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Diversity and Inclusion has been on the agenda of organizations in recent decades, pressured by civil society movements and the need for companies to operate in global markets. Even so, there were no significant advances in the panorama of diversity and inclusion in the labor market, as prejudice against the unknown and the different remains. The aim of this study was to analyze strategies for addressing unconscious biases in Diversity and Inclusion programs in the Big Four's workplace. The research carried out a documental analysis using the descriptive content analysis technique and data collection took place through access to publicly available corporate materials between the years 2018 and 2022. However, the first reports included in the research were from the year 2013, beginning of electronic disclosure. Among the results of this study, it was possible to identify that neuroscience is presented as a theoretical basis and that training has been the most used strategy for this approach. The top leadership of the companies has publicly committed to Diversity and Inclusion goals and that the four companies seek to achieve levels of diversity also in the composition of leadership at all levels.

Abstract Background Breast cancer is a prevalent form of cancer among women worldwide, often accompanied by physical and psychological side effects due to the disease and the treatment’s aggressiveness. Regular physical exercise has emerged as a non-pharmacological approach to improve the quality of life of breast cancer survivors. We herein report the protocol of the WaterMama Study, which aims to evaluate the effects of land- or water-based aerobic exercise programs, compared to a health education program, on cancer-related fatigue and other health-related outcomes in breast cancer survivors. Methods The WaterMama trial is a randomized, single-blinded, three-arm, parallel, superiority trial. We aim to recruit 48 women ≥ 18 years of age who have completed primary treatment for stage I–III breast cancer. Participants are randomly allocated in a 1:1:1 ratio to 12-week interventions of aerobic exercise training programs either in the aquatic or land environment (two weekly 45-min sessions) plus health education (a weekly 45-min session), or an active-control group receiving health education alone (a weekly 45-min session). The primary outcome is cancer-related fatigue, and the secondary outcomes include cardiorespiratory fitness, muscular performance, muscle morphology, functional capacity, mental health, cognitive function, pain, and quality of life. Outcomes assessments are conducted before and after the 12-week intervention period. The analysis plan will employ an intention-to-treat approach and per protocol criteria. Discussion Our conceptual hypothesis is that both aerobic exercise programs will positively impact primary and secondary outcomes compared to the health education group alone. Additionally, due to its multi-component nature, we expect the aquatic exercise program promote more significant effects than the land exercise program on cancer-related fatigue, muscular outcomes, and pain. Trial registration The study was prospectively registered at ClinicalTrials.gov NCT05520515. Registered on August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05520515

Abstract The hypothalamic arcuate nucleus (ARH) contains neurons vital for maintaining energy homeostasis that sense and respond to changes in blood-borne metabolic hormones. Despite its juxtaposition to the median eminence (ME), a circumventricular organ lacking a blood-brain barrier and thus exposed to circulating molecules, only a few ventral ARH neurons perceive these extravasating metabolic signals due to a poorly understood ME/ARH diffusion barrier. Here, we show in male mice that aggrecan, a perineural-net proteoglycan deposited by orexigenic ARH neurons, creates a peculiar ventrodorsal diffusion gradient. Fasting enhances aggrecan deposition more dorsally, reinforcing the diffusion barrier, particularly around neurons adjacent to fenestrated capillary loops that enter the ARH. The disruption of aggrecan deposits results in unregulated diffusion of blood-borne molecules into the ARH and impairs food intake. Our findings reveal the molecular nature and plasticity of the ME/ARH diffusion barrier, and indicate its physiological role in hypothalamic metabolic hormone sensing.

