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EF Porto,1,2 AAM Castro,1,3 VGS Schmidt,4 HM Rabelo,4 C Kümpel,2 OA Nascimento,5 JR Jardim5 1Pulmonary Rehabilitation Center, Federal University of São Paulo, 2Adventist University, São Paulo, 3Federal University of Pampa, Rio Grande do Sul, 4Pulmonary Rehabilitation Center, Adventist University, 5Respiratory Diseases, Pulmonary Rehabilitation Center, Federal University of São Paulo, São Paulo, Brazil Abstract: Patients with chronic obstructive pulmonary disease (COPD) fall frequently, although the risk of falls may seem less important than the respiratory consequences of the disease. Nevertheless, falls are associated to increased mortality, decreased independence and physical activity levels, and worsening of quality of life. The aims of this systematic review was to evaluate information in the literature with regard to whether impaired postural control is more prevalent in COPD patients than in healthy age-matched subjects, and to assess the main characteristics these patients present that contribute to impaired postural control.Methods: Five databases were searched with no dates or language limits. The MEDLINE, PubMed, EMBASE, Web of Science, and PEDro databases were searched using “balance”, “postural control”, and “COPD” as keywords. The search strategies were oriented and guided by a health science librarian and were performed on March 27, 2014. The studies included were those that evaluated postural control in COPD patients as their main outcome and scored more than five points on the PEDro scale. Studies supplied by the database search strategy were assessed independently by two blinded researchers.Results: A total of 484 manuscripts were found using the “balance in COPD or postural control in COPD” keywords. Forty-three manuscripts appeared more than once, and 397 did not evaluate postural control in COPD patients as the primary outcome. Thus, only 14 studies had postural control as their primary outcome. Our study examiners found only seven studies that had a PEDro score higher than five points. The examiners’ interrater agreement was 76.4%. Six of those studies were accomplished with a control group and one study used their patients as their own controls. The studies were published between 2004 and 2013.Conclusion: Patients with COPD present postural control impairment when compared with age-matched healthy controls. Associated factors contributing to impaired postural control were muscle weakness, physical inactivity, elderly age, need for supplemental oxygen, and limited mobility. Keywords: posture, balance, chronic obstructive pulmonary disease, postural control, systematic review

Early-life experiences, especially during critical periods of development and growth, can have long-lasting effects on adult phenotypes. Parents are a crucial part of the offspring early-life environment, particularly in mammals (e.g., via pregnancy), and parental behaviors (e.g., maternal exercise) can modify the early-life environment experienced by offspring. Such changes might be beneficial or detrimental, depending on how they affect offspring development and growth or interact with other key parental behaviors (e.g., nursing). We used mice from a long-term artificial selection experiment for high voluntary wheel-running behavior to determine whether maternal exercise opportunity affected (1) maternal physical activity, (2) maternal care behavior, or (3) offspring physical activity and body composition. Eighty prospective dams (40 from 4 selectively bred High Runner [HR] lines and 40 from 4 non-selected Control [CON] lines) were housed with continuous wheel access starting two weeks prior to breeding and ending 10 days postpartum, after which dams were housed without wheels until offspring weaning (21 days postpartum). An additional 100 dams (50 HR, 50 CON) were housed without wheels. Prospective dams from HR lines ran more revolutions/day (mainly by running faster) than those from CON lines when individually housed and in the days leading up to, but not after, birth. During postpartum days 1-5, HR and CON dams with wheels tended to exhibit less maternal behavior than those without (P Wheel = 0.0672). During post-partum days 6-10, HR dams with wheels continued to exhibit less maternal behavior than those without, whereas CON dams with wheels exhibited more than those without (P Linetype*Wheel = 0.0218). The proportion of dams giving birth did not differ among groups. However, CON dams with wheels were less likely to have litter death between birth and weaning than those without wheels, whereas the opposite was true for HR dams (P Linetype*Wheel = 0.0447). Both HR and CON dams with wheels had litters with a higher proportion of females at weaning than those without wheels (P Wheel = 0.0129). Maternal wheel access had few statistically significant effects on offspring, but may have resulted in developmental delays (e.g., delayed eye opening and decreased lean mass at weaning and sexual maturity). Additionally, maternal wheel access and sex may have interacted to affect wheel-running distance (P Sex*Wheel = 0.0683) and duration (P Sex*Wheel = 0.0926); female offspring from dams with wheels ran fewer revolutions per day, by running fewer minutes per day, than from dams without wheels, whereas males ran more. However, maternal exercise had no statistically significant effects on offspring food consumption (mass-adjusted), home-cage activity, open-field behavior, the reproductive characteristics of offspring, their adult body composition, nor relative organ masses; nor did maternal wheel access have statistically significant effects on grand-offspring food consumption, body composition or voluntary exercise behavior. Overall, our results provide some support for maternal exercise opportunity altering maternal care behavior. Altered maternal care could explain the observed trends in offspring survival, development, and voluntary exercise behavior. However, these effects did not have apparent long-lasting impacts on offspring or grand-offspring body composition or reproductive characteristics., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: The aim of this study was to assess how pandemic-related health concerns and discrimination affected cancer screenings among Asian American women (AAW)., Methods: A two-phase explanatory mixed-methods study was conducted. In phase 1, a survey was distributed among AAW eligible for lung, breast, or colorectal cancer screening to assess delays during the pandemic, concerns about contracting coronavirus disease 2019 (COVID-19), barriers to care, and experiences of discrimination. In phase 2, four qualitative focus group discussions, stratified by generational status and history of delayed cancer screening, were conducted to explore a priori domains of interest on cancer screening during the pandemic and perceived discrimination. Logistic regression analyses were performed to identify factors associated with delays, followed by deductive thematic qualitative analysis., Results: In phase 1, of 225 participants recruited, 166 met the inclusion criteria (74%). Most participants were first-generation Americans (67%), were employed (65%), and had higher education (67% with a master's degree or higher). Forty percent reported delays in cancer screening. Factors associated with delays included worry about contracting COVID-19 (adjusted odds ratio, 2.57; 95% confidence interval, 1.05-6.28; P = .038) and spreading it to family or friends (adjusted odds ratio, 5.78; 95% confidence interval, 1.50-22.3; P = .011). No association between discrimination and delayed cancer screening was found. In phase 2, focus group discussions (n = 19) revealed that first-generation women who delayed screening faced barriers due to a fear of infection and perceived discrimination. Perceived discrimination affected daily behaviors and sense of safety, though less so in medical settings., Conclusions: Delays in cancer screening among AAW were associated with patients' concerns about contracting and spreading COVID-19. Radiology practices can lead collaborative efforts on cancer screening campaigns that emphasize early detection and promote psychological safety., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Human serum albumin (HSA) has a strong binding affinity for heme b, forming a complex in a 1:1 ratio with the co-factor ([HSA-Fe III heme]). This system displays spectroscopic and functional properties comparable to globins when chemical derivatives mimicking them are incorporated into the protein matrix. The aim of this study is to generate globin-like systems using [HSA-Fe III heme] as a protein template and binding N-donor ligands (imidazole, Im; and 1-methylimidazole, 1-MeIm) to construct artificial [HSA-Fe(heme)-(N-donor)] complexes. Their electronic structure and binding thermodynamics are investigated using UV-vis and (synchronous) fluorescence spectroscopies, while ligand-protein interactions are visualized using docking simulations. The imidazole derivatives have a strong affinity for [HSA-Fe III heme] (K ∼ 10 4 -10 6 ), where the spontaneous binding of Im and 1-MeIm are dominated by entropic and enthalpic effects, respectively. The reduced form of the [HSA-Fe(heme)-(N-donor)] complexes demonstrate nitrite reductase (NiR) activity similar to that observed in globins, but with significant differences in their rates. [HSA-Fe II heme-(1-MeIm)] reduces nitrite ∼4× faster than the Im analogue, and ∼ 30× faster than myoglobin (Mb). The enhanced NiR activity of [HSA-Fe II heme-(1-MeIm)] is a cumulative effect of several factors including a slightly expanded and more optimal heme binding pocket, nearby residues as possible proton sources, and a H-bonding interaction between 1-MeIm and residues Arg160 and Lys181 that may have a long-distance influence on the heme π electron density., 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 © 2024 Elsevier Inc. All rights reserved.)

