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.

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.

Kinin B1 receptor and TLR4 interaction in inflammatory response.

OBJECTIVE: We aimed to broaden our understanding of a potential interaction between B1R and TLR4, considering earlier studies suggesting that lipopolysaccharide (LPS) may trigger B1R stimulation. METHODS: We assessed the impact of DBK and LPS on the membrane potential of thoracic aortas from C57BL/6, B1R, or TLR4 knockout mice. Additionally, we examined the staining patterns of these receptors in the thoracic aortas of C57BL/6 and in endothelial cells (HBMEC). RESULTS: DBK does not affect the resting membrane potential of aortic rings in C57BL/6 mice, but it hyperpolarizes preparations in B1KO and TLR4KO mice. The hyperpolarization mechanism in B1KO mice involves B2R, and the TLR4KO response is independent of cytoplasmic calcium influx but relies on potassium channels. Conversely, LPS hyperpolarizes thoracic aorta rings in both C57BL/6 and B1KO mice, with the response unaffected by a B1R antagonist. Interestingly, the absence of B1R alters the LPS response to potassium channels. These activities are independent of nitric oxide synthase (NOS). While exposure to DBK and LPS does not alter B1R and TLR4 mRNA expression, treatment with these agonists increases B1R staining in endothelial cells of thoracic aortic rings and modifies the staining pattern of B1R and TLR4 in endothelial cells. Proximity ligation assay suggests a interaction between the receptors. CONCLUSION: Our findings provide additional support for a putative connection between B1R and TLR4 signaling. Given the involvement of these receptors and their agonists in inflammation, it suggests that drugs and therapies targeting their effects could be promising therapeutic avenues worth exploring.

Astrocytes as a target for Nogo-A and implications for synapse formation in vitro and in a model of acute demyelination.

Central nervous system (CNS) function depends on precise synaptogenesis, which is shaped by environmental cues and cellular interactions. Astrocytes are outstanding regulators of synapse development and plasticity through contact-dependent signals and through the release of pro- and antisynaptogenic factors. Conversely, myelin and its associated proteins, including Nogo-A, affect synapses in a inhibitory fashion and contribute to neural circuitry stabilization. However, the roles of Nogo-A-astrocyte interactions and their implications in synapse development and plasticity have not been characterized. Therefore, we aimed to investigate whether Nogo-A affects the capacity of astrocytes to induce synaptogenesis. Additionally, we assessed whether downregulation of Nogo-A signaling in an in vivo demyelination model impacts the synaptogenic potential of astrocytes. Our in vitro data show that cortical astrocytes respond to Nogo-A through RhoA pathway activation, exhibiting stress fiber formation and decreased ramified morphology. This phenotype was associated with reduced levels of GLAST protein and aspartate uptake, decreased mRNA levels of the synaptogenesis-associated genes Hevin, glypican-4, TGF-ß1 and BDNF, and decreased and increased protein levels of Hevin and SPARC, respectively. Corroborating these findings, conditioned medium from Nogo-A-treated astrocytes suppressed the formation of structurally and functionally mature synapses in cortical neuronal cultures. After cuprizone-induced acute demyelination, we observed reduced immunostaining for Nogo-A in the visual cortex accompanied by higher levels of Hevin expression in astrocytes and an increase in excitatory synapse density. Hence, we suggest that interactions between Nogo-A and astrocytes might represent an important pathway of plasticity regulation and could be a target for therapeutic intervention in demyelinating diseases in the future.

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.

PU.1 Regulates Ig Light Chain Transcription and Rearrangement in Pre-B Cells during B Cell Development.