Objetivo: Apresentar proposta sobre um conjunto de indicadores de desempenho que podem ser utilizados nas auditorias dos tribunais de contas estaduais para avaliar a eficácia dos gastos orçamentários com a saúde pública. Metodologia: Trata-se de uma pesquisa quantitativa, com aplicação de técnicas estatísticas relacionadas a Data Envelopment Analysis (DEA) em dois estágios e estimação de modelos longitudinais lineares de regressão para dados em painel curto strongly balanced, sobre os gastos orçamentários realizados no período de 2015 a 2019 pelos Estados e Distrito Federal sobre a saúde pública. Resultados: Constatou-se que não há uso de indicadores de desempenho na elaboração e execução dos PPAs pelos governos, para avaliar a eficácia dos gastos com ações públicas; que a menção sobre “indicadores de desempenho”, refere-se exclusivamente a percentuais para comparar o que foi realizado em relação ao que foi previsto; que foram encontrados registros de ações públicas em duplicidade nos PPAs por alguns entes, e que foi identificado superavaliação nos registros dos recursos previstos na maioria dos PPAs. O grau de explicação estatística do conjunto de indicadores proposto alcançou em média 87% de confiança estatística. Nenhum ente público apresentou eficácia em 100% nos gastos realizados. 69% dos auditores dos tribunais de contas legitimaram o conjunto de indicadores proposto para avaliar a eficácia dos gastos com a saúde pública estadual. Por fim, conclui-se que os indicadores de avaliação de desempenho propostos podem ser utilizados para verificar a eficácia dos gastos com a saúde pública estadual. Contribuições do estudo: Apresenta indicadores de desempenho, criado por meio de método estatístico, para avaliar a eficácia dos gastos com a saúde pública estadual, uma vez que a literatura especializada indica pouca ou nenhuma discussão a respeito. Indica que as ações inseridas nos PPAs não são auditadas pelos tribunais de contas e que o poder legislativo é omisso na fiscalização entre o que é previsto e realizado, considerando que há ações repetidas e superavaliadas.

The crystallographic structure of the FolB enzyme from Mycobacterium tuberculosis (MtFolB), complexed with its inhibitor 8-mercaptoguanine (8-MG), was elucidated at a resolution of 1.95 Å. A novel series of S8-functionalized 8-MG derivatives were synthesised and evaluated as in vitro inhibitors of dihydroneopterin aldolase (DHNA, EC 4.1.2.25) activity of MtFolB. These compounds exhibited IC50 values in the submicromolar range. Evaluation of the activity for five compounds indicated their inhibition mode and inhibition constants. Molecular docking analyses were performed to determine the enzyme-inhibitor intermolecular interactions and ligand conformations upon complex formation. The inhibitory activities of all compounds against the M. tuberculosis H37Rv strain were evaluated. Compound 3e exhibited a minimum inhibitory concentration in the micromolar range. Finally, Compound 3e showed no apparent toxicity in both HepG2 and Vero cells. The findings presented herein will advance the quest for novel, specific inhibitors targeting MtFolB, an attractive molecular target for TB drug development.

Summary: Irisin, an exercise-induced myokine, is known to be able to regulate bone metabolism. However, the underlying mechanisms regarding the effects of irisin on senile osteoporosis have not been fully elucidated. Here, we demonstrated that irisin can inhibit bone mass loss and bone microarchitecture alteration in senile osteoporosis mouse model. In addition, irisin has effects on bone remodeling that is in favor of bone formation. Remarkably, irisin induced autophagy in osteocytes demonstrated by increased LC3-positive osteocytes, and increased autophagy-related genes and proteins. In vitro analysis revealed that Irisin can prevent mitochondrial oxidative damage. Furthermore, irisin can obviously induce osteocyte mitophagy and increased phosphorylation of Ampk and Ulk1. Inhibition of Ampk signaling recapitulated the biological effect of irisin loss, accompanied by the markedly lower expression of Ulk1. Taken together, our findings show that irisin reduces age-related bone loss by inducing osteocyte mitophagy via Ampk-dependent activation of Ulk1.

Francesca Alberton,1 Laura Galli,2 Riccardo Lolatto,2 Caterina Candela,1 Nicola Gianotti,2 Matteo Chiurlo,2 Martina Ranzenigo,2 Martina Strano,2 Alessia Uglietti,3 Antonella Castagna1,2 1Infectious Diseases Unit, Vita Salute San Raffaele University, Milan, Italy; 2Infectious Diseases Unit, San Raffaele Scientific Institute, Milan, Italy; 3Medical Affairs Department, Infectious Diseases and Vaccines & Rare Diseases, Johnson&Johnson, Milan, ItalyCorrespondence: Alessia Uglietti, Medical Affairs Department, Infectious Disease and Vaccines & Rare Diseases, Johnson&Johnson, viale Fulvio Testi 280/6, Milan, 20126, Italy, Tel +39-344 2665502, Email augliett@its.jnj.comObjective: To evaluate the virological outcome of darunavir–cobicistat (DRVc)‐based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination.Methods: This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc‐based regimen with HIV‐RNA > 50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV‐RNA < 50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA < 50 copies/mL, last available visit, or loss to follow‐up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS.Results: A total of 176 individuals were included, and 120 (68.2%) achieved < 50 HIV‐RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004– 1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant–bearing protease inhibitor–resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up.Conclusion: Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.Keywords: HIV infection, antiretroviral therapy, ART, darunavir–cobicistat, DRVc, virological failure, VF

