Postnatal Zika virus infection leads to morphological and cellular alterations within the neurogenic niche.

The Zika virus received significant attention in 2016, following a declaration by the World Health Organization of an epidemic in the Americas, in which infections were associated with microcephaly. Indeed, prenatal Zika virus infection is detrimental to fetal neural stem cells and can cause premature cell loss and neurodevelopmental abnormalities in newborn infants, collectively described as congenital Zika syndrome. Contrastingly, much less is known about how neonatal infection affects the development of the newborn nervous system. Here, we investigated the development of the dentate gyrus of wild-type mice following intracranial injection of the virus at birth (postnatal day 0). Through this approach, we found that Zika virus infection affected the development of neurogenic regions within the dentate gyrus and caused reactive gliosis, cell death and a decrease in cell proliferation. Such infection also altered volumetric features of the postnatal dentate gyrus. Thus, we found that Zika virus exposure to newborn mice is detrimental to the subgranular zone of the dentate gyrus. These observations offer insight into the cellular mechanisms that underlie the neurological features of congenital Zika syndrome in children.

Polytraumatization, defense mechanisms, PTSD and complex PTSD in Indian adolescents: a mediation model.

BACKGROUND: Adolescence is recognized as a particularly susceptible developmental period for experiencing multiple types of Adverse Childhood Experiences (ACE), increasing the vulnerability to higher levels of Post-Traumatic Stress Disorder (PTSD) and Complex PTSD symptoms. Some studies found that defense mechanisms play an important role on the association between ACE and psychological symptoms. METHODS: We analyzed the associations between direct and indirect exposure to ACE and PTSD and Complex PTSD (affective dysregulation, negative self-concept and disturbances in relationships) through the mediation role of mature defense mechanisms: mature, neurotic, and immature defense mechanisms in Indian adolescents. A sample of 411 Indian adolescents (M = 14.2 years old; S.D. = 0.5) completed validated self-report questionnaires. Serial multiple mediation models were tested by conducting a structural equation modelling employing Preacher and Hayes' procedures (2008). RESULTS: Immature and neurotic defense mechanisms mediated the association between direct exposure to ACE with PTSD symptoms. Immature defense mechanisms were mediators of the relationship between direct exposure to ACE and Complex PTSD symptoms clusters. CONCLUSIONS: Maladaptive defense mechanisms can disturb the process of self-regulation and emotion regulation capabilities in coping with traumatic experiences, leading to higher PTSD and Complex PTSD symptoms severity.

Spi-C and PU.1 Counterregulate Rag1 and Igκ Transcription to Effect Vκ-Jκ Recombination in Small Pre-B Cells.

B cell development requires the ordered rearrangement of Ig genes encoding H and L chain proteins that assemble into BCRs or Abs capable of recognizing specific Ags. Igκ rearrangement is promoted by chromatin accessibility and by relative abundance of RAG1/2 proteins. Expression of the E26 transformation-specific transcription factor Spi-C is activated in response to dsDNA double-stranded breaks in small pre-B cells to negatively regulate pre-BCR signaling and Igκ rearrangement. However, it is not clear if Spi-C regulates Igκ rearrangement through transcription or by controlling RAG expression. In this study, we investigated the mechanism of Spi-C negative regulation of Igκ L chain rearrangement. Using an inducible expression system in a pre-B cell line, we found that Spi-C negatively regulated Igκ rearrangement, Igκ transcript levels, and Rag1 transcript levels. We found that Igκ and Rag1 transcript levels were increased in small pre-B cells from Spic-/- mice. In contrast, Igκ and Rag1 transcript levels were activated by PU.1 and were decreased in small pre-B cells from PU.1-deficient mice. Using chromatin immunoprecipitation analysis, we identified an interaction site for PU.1 and Spi-C located in the Rag1 promoter region. These results suggest that Spi-C and PU.1 counterregulate Igκ transcription and Rag1 transcription to effect Igκ recombination in small pre-B cells.

