferase ASH1L, once activated by MRG15, helps XPC and TFIIH to navigate through chromatin and induce global-genome NER hotspots. Upon UV irradiation, ASH1L adds H3K4me3 all over the genome (except in active gene promoters), thus priming chromatin for XPC relocations from native to damaged DNA. The ASH1L-MRG15 complex further recruits the histone chaperone FACT to DNA lesions. In the absence of ASH1L, MRG15 or FACT, XPC is misplaced and persists on damaged DNA without being able to deliver the lesions to TFIIH. We conclude that ASH1L-MRG15 makes damage verifiable by the NER machinery through the sequential deposition of H3K4me3 and FACT.

Background Benefit–risk assessment (BRA) is used in multiple phases along the health technology’s life-cycle to evaluate the balance between the benefits and risks, as it is fundamental to all stakeholders. BRA and its methodological approaches have been applied primarily in the context of regulatory agencies. However, BRA’s application and extent in the context of health technology assessment (HTA) bodies remain less clear. Our goal is to perform a scoping review to identify and map methodological guidelines and publications on methods of BRA. This will be done considering the different phases of the life-cycle of health technologies to underline both the depth and extent of research concerning BRA, especially in the context of HTA.Methods and analysis This scoping review protocol was developed following the framework proposed by Arksey and O’Malley, and the updated guidelines by the Joanna Briggs Institute. We will include methodological publications that provide recommendations or guidelines on methods for BRA. We will conduct electronic searches on Medline (PubMed) and EMBASE (Ovid) databases; manual searches on the main websites of HTA bodies and drug regulatory organisations; and contact experts in the field. Systematic extraction forms will be used to screen and assess the identified publications by independent assessors. We will provide a qualitative synthesis using descriptive statistics and visual tools. Results will be summarised in systematic evidence tables and comparative evidence scoping charts.Ethics and dissemination This review will use data publicly available and does not require ethics approval. The results of this scoping review will contribute to scientific knowledge and act as a basis for methodologists, guideline developers and researchers for the development of BRA to inform regulatory decisions, reimbursement and coverage decision making. The results will be disseminated through peer-reviewed articles, conferences, policy briefs and workshops.Trial registration number Open Science Framework (https://doi.org/10.17605/OSF.IO/69T3V).

The molecular events of protein misfolding and self-aggregation of tau and amylin are associated with the progression of Alzheimer’s and diabetes, respectively. Recent studies suggest that tau and amylin can form hetero-tau-amylin oligomers. Those hetero-oligomers are more neurotoxic than homo-tau oligomers. So far, the detailed interactions between the hetero-oligomers and the neuronal membrane are unknown. Using multiscale MD simulations, the lipid binding and protein folding behaviors of hetero-oligomers on asymmetric lipid nanodomains or raft membranes were examined. Our raft membranes contain phase-separated phosphatidylcholine (PC), cholesterol, and anionic phosphatidylserine (PS) or ganglioside (GM1) in one leaflet of the lipid bilayer. The hetero-oligomers bound more strongly to the PS and GM1 than other lipids via the hydrophobic and hydrophilic interactions, respectively, in the raft membranes. The hetero-tetramer disrupted the acyl chain orders of both PC and PS in the PS-containing raft membrane, but only the GM1 in the GM1-containing raft membrane as effectively as the homo-tau-tetramer. We discovered that the alpha-helical content in the heterodimer was greater than the sum of alpha-helical contents from isolated tau and amylin monomers on both raft membranes, indicative of a synergetic effect of tau-amylin interactions in surface-induced protein folding. Our results provide new molecular insights into understanding the cross-talk between Alzheimer’s and diabetes.

En este artículo se explora la función de los estudios literarios en y para la educación general desde la perspectiva de una pedagogía crítica y descolonizadora. Se organiza en tres partes. Primero, se discute la educación general entendida como ecología de saberes, término propuesto por el sociólogo portugués Boaventura de Sousa Santos para reconocer e integrar la diversidad epistemológica como práctica descolonizadora. En la segunda parte, se evalúa el concepto de paratopía formulado por el lingüista francés Dominique Maingueneau para caracterizar el lugar imposible o la condición paradójica del discurso literario. Se sostiene que es esta cualidad paratópica, que opera en diversos niveles, lo que hace de los estudios literarios un instrumento provechoso para las aspiraciones integradoras de la educación general pensada como ecología de saberes. Por último, se incluye una estimación de los estudios literarios en y para la educación general mediante la instrumentalización del carácter dialógico e intertextual de la literatura como estrategia para la praxis descolonizadora.