Introduction and Objectives: Percutaneous left atrial appendage occlusion (LAAO) is a viable option to mitigate bleeding and stroke risks in patients with atrial fibrillation (AF) who are not eligible for oral anticoagulation. Its safety and efficacy in cancer patients remain unclear due to their exclusion from trials. This study aimed to compare short- and long-term LAAO outcomes between cancer and non-cancer patients., Methods: Retrospective single centre study of 361 consecutive patients who underwent LAAO between april-2010 and december-2023 were included. Short-term outcomes included periprocedural complications, 30-day hospital readmission and mortality. Long-term outcomes included the composite of stroke, bleeding, and mortality and each component assessed separately., Results: The study included 93 cancer patients (54 % active, 46 % in remission) and 268 non-cancer patients. Baseline characteristics were similar, including ischemic and bleeding risk profiles (CHA 2 DS 2 -VASc: 4.5 ± 1.4 vs. 4.4 ± 1.5; HAS-BLED: 3.3 ± 0.9 vs. 3.2 ± 0.9), previous stroke and total bleeding events. Short-term outcomes showed no significant differences in periprocedural complications (7 % vs. 6 %), 30-day readmission (2 % vs. 3 %), or 30-day mortality (0 % vs. 1.5 %). Over 32 months, there was no significant difference regarding the composite endpoint (p = 0.067), stroke (SHR 0.54; p = 0.25) or bleeding events (SHR 1.36; p = 0.35). LAAO was effective in terms of stroke reduction in cancer and non-cancer patients (p = 0.027 and p = 0.006, respectively). All-cause mortality rates were higher in cancer patients (p = 0.002), mainly due to cancer progression and infections., Conclusions: LAAO procedure was safe and effective in both populations. Cancer patients experienced higher rates of all-cause mortality, with no differences in stroke and bleeding outcomes between groups., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V.)

We and others have shown that application of high-level mechanical loading promotes the formation of transient plasma membrane disruptions (PMD) which initiate mechanotransduction. We hypothesized that increasing osteocyte cell membrane fragility, by disrupting the cytoskeleton-associated protein β2-spectrin (Sptbn1), could alter osteocytic responses and bone adaptation to loading in a PMD-related fashion. In MLO-Y4 cells, treatment with the spectrin-disrupting agent diamide or knockdown of Sptbn1 via siRNA increased the number of PMD formed by fluid shear stress. Primary osteocytes from an osteocyte-targeted DMP1-Cre Sptbn1 conditional knockout (CKO) model mimicked trends seen with diamide and siRNA treatment and suggested the creation of larger PMD, which repaired more slowly, for a given level of stimulus. Post-wounding cell survival was impaired in all three models, and calcium signaling responses from the wounded osteocyte were mildly altered in Sptbn1 CKO cultures. Although Sptbn1 CKO mice did not demonstrate an altered skeletal phenotype as compared to WT littermates under baseline conditions, they showed a blunted increase in cortical thickness when subjected to an osteogenic tibial loading protocol as well as evidence of increased osteocyte death (increased lacunar vacancy) in the loaded limb after 2 weeks of loading. The impaired post-wounding cell viability and impaired bone adaptation seen with Sptbn1 disruption support the existence of an important role for Sptbn1, and PMD formation, in osteocyte mechanotransduction and bone adaptation to mechanical loading., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Past research has been inconclusive regarding the specificity of associations between discrete pleasurable emotions and internalizing symptoms. Contentment may be especially relevant to depression, whereas tranquillity may be especially relevant to worry. The goal of the current research was to clarify the mixed findings regarding the relation between pleasure deficits and internalizing psychopathology., Methods: Participants from three samples (Total N = 757) completed alternative measures of depression and pleasurable emotions. Participants in Study 1 also completed a measure of anticipatory and consummatory pleasure, and close peers to a subset of participants (N = 64) reported their perceptions of participants' depression severity. Participants in Studies 2 and 3 also completed a measure of worry., Results: Across the three samples, contentment was significantly negatively associated with self-reported depression. This association could not be accounted for by tranquillity, cheerfulness, anticipatory pleasure, or consummatory pleasure. Contentment was also strongly negatively associated with peer-reported depression. Contentment was more strongly associated with depression than was cheerfulness. However, the strength of the association between contentment and depression relative to the strength of the association between tranquillity and depression depended on how contentment and depression were measured. Conversely, tranquillity was more strongly associated with worry than were contentment or cheerfulness., Conclusions: This study provides further evidence of the potential importance of the role of contentment in depression and tranquillity in worry. It may be useful to attend to contentment when assessing and treating depression and to attend to tranquillity when assessing and treating elevated worry., (© 2024 The Author(s). British Journal of Clinical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Alzheimer's disease (AD) stands as the predominant contributor to dementia cases. The ongoing developments in our understanding of its pathogenesis have sparked the interest of researchers, driving them to explore innovative treatment approaches. Existing therapies incorporating cholinesterase inhibitors and/or NMDA antagonists have shown limited improvement in alleviating symptoms. This, in turn, highlights the urgency for the pursuit of more effective therapeutic options. Given the annual rise in the number of individuals affected by dementia, it is imperative to allocate resources and efforts towards the exploration of novel therapeutic options. This review aims to provide a comprehensive overview of the AD-related hypotheses, along with the computational approaches employed in research within each hypothesis. In this comprehensive review, the authors shed light on using various computational tools, including diverse case studies, in the pursuit of finding efficacious treatments for AD. The development of more sophisticated diagnostic techniques is crucial, enabling early detection and intervention in the battle against this challenging condition. The potential treatments investigated in this analysis are poised to assume ever more significant functions in both preventing and treating AD, ultimately enhancing the management of the condition and the overall well-being of individuals affected by AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