Implications from COVID-19 for future pandemic global health governance.

BACKGROUND: Limitations of current global health governance revealed during the COVID-19 pandemic can inform the ongoing deliberations of an international treaty on pandemics. OBJECTIVES: To report on WHO definitions for governance and the enforcement of treaties in the context of a proposed international treaty on pandemics. SOURCES: This narrative review was based on keyword searches related to public health, global health governance, and enforcement in PubMed/Medline and Google Scholar. Snowballing for additional articles followed the keyword search review. CONTENT: WHO lacks a consistent definition of global health governance. Moreover, in its current state, the proposed international treaty on pandemics lacks articulated compliance, accountability, or enforcement mechanisms. Findings reveal that humanitarian treaties often fail to achieve their aims absent clear enforcement mechanisms. The proposed international treaty on public health is garnering a range of perspectives. Decision-makers should evaluate whether a globally aligned definition of global health governance is needed. Decision-makers should also consider whether the proposed international treaty on pandemics should be opposed if it lacks sufficiently clear compliance, accountability, and enforcement mechanisms. IMPLICATIONS: To our knowledge, this narrative review is believed to be the first of its kind to search scientific-oriented databases regarding governance and international pandemic treaties. The review includes several findings that advance the literature. These findings, in turn, reveal two key implications for decision-makers. First, whether an aligned definition for governance addressing compliance, accountability, and enforcement mechanisms is needed. Second, whether a draft treaty lacking enforcement mechanisms should be approved.

Vaccines and therapeutics for immunocompromised patients with COVID-19.

The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches.

A multinational Delphi consensus to end the COVID-19 public health threat.

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Obstacles to Glioblastoma Treatment Two Decades after Temozolomide.

Glioblastomas are considered the most common and aggressive primary brain tumor in adults, with an average of 15 months' survival rate. The treatment is surgery resection, followed by chemotherapy with temozolomide, and/or radiotherapy. Glioblastoma must have wild-type IDH gene and some characteristics, such as TERT promoter mutation, EGFR gene amplification, microvascular proliferation, among others. Glioblastomas have great heterogeneity at cellular and molecular levels, presenting distinct phenotypes and diversified molecular signatures in each tumor mass, making it difficult to define a specific therapeutic target. It is believed that the main responsibility for the emerge of these distinct patterns lies in subcellular populations of tumor stem cells, capable of tumor initiation and asymmetric division. Studies are now focused on understanding molecular mechanisms of chemoresistance, the tumor microenvironment, due to hypoxic and necrotic areas, cytoskeleton and extracellular matrix remodeling, and in controlling blood brain barrier permeabilization to improve drug delivery. Another promising therapeutic approach is the use of oncolytic viruses that are able to destroy specifically glioblastoma cells, preserving the neural tissue around the tumor. In this review, we summarize the main biological characteristics of glioblastoma and the cutting-edge therapeutic targets that are currently under study for promising new clinical trials.

RNA exosome drives early B cell development via noncoding RNA processing mechanisms.

B cell development is linked to successful V(D)J recombination, allowing B cell receptor expression and ultimately antibody secretion for adaptive immunity. Germline noncoding RNAs (ncRNAs) are produced at immunoglobulin (Ig) loci during V(D)J recombination, but their function and posttranscriptional regulation are incompletely understood. Patients with trichohepatoenteric syndrome, characterized by RNA exosome pathway component mutations, exhibit lymphopenia, thus demonstrating the importance of ncRNA surveillance in B cell development in humans. To understand the role of RNA exosome in early B cell development in greater detail, we generated mouse models harboring a B cell-specific cre allele (Mb1cre), coupled to conditional inversion-deletion alleles of one RNA exosome core component (Exosc3) or RNase catalytic subunits (Exosc10 or Dis3). We noticed increased expression of RNA exosome subunits during V(D)J recombination, whereas a B cell developmental blockade at the pro-B cell stage was observed in the different knockout mice, overlapping with a lack of productive rearrangements of VDJ genes at the Ig heavy chain (Igh). This unsuccessful recombination prevented differentiation into pre-B cells, with accumulation of ncRNAs and up-regulation of the p53 pathway. Introduction of a prearranged Igh VDJ allele partly rescued the pre-B cell population in Dis3-deficient cells, although V-J recombination defects were observed at Ig light chain kappa (Igκ), preventing subsequent B cell development. These observations demonstrated that the RNA exosome complex is important for Igh and Igκ recombination and establish the relevance of RNA processing for optimal diversification at these loci during B cell development.