Abstract Background Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world. Methods A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery. Results The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4–6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p

The objective of this experiment was to evaluate the effect of 2 feeding systems and 5 breeding groups on the growth performance, biometric features, and stomach morphology of feedlot goat kids. The experiment utilized gender as a randomized blocking factor in a 5 × 2 factorial scheme. The study goats were from the Alpine, Anglo-Nubian, 1/2 Boer x Alpine, 3/4 Boer x Alpine, and 7/8 Boer x Alpine breeds. Half of the goats were fed an experimental diet, whereas the other half were given the same diet supplemented with 1.5 L milk daily. The kids were slaughtered after they attained 30 kg body weight. The 1/2 Boer x Alpine goats showed superior growth performance because they exhibiting considerable heterosis. These animals are especially easy to use given that there is no need to maintain cross-bred females (½ Boer x Alpine e ¾ Boer x Alpine) in the flock. Using milk in the feed the animals does not adversely affect growth performance or biometric features. Moreover, it helps to reduce the total weight of the stomach and leads to a 51.39% savings on feed. Dietary supplementation of milk in goat feed is recommended so long as there is excess milk available on the property.

The aim of this study was to evaluate the effect of cross breeding, finishing system, and gender on the relative growth of carcass tissues of dairy kids. Seventy eight kids (39 male and 39 female) from five breed types were used: Alpine; ½ Boer + ½ Alpine (½ BA); ½ Nubian + ½ Alpine (½ ANA); ¾ Boer + ¼ Alpine (¾ BA); and ½ Nubian + ¼ Boer + ¼ Alpine (TC). Kids were distributed into two finishing systems: in pasture with doe (FS1) and weaned in feedlot (FS2). Kids were slaughtered at a mean age of 128.4 ± 7.9 days and mean live weight of 22.07 kg. The mean weight of half carcasses was 5.09 kg. To determine allometric growth, we used the exponential equation Y= aXb. In the half carcass, muscle tissue showed comparatively early growth in group ½ BA, whereas fat tissue of animals in FS1 had relatively late growth. Females exhibited early growth of muscle tissue, while in males this tissue was intermediate. The ½ BA first-cross improved carcass characteristics by enhancing the growth of muscle tissue.

Fundamentado no interacionismo sociodiscursivo (BRONCKART, 1999), este artigo objetiva realizar uma análise por meio do folhado textual, enfatizando as vozes e modalizações presentes no discurso político proferido pela presidente Dilma Rousseff, na abertura da 68º Assembleia-Geral da ONU. Além disso, mostraremos como essas vozes repercutem em outros textos, a partir da análise de uma charge eletrônica relativa a esse discurso. A escolha do discurso proferido pela presidente, nessa ocasião, justificase pelo destaque que recebeu da mídia brasileira, principalmente quanto à manifestação da presidente em relação à espionagem norte-americana sofrida pelo Brasil. A escolha da charge eletrônica deu-se devido ao gênero estar ligado a acontecimentos atuais, ser essencialmente crítico e polifônico (ROMUALDO, 2000) e sua significação ser construída relacionada a fatos políticos. A análise do discurso da presidente possibilitou-nos verificar como os mecanismos enunciativos contribuem para a construção de uma imagem ideológica do evento em si, de eventos políticos concomitantes e da própria presidente. Na análise da charge, apontamos a relação dialógica existente entre os textos, a partir de elementos verbais e não-verbais; e, dada à ironia característica do gênero, notamos que o texto orienta o leitor para um único ponto de vista da situação política brasileira.