AbstractMuscle-tendon unit (MTU) morphology and physiology are likely major determinants of locomotor performance and therefore Darwinian fitness. However, the relationships between underlying traits, performance, and fitness are complicated by phenomena such as coadaptation, multiple solutions, and trade-offs. Here, we leverage a long-running artificial selection experiment in which mice have been bred for high levels of voluntary running to explore MTU adaptation, as well as the role of coadaptation, multiple solutions, and trade-offs, in the evolution of endurance running. We compared the morphological and contractile properties of the triceps surae complex, a major locomotor MTU, in four replicate selected lines to those of the triceps surae complex in four replicate control lines. All selected lines have lighter and shorter muscles, longer tendons, and faster muscle twitch times than all control lines. Absolute and normalized maximum shortening velocities and contractile endurance vary across selected lines. Selected lines have similar or lower absolute velocities and higher endurance than control lines. However, normalized shortening velocities are both higher and lower in selected lines than in control lines. These findings potentially show an interesting coadaptation between muscle and tendon morphology and muscle physiology, highlight multiple solutions for increasing endurance running performance, demonstrate that a trade-off between muscle speed and endurance can arise in response to selection, and suggest that a novel physiology may sometimes allow this trade-off to be circumvented.

The diabetic foot interacts with anatomical, vascular, and neurological factors that challenge clinical practice. This study aimed to compile the primary scientific evidence based on a review of the main guidelines, in addition to articles published on the Embase, Lilacs, and PubMed platforms. The European Society of Cardiology system was used to develop recommendation classes and levels of evidence. The themes were divided into six chapters (Chapter 1 - Prevention of foot ulcers in people with diabetes; Chapter 2 - Pressure relief from foot ulcers in people with diabetes; Chapter 3 -Classifications of diabetic foot ulcers; Chapter 4 - Foot and peripheral artery disease; Chapter 5 - Infection and the diabetic foot; Chapter 6 - Charcot's neuroarthropathy). This version of the Diabetic Foot Guidelines presents essential recommendations for the prevention, diagnosis, treatment, and follow-up of patients with diabetic foot, offering an objective guide for medical practice., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2024 The authors.)

Objectives: Misophonia is a little-understood disorder in which certain sounds cause a strong emotional response in those who experience it. People who are affected by misophonia may find that noises like loud chewing, pen clicking, and/or sniffing trigger intense frustration, anger, or discomfort. The relationship of misophonia with other auditory disorders including loudness hyperacusis, tinnitus, and hearing loss is largely underexplored. This project aimed to investigate the prevalence and hearing-health comorbidities of misophonia in a college-aged population by using an online survey., Design: A total of 12,131 undergraduate and graduate students between the ages of 18 and 25 were given the opportunity to answer an in-depth online survey. These students were sampled in a roughly 50 of 50 sex distribution. The survey was created using Qualtrics and included the following components: electronic consent, demographics questionnaire, Misophonia Questionnaire (MQ), Khalfa's Hyperacusis Questionnaire (HQ), Tinnitus and Hearing Survey, and Tinnitus Functional Index (TFI). To be eligible for compensation, answers for each of the above components were required, with the exception of the TFI, which was only presented to students who indicated that they experienced tinnitus. Respondents were determined to have high or possible likelihood of having misophonia if they gave specific answers to the MQ's Emotion and Behavior Scale or the MQ Severity Scale., Results: After excluding duplicate responses and age-related outliers, 1,084 responses were included in the analysis. Just over 20% (n = 217) of the sample was determined to have a high or probable likelihood of having misophonia. The sample was primarily White, female, and of mid-to-high socioeconomic status. There was a strong positive correlation between MQ total scores and HQ total scores. High likelihood misophonia status showed a significant relationship with self-reported hearing loss and tinnitus. No statistically significant relationship was found between misophonia and age, ethnicity, or socioeconomic status. MQ total scores differed significantly when separating respondents by sex, self-reported tinnitus, and loudness hyperacusis. White respondents had significantly higher MQ total scores than Asian/Asian American respondents., Conclusions: The estimated prevalence of misophonia was about 8% to 20% of the sample, which agrees with most of the currently published research examining misophonia symptoms in collegiate populations. Results of data analysis suggest that misophonia severity may be related to loudness hyperacusis, sex, and possibly tinnitus. Future studies are needed to further examine the characteristics of these relationships, possibly in populations more optimized to reflect the general population or those with hearing-health disorders., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The endocrine disruptors (EDCs) are an important group of emerging contaminants, and their mitigation has been a huge challenge due to their chemistry complexity and variety of these compounds. The traditional treatments are inefficient to completely remove EDCs, and adsorptive processes are the major alternative investigated on their removal. Also, the use of EDCs degrading enzymes has been encouraged due to ecofriendly approach of biocatalytic processes. This paper highlights the occurrence, classification, and toxicity of EDCs with special focus in the use of enzyme-based and adsorptive technologies in the elimination of EDCs from ambiental matrices. Numerous prior reviews have focused on the discussions toward these technologies. However, the literature lacks theoretical discussions about important aspects of these methods such as the mechanisms of EDCs adsorption on the adsorbent surface or the interactions between degrading enzymes - EDCs. In this sense, theoretical calculations combined to experimental studies may help in the development of more efficient technologies to EDCs mitigation. In this review, we point out how computational tools such as molecular docking and molecular dynamics have to contribute to the design of new adsorbents and efficient catalytic processes towards endocrine disruptors mitigation., 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 © 2023 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to assess if a color scale in the endotracheal tube (ETT) can help operators to correctly select the size and depth of placement of the ETT and decrease the time required to complete the procedure and compared with the usual numeric ETT scale in a mannequin model., Study Design: The study was conducted in eight centers. Each size of the ETT was identified with a different color. The experimental ETTs had two different colored areas, one for the mouthpiece and another to identify where the ETT should be taped above the lip (an area of 1 cm. The operators were trained as part of the protocol using an instructional video. Four clinical scenarios requiring endotracheal intubation were designed and randomly assigned. Each operator had to select the size and depth of ETT based on the birth weight (BW), and then had to perform four intubations., Results: A total of 108 operators performed 432 intubations. No differences were found in the correct placement and selection of the ETT. Median time (in seconds) required for intubation using numeric versus experimental tube was: for ETT Ø NRP (Neonatal Resuscitation Program) 2.5, 11.5 versus 8 ( p  < 0.001), ETT Ø 3, 12 versus 10 ( p  < 0.001), ETT Ø 3.5, 15.5 versus12 ( p  = 0.003), ETT Ø 4, 12 versus11 ( p  = 0.019)., Conclusion: No significant difference was observed in the selection and correct placement of the ETT. However, the intubation time was significantly shorter using the experimental ETT. This device could improve the effectiveness of intubation by reducing the time needed to properly place the ETT at mid trachea., Key Points: · It is an innovative intervention to try to solve a great inconvenience of daily practice.. · The study also raises the difficulty in maintaining the ability of endotracheal intubation.. · It proposes a scale that ensures the correct location with a safe fixation zone.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The COVID-19 pandemic overwhelmed health facilities and presented healthcare workers (HCWs) with a new infectious disease threat. In addition to a sanitary crisis, Brazil still had to face major political, economic, and social challenges. This study aimed to investigate mental health outcomes in frontline HCWs in different regions of the country and at different epidemic times. We also sought to identify the main risk factors associated with these outcomes., Methods: A cross-sectional online survey using respondent-driven sampling was conducted to recruit physicians (n = 584), nurses (n = 997), and nurse technicians (n = 524) in 4 regions of Brazil (North, Northeast, Southeast, and South) from August 2020 to July 2021. We used standardized instruments to screen for common mental disorders (CMD)(SRQ-20), alcohol misuse (AUDIT-C), depression (PHQ-9), anxiety (GAD-7), and post-traumatic stress disorder (PTSD)(PCL-5). Gile's successive sampling estimator was used to produce weighted estimates. We created a three-cluster data set for each HCW category and developed a hierarchical regression model with three levels: individual characteristics; workplace-related aspects; COVID-19 personal experience. The impact of the epidemic moment on the outcomes was also studied., Results: The prevalence of probable CMD was 26.8-36.9%, alcohol misuse 8.7-13.6%, depression 16.4-21.2%, anxiety 10.8-14.2%, and PTSD 5.9-8.0%. We found a stronger association between mental health outcomes and the following factors: history of psychiatric disorders, female gender, and clinical comorbidities (level 1); work overload and family isolation (level 2); sick leave (level 3). Epidemic variables, such as the number of deaths and trend of deaths by COVID-19, had almost no impact on the outcomes., Conclusion: An alarmingly high prevalence of depression and anxiety was found in Brazilian frontline HCWs. Individual factors were the most strongly associated with mental health outcomes. These findings indicate the need to develop programs that provide emotional support, identify professionals at risk and refer them to specialized treatment when necessary., 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We investigated whether and how emotional information would affect analogical reasoning. We hypothesized that task-irrelevant emotional information would impair performance whereas task-relevant emotional information would enhance it. In Study 1, 233 undergraduates completed a novel version of the People Pieces Task (Emotional Faces People Task), an analogical reasoning task in which the task characters displayed emotional or neutral facial expressions (within-participants). The emotional faces were relevant or irrelevant to the task (between-participants). We simulated the behavioral results using the Learning and Inference with Schemas and Analogies (LISA) model of relational reasoning. LISA is a neurally plausible, symbolic-connectionist computational model of analogical reasoning. In comparison to neutral trials, participants were slower but more accurate on emotion-relevant trials, and were faster but less accurate on emotion-irrelevant trials. Simulations using the LISA model demonstrated that it is possible to account for the effects of emotional information on reasoning in terms of how emotional stimuli attract attention during a reasoning task. In Study 2, 255 undergraduates completed the Emotional Faces People Task at either a high- or low-working memory load. The high working memory load condition of Study 2 replicated the findings of Study 1, showing that participants were more accurate on emotion-relevant trials than on emotion-irrelevant trials; in Study 2, this increased accuracy could not be accounted for by a speed-accuracy tradeoff. The working memory manipulation influenced the manner in which the congruence (with the correct answer) of emotion-irrelevant emotion influenced performance. Simulations using the LISA model showed that manipulating the salience of emotion, the error penalty, as well as vigilance (which determines the likelihood that LISA will notice it has attended to an irrelevant relation), could reasonably reproduce the behavioral results of both low and high working memory load conditions of Study 2., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Despite significant advances in health care, many patients from medically under-served populations are impacted by existing health care disparities. Radiologists are uniquely positioned to decrease health disparities and advance health equity efforts in their practices. However, literature on practical tools for advancing radiology health equity efforts applicable to a wide variety of patient populations and care settings is lacking. Therefore, this article seeks to equip radiologists with an evidence-based and practical knowledge tool kit of health equity strategies, presented in terms of four pillars of research, clinical care, education, and innovation. For each pillar, equity efforts across diverse patient populations and radiology practice settings are examined through the lens of existing barriers, current best practices, and future directions, incorporating practical examples relevant to a spectrum of patient populations. Health equity efforts provide an opportune window to transform radiology through personalized care delivery that is responsive to diverse patient needs. Guided by compassion and empathy as core principles of health equity, the four pillars provide a helpful framework to advance health equity efforts as a step toward social justice in health.

