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Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.

In October 2012, the Haitian Ministry of Health and the US CDC were notified of 25 recent dengue cases, confirmed by rapid diagnostic tests (RDTs), among non-governmental organization (NGO) workers. We conducted a serosurvey among NGO workers in Léogane and Port-au-Prince to determine the extent of and risk factors for dengue virus infection. Of the total 776 staff from targeted NGOs in Léogane and Port-au-Prince, 173 (22%; 52 expatriates and 121 Haitians) participated. Anti-dengue virus (DENV) IgM antibody was detected in 8 (15%) expatriates and 9 (7%) Haitians, and DENV non-structural protein 1 in one expatriate. Anti-DENV IgG antibody was detected in 162 (94%) participants (79% of expatriates; 100% of Haitians), and confirmed by microneutralization testing as DENV-specific in 17/34 (50%) expatriates and 42/42 (100%) Haitians. Of 254 pupae collected from 68 containers, 65% were Aedes aegypti; 27% were Ae. albopictus. Few NGO workers reported undertaking mosquito-avoidance action. Our findings underscore the risk of dengue in expatriate workers in Haiti and Haitians themselves.

Human immunodeficiency virus-type 1 (HIV-1) remains one of the leading contributors to the global burden of disease, and novel antiretroviral agents with alternative mechanisms are needed to cure this infection. Here, we describe an exploratory attempt to optimize the antiretroviral properties of benfluron, a cytostatic agent previously reported to exhibit strong anti-HIV activity likely based on inhibitory actions on virus transcription and Rev-mediated viral RNA export. After obtaining six analogs designed to modify the benzo[c]fluorenone system of the parent molecule, we examined their antiretroviral and toxicity properties together with their capacity to recognize the Rev Recognition Element (RRE) of the virus RNA and inhibit the RRE–Rev interaction. The results indicated that both the benzo[c] and cyclopentanone components of benfluron are required for strong RRE–Rev target engagement and antiretroviral activity and revealed the relative impact of these moieties on RRE affinity, RRE–Rev inhibition, antiviral action and cellular toxicity. These data provide insights into the biological properties of the benzo[c]fluorenone scaffold and contribute to facilitating the design of new anti-HIV agents based on the inhibition of Rev function.

Abstract Small synthetic molecules mimicking the three-dimensional structure of α-helices may find applications as inhibitors of therapeutically relevant protein-protein and protein-nucleic acid interactions. However, the design and use of multi-facial helix mimetics remains in its infancy. Here we describe the synthesis and application of novel bilaterally substituted p-terphenyl compounds containing positively-charged aminoalkyl groups in relative 1,4 positions across the aromatic scaffold. These compounds were specifically designed to mimic all faces of the arginine-rich α-helix of the HIV-1 protein Rev, which forms deeply embedded RNA complexes and plays key roles in the virus replication cycle. Two of these molecules recognized the Rev site in the viral RNA and inhibited the formation of the RRE-Rev ribonucleoprotein complex, a currently unexploited target in HIV chemotherapy. Cellular assays revealed that the most active compounds blocked HIV-1 replication with little toxicity, and likely exerted this effect through a multi-target mechanism involving inhibition of viral LTR promoter-dependent transcription and Rev function. Further development of this scaffold may open new avenues for targeting nucleic acids and may complement current HIV therapies, none of which involve inhibitors interfering with the gene regulation processes of the virus.

Current research on antiretroviral therapy is mainly focused in the development of new formulations or combinations of drugs belonging to already known targets. However, HIV-1 infection is not cured by current therapy and thus, new approaches are needed. Bevirimat was developed by chemical modification of betulinic acid, a lupane-type pentacyclic triterpenoid (LPT), as a first-in-class HIV-1 maturation inhibitor. However, in clinical trials, bevirimat showed less activity than expected because of the presence of a natural mutation in Gag protein that conferred resistance to a high proportion of HIV-1 strains. In this work, three HIV-1 inhibitors selected from a set of previously screened LPTs were investigated for their targets in the HIV-1 replication cycle, including their maturation inhibitor effect. LPTs were found to inhibit HIV-1 infection acting as promiscuous compounds with several targets in the HIV-1 replication cycle. LPT12 inhibited HIV-1 infection mainly through reverse transcription, integration, viral transcription, viral proteins (Gag) production and maturation inhibition. LPT38 did it through integration, viral transcription or Gag production inhibition and finally, LPT42 inhibited reverse transcription, viral transcription or Gag production. The three LPTs inhibited HIV-1 infection of human primary lymphocytes and infections with protease inhibitors and bevirimat resistant HIV-1 variants with similar values of IC50. Therefore, we show that the LPTs tested inhibited HIV-1 infection through acting on different targets depending on their chemical structure and the activities of the different LPTs vary with slight structural alterations. For example, of the three LPTs under study, we found that only LPT12 inhibited infectivity of newly-formed viral particles, suggesting a direct action on the maturation process. Thus, the multi-target behavior gives a potential advantage to these compounds since HIV-1 resistance can be overcome by modulating more than one target.

