Total synthesis of the potent immunosuppressant (-)-Pironetin

A convergent and efficient total synthesis of (-)-pironetin, a compound that shows plant growth regulatory activity, and is immunosuppressive as well as having remarkable antitumoral activity, is described. The synthesis required 19 steps from N-propionyl oxazolidinone (S)-9 and produced the desired product in 11% overall yield.6628

Autonomic dysregulation and self‐injurious thoughts and behaviours in children and young people: A systematic review and meta‐analysis

Background: self-injurious thoughts and behaviours (SITBs) have been associated with dysfunction of the Autonomic Nervous System (ANS) in children and young people, suggesting that objective ANS measures may aid assessment of suicide risk, but a systematic synthesis of this literature is currently lacking.Methods: following a pre-registered protocol (PROSPERO CRD42022327605), we conducted a systematic search of PubMed, Medline, Embase, PsycINFO, and Web of Science, for empirical studies published until 10th May 2022 that compared indices of ANS functioning in individuals aged 0–25 years with versus without SITBs, or reported continuous associations between ANS measures and SITBs. Study quality was assessed with the Newcastle-Ottawa Scales. Pooled effect sizes (Hedge's g) were estimated with random-effects meta-analytic models.Results: twenty studies (1979 participants) were included in our systematic review, with 16 included in meta-analyses. Results suggested that SITBs were associated with altered cardiac indices of arousal (g = −0.328, p < 0.001), which was driven by lower heart rate variability in individuals with SITBs (g = −0.375, p = 0.025). Overall results for electrodermal activity were not significant (g = 0.026, p = 0.857), but subgroup analyses showed increased activity in studies of individuals who engaged specifically in non-suicidal self-harm (g = 0.249, p = 0.014) but decreased activity in the remaining studies (g = −0.567, p = 0.004).Conclusions: our systematic review and meta-analysis found evidence of reduced parasympathetic regulation as well as more tentative evidence of altered electrodermal activity in children and young people displaying SITBs. Future longitudinal studies should test the clinical utility of these markers for detecting and monitoring suicide risk

Fractal dimension of large aggregates under different flocculation conditions

The two-dimensional fractal dimension (Df) of large aggregates of kaolin (> 540 μm) during the shear flocculation process for kaolin solution was investigated using non-intrusive in situ image-based acquisition system. Separate experiments were also carried out for three different sized sub-ranges of large aggregates (0.540–1.125 mm; 1.125–1.750 mm; 1.750–2.375 mm). Digital images were taken at a frequency of 10 Hz for 10 s for each different pairs of gradients of velocity (Gf) of 20 and 60 s− 1 and flocculation times of 2; 3; 4; 5; 10; 20; 30; 60; 120 and 180 min. For the same conditions, particle size distribution (PSD) was also determined. Under the investigated conditions, the lowest Gf produced the greatest Df (1.69) at a flocculation time of 30 min for the whole range of aggregates. Also, the evolution of the longest length of aggregate (l) and Df with time, showed that the dynamic steady-state was reached at different times for each shear rate and l ranges. However, Df varied for each size sub-range (ca. 1.1 to 1.8). Finally, the behavior of the aggregate structure may be understood by the predominance of different aggregation mechanisms such as cluster-cluster for Gf of 60 s− 1 and particle-cluster for Gf of 20 s− 1