There are few studies in the literature concerning the reliability and validity of the quantification of muscle architecture parameters using ultrasound that also report important information such as typical error of measurement (TEM) and intraclass correlation coefficient (ICC). The aim of this study was to use ultrasound imaging to quantify fiber length (FL) and pennation angle (PA) of the gastrocnemius muscle and to determine the reliability and reproducibility of these measurements. Two images of each gastrocnemius of 19 young healthy subjects were acquired using ultrasound equipment (7.5 MHz), in two visits. FL and PA were measured five times on each image, for a total of twenty measurements of each parameter. The overall reliability of the 760 measurements was determined through coefficients of variation (CV), ICC and TEM. The CV of FL ranged from 1.67 to 4.44% and from 3.8 to 11.62% for the PA. All ICC were within the high reliability range, with the exception of the between-visits PA value of the medial gastrocnemius (0.67). The two highest TEM values (3.1° and 3.7°) correspond to the two lowest ICC values (0.67 and 0.83), referring to repeated between-visit measurements of the medial and lateral gastrocnemius. FL measurements of the medial and lateral gastrocnemius had a TEM of 2.17 and 2.25 respectively. The results showed that ultrasound-based measurement of FL and PA exhibits high reliability.

The network of protein–protein interactions of the Dictyostelium discoideum autophagy pathway was investigated by yeast two-hybrid screening of the conserved autophagic proteins Atg1 and Atg8. These analyses confirmed expected interactions described in other organisms and also identified novel interactors that highlight the complexity of autophagy regulation. The Atg1 kinase complex, an essential regulator of autophagy, was investigated in detail here. The composition of the Atg1 complex in D. discoideum is more similar to mammalian cells than to Saccharomyces cerevisiae as, besides Atg13, it contains Atg101, a protein not conserved in this yeast. We found that Atg101 interacts with Atg13 and genetic disruption of these proteins in Dictyostelium leads to an early block in autophagy, although the severity of the developmental phenotype and the degree of autophagic block is higher in Atg13-deficient cells. We have also identified a protein containing zinc-finger B-box and FNIP motifs that interacts with Atg101. Disruption of this protein increases autophagic flux, suggesting that it functions as a negative regulator of Atg101. We also describe the interaction of Atg1 kinase with the pentose phosphate pathway enzyme transketolase (TKT). We found changes in the activity of endogenous TKT activity in strains lacking or overexpressing Atg1, suggesting the presence of an unsuspected regulatory pathway between autophagy and the pentose phosphate pathway in Dictyostelium that seems to be conserved in mammalian cells.

The concept of metacontingency describes a contingent relation between the coordination of two or more individual's behavior and a selecting consequence. The concept provides several insightful avenues for experimental investigation of social behavior and behavior of people in groups. The present study explores the question of whether operant behavior of individuals and coordinated behavior of multiple individuals can be distinguished as two different conditionable units of analysis. We used rates of individual responding maintained by ratio or interval schedules of reinforcement as a baseline to evaluate the effect of consequences contingent on coordinated behavior of 27 participants in groups of three. Coordination demanded temporal spacing between responses of three participants superimposed on the variable interval or variable ratio individual reinforcement schedules. The results showed that contingency on coordinated behaviors resulted in an increased rate of coordination along with a decreased rate of responding to individual schedules. Interresponse times (IRTs) from all participants were sensitive to the coordination contingency. We discuss the need to distinguish units of analysis that describe individual behavior and units describing coordinated behavior, although these units may occur simultaneously. Keywords Schedules of reinforcement * coordination * metacontingencies, An interesting and challenging characteristic of social behavior is that reinforcement of one individual's behavior usually depends at least partly on another individual's behavior. Thus, individual behavior becomes a discriminative [...]

ABSTRACT BACKGROUND AND OBJECTIVES: Fear of movement and re/injury (kinesiophobia) is factor associated to chronic pain and incapacity. Since elderly population is highly affected by chronic health problems followed by pain, especially musculoskeletal problems, it is important to understand the impact of pain-related fear on elderly females' health. This study aimed at determining the incidence of kinesiophobia in elderly females assisted in a geriatrics and gerontology ambulatory, as well as at investigating possible correlations with physical performance and other health and socio-demographic variables. METHODS: This is a crossover exploratory study with nonprobabilistic convenience sample of 30 elderly females, carried out with interviews, physical tests and medical charts review. Patients were evaluated for the presence of kinesiophobia, physical performance and other variables related to chronic musculoskeletal pain, in addition to socio-demographic information. RESULTS: There has been kinesiophobia in 80% of the sample. There has been significant moderate correlation between physical performance and kinesiophobia (r=541; p=0.002). No other correlations were found. CONCLUSION: Data have shown high incidence of kinesiophobia among evaluated elderly females, in addition to physical performance impairment associated to it.