Myrcia genus plants, like Myrcia pubipetala, traditionally used as hypoglycemic agents, hold promise for Type 1 Diabetes Mellitus (DM1) research but need more comprehensive chemical and pharmacological investigation. This is an experimental study involving controlled administration of treatments to a group of rats to assess their effects compared with a control group, investigating the effects of M. pubipetala on alloxan-induced Type 1 Diabetes Mellitus in rats. After the induction of diabetes, the rats received the hydroalcoholic extract (HAE) or aqueous fraction (AF) (25, 50, 100, or 150 mg kg-1) of M. pubipetala, or water. The results showed that diabetic rats presented cell damage in kidneys, oxidative stress, and high levels of glucose and triglycerides in their plasma and erythrocytes. The HAE (150 mg kg-1), per se, reduced lipid and protein oxidation, and the AF (150 mg kg-1) decreased lipoperoxidation. AF (150 mg kg-1), per se, decreased triglyceride levels. Conclusion: treatment with HAE and AF reduced oxidative damage, positively modulated antioxidant defenses, and exerted hypoglycemic and hypolipidemic effects, representing a potential adjuvant treatment for diabetes.

Purpose: To evaluate the effect of intraoperative ablation on the viability, distribution, phenotype, and potential for culture expansion of bursal cells harvested during arthroscopic rotator cuff surgery. Methods: Tissue was collected during primary arthroscopic rotator cuff repair on 6 healthy, randomly selected patients from a fellowship-trained surgeon’s practice between September 2020 and January 2021. There were 3 women (aged 60 ± 8 years) and 3 men (aged 61 ± 10 years). At the time of surgery, subacromial bursal tissue was subjected to no ablation, 1 second of ablation, or 3 seconds of ablation. Tissues were collected by an autograft harvesting system connected to an arthroscopic shaver and a pituitary grasper. Tissue fragments from each condition were sampled for viability testing or cell isolation. A viability kit with confocal microscopy was used to assess live and dead cells. Cell isolation consisted of collagenase digestion or placing tissue fragments onto tissue culture–treated plates that induced migration of cells out of the tissue. Cell proliferation rates were monitored and surface markers for mesenchymal stem cells (MSC) and pericytes were analyzed via multicolor flow cytometry. Results: Increased ablation time significantly reduced cell viability. The mean percentage of live cells was 55.2% ± 27.2% (range, 26%-90% live) in the control group, 46.8% ± 23.8% (range, 9.6%-69.6%, P = .045) in the short-ablation group, and 35.5% ± 19% (range, 11%-54%, P = .03) in the long-ablation group. No significant differences in population doubling level (1.6 ± 0.5 days) and population doubling time (6.7 ± 2.4 days) were observed in cells from any treatment. The surface marker profile indicated an MSC phenotype with absence of a pericyte population. Ablation or cell isolation procedure had no significant effect on the surface marker profile of isolated cells. Conclusions: Radiofrequency ablation significantly reduced the overall tissue viability but had no significant effect on cell proliferation or expression of surface markers on isolated subacromial bursal cells harvested arthroscopically. Clinical Relevance: Analysis of the viability and performance of cells harvested after the use of ablation devices using mechanical surgical collection during rotator cuff repair surgery could further our understanding of subacromial bursal tissue and its potential role in augmenting rotator cuff repair healing.