Aim: To develop and validate a self-administered population-specific survey, available in Spanish, Portuguese, and English, which investigates the prevalence of voice symptoms and perceptions of risk factors associated with training among prospective teachers., Methods: The present study had three stages: the first stage included a literature review and content validation by experts that supported the survey development. From this phase, we defined five aspects of the Prospective Teacher's Voice Questionnaire (PTVQ): (1) target population, (2) research objectives, (3) questions to be included, (4) scales for the answers, and (5) relevance, comprehensiveness, clarityclarity, and understandability of the questions. This process was performed in parallel for the three languages (Spanish, Portuguese, and English). The second stage included pilot testing. This involved administering the first draft of the survey to a group of 120 students to evaluate the feasibility and effectiveness of the survey instrument, identify any potential problems with the survey, and refine the instrument based on feedback from the pilot participants. The third stage includes the restructuring of the questionnaire's voice quality section to eliminate redundant questions. Through Principal Component Analysis, multicollinear variables were condensed, facilitating the removal of redundant items, and ensuring that the final questionnaire comprised only the most relevant and discriminative questions., Results and Discussion: The final version of the survey, available in Spanish, Portuguese, and English, consists of four sections with a total of 57 questions. The development of the PTVQ represents a significant step toward better understanding and addressing voice disorders among prospective teachers. Future research could further refine the questionnaire and explore its predictive validity in identifying individuals at risk of voice disorders early in their teaching careers. Additionally, interventions based on the findings from the PTVQ could be developed to support the voice health and well-being of prospective teachers, ultimately improving teaching quality and job satisfaction in educational settings., Competing Interests: Declaration of Competing Interest No conflict of interest exists., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.

The COVID-19 pandemic caused drastic social changes for many people, including separation from friends and coworkers, enforced close contact with family, and reductions in mobility. Here we assess the extent to which people's evolutionarily-relevant basic motivations and goals-fundamental social motives such as Affiliation and Kin Care-might have been affected. To address this question, we gathered data on fundamental social motives in 42 countries ( N  = 15,915) across two waves, including 19 countries ( N   =  10,907) for which data were gathered both before and during the pandemic (pre-pandemic wave: 32 countries, N  = 8998; 3302 male, 5585 female; M age   =  24.43, SD  = 7.91; mid-pandemic wave: 29 countries, N  = 6917; 2249 male, 4218 female; M age   =  28.59, SD  = 11.31). Samples include data collected online (e.g., Prolific, MTurk), at universities, and via community sampling. We found that Disease Avoidance motivation was substantially higher during the pandemic, and that most of the other fundamental social motives showed small, yet significant, differences across waves. Most sensibly, concern with caring for one's children was higher during the pandemic, and concerns with Mate Seeking and Status were lower. Earlier findings showing the prioritization of family motives over mating motives (and even over Disease Avoidance motives ) were replicated during the pandemic. Finally, well-being remained positively associated with family-related motives and negatively associated with mating motives during the pandemic, as in the pre-pandemic samples. Our results provide further evidence for the robust primacy of family-related motivations even during this unique disruption of social life., Competing Interests: None., (© 2022 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions., Competing Interests: Conflict of InterestThe authors declare no conflict of interest., (© The Society for Affective Science 2022.)

How does psychology vary across human societies? The fundamental social motives framework adopts an evolutionary approach to capture the broad range of human social goals within a taxonomy of ancestrally recurring threats and opportunities. These motives-self-protection, disease avoidance, affiliation, status, mate acquisition, mate retention, and kin care-are high in fitness relevance and everyday salience, yet understudied cross-culturally. Here, we gathered data on these motives in 42 countries (N = 15,915) in two cross-sectional waves, including 19 countries (N = 10,907) for which data were gathered in both waves. Wave 1 was collected from mid-2016 through late 2019 (32 countries, N = 8,998; 3,302 male, 5,585 female; M age  = 24.43, SD = 7.91). Wave 2 was collected from April through November 2020, during the COVID-19 pandemic (29 countries, N = 6,917; 2,249 male, 4,218 female; M age  = 28.59, SD = 11.31). These data can be used to assess differences and similarities in people's fundamental social motives both across and within cultures, at different time points, and in relation to other commonly studied cultural indicators and outcomes., (© 2022. The Author(s).)