Leishmaniasis, caused by protozoa of the genus Leishmania , encompasses a group of neglected diseases with diverse clinical and epidemiological manifestations that can be fatal if not adequately and promptly managed/treated. The current chemotherapy options for this disease are expensive, require invasive administration and often lead to severe side effects. In this regard, our research group has previously reported the potent anti- Leishmania activity of two coordination compounds (complexes) derived from 1,10-phenanthroline-5,6-dione (phendione): [Cu(phendione) 3 ].(ClO 4 ) 2 .4H 2 O and [Ag(phendione) 2 ].ClO 4 . The present study aimed to evaluate the effects of these complexes on leishmanolysin (gp63), a virulence factor produced by all Leishmania species that plays multiple functions and is recognized as a potential target for antiparasitic drugs. The results showed that both Ag-phendione (-74.82 kcal/mol) and Cu-phendione (-68.16 kcal/mol) were capable of interacting with the amino acids comprising the active site of the gp63 protein, exhibiting more favorable interaction energies compared to phendione alone (-39.75 kcal/mol) or 1,10-phenanthroline (-45.83 kcal/mol; a classical gp63 inhibitor) as judged by molecular docking assay. The analysis of kinetic parameters using the fluorogenic substrate Z-Phe-Arg-AMC indicated V max and apparent K m values of 0.064 µM/s and 14.18 µM, respectively, for the released gp63. The effects of both complexes on gp63 proteolytic activity were consistent with the in silico assay, where Ag-phendione exhibited the highest gp63 inhibition capacity against gp63, with an IC 50 value of 2.16 µM and the lowest inhibitory constant value (K i = 5.13 µM), followed by Cu-phendione (IC 50 = 163 µM and K i = 27.05 µM). Notably, pretreatment of live L. amazonensis promastigotes with the complexes resulted in a significant reduction in the expression of gp63 protein, including the isoforms located on the parasite cell surface. Both complexes markedly decreased the in vitro association indexes between L. amazonensis promastigotes and THP-1 human macrophages; however, this effect was reversed by the addition of soluble gp63 molecules to the interaction medium. Collectively, our findings highlight the potential use of these potent complexes in antivirulence therapy against Leishmania , offering new insights for the development of effective treatments for leishmaniasis.

