Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction

Angiotensin II (Ang II) is a natural mammalian hormone that has been described to exhibit antiplasmodial activity therefore constituting a promising alternative for the treatment of malaria. Despite its promise, the development of Ang II as an antimalarial is limited by its potent induction of vasoconstriction and its rapid degradation within minutes. Here, we used peptide design to perform targeted chemical modifications to Ang II to generate conformationally restricted (disulfide-crosslinked) peptide derivatives with suppressed vasoconstrictor activity and increased stability. Designed constrained peptides were synthesized chemically and then tested for antiplasmodial activity. Two lead constrained peptides were identified (i.e., peptides 1 and 2), each composed of 10 amino acid residues. These peptides exhibited very promising activity in both our Plasmodium gallinaceum ( > 80%) and Plasmodium falciparum ( > 40%) models, an activity that was equivalent to that of Ang II, and led to complete suppression of vasoconstriction. In addition, peptide 5 exhibited selective activity towards the pre-erythrocytic stage (98% of activity against P. gallinaceum), thus suggesting that it may be possible to design peptides that target specific stages of the malaria life cycle. The Ang II derived stable scaffolds presented here may provide the basis for development of a new generation of peptide-based drugs for the treatment of malaria

Prevalência de ansiedade em trabalhadores da fundação dos esportes do Piauí – FUNDESPI / Prevalence of anxiety in workers from the sports foundation of Piauí – FUNDESPI

A ansiedade é uma sensação de emoção desagradável que caracterizam sintomas de tensão muscular e apreensão. De acordo com os fatores físicos, eles estão caracterizados por um alto índice de elevação na ativação do sistema nervoso autônomo, e em relação aos fatores motores, que implicam simplesmente com a mal adaptação de comportamento. O trabalho teve como objetivo avaliar nível de ansiedade em trabalhadores da Fundação dos Esportes do Piauí localizada na cidade de Teresina. Trata-se de um estudo descritivo, transversal com abordagem quantitativa desenvolvida com 39 trabalhadores. A coleta de dados ocorreu no mês de outubro de 2019, após a aprovação do Comitê de Ética em Pesquisa. Para esta etapa utilizou-se dois instrumentos: questionário sociodemográfico da atividade laboral e hábitos de vida e o Inventário de Ansiedade de Beck. Após a coleta os dados foram tabulados no programa Excel e disposto em tabelas e gráficos. Como resultado constatou-se que trabalhadores de setores administrativos apresentam percentuais expressivos de ansiedade com ênfase para o tipo suave do transtorno mental. A presença destes distúrbios entre os trabalhadores mostrou-se de modo direto associada a tais fatores como: consumo de bebidas estimulantes, prática casualmente de atividade física e poucas horas de sono.

Prevalência de dor lombar na equipe de enfermagem de um hospital estadual / Prevalence of low back pain in the nursing staff of a state hospital