B cell development and Ig rearrangement are governed by cell type- and developmental stage-specific transcription factors. PU.1 and Spi-B are E26-transformation-specific transcription factors that are critical for B cell differentiation. To determine whether PU.1 and Spi-B are required for B cell development in the bone marrow, Spi1 (encoding PU.1) was conditionally deleted in B cells by Cre recombinase under control of the Mb1 gene in Spib (encoding Spi-B)-deficient mice. Combined deletion of Spi1 and Spib resulted in a lack of mature B cells in the spleen and a block in B cell development in the bone marrow at the small pre-B cell stage. To determine target genes of PU.1 that could explain this block, we applied a gain-of-function approach using a PU.1/Spi-B-deficient pro-B cell line in which PU.1 can be induced by doxycycline. PU.1-induced genes were identified by integration of chromatin immunoprecipitation-sequencing and RNA-sequencing data. We found that PU.1 interacted with multiple sites in the Igκ locus, including Vκ promoters and regions located downstream of Vκ second exons. Induction of PU.1 induced Igκ transcription and rearrangement. Upregulation of Igκ transcription was impaired in small pre-B cells from PU.1/Spi-B-deficient bone marrow. These studies reveal an important role for PU.1 in the regulation of Igκ transcription and rearrangement and a requirement for PU.1 and Spi-B in B cell development.

A four-step process for building sustainable access to diagnosis and treatment of Chagas disease.

The vast majority of people with Chagas disease (CD) are undiagnosed and untreated. Improving access to diagnosis and treatment for CD involves confronting a wide range of barriers. This report discusses a collaborative approach to eliminate barriers and increase the availability of CD testing and treatment. Potential areas for intervention are selected based on burden of disease, support of local champions, and commitment from national and local authorities. A 4D approach (diagnose, design, deliver, and demonstrate impact) is then implemented. The diagnose step involves gathering key stakeholders at a seminar to collaboratively identify important barriers and propose solutions. The design step creates a specific plan to act upon the seminar's conclusions with consensus on core indicators. The deliver step entails implementing the plan at pilot locations, while simultaneously strengthening health system capacity for CD testing and treatment. Lastly, the demonstrate impact step compares baseline data with annual post-implementation data to measure progress. In Colombia, this approach has helped simplify testing procedures and increase CD testing and treatment access in pilot communities, though challenges remain. The 4D approach represents one of several pathways toward ensuring that the best therapeutic and diagnostic products reach people affected by neglected tropical diseases.

Una amplia mayoría de las personas con la enfermedad de Chagas no reciben diagnóstico ni tratamiento. Para mejorar el acceso al diagnóstico y al tratamiento de esta enfermedad es necesario superar multiples obstáculos. En el presente informe se considera un método colaborativo diseñado para superar las barreras y aumentar la disponibilidad de las pruebas de detección y el tratamiento de la enfermedad de Chagas. Se seleccionan los posibles ámbitos de intervención en función de la carga de enfermedad, el apoyo por parte de los líderes locales y el compromiso de las autoridades locales y nacionales. Posteriormente, se aplica un método 4D basado en cuatro pasos: diagnóstico, diseño, desarrollo y demonstración de impacto. El paso correspondiente al diagnóstico consiste en reunir en un seminario a los principales socios con el fin de establecer de manera colaborativa las barreras más importantes y ofrecer soluciones. En el paso de diseño, se elabora un plan específico para actuar conforme a las conclusiones del seminario de manera consensuada sobre los indicadores centrales. El paso de ejecución supone la aplicación del plan en las ubicaciones piloto, al tiempo que se fortalece la capacidad de los sistemas de salud en lo relativo a las pruebas de detección y el tratamiento de la enfermedad de Chagas. Finalmente, en el paso de demonstración de impacto se comparan los datos iniciales con los datos anuales posteriores a la ejecución para evaluar el progreso. En Colombia, este enfoque ha contribuido a simplificar los procedimientos de las pruebas de detección y brindar mayor acceso a la detección y el tratamiento de la enfermedad de Chagas en las comunidades piloto, si bien todavía hay retos que superar. El método de cuatro pasos es una de las diferentes vías para garantizar que los mejores productos de tratamiento y diagnóstico estén al alcance de las personas afectadas por las enfermedades tropicales desatendidas.