Background: Ending December 2019, the world had to face to COVID-19. Latin America and the Caribbean suffered the effects where the contiguous and the number of deaths has been significant. Studies indicate that older adults with some degree of cognitive impairment are at greater risk of worsening their cognitive status and mental health, for this reason it's exposed that social isolation and loneliness has harmful effects on the health of this population. This mini-review inquires on the effects of COVID-19 due to social isolation on neuropsychiatric symptoms (NPS) in Latin American older adults with and without dementia., Method: A search was carried out in PubMed, SCOPUS, and ScienceDirect identifying all articles published up to July 31, 2021 using the keywords "social isolation", "lockdown", "quarantine", "COVID-19",, "neuropsychiatric symptoms ", "neurobehavioral", "dementia"," mild cognitive impairment "," Older People ", "aging", "elderly". Two independent reviewers screened and selected appropriate articles and a third researcher helped resolve disagreements. The selected articles met the following criteria: written in English, Spanish or Portuguese, original article; focused on elderly subjects, articles that provided information on the NPS effects in Latin American populations during the COVID-19 pandemic. The review was based on the PRISMA Statement and used the SIGN criteria., Result: From 61 articles recovered from electronic databases (PubMed, Science Direct and Scopus) 10 of them were chosen for this review. The majority of the articles reported in a general way a negative impact on the mental health of the population in Latin America. They referred to a significant increase in the anxiety and depression symptoms. The majority of the articles were studies developed in Brazil, Argentina and Chile., Conclusion: The COVID-19 has shown a negative impact on the mental health of older adults. Latin America is a region with important socio-sanitary problems which increase the impact of the pandemic in SNP, especially in older adults. It's necessary to increase the studies in Latin America that glimpse the real situation in the region., (© 2021 the Alzheimer's Association.)

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martins, Lavados, Secchi, Brainin, Ameriso, Gongora-Rivera, Sacks, Cantú-Brito, Alvarez Guzman, Pérez-Romero, Muñoz Collazos, Barboza, Arauz, Abanto Argomedo, Novarro-Escudero, Amorin Costabile, Crosa, Camejo, Mernes, Maldonado, Mora Cuervo, Pontes Neto, Silva, Carbonera, Souza, Sousa, Flores, Melgarejo, Santos Carquin, Hoppe, Carvalho, Mont'Alverne, Amaya, Bayona, Navia González, Duran, Urrutia, Araujo, Feigin and Nogueira.)

Electrical injuries can occur in pregnant women but currently their incidence is not completely known. Notwithstanding, those represent clinical important events such maternal and fetal death, which can be avoided if properly managed. The objective of this paper is to describe the results of electrical injury (high and low voltage), in pregnant women in scientific reports. A systematic search was performed with keywords "electrical injuries", "lightning injuries", "lightning strike", "pregnant women" and "pregnancy", using the databases: MedLine, Scielo, Lilacs, Clinical key, Web of Science, Scopus, Springer, Science Direct, Embase and Medic Latina. Filters like language, time, design and availability of text were not used. Descriptive analyses were carried out for variables such as maternal-fetal consequences, voltage and type of exposure, based on the reports identified. From the total 74 cases identified, 71.1% survived after the exposition. From the total live-births 28.6% did not show any alteration, 7.1% presented maceration and burns, while 64.3% had another outcome. Electric injury leads to fetal compromise and death in exposed pregnant women, mainly in the first hours after the injury. However, monitoring should be continued for the risk of complications such as placenta abruption, oligohydramnios and fetal distress. It is possible an underreporting of these events., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