As Lesões por Esforços Repetitivos (LER) e os Distúrbios Osteomusculares Relacionados ao Trabalho (DORT), são síndromes que atingem o sistema músculo esquelético, desencadeadas pelo esgotamento físico das estruturas anatômicas do sistema osteomuscular. O objeto deste estudo foi identificar o perfil das lesões músculo esqueléticas ocasionadas durante o trabalho da enfermagem. Trata-se de um estudo descritivo, exploratória, com abordagem quantitativa, realizado por meio de um Questionário Nórdico de Sintomas Osteomusculares (QNSO). A coleta de dados ocorreu em um Hospital Estadual da cidade de Luzilândia- Piauí, com 21 profissionais da equipe de Enfermagem. Quanto aos resultados o perfil sociodemográfico dos entrevistados se caracterizou por profissionais jovens, com média de idade de 33,14 anos, do sexo feminino (90,5%), solteiros (61,9%), de cor parda (81%), com ensino médio completo (71,4%), técnicos de enfermagem (71,4%), com renda mensal que de um a três salários mínimo (95,2%). Sobressaíram os profissionais que não praticavam atividade física, nenhum deles fumam, porém a maioria ingeri bebida alcoólica e café regularmente. O estudo identificou elevada prevalência de LER/DORT em trabalhadores de enfermagem, pois 62% referiram algum sintoma nos últimos doses meses. Esses sintomas representaram frequência e intensidade de dor moderada, principalmente em pessoas de 23 a 29 anos (46,1%), do sexo feminino (92,3%) e técnicos de enfermagem (77%), havendo correlação entre essas variáveis. A dor foi mais prevalente na região lombar, em especial naqueles que trabalha em pé, quando inclinar o tronco, da repetitividade das mãos/dedos, precisão com os dedos, aplicar força com as mãos ou dedos, manipular cargas entre 1-4 kg, manipular cargas superiores a 4 KG, levantar e deslocar cargas entre 10- 20 KG, levantar e deslocar cargas superior a 20 KG e a intensidade da dor a maioria respondeu que muito se relaciona com a intensidade da dor e de forma moderada. Diante do levantamento deste estudo foi possível alcançar o objetivo proposto e identificar alta prevalência do LER/DORT, em especial em profissionais de 23 a 29 anos, técnicos de enfermagem e mulheres, com maior destaque para a região lombar e de moderada intensidade de três a quatro vezes na semana

Ticks as potential vectors of Mycobacterium leprae: Use of tick cell lines to culture the bacilli and generate transgenic strains.

Leprosy is an infectious disease caused by Mycobacterium leprae and frequently resulting in irreversible deformities and disabilities. Ticks play an important role in infectious disease transmission due to their low host specificity, worldwide distribution, and the biological ability to support transovarial transmission of a wide spectrum of pathogens, including viruses, bacteria and protozoa. To investigate a possible role for ticks as vectors of leprosy, we assessed transovarial transmission of M. leprae in artificially-fed adult female Amblyomma sculptum ticks, and infection and growth of M. leprae in tick cell lines. Our results revealed M. leprae RNA and antigens persisting in the midgut and present in the ovaries of adult female A. sculptum at least 2 days after oral infection, and present in their progeny (eggs and larvae), which demonstrates the occurrence of transovarial transmission of this pathogen. Infected tick larvae were able to inoculate viable bacilli during blood-feeding on a rabbit. Moreover, following inoculation with M. leprae, the Ixodes scapularis embryo-derived tick cell line IDE8 supported a detectable increase in the number of bacilli for at least 20 days, presenting a doubling time of approximately 12 days. As far as we know, this is the first in vitro cellular system able to promote growth of M. leprae. Finally, we successfully transformed a clinical M. leprae isolate by inserting the reporter plasmid pCHERRY3; transformed bacteria infected and grew in IDE8 cells over a 2-month period. Taken together, our data not only support the hypothesis that ticks may have the potential to act as a reservoir and/or vector of leprosy, but also suggest the feasibility of technological development of tick cell lines as a tool for large-scale production of M. leprae bacteria, as well as describing for the first time a method for their transformation

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Women's Poorer Satisfaction With Their Sex Lives Following Gynecologic Cancer Treatment

Gynecologic cancer treatment can lead to anatomical changes in the genitalia that may impair sexual response. As a result, the authors aimed to assess women's self-perceptions of their sex lives following gynecologic cancer treatment and the impact of such treatment on sexual function. Thirty sexually active women were examined. At the first meeting with a physician sex therapist, women were asked about their satisfaction with their sexual activities prior to and after gynecologic cancer treatment, either with a partner or alone, and how many times per month they had sexual intercourse prior to the cancer diagnosis and after treatment. Women reported significantly worse sex lives and a significantly lower frequency of sexual relations following cancer treatment. All participants reported pain on vaginal penetration and feeling uncomfortable in discussing their sexual difficulties with the oncologist. The findings show that women experienced impaired sexual function, as well as poorer quality of sexual function, following gynecologic cancer treatment. Nurses should provide basic guidelines about sexual function to all patients who undergo treatment for gynecologic cancer