Uncaria species are used in traditional medicine and are considered of high therapeutic value and economic importance. This work describes the assembly and annotation of the chloroplast genomes of U. guianensis and U. tomentosa, as well as a comparative analysis. The genomes were sequenced on MiSeq Illumina, assembled with NovoPlasty, and annotated using CHLOROBOX GeSeq. Addictionaly, comparative analysis were performed with six species from NCBI databases and primers were designed in Primer3 for hypervariable regions based on the consensus sequence of 16 species of the Rubiaceae family and validated on an in-silico PCR in OpenPrimeR. The genome size of U. guianensis and U. tomentosa was 155,505 bp and 156,390 bp, respectively. Both Species have 131 genes and GC content of 37.50%. The regions rpl32-ccsA, ycf1, and ndhF-ccsA showed the three highest values of nucleotide diversity within the species of the Rubiaceae family and within the Uncaria genus, these regions were trnH-psbA, psbM-trnY, and rps16-psbK. Our results indicates that the primer of the region ndhA had an amplification success for all species tested and can be promising for usage in the Rubiaceae family. The phylogenetic analysis recovered a congruent topology to APG IV. The gene content and the chloroplast genome structure of the analyzed species are conserved and most of the genes are under negative selection. We provide the cpDNA of Neotropical Uncaria species, an important genomic resource for evolutionary studies of the group., (© 2023. The Author(s).)

Fructose (C 6 H 12 O 6 ) is acutely obesogenic and is a risk factor for hypertension, cardiovascular disease, and nonalcoholic fatty liver disease. However, the possible long-lasting effects of early-life fructose consumption have not been studied. We tested for effects of early-life fructose and/or wheel access (voluntary exercise) in a line of selectively bred High Runner (HR) mice and a non-selected Control (C) line. Exposures began at weaning and continued for 3 weeks to sexual maturity, followed by a 23-week "washout" period (equivalent to ∼17 human years). Fructose increased total caloric intake, body mass, and body fat during juvenile exposure, but had no effect on juvenile wheel running and no important lasting effects on adult physical activity or body weight/composition. Interestingly, adult maximal aerobic capacity (VO 2 max) was reduced in mice that had early-life fructose and wheel access. Consistent with previous studies, early-life exercise promoted adult wheel running. In a 3-way interaction, C mice that had early-life fructose and no wheel access gained body mass in response to 2 weeks of adult wheel access, while all other groups lost mass. Overall, we found some long-lasting positive effects of early-life exercise, but minimal effects of early-life fructose, regardless of the mouse line.

We carried out theoretical and experimental analyses of ZnO and ZnS nanoparticles as smart semiconductor materials in light-activated antimicrobial coating for application in masks. We used low-cost hydrothermally processable precursors to direct the growth of the coatings on cotton fabric. Both ZnO and ZnS coatings had high reactivities as disinfection agents in photocatalysis reactions for the degradation of a methylene blue dye solution. Also, these coatings showed excellent UV protection properties. For understanding at the molecular level, the broad-spectrum biological activities of the ZnO and ZnS coatings against Fusarium Oxysporum fungi, Escherichia coli bacteria, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus and their variants, were investigated computationally. Hexagonal Zn 6 O 6 and Zn 6 S 6 clusters were used as models for the simulations through excited- and ground-state calculations. The theoretical findings show that changes in the local chemical environment in these excited systems have a profound impact on their physical and chemical properties and thus, can provide a better understanding to engineer new functional materials in light-activated antimicrobial coatings for the mitigation of SARS-CoV-2 infection., Competing Interests: 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., (© 2022 Elsevier Ltd. All rights reserved.)

We compared the fecal microbial community composition and diversity of four replicate lines of mice selectively bred for high wheel-running activity over 81 generations (HR lines) and four non-selected control lines. We performed 16S rRNA gene sequencing on fecal samples taken 24 h after weaning, identifying a total of 2074 bacterial operational taxonomic units. HR and control mice did not significantly differ for measures of alpha diversity, but HR mice had a higher relative abundance of the family Clostridiaceae. These results differ from a study of rats, where a line bred for high forced-treadmill endurance and that also ran more on wheels had lower relative abundance of Clostridiaceae, as compared with a line bred for low endurance that ran less on wheels. Within the HR and control groups, replicate lines had unique microbiomes based on unweighted UniFrac beta diversity, indicating random genetic drift and/or multiple adaptive responses to selection., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Organophosphorus compounds (OP) make up an important class of inhibitors, mostly employed as pesticides, even as chemical weapons. These toxic substances act through the inhibition of the acetylcholinesterase (AChE) enzyme, which results in elevated synaptic acetylcholine (ACh) levels, leading to serious adverse effects under the cholinergic syndrome. Many reactivators have been developed to combat the toxic effects of these AChE inhibitors. In this line, the oximes highlight because of their good reactivating power of cholinesterase enzymes. To date, no universal antidotes can reactivate AChE inhibited by any OP agent. This review summarizes the intoxication process by neurotoxic OP agents, along with the development of reactivators capable of reversing their effects, approaching aspects like the therapeutic and toxicological profile of these antidotes. Computational methods and conscious in vitro studies, capable of significantly predicting the toxicological profile of these drug candidates, might support the process of development of these reactivators before entering in vivo studies in animals, and then clinical trials. These approaches can assist in the design of safer and more effective molecules, reducing related cost and time for the process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A trade-off between locomotor speed and endurance occurs in various taxa, and is thought to be underpinned by a muscle-level trade-off. Among four replicate high runner (HR) lines of mice, selectively bred for voluntary wheel-running behavior, a negative correlation between average running speed and time spent running has evolved. We hypothesize that this trade-off is due to changes in muscle physiology. We studied the HR lines at generation 90, at which time one line (L3) is fixed for the mini-muscle phenotype, another is polymorphic (L6) and the others (L7, L8) lack mini-muscle individuals. We used in situ preparations to quantify the contractile properties of the triceps surae muscle complex. Maximal shortening velocity varied significantly, being lowest in mini-muscle mice (L3 mini=25.2 mm s-1, L6 mini=25.5 mm s-1), highest in normal-muscle mice L6 and L8 (40.4 and 50.3 mm s-1, respectively) and intermediate in normal-muscle L7 mice (37.2 mm s-1). Endurance, measured both as the slope of the decline in force and the proportion of initial force that could be sustained, also varied significantly. The slope was shallowest in mini-muscle mice (L3 mini=-0.00348, L6 mini=-0.00238), steepest in lines L6 and L8 (-0.01676 and -0.01853), and intermediate in L7 (-0.01145). Normalized sustained force was highest in mini-muscle mice (L3 mini=0.98, L6 mini=0.92) and lowest in L8 (0.36). There were significant, negative correlations between velocity and endurance metrics, indicating a muscle-level trade-off. However, this muscle-level trade-off does not seem to underpin the organismal-level speed and endurance trade-off previously reported as the ordering of the lines is reversed: the lines that run the fastest for the least time have the lowest muscle complex velocity and highest endurance., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