A ampla maioria das pessoas com doença de Chagas não é diagnosticada nem é tratada. Para melhorar o acesso ao diagnóstico e ao tratamento desta doença, é necessário superar uma série de barreiras. Neste relato, é exposta uma abordagem colaborativa com o objetivo de vencer as barreiras e aumentar a disponibilidade do exame de detecção da doença de Chagas. As possíveis áreas de intervenção são selecionadas de acordo com a carga de doença, o apoio de defensores da causa e o compromisso das autoridades nacionais e locais. Uma abordagem em 4Ds (diagnóstico, desenho, desenvolvimento e demonstração de impacto) é implementada. No passo ''diagnóstico'', um seminário com os principais atores é realizado para identificarem as maiores barreiras e proporem soluções de modo colaborativo. No passo ''desenho'', um plano de ação é elaborado a partir das conclusões tiradas do seminário mediante o consenso sobre os indicadores básicos. No passo ''desenvolvimento'', o plano é implementado em áreas-piloto e, em paralelo, a capacidade do sistema de saúde de realizar os exames de detecção e o tratamento da doença de Chagas é reforçada. Por último, no passo ''demonstração de impacto'', os dados de referência são comparados aos dados anuais pós-implementação com o objetivo de avaliar o progresso. Na Colômbia, apesar de persistirem os desafios, esta abordagem contribuiu para simplificar o procedimento para o exame de detecção da doença de Chagas, aumentar o número de exames realizados e melhorar o acesso ao tratamento nas comunidades-piloto. A abordagem em 4Ds representa um dos vários cursos a serem seguidos para garantir que os melhores recursos diagnósticos e terapêuticos cheguem até as pessoas afetadas por doenças tropicais negligenciadas.

Increasing access to comprehensive care for Chagas disease: development of a patient-centered model in Colombia.

Worldwide, over 6 million people are infected with Trypanosoma cruzi, the pathogen that causes Chagas disease (CD). In the Americas, CD creates the greatest burden in disability-adjusted life years of any parasitic infection. In Colombia, 437 000 people are infected with T. cruzi, of whom 131 000 suffer from cardiomyopathy. Colombia's annual costs for treating patients with advanced CD reach US$ 175 016 000. Although timely etiological treatment can significantly delay or prevent development of cardiomyopathy-and costs just US$ 30 per patient-fewer than 1% of people with CD in Colombia and elsewhere receive it. This represents a missed opportunity for increasing patients' healthy, productive years of life while significantly reducing the economic burden on the health care system. Key barriers are complexities and delays in the diagnosis and treatment process, lack of awareness of CD among both patients and health care professionals, and administrative barriers at the primary care level. In 2015, stakeholders from government, academia, nongovernmental organizations, and patient associations participated in a seminar in the city of Bogotá on eliminating barriers to diagnosis and treatment for CD. The seminar gave birth to a model of care for increasing patient access, including a patient road map that simplifies diagnostic and treatment processes, shifting them from specialists to primary care facilities. The patient road map was implemented in a pilot project in four endemic communities beginning in 2016, with the goal of testing and refining the model so it can be implemented nationally. This article describes key components in the development of a new, recently implemented model of care for CD in Colombia.