IntroductionClaw lesions significantly contribute to lameness, greatly affecting sow welfare. This study investigated different factors that would impact the severity of claw lesions in the sows of Brazilian commercial herds.MethodsA total of 129 herds (n = 12,364 sows) were included in the study. Herds were in the Midwest, Southeast, or South regions of Brazil. Inventory sizes were stratified into 250–810 sows, 811–1,300 sows, 1,301–3,000 sows, and 3,001–10,000 sows. Herds belonged to Cooperative (Coop), Integrator, or Independent structures. The herd management was conducted either maintaining breeds from stock on-site (internal), or through purchase of commercially available genetics (external). Herds adopted either individual crates or group housing during gestation. Within each farm, one randomly selected group of sows was scored by the same evaluator (two independent experts evaluated a total of 129 herds) from 0 (none) to 3 (severe) for heel overgrowth and erosion (HOE), heel-sole crack (HSC), separation along the white line (WL), horizontal (CHW) and vertical (CVW) wall cracks, and overgrown toes (T), or dewclaws (DC) in the hind legs after parturition. The study assessed differences and similarities between herds using Principal Component Analysis (PCA) and Hierarchical Agglomerative Clustering (HAC) analysis. The effects of factors (i.e., production structure, management, housing during gestation, and region) were assessed using the partial least squares method (PLS).Results and discussionHeel overgrowth and erosion had the highest prevalence, followed by WL and CHW, while the lowest scores were observed for T, DC, and CVW. Herds were grouped in three clusters (i.e., C1, C2, and C3). Heel overgrowth and erosion, HSC, WL, CHW, CVW, and T were decreased by 17, 25, 11, 25, 21, and 17%, respectively, in C3 compared to C1 and 2 combined. Independent structure increased the L-Index in all three clusters. Furthermore, individual housing increased the L-Index regardless of the cluster. The results suggest that shifting toward larger, more technologically advanced herds could potentially benefit claw health. Additionally, adopting group gestation housing appears to mitigate the adverse effects on claw health, although further validation is necessary, as Brazil has only recently transitioned from individual housing practices.

Objective: To present a proposal on a set of performance indicators that can be used in audits of state audit courts to assess the effectiveness of budget spending on public health. Methodology: This is quantitative research, with the application of statistical techniques related to Data Envelopment Analysis (DEA) in two stages and estimation of linear longitudinal regression models for strongly balanced short panel data, on the budget expenditures made in the period from 2015 to 2019 by the States and the Federal District on public health. Results: It was found that there is no use of performance indicators in the elaboration and execution of Multi-Annual Plans (MAPs) by governments to evaluate the effectiveness of spending on public actions; that the mention of "performance indicators" refers exclusively to percentages to compare what was accomplished in relation to what was predicted; that records of duplicate public actions were found in the MAPs by some entities, and that overvaluation was identified in the records of the resources provided for in most of the MAPs. The degree of statistical explanation of the proposed set of indicators reached an average of 87% of statistical confidence. None of the public entities was 100% effective in the expenditures made. 69% of the auditors of the Courts of Auditors legitimized the set of indicators proposed to evaluate the effectiveness of state public health spending. Finally, it is concluded that the proposed performance evaluation indicators can be used to verify the effectiveness of state public health spending. Contributions of the study: It presents performance indicators, created by means of a statistical method, to evaluate the effectiveness of spending on state public health, since the specialized literature indicates little or no discussion about it. It indicates that the actions included in the MAPs are not audited by the courts of auditors and that the legislative branch is silent in the supervision between what is foreseen and what is carried out, considering that there are repeated and overvalued actions.

Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of Paraná (96 sites), with a few additional sites in the neighbouring states of São Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery.Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences.

IntroductionAntifolates were among the first broad-spectrum compounds used as antimycobacterial agents and can still be of use when no other therapeutic options are available. The discovery of compounds targeting the essential folate synthesis pathway could lead to new therapeutic agents to treat tuberculosis (TB). In particular, the enzyme required for the conversion of 7,8-dihydroneopterin (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) and glycolaldehyde (GA) in the folate pathway (MtbFolB, a dihydroneopterin aldolase - DHNA, EC 4.1.2.25), has received little attention as a potential drug target so far, as it is acting upstream of the clinically validated targets dihydropteroate synthase (DHPS; EC 2.5.1.15) and dihydrofolate reductase (DHFR; EC 1.5.1.3).MethodsWe conducted a small-scale diversity screening to identify MtbFolB inhibitors using a microplate-based enzyme inhibition assay. A total of 6,074 compounds were assembled, tested and confirmed in dose-response studies. A preliminary structure activity analysis was performed for the validated hit compounds, along with kinetic inhibition, time-dependent inhibition, as well as docking studies. ResultsThe screening resulted in the selection of 19 hits spanning 5 independent clusters. Dose-response studies of re-synthesized hits and newly synthesized derivatives displayed compounds with IC50 values ranging from 2.6 to 47 µM. The structure activity analysis revealed that bi-sulfonamide compounds could be explored for further optimizations. Docking studies highlighted two modes of binding for pyrazol-3-one compounds and, for the sulfonamide series, indicated several interactions with the catalytic Tyrosine-54 (Tyr54D) and Lysine-99 (Lys99A) residues of MtbFolB. DiscussionThrough this work, we established that the MtbFolB assay was able to select small molecules with inhibitory activities, opening prospects for larger scale screening. The sulfonamide compound 13 was also identified as the first compound directed against MtbFolB with an antimycobacterial activity.