The gut microbiome can affect various aspects of both behavior and physiology, including exercise ability, but effects on voluntary exercise have rarely been studied. We studied females from a selection experiment in which 4 replicate High Runner (HR) lines of mice are bred for voluntary exercise and compared with 4 non-selected control (C) lines. HR and C mice differ in several traits that likely interact with the gut microbiome, including higher daily running distance, body temperatures when running, spontaneous physical activity when housed without wheels, and food consumption. After two weeks of wheel access to reach a stable plateau in daily running, mice were administered broad-spectrum antibiotics for 10 days. Antibiotic treatment caused a significant reduction in daily wheel-running distance in the HR mice (-21%) but not in the C mice. Antibiotics did not affect body mass or food consumption in either HR or C mice, and we did not observe sickness behavior. Wheel running by HR mice did not recover during the 12 days following cessation of antibiotics. The decreased wheel-running in HR but not C mice, with no apparent negative side effects of antibiotics, suggests that the HR microbiome is an important component of their high-running phenotype., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: To describe success and failure (S&F) after lumbar spine surgery in terms equally understandable across the entire health ecosystem., Methods: Back and leg pain and disability were prospectively recorded before and up to 12 months after the procedure. Satisfaction was recorded using a Likert scale. Initially, patients were classified as satisfied or unsatisfied. Optimal satisfaction/unsatisfaction cutoff values for disability and pain were estimated with ROC curves. Satisfied and unsatisfied groups underwent a second subdivision into four subcategories: success (satisfied AND pain and disability concordant with cutoff values), incomplete success (satisfied AND pain and disability nonconformant with cutoff values), incomplete failure (unsatisfied AND pain and disability nonconformant with cutoff values), and failure (unsatisfied AND pain and disability concordant with cutoff values)., Results: A total of 486 consecutive patients were recruited from 2019-2021. The mean values of preoperative PROMs were ODI 42.2 (+ 16.4), NPRS back 6.6 (+ 2.6) and NPRS leg 6.2 points (+ 2.9). Of the total, 80.7% were classified as satisfied, and 19.3% were classified as unsatisfactory. The optimal disability and pain cutoff values for satisfaction/unsatisfaction (NPRS = 6, AND ODI = 27) defined a subdivision: 59.6% were classified as success, 20.4% as incomplete success, 7.1% as incomplete failure and 12.4% as failure. The descriptions of each group were translated to the following: success-all patients were satisfied and presented no or only mild to tolerable pain and no or borderline disability; incomplete success - all patients were satisfied despite levels of pain and/or disability worse than ideal for success; incomplete failure - all patients were not satisfied despite levels of pain and/or disability better than expected for failure; failure - all patients were unsatisfied and presented moderate to severe pain and disability., Conclusion: It is possible to report S&F after surgery for DDL with precise and meaningful operational definitions focused on the experience of the patient., (© 2022. The Author(s).)

The future of land use and cover change in Brazil, particularly due to deforestation and forest restoration processes, is critical for the future of global climate and biodiversity, given the richness of its five biomes. These changes in Brazil depend on the interlink between global factors due to its role as one of the main exporters of commodities globally and the national to local institutional, socioeconomic, and biophysical contexts. Aiming to develop scenarios that consider the balance between global (e.g., GDP growth, population growth, per capita consumption of agricultural products, international trade policies, and climatic conditions) and local factors (e.g., land use, agrarian structure, agricultural suitability, protected areas, distance to roads, and other infrastructure projects), a new set of land-use change scenarios for Brazil were developed that aligned with the global structure Shared Socioeconomic Pathways (SSPs) and Representative Concentration Pathway (RCPs) developed by the global change research community. The narratives of the new scenarios align with SSP1/RCP 1.9 (Sustainable development scenario), SSP2/RCP 4.5 (Middle of the road scenario), and SSP3/RCP 7.0 (Strong inequality scenario). The scenarios were developed by combining the LuccME spatially explicit land change allocation modeling framework and the INLAND surface model to incorporate the climatic variables in water deficit. Based on detailed biophysical, socioeconomic, and institutional factors for each biome in Brazil, we have created spatially explicit scenarios until 2050, considering the following classes: forest vegetation, grassland vegetation, planted pasture, agriculture, a mosaic of small land uses, and forestry. The results aim to detail global models regionally. They could be used regionally to support decision-making and enrich the global analysis., Competing Interests: NO authors have competing interests.

The main objective of this review is to identify the most frequently isolated bacteria in patients with infections related to nipple piercings in case reports and case series. In addition, the aim is to describe clinical manifestations and antecedents. There is a protocol of this review. The terms "bacterial infections", "nipple piercing" and their synonyms were considered. Pubmed/Medline, Scopus, Embase, Web of Science core collection and Ovid/Medline databases were searched until November 15, 2021 without date or language restrictions. Two authors extracted the articles and three other authors performed the selection, first by title and abstract, and second by full-text revision. Discrepancies were resolved with yet two other authors. Quality was assessed using the Joanna Briggs checklists. Finally, data extraction was realized. A total of 1,531 articles were extracted, of which 20 articles were included, and one article was added by hand-searching. The final number of articles included was 21, all of them with acceptable quality of evidence. Twenty-seven patients were considered (23 women and 4 men), aged between 15-60 years old. The most frequent bacterial genus in case reports and case series was Staphylococcus (n=10), and the most frequent species was M. fortuitum (n=6), although etiology seems to be diverse. The breast was the main affected organ, and the most frequent findings were fluid collection, pain, erythema, granulation tissue and swelling. The suspicion of infection by this bacterial species could be taken into account when it is associated with nipple piercings; however, larger studies are required to give a conclusion based on the evidence., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Acuña-Chávez et al.)