En todo el mundo, hay más de 6 millones de personas infectadas por el Trypanosoma cruzi, el agente patógeno causante de la enfermedad de Chagas. En la Región de las Américas, esta es la infección parasitaria que tiene la mayor carga en cuanto a años de vida ajustados en función de la discapacidad. En Colombia, 437 000 personas están infectadas por el T. cruzi; de ese total, 131 000 sufren de miocardiopatía. En ese país, el costo anual de tratar a los pacientes que tienen la enfermedad de Chagas se ubica en US$ 175 016 000. A pesar de que un tratamiento etiológico oportuno puede retrasar o prevenir significativamente la aparición de una miocardiopatía ­a un costo de apenas US$ 30 por paciente­ menos de 1% de las personas con enfermedad de Chagas en Colombia y otros países lo reciben. Esto implica que se pierde la oportunidad de incrementar el número de años de vida saludables y productivos de los pacientes y, al mismo tiempo, reducir significativamente la carga económica que soporta el sistema de atención de salud. Los obstáculos clave son la complejidad y las demoras en los procesos de diagnóstico y tratamiento, la falta de conocimiento sobre la enfermedad de Chagas por parte de los pacientes y de los profesionales de la salud, y las barreras administrativas que existen a nivel de la atención primaria.En el 2015, representantes del gobierno, la comunidad académica, organizaciones no gubernamentales y asociaciones de pacientes participaron en un seminario en Bogotá sobre la eliminación de las barreras al diagnóstico y el tratamiento de la enfermedad de Chagas. En este seminario se elaboró un modelo de atención para aumentar el acceso de los pacientes, incluida una hoja de ruta centrada en el paciente que simplifica los procesos de diagnóstico y tratamiento al trasladarlos de los especialistas a los establecimientos de atención primaria. La hoja de ruta centrada en el paciente se aplicó a principios del 2016 como parte de un proyecto piloto que se puso en marcha en cuatro comunidades endémicas con el objetivo de poner a prueba y perfeccionar el modelo para luego poder aplicarlo en todo el país. En este artículo se describen los componentes clave que se usaron para crear un modelo de atención de la enfermedad de Chagas puesto en marcha recientemente en Colombia.

Em todo o mundo, cerca de 6 milhões de pessoas são infectadas pelo Trypanosoma cruzi, o patógeno causador da doença de Chagas. Nas Américas, esta infecção parasitária é responsável pela maior carga de anos de vida perdidos ajustados por incapacidade. Na Colômbia, estima-se que 437 mil pessoas são infectadas pelo T. cruzi, das quais 131 mil têm miocardiopatia. O custo anual para tratar os pacientes com doença de Chagas em estágio avançado chega a US$ 175.016.000. Embora o tratamento oportuno mirando o agente etiológico possa postergar significativamente, ou prevenir, a ocorrência de miocardiopatia, ao custo de apenas US$ 30 por paciente, menos de 1% dos portadores da doença de Chagas é tratado na Colômbia e em outros lugares. Representa uma perda de oportunidade de prolongar os anos de vida saudável e produtiva dos pacientes e de reduzir consideravelmente o ônus econômico ao sistema de saúde. Os principais entraves são a complexidade e a demora do processo de diagnóstico e tratamento, a falta de conhecimento sobre a doença por parte dos pacientes e dos profissionais da saúde e os obstáculos administrativos ao nível da atenção primária. Em 2015, interessados diretos de setores do governo, comunidade acadêmica, organizações não governamentais e associações de pacientes participaram de um seminário realizado na cidade de Bogotá em que discutiram como eliminar as barreiras ao diagnóstico e ao tratamento da doença de Chagas. Deste seminário nasceu um modelo para aumentar o acesso dos pacientes à atenção à saúde, com a preparação de um guia simplificado para o diagnóstico e o tratamento e a transição do atendimento dos serviços especializados aos serviços de atenção primária. Como parte de um projeto-piloto, a partir de 2016, o guia do paciente foi implantado em quatro comunidades endêmicas com o propósito de testar e aprimorar o modelo para que possa ser implantado em todo o país. O presente artigo descreve os principais componentes deste modelo de atenção para a doença de Chagas recém-implantado na Colômbia.

Effects of somatotrophic axis (GH/GHR) double transgenesis on structural and molecular aspects of the zebrafish immune system.