The effects of physical exercise on cerebral function have been reported in various research studies, thereby leading to better understanding of the brain's cellular mechanisms related to adaptations concerning physical exercise and the different cell responses which become compromised regarding chronic mechanisms. Relearning patterns of movement may thus be an alternative clinical approach affecting cognition and brain plasticity. Recent evidence has shown that neurogenesis can become increased by exercise; nevertheless, moderation mechanisms and the times involved in this process are not at all clear. This review thus provides an update for understanding physical exercise-induced neurogenesis, covering mediating mechanisms and maturation. This is important as glial cell mechanisms are signals activating the neurons and synaptically influencing them, as well as their development, transmission and plasticity via a series of secreted signals depending on contact in human beings. Neurogenesis thus represents a natural model for understanding how new neurons become regenerated and incorporated into brain circuits, thus representing therapeutic potential regarding delay or repair of brain damage caused by injury or disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Wrestling was an important part of the ancient Olympic Games and is still one of the most popular events of the modern Olympic Games. Studies indicate that general physiologic profile of successful wrestlers is high anaerobic power and capacity, muscular strength, above average aerobic power, exceptional flexibility, fat free mass, and a mesomorphic somatotype., Objectives: The objective of the present study was to evaluate anthropometric characteristics and physical performance of elite male wrestlers., Patients and Methods: The Colombian Wrestling Team was evaluated while in preparation for the Olympic Games (n = 21; age, 27.9 ± 6.7 years). Athletes were tested on anthropometric and fitness parameters: body composition, somatotype distribution according to Heath-Carter, aerobic capacity, vertical jump, and anaerobic power., Results: The evaluations showed a mean body fat percentage of 13.6% ± 3.0% (95% CI, 12.2%-15%), muscle mass of 46.4% ± 2.2% (95% CI, 45.4%-47.4%), Ponderal index of 41.0 ± 1.8 (95% CI, 40.2-41.8), body adiposity index (BAI) 25.1 ± 3.6 (95% CI, 23.5-26.8), and somatotype distribution mesomorphic-ectomorph (5.3-1.6-3.8). Mean aerobic capacity was 45.9 ± 6.6 mL/kg/min (95% CI, 42.8-48.9), vertical jump was 36.4 ± 6.6 cm (95% CI, 11.8-16.6), and anaerobic power was 92.6 ± 19.5 kg/s (95% CI, 83.7-101.5)., Conclusions: These results provided a profile of elite wrestlers that could be used as training targets for developing athletes. The results may also provide information for training and tactical planning.

This is not an attempt to analyze the Last Universal Common Ancestor (LUCA) to understand the origin of living systems. We do not know what came before Gilberts' RNA world. Our analysis starts with the RNA world and with genes (biological replicators alla Dawkings) made up of RNA proteins with enzymatic catalytic functions within units that are not yet modern cells. We offer a scenario where cellular entities are very simple and without individuality; they are only simple primary units of selection (the first level of selection) in which replicators compete in the most Darwinian manner, totally deprived of cooperation and interactions among genes. The information processing system of this RNA world is inaccurate and inefficient when compared to that found in organisms that came later. Among the "genes" and the entities that harbor them, high mutation rate was the most prevalent source of variability and the only inheritance was through lateral gene transfer of mobile elements. There were no chromosomes or any other genomic organization. As millions of years accumulated, complex and organized biological structures and processes evolved thanks to the variability mustered up mostly by lateral gene transfers and mutations. With micro- and mini-satellites, lateral gene transfers became indispensable devices of selection to mold variability. Competition and Darwinian selection gave way to a new transition in evolution, one I consider ineluctable, in which cooperation among interactive genes prevailed for the sake of higher fitness. Compartmentalization constituted a major transition in evolution that spurted new types of genome organization. Minichromosomes is one of these; cellular membranes and cytoplasmic structures completed the picture of the primitive cell. However, the much talked about phylogenetic tree does not exit in that ancient LUCA. The tree has no organism at its base; only clusters of genes evoke a fragile beginning for the increasingly complex cell types that were to emerge later.

Our theory is embarrassingly simple. What made today's prokaryotes and modern cyanobacteria so robust is the fact that in their origin, back in the Archean (3 billion years ago), selection did not play a central role in evolution, it had only a transitory role. Asexual reproduction, mutation, drift and sampling variance in local demes were more important especially when they were accompanied by population catastrophes, where millions perished. Metazoans are generally macroscopic, sexually reproducing, ecologically specialized organisms whose history is full of extinctions and radiations leading to morphological change. On the other hand, prokaryotes, thanks to their origin, avoid extinction because as a group they have slowly evolved as generalists. Specialization appears to be less important than ecological versatility and metabolic unspecialization. Modern cyanobacteria keep on using that strategy.