Previous research examining links between psychopathology and emotions in daily life have largely focused on disorder-specific patterns of mean-level positive and negative affect. In this study, we examined three transdiagnostic dimensions of psychopathology, namely depression, worry, and rumination, and their association with the intensity, frequency, and differentiation of discrete emotion categories endorsed in daily life. Three independent samples of young adults (total n = 614) completed baseline measures assessing depression, worry, and rumination followed by a 1-week daily diary procedure. Daily diaries assessed the following emotion categories: "tranquility," "contentment," "happiness," "excitement," "pride," "sadness," "boredom," "guilt," "fear," and "anger." Intensity, frequency, and differentiation were all calculated from daily emotion ratings. Psychopathology was associated with intensity and frequency of pleasant emotion, with intensity showing stronger associations. Intensity of contentment and happiness were most strongly associated with all three forms of psychopathology, whereas pride had the weakest associations. Psychopathology was associated with intensity and frequency of unpleasant emotions, with frequency tending to show stronger associations. Frequency of sadness and boredom were most strongly associated with depression, whereas the frequency and intensity of fear were similarly associated with depression and worry. Although psychopathology was associated with pleasant and unpleasant emotion differentiation, to our surprise, effect sizes were negligible to small. Clinical implications and recommendations for future research are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Skeletal muscles attach to bone at their origins and insertions, and the interface where tendon meets bone is termed the attachment site or enthesis. Mechanical stresses at the muscle/tendon-bone interface are proportional to the surface area of the bony attachment sites, such that a larger attachment site will distribute loads over a wider area. Muscles that are frequently active and/or are of larger size should cause attachment sites to hypertrophy (training effect); however, experimental studies of animals subjected to exercise have provided mixed results. To enhance our ability to detect training effects (a type of phenotypic plasticity), we studied a mouse model in which 4 replicate lines of High Runner (HR) mice have been selectively bred for 57 generations. Selection is based on the average number of wheel revolutions on days 5 & 6 of a 6-day period of wheel access as young adults (6-8 weeks old). Four additional lines are bred without regard to running and serve as non-selected controls (C). On average, mice from HR lines voluntarily run ~3 times more than C mice on a daily basis. For this study, we housed 50 females (half HR, half C) with wheels (Active group) and 50 (half HR, half C) without wheels (Sedentary group) for 12 weeks starting at weaning (~3 weeks old). We tested for evolved differences in muscle attachment site surface area between HR and C mice, plastic changes resulting from chronic exercise, and their interaction. We used a precise, highly repeatable method for quantifying the three-dimensional (3D) surface area of four muscle attachment sites: the humerus deltoid tuberosity (the insertion point for the spinodeltoideus, superficial pectoralis, and acromiodeltoideus), the femoral third trochanter (the insertion point for the quadratus femoris), the femoral lesser trochanter (the insertion point for the iliacus muscle), and the femoral greater trochanter (insertion point for the middle gluteal muscles). In univariate analyses, with body mass as a covariate, mice in the Active group had significantly larger humerus deltoid tuberosities than Sedentary mice, with no significant difference between HR and C mice and no interaction between exercise treatment and linetype. These differences between Active and Sedentary mice were also apparent in the multivariate analyses. Surface areas of the femoral third trochanter, femoral lesser trochanter, and femoral greater trochanter were unaffected by either chronic wheel access or selective breeding. Our results, which used robust measurement protocols and relatively large sample sizes, demonstrate that muscle attachment site morphology can be (but is not always) affected by chronic exercise experienced during ontogeny. However, contrary to previous results for other aspects of long bone morphology, we did not find evidence for evolutionary coadaptation of muscle attachments with voluntary exercise behavior in the HR mice., (© 2021 Anatomical Society.)

Studies of risk perception and risk communication concerning the nuclear area are quite common in scientific literature. However, though numerous studies on this topic point to the importance of scientific and technological knowledge in facilitating the reduction of perceived risks, there are few papers that effectively discuss the role of education in risk communication on the subject, particularly in Brazil. The objective of the present work was to reflect on this problem by analyzing the results obtained from two case studies on the implementation of the Brazilian Multipurpose Reactor, in the city of Iperó, in the state of São Paulo, Brazil. As was verified in the investigation, most participants of the study had high perception of risk with respect to the implementation of the reactor. Nevertheless, although important in the project of the reactor implementation, it was verified that the state, municipal and community schools of the city of Iperó had not participated, in the public hearings nor had they discussed the issue inside the school community, until the moment of the research.

In this study, we systematically investigated the electronic structure, spectroscopic (nuclear magnetic resonance, infrared, Raman, electron ionization mass spectrometry, UV-Vis, circular dichroism, and emission) properties, and tautomerism of halogenated favipiravir compounds (fluorine, chlorine, and bromine) from a computational perspective. Additionally, the effects of hydration on the proton transfer mechanism of the tautomeric forms of the halogenated favipiravir compounds are discussed. Our results suggest that spectroscopic properties allow for the elucidation of such tautomeric forms. As is well-known, the favipiravir compound has excellent antiviral properties and hence was recently tested for the treatment of new coronavirus (SARS-CoV-2). Through in silico modeling, in the current study, we evaluate the role of such tautomeric forms in order to consider the effect of drug-metabolism in the inhibition process of the main protease (M pro ) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 virus. According to the molecular docking, all halogenated compounds presented a better interaction energy than the co-crystallized active ligand (-3.5 kcal mol -1 ) in the viral RdRp, in both wild-type (-6.3 to -6.5 kcal mol -1 ) and variant (-5.4 to -5.6 kcal mol -1 ) models. The variant analyzed for RdRp (Y176C) decreases the affinity of the keto form of the compounds in the active site, and prevented the ligands from interacting with RNA. These findings clearly indicated that all these compounds are promising as drug candidates for this molecular target., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

While nursing, mammals progress through critical developmental periods for the cardiovascular, musculoskeletal, and central nervous systems. The suckling period in mammals is therefore especially vulnerable to environmental factors that may affect the "developmental programming" of many complex traits. As a result, various aspects of maternal behavior and physiology can influence offspring in ways that have lasting effects into adulthood. Several recent studies of animal models have shown that maternal effects can partially program adult activity behaviors, which has important implications for health and locomotor performance. Here, we used cross-fostering to test for possible maternal effects on adult wheel-running behavior (voluntary exercise), maximal aerobic capacity during forced exercise (VO 2 max), body mass and composition, and organ masses. Subjects were from a line of mice that has been selectively bred for ∼90 generations for high voluntary wheel-running behavior (High Runner; HR) and a non-selected Control (C) line. Adult HR mice run ∼3-fold the daily distances of C mice and have evolved other differences associated with exercise capacity, including elevated VO 2 max, reduced body mass and fat mass, and larger hearts. At birth, we fostered offspring to create 4 experimental groups: C pups to other C dams (in-foster), HR pups to other HR dams (in-foster), C pups to HR dams (cross-foster), HR pups to C dams (cross-foster). Thus, all pups were fostered to a different mother. Mice were weaned 3 weeks later, and adult testing began at ∼6 weeks of age. At weaning, pups raised by HR dams were smaller than those raised by C dams for both sexes and as expected, HR pups raised by HR dams weighed less than C pups raised by C dams. As adults, mice raised by HR dams continued to have reduced body masses. As expected, adult HR mice ran approximately 3-fold more than their C counterparts and females ran more than males. However, cross-fostering did not statistically affect any aspect of wheel-running behavior (distance, duration, speed). Similarly, with body mass as a covariate, HR mice had higher VO 2 max than C mice, and males had higher VO 2 max than females, but cross-fostering had no effect. With body mass as a covariate, cross-fostering had variable effects on adult organ masses in a sex-specific manner. Overall, our results indicate that development of the adult High Runner phenotype does not require rearing by an HR dam, suggesting that high adult activity in humans may be independent of high maternal activity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The sphingomyelin pathway is important in cell regulation and determining cellular fate. Inhibition of sphingosine kinase isoform 1 (SK1) within this pathway, leads to a buildup of sphingosine and ceramide, two molecules directly linked to cell apoptosis, while decreasing the intracellular concentration of sphingosine-1-phosphate (S1P), a molecule linked to cellular proliferation. Recently, an inhibitor capable of inhibiting SK1 in vitro was identified, but also shown to be ineffective in vivo. A set of compounds designed to assess the impact of synthetic modifications to the hydroxynaphthalene ring region of the template inhibitor with SK1 to obtain a compound with increased efficacy in vivo. Of these fifteen compounds, 4A was shown to have an IC 50  = 6.55 μM with improved solubility and in vivo potential., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Understanding the effects of metabolism on the rational design of novel and more effective drugs is still a considerable challenge. To the best of our knowledge, there are no entirely computational strategies that make it possible to predict these effects. From this perspective, the development of such methodologies could contribute to significantly reduce the side effects of medicines, leading to the emergence of more effective and safer drugs. Thereby, in this study, our strategy is based on simulating the electron ionization mass spectrometry (EI-MS) fragmentation of the drug molecules and combined with molecular docking and ADMET models in two different situations. In the first model, the drug is docked without considering the possible metabolic effects. In the second model, each of the intermediates from the EI-MS results is docked, and metabolism occurs before the drug accesses the biological target. As a proof of concept, in this work, we investigate the main antiviral drugs used in clinical research to treat COVID-19. As a result, our strategy made it possible to assess the biological activity and toxicity of all potential by-products. We believed that our findings provide new chemical insights that can benefit the rational development of novel drugs in the future., (© 2021. The Author(s).)