Atenção ao idoso na estratégia de Saúde da Família: atuação do enfermeiro

Este estudo objetivou descrever a consulta de enfermagem ao idoso realizada na ESF; identificar possíveis dificuldades na atenção à saúde do idoso, bem como os cursos de qualificação profissional realizados e as necessidades de aprendizagem. Os dados foram coletados por meio da entrevista semiestruturada e submetidos à análise descritiva e temática. Foram entrevistadas 12 enfermeiras, a maioria estando na faixa etária de anos de formada (41%) em instituição particular (75%). Emergiram duas categorias temáticas: consulta de enfermagem ao idoso na ESF e qualificação profissional para a atenção à saúde do idoso. Foi considerado como desafio na realização da consulta de enfermagem a obtenção de dados fidedignos, a resolutividade e o apoio familiar. Os cursos para qualificar a atenção ao idoso ocorreram durante o período de graduação, destacando a falta de oportunidade, a pouca oferta e a necessidade de se aprofundar sobre o processo de envelhecimento.Este estudio tuvo como objetivo describir la consulta de enfermería realizada por el anciano en la ESF; identificar posibles dificultades en la atención a la salud del anciano, así como los cursos de calificación profesional realizados y las necesidades de aprendizaje. Los datos fueron recogidos a través de la entrevista semiestructurada y sometidos al análisis descriptivo temático. Fueron entrevistadas doce enfermeras, estando la mayoría situadas en la faja etaria de 23 a 28 años (66%), con 1-2 años de graduadas (41%) en instituciones particulares (75%). Emergieron dos categorías temáticas: consulta de enfermería del anciano en la ESF y calificación profesional para la atención de la salud del anciano. Fue considerado como desafío en la realización de la consulta de enfermería la obtención de datos fidedignos, la resolutividad y el apoyo familiar. Los cursos para calificar la atención al anciano, tuvieron lugar durante el período de graduación, destacándose la falta de oportunidad, la poca oferta y la necesidad de profundizar sobre el proceso de envejecimiento.This study aimed to describe the nursing consultation for the elderly provided at the Family Health Strategy (ESF, acronym in Portuguese); identify possible difficulties in delivering health care to the elderly, as well as the professional qualification courses performed and the learning needs. Data were collected through semi-structured interviews and submitted to descriptive and thematic analysis. Interviews were performed with 12 nurses, most with ages between years since graduation (41%) in private institutions (75%). Two thematic categories emerged from the analysis: nursing consultation for the elderly performed at ESF and professional qualification in health care for the elderly. Obtaining reliable data in the nursing consultation, resolution and family support were considered as challenges. The courses to qualify professionals for elderly care occurred during their graduation course, highlighting the lack of opportunity, the short supply and the need for deeper studies about the aging process

Does caffeine ingestion before a short-term sprint interval training promote body fat loss?

We investigated the effect of caffeine ingestion combined with a 2-wk sprint interval training (SIT) on training-induced reductions in body adiposity. Twenty physically-active men ingested either 5 mg/kg of cellulose as a placebo (PLA, n=10) or 5 mg/kg of caffeine (CAF, n=10) 60 min before each SIT session (13×30 s sprint/15 s of rest). Body mass and skinfold thickness were measured pre- and post-training. Energy expenditure was measured at rest, during exercise, and 45 min after exercise in the first SIT session. Body fat was similar between PLA and CAF groups at pre-training (P\u3e0.05). However, there was a significant decrease in body fat after training in the CAF group (−5.9±4.2%, P\u3c0.05) but not in PLA (1.5±8.0%, P\u3e0.05). There was no difference in energy expenditure at rest and during exercise between PLA and CAF groups (P\u3e0.05), but the post-exercise energy expenditure was 18.3±21.4% greater in the CAF than in the PLA group (P\u3c0.05). In conclusion, caffeine ingestion before SIT sessions induced a body fat loss that may be associated with higher post-exercise energy expenditure

Effects of pollution on adolescent mental health: a systematic review protocol.

BACKGROUND: Whilst there is little uncertainty about the deleterious impact of pollution on human and planetary health, pollution's impact on adolescent mental health is less well understood. This is particularly true for young people in underdeveloped and developing world contexts, about whom research is generally lacking. Furthermore, although adolescent resilience continues to be a research priority, little attention has been paid to adolescent pathways of resilience in the face or aftermath of pollution exposure. The objective of this study will be to examine the associations between pollution and mental health in 10- to 24-year-olds (i.e. adolescents). METHODS: We designed and registered a study protocol for a systematic review of studies which link pollution and mental health in adolescents. We will include observational studies (e.g. cohort, case-control, time series analyses) that assess the associations between exposure to any form of pollution and the mental health of 10- to 24-year-olds. The primary outcome will be symptoms associated with neurodevelopmental disorders; disruptive, impulse-control, and conduct disorders; depressive disorders; anxiety disorders; substance disorders; and schizophrenia. No secondary outcomes will be considered. Literature searches will be conducted in multiple electronic databases (from inception onwards), including PubMed, MEDLINE, SCOPUS, Web of Science, CINAHL, PsycINFO, SciELO, ERIC, and Africa-Wide. Two investigators will independently screen all citations, full-text articles, and abstract data. The methodological quality (or bias) of included studies will be appraised using appropriate tools. We will provide a narrative synthesis of the evidence. DISCUSSION: This systematic review will evaluate the evidence on the associations between pollution and the mental health of 10- to 24-year-olds. Our findings will be of potential interest to multiple audiences (including adolescent patients/clients, their families, caregivers, healthcare professionals, scientists, and policy makers) and could be used to develop prevention and intervention strategies as well as focus future research. Results will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020176664

Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

<p>Abstract</p> <p>Background</p> <p>In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system.</p> <p>Methods</p> <p>We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both <it>in vitro </it>in immune cells from mice and human, and <it>in vivo </it>in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after <it>in vitro </it>treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice <it>in vivo </it>treatment.</p> <p>Results</p> <p>None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-<it>γ </it>production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. <it>In vivo </it>treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity.</p> <p>Conclusions</p> <p>Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.</p

Cortisol coregulation in fish

Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations

Social representations of AIDS and their quotidian interfaces for people living with HIV

This qualitative descriptive study, guided by the Social Representations Theory, aimed to describe the content of the social representations regarding the Acquired Immunodeficiency Syndrome (AIDS) for seropositive individuals in outpatient monitoring of the public health network and to analyze the interface of the social representations of AIDS with the quotidian of the individuals living with human immunodeficiency virus (HIV), especially in the adherence to treatment process Interviews were conducted with 30 seropositive individuals and the manual content analysis technique was used. From the analysis, six categories emerged that re-translated the quotidian of seropositive people permeated by the stigma, prejudice, struggle for life and the need for the continuous use of antiretrovirals. AIDS was assimilated to chronic diseases such as diabetes, showing a trend of transformation of the social representation of AIDS, substituting the idea of death, with life. It is concluded that people living with HIV are more optimistic due to effective treatments for the control of the disease.Se trata de un estudio cualitativo descriptivo orientado por la Teoría de las Representaciones Sociales, que objetivó describir el contenido de las representaciones sociales acerca de la Síndrome de Inmunodeficiencia Adquirida (SIDA) para los usuarios seropositivos en acompañamiento de ambulatorio en la red pública de salud y analizar la interconexión de las representaciones sociales del Sida con lo cotidiano de los individuos que viven con el virus de la inmunodeficiencia humana (HIV), especialmente al proceso de adhesión al tratamiento. Se realizaron entrevistas con 30 individuos seropositivos. Se utilizó la técnica de análisis de contenido manual. Del análisis, emergieron seis categorías que tradujeron lo cotidiano de seropositivos impregnados por el estigma, prejuicio, lucha por la vida y la necesidad del uso continuo de antirretrovirales. El Sida fue comparado a enfermedades crónicas como la diabetes, evidenciando una tendencia de transformación de la representación social del Sida, substituyendo la idea de muerte, por la de vida. Se concluye que las personas que conviven con HIV están más optimistas debido a los tratamientos eficaces en el control de la enfermedad.Trata-se de estudo qualitativo descritivo, norteado pela teoria das representações sociais. Objetivou-se descrever o conteúdo das representações sociais acerca da síndrome de imunodeficiência adquirida (AIDS) para os usuários soropositivos, em acompanhamento ambulatorial da rede pública de saúde, e analisar a interface das representações sociais da AIDS com o cotidiano dos indivíduos que vivem com o vírus da imunodeficiência humana (HIV), especialmente no processo de adesão ao tratamento. Realizaram-se entrevistas com 30 indivíduos soropositivos. Utilizou-se a técnica de análise de conteúdo manual. Da análise, emergiram seis categorias que retraduziram o cotidiano de soropositivos, permeados pelo estigma, preconceito, luta pela vida e a necessidade do uso contínuo de antirretrovirais. A AIDS foi assimilada a doenças crônicas como diabetes, evidenciando tendência para transformação da representação social da AIDS, substituindo a ideia de morte, por vida. Conclui-se que as pessoas que convivem com HIV estão mais otimistas devido aos tratamentos eficazes no controle da doença