Association between advertising patterns and ultra-processed food in small markets. / Associação entre padrão de publicidade e alimento ultraprocessado em pequenos mercados.

This article aims to characterize the advertising appeals present in the food environment to market ultra-processed foods and to analyze the nutritional profile of these foods according to PAHO criteria and the presence of food additives. Cross-sectional study, with data audited in 20 small supermarkets in São Paulo. The INFORMAS protocol was used to classify the advertising messages. The foods were classified according to NOVA. The PAHO profile model was used to classify foods high in critical nutrients. Advertising patterns were identified by factor analysis. The association between patterns and food groups was investigated by linear regression. More than 95% of the ultraprocessed foods had at least 1 critical nutrient in excess. There was a positive association between the new brand, fun and advantageous pattern with snacks, ready-made products, dairy products and cookies; between the new brand and suggested use pattern with dairy products. The standardization of food advertising in small retail stores is associated with offering snacks, dairy products, ready-to-eat foods and cookies, products that exceed critical nutrients.

O objetivo deste artigo é caracterizar os apelos publicitários presentes no ambiente alimentar para comercializar alimentos ultraprocessados e analisar o perfil nutricional desses alimentos segundo critérios da OPAS e presença de aditivos alimentares. Estudo transversal, com dados auditados em 20 pequenos supermercados de São Paulo. O protocolo INFORMAS foi utilizado para classificar as mensagens publicitárias. Os alimentos foram classificados segundo a NOVA. O perfil nutricional da OPAS foi utilizado para classificar os alimentos elevados em nutrientes críticos. Os padrões de publicidade foram identificados por análise fatorial. A associação entre os padrões e os grupos de alimentos foi investigada por regressão linear. Mais de 95% dos alimentos ultraprocessados tinham pelo menos um nutriente crítico em excesso. Verificou-se associação positiva entre o padrão nova marca, divertido e vantajoso com salgadinhos, produtos pré-prontos, lácteos e biscoitos, e entre o padrão nova marca e uso sugerido com lácteos. A padronização da publicidade de alimentos nos pequenos comércios varejistas está associada à oferta de salgadinhos, produtos lácteos, alimentos pré-prontos e biscoitos, produtos que excedem em nutrientes críticos.

Associação entre padrão de publicidade e alimento ultraprocessado em pequenos mercados / Association between advertising patterns and ultra-processed food in small markets

Resumo O objetivo deste artigo é caracterizar os apelos publicitários presentes no ambiente alimentar para comercializar alimentos ultraprocessados e analisar o perfil nutricional desses alimentos segundo critérios da OPAS e presença de aditivos alimentares. Estudo transversal, com dados auditados em 20 pequenos supermercados de São Paulo. O protocolo INFORMAS foi utilizado para classificar as mensagens publicitárias. Os alimentos foram classificados segundo a NOVA. O perfil nutricional da OPAS foi utilizado para classificar os alimentos elevados em nutrientes críticos. Os padrões de publicidade foram identificados por análise fatorial. A associação entre os padrões e os grupos de alimentos foi investigada por regressão linear. Mais de 95% dos alimentos ultraprocessados tinham pelo menos um nutriente crítico em excesso. Verificou-se associação positiva entre o padrão nova marca, divertido e vantajoso com salgadinhos, produtos pré-prontos, lácteos e biscoitos, e entre o padrão nova marca e uso sugerido com lácteos. A padronização da publicidade de alimentos nos pequenos comércios varejistas está associada à oferta de salgadinhos, produtos lácteos, alimentos pré-prontos e biscoitos, produtos que excedem em nutrientes críticos.