The development of bifunctional catalysts is of great interest in fine chemistry, since they are capable of promoting multicatalytic reactions involved in several important industrial processes. Iron oxyhydroxides have been identified as low-cost bifunctional catalysts. However, their applications are limited due to their weak acid character. Thus, elaborated modifications of these systems can significantly contribute to increasing their activities and selectivity. This work consists in the study, through DFT calculations, of the properties of the bulk and the surface of feroxyhyte (δ-FeOOH) doped with niobium, as a potential bifunctional catalyst. We identified the formation of stronger van der Waals interactions among the doped δ-FeOOH layers, which can increase the thermal stability of the catalyst. In addition, evidence has been found that the insertion of Nb increases Brönsted acidity and gives rise to new Lewis acid sites on the catalyst surface., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The pyramided genetically modified maize (Zea mays [L.]) event MON 95379, expressing the Cry1B.868 and Cry1Da&#95;7 proteins, was designed to protect against larval feeding damage by the fall armyworm, Spodoptera frugiperda (FAW). Here, we conducted laboratory, greenhouse, and field studies to assess the dose and field efficacy of MON 95379 against FAW and inform the development of insect resistance management plans., Results: The Cry1B.868 and Cry1Da&#95;7 proteins were active against susceptible FAW neonates in diet-incorporation bioassays: median lethal concentration [LC 50 ] (95% CI) = 62.8 (42.6-87.6) μg/ml diet for Cry1B.868 and 9.4 (5.3-18.6) μg/ml diet for Cry1Da&#95;7. In laboratory leaf disc bioassays, MON 95379 maize and experimental maize lines expressing the individual components were effective in controlling susceptible FAW. In whole-plant assays, MON 95379 controlled FAW resistant to the Cry1A.105 and Cry2Ab2 proteins. Likewise, under field conditions, MON 95379 maize expressing Cry1B.868 and Cry1Da&#95;7 was highly effective at protecting plants against the larval feeding of FAW., Conclusions: The expression of Cry1B.868 and Cry1Da&#95;7 in MON 95379 consistently protected maize plants against larval feeding by FAW and represents an alternative to manage trait resistance issues in South America. © 2021 Bayer Crop Science-US. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2021 Bayer Crop Science-US. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Two new series of hitherto unknown dipeptides, containing an electrophilic nitrile or a non-electrophilic 2-amino-1,3,4-oxadiazole moiety were synthesized and evaluated in vitro as Cathepsin K (Cat K) inhibitors. From 14 compounds obtained, the oxadiazole derivatives 10a, 10b, 10e, and 10g acted as enzymatic competitive inhibitors with Ki values between 2.13 and 7.33 µM. Molecular docking calculations were carried out and demonstrated that all inhibitors performed hydrogen bonds with residues from the enzyme active site, such as Asn18. The best inhibitors (10a, 10b, 10g) could also perform these bonds with Cys25, and 10a showed the most stabilizing interaction energy (-134.36 kcal mol -1 ) with the active cavity. For the first time, derivatives based in 2-amino-1,3,4-oxadiazole scaffolds were evaluated, and the results suggested that this core displays a remarkable potential as a building block for Cat K inhibitors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A new and more aggressive strain of coronavirus, known as SARS-CoV-2, which is highly contagious, has rapidly spread across the planet within a short period of time. Due to its high transmission rate and the significant time-space between infection and manifestation of symptoms, the WHO recently declared this a pandemic. Because of the exponentially growing number of new cases of both infections and deaths, development of new therapeutic options to help fight this pandemic is urgently needed. The target molecules of this study were the nitro derivatives of quinoline and quinoline N-oxide. Computational design at the DFT level, docking studies, and molecular dynamics methods as a well-reasoned strategy will aid in elucidating the fundamental physicochemical properties and molecular functions of a diversity of compounds, directly accelerating the process of discovering new drugs. In this study, we discovered isomers based on the nitro derivatives of quinoline and quinoline N-oxide, which are biologically active compounds and may be low-cost alternatives for the treatment of infections induced by SARS-CoV-2.

Selection experiments can elucidate the varying course of adaptive changes across generations. We examined the appendicular skeleton of house mice from four replicate High Runner (HR) lines bred for physical activity on wheels and four non-selected Control (C) lines. HR mice reached apparent selection limits between generations 17 and 27, running ~3-fold more than C. Studies at generations 11, 16, and 21 found that HR mice had evolved thicker hindlimb bones, heavier feet, and larger articular surface areas of the knee and hip joint. Based on biomechanical theory, any or all of these evolved differences may be beneficial for endurance running. Here, we studied mice from generation 68, plus a limited sample from generation 58, to test whether the skeleton continued to evolve after selection limits were reached. Contrary to our expectations, we found few differences between HR and C mice for these later generations, and some of the differences in bone dimensions identified in earlier generations were no longer statistically significant. We hypothesize that the loss of apparently coadapted lower-level traits reflects (1) deterioration related to a gradual increase in inbreeding and/or (2) additional adaptive changes that replace the functional benefits of some skeletal changes., (© 2020 Anatomical Society.)

Behavioral addictions can come in many forms, including overeating, gambling and overexercising. All addictions share a common mechanism involving activation of the natural reward circuit and reinforcement learning, but the extent to which motivation for natural and drug rewards share similar neurogenetic mechanisms remains unknown. A unique mouse genetic model in which four replicate lines of female mice were selectively bred (>76 generations) for high voluntary wheel running (High Runner or HR lines) alongside four non-selected control (C) lines were used to test the hypothesis that high motivation for exercise is associated with greater reward for cocaine (20 mg/kg) and methylphenidate (10 mg/kg) using the conditioned place preference (CPP) test. HR mice run ~three times as many revolutions/day as C mice, but the extent to which they have increased motivation for other rewards is unknown. Both HR and C mice displayed significant CPP for cocaine and methylphenidate, but with no statistical difference between linetypes for either drug. Taken together, results suggest that selective breeding for increased voluntary running has modified the reward circuit in the brain in a way that increases motivation for running without affecting cocaine or methylphenidate reward., (© 2020 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)