Bizarre parosteal osteochondromatous proliferations, also known as Nora’s lesions, are rare benign tumors with a high recurrence rate. They are often difficult to identify because of their similar appearance to other tumors. We describe a 25-year-old healthy female patient with bizarre parosteal osteochondromatous proliferations in an uncommon location on the pelvic ilium, presenting with unique clinical findings of abdominal pain and femoral paresthesia and showing atypical radiographic findings. To the best of our knowledge, this is one of the very few cases ever reported in the literature of Nora’s lesion in this particular location and possibly the first case ever with this specific presentation. The lesions’ radiographic images, combined orthopedic and general surgery procedures, and histological analysis are detailed. The patient’s continued 4-year follow-up has demonstrated no symptoms or evidence of recurrence.

Abstract Background Low back pain (LBP) is the leading cause of years lived with disability worldwide. Public safety workers are highly exposed to physically demanding activities and inappropriate postures, increasing the risk of experiencing LBP. Smartphone app-based self-managed interventions may be an alternative for chronic non-specific LBP (CNSLBP) treatment. This study aims to evaluate the effectiveness of a smartphone app-based self-managed exercise program plus health education, compared to a health education program alone, on neuromuscular and perceptual outcomes in police officers and firefighters with CNSLBP. Methods This is a parallel, two-armed, blinded evaluator randomized clinical trial. Police officers and firefighters (from public safety institutions in the Rio Grande do Sul state, Brazil) will be randomly assigned to a m-health self-managed exercise program (twice a week) plus health education or health education alone. Self-management exercise program components are mobility and core resistance exercises, available on the app. Follow-ups will be conducted post-treatment (8 weeks) and 16 weeks after randomization. The co-primary outcomes will be pain intensity and disability post-treatment (8 weeks). Secondary outcomes will be biopsychosocial factors related to CNSLBP. Discussion We hypothesize that the effects of a smartphone app-based self-managed exercise program on co-primary and secondary outcomes will be superior, compared to the health education only in public safety workers with CNSLBP. Trial registration The study was prospectively registered at ClinicalTrials.gov (NCT05481996. Registered on August 01, 2022).

Abstract Background Type 2 diabetes mellitus (T2D) is a serious global health problem, and exercise is considered an essential non-pharmacological tool in T2D prevention and treatment. During periods of social isolation experienced by the COVID-19 pandemic, home-based exercise programs were strongly recommended as a strategy to facilitate exercise practice and reduce the negative impacts of social isolation. Remotely supervised exercise stands out as an easily accessible strategy after the pandemic, as it is a tool that aims to facilitate access to exercise by this population. The purpose of the RED study is to verify the effects of a remotely supervised home-based exercise program compared to a control group on cardiometabolic, functional, and psychosocial outcomes in patients with T2D. Methods Participants are randomized into the control group (CG) and the intervention group (IG). Participants allocated to the CG receive recommendations for the practice of physical activity based on information from chapters of the Physical Activity Guide for the Brazilian Population, while the IG will perform a 12-week home-based exercise program supervised remotely by video call. The intervention has a weekly frequency of two sessions per week on non-consecutive days during the first 6 weeks and three sessions per week on non-consecutive days for the remaining 6 weeks. The RED study has HbA1c as the primary outcome, and the participants’ cardiometabolic, functional, and psychosocial parameters are assessed at baseline (week 0) and post-intervention (week 13). Discussion Expected results of the proposed study will provide the knowledge base of health professionals and deliver more evidence for a growing area, i.e., home-based exercise and T2D. Additionally, this protocol aims to verify and demonstrate whether this program can be accessible and effective for different health outcomes in patients with T2D. Trial registration The RED study protocol was prospectively registered at ClinicalTrials.gov (NCT05362071). Date registered April 6, 2022. https://clinicaltrials.gov/ct2/show/NCT05362071 .