Abstract This article aims to characterize the advertising appeals present in the food environment to market ultra-processed foods and to analyze the nutritional profile of these foods according to PAHO criteria and the presence of food additives. Cross-sectional study, with data audited in 20 small supermarkets in São Paulo. The INFORMAS protocol was used to classify the advertising messages. The foods were classified according to NOVA. The PAHO profile model was used to classify foods high in critical nutrients. Advertising patterns were identified by factor analysis. The association between patterns and food groups was investigated by linear regression. More than 95% of the ultraprocessed foods had at least 1 critical nutrient in excess. There was a positive association between the new brand, fun and advantageous pattern with snacks, ready-made products, dairy products and cookies; between the new brand and suggested use pattern with dairy products. The standardization of food advertising in small retail stores is associated with offering snacks, dairy products, ready-to-eat foods and cookies, products that exceed critical nutrients.

Achieving global equity for COVID-19 vaccines: Stronger international partnerships and greater advocacy and solidarity are needed.

Peter Figueroa and co-authors advocate for equity in the worldwide provision of COVID-19 vaccines.

Global public health security and justice for vaccines and therapeutics in the COVID-19 pandemic.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.

A reforma trabalhista e as implicações para a saúde do trabalhador / Labor reform and its implications for workers' health

A Lei n. 13.467/2017, conhecida como Reforma Trabalhista, trouxe várias modificações ao texto da Consolidação das Leis do Trabalho. Várias dessas mudanças desrespeitam as normas relativas à saúde do trabalhador, dispostas tanto na Constituição Federal de 1988 quanto na legislação infraconstitucional. O objetivo deste estudo foi identificar e analisar as possíveis implicações da Reforma Trabalhista para a saúde do trabalhador, tendo em vista os regramentos constitucionais. Para o desenvolvimento do estudo, utilizou-se a metodologia qualitativa com adoção da técnica de análise de conteúdo de documentos. Foram analisadas quatro alterações propostas pela Lei n. 13.467/2017, quais sejam: a possibilidade de alterar o enquadramento do grau de insalubridade mediante negociação coletiva; a possibilidade de reduzir o intervalo intrajornada também por negociação coletiva; a possibilidade de trabalho em condições insalubres durante a gravidez/fase de lactação; e a liberação da terceirização de qualquer atividade. Verificou-se que a "modernização" trazida pela reforma trabalhista consiste, na realidade, na desconstrução da estrutura constitucional e infraconstitucional de proteção ao trabalhador, com desrespeito aos padrões de saúde e segurança até então presentes no ordenamento jurídico brasileiro. Como consequência, o estudo aponta para a probabilidade de aumento nos números de acidentes de trabalho e de doenças relacionadas ao trabalho.

Law 13.467/2017, known as the Labor Reform, brought several modifications to the text of the Consolidation of Labor Laws. Several of these changes disregard the norms related to workers' health, both in the Federal Constitution of 1988 and in the infraconstitutional legislation. The objective of this study was to identify and analyze the possible implications of the Labor Reform for workers' health, considering the constitutional regulations. For the development of the study, the qualitative methodology was used with the adoption of the document content analysis technique. Four amendments proposed by Law 13.467/2017 were analyzed, namely: the possibility of changing the framework of the degree of unhealthiness through collective bargaining; the possibility of reducing the work break also through collective bargaining; the possibility of working in unhealthy conditions during pregnancy/ lactation, and the liberation of outsourcing of any activity. It was found that the "modernization" brought by the labor reform consists, in fact, in the deconstruction of the constitutional and infraconstitutional structure of worker protection, with disregard for health and safety standards hitherto present in the Brazilian legal system. As a consequence, the study points to the likelihood of an increase in the number of accidents at work and work-related diseases.