The development of growth hormone (GH) transgenic fish has been shown to be a promising method to improve growth rates. However, the role of GH is not restricted only to processes involved in growth. Several others physiological processes, including immune function, are impaired due to GH imbalances. Given the importance of generating GH transgenic organisms for aquaculture purposes, it is necessary to develop strategies to reduce or compensate for the collateral effects of GH. We hypothesized that the generation of double transgenic fish that overexpress GH and growth hormone receptor (GHR) in the skeletal muscle could be a possible alternative to compensate for the deleterious effects of GH on the immune system. Specifically, we hypothesized that increased GHR amounts in the skeletal muscle would be able to reduce the level of circulating GH, attenuating the GH signaling on the immune cells while still increasing the growth rate. To test this hypothesis, we evaluated the size of the immune organs, T cell content in the thymus and head kidney, and expression of immune-related genes in double-transgenic fish. Contrary to our expectations, we found that the overexpression of GHR does not decrease the deleterious effect of GH excess on the size of the thymus and head kidney, and in the content of CD3(+) and CD4(+) cells in the thymus and head kidney. Unexpectedly, the control GHR transgenic group showed similar impairments in immune system parameters. These results indicate that GHR overexpression does not reverse the impairments caused by GH and, in addition, could reinforce the damage to the immune functions in GH transgenic zebrafish.

Impairment of the immune system in GH-overexpressing transgenic zebrafish (Danio rerio).

Growth hormone (GH) is an important regulator of immune functions in vertebrates, and it has been intensively reported a series of stimulatory actions of this hormone over on the immune system. Within aquaculture, overexpression of GH has been considered a promising alternative for promoting higher growth rates in organisms of commercial interest. Considering the various pleiotropic effects of GH, there are still few studies that aim to understand the consequences of the excess of GH on the physiological systems. In this context, our goal was to present the effects of the overexpression of GH on immune parameters using a model of zebrafish (Danio rerio) that overexpress this hormone. The results showed that GH transgenic zebrafish had 100% of mortality when immunosuppressed with dexamethasone, revealing a prior weakening of the immune system in this lineage. Morphometric analysis of thymus and head kidney revealed a reduction in the area of these structures in transgenic zebrafish. Moreover, the phenotypic expression of CD3 and CD4 thymocytes was also depreciated in transgenic zebrafish. Furthermore, a decrease was noted in the expression of genes RAG-1 (60%), IKAROS (50%), IL-1ß (55%), CD4 (60%) and CD247 (40%), indicating that development parameters, of innate and acquired immunity, are being harmed. Based on these results, it can be concluded that the excess of GH impairs the immune functions in GH transgenic zebrafish, indicating that the maintenance of normal levels of this hormone is essential for the functioning of immunological activities.

Coping Styles and Defense Mechanisms Mediate Associations Between Exposure to Adverse Childhood Experiences and CPTSD Symptoms in Faroese Adolescents.

Background: The experience of several adverse childhood experiences (ACEs) has been shown to be associated with Post-Traumatic Stress Disorder (PTSD) and Disturbances in Self-Organization (DSO) symptoms among adolescents. Defense mechanisms and coping styles are psychological processes involved in the association of ACEs with PTSD and DSO symptoms. However, there is a lack of research on the joint association of these variables among Faroese adolescents. Aim: The aim of this study was to analyze the effect of exposure to ACEs on PTSD and DSO symptoms trough the indirect effect of defense mechanisms and coping styles in a sample of Faroese adolescents. Method: Six hundred and eighty-seven Faroese adolescents were recruited from 19 schools. Participants responded to validated self-report questionnaires. A multiple step mediation and a serial mediation methodology were conducted through structural equation modeling. Results: Exposure to ACEs was linked to PTSD and DSO symptoms through the indirect effect of immature defense mechanisms, emotional coping, and detachment coping. Exposure to ACEs was linked to PTSD symptoms through rational coping. Conclusions: The results suggest a mutual relationship between defense mechanisms and coping styles in coping with multiple adversity among adolescents.

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.

Influence of COVID-19 on trust in routine immunization, health information sources and pandemic preparedness in 23 countries in 2023.

It is unclear how great a challenge pandemic and vaccine fatigue present to public health. We assessed perspectives on coronavirus disease 2019 (COVID-19) and routine immunization as well as trust in pandemic information sources and future pandemic preparedness in a survey of 23,000 adults in 23 countries in October 2023. The participants reported a lower intent to get a COVID-19 booster vaccine in 2023 (71.6%), compared with 2022 (87.9%). A total of 60.8% expressed being more willing to get vaccinated for diseases other than COVID-19 as a result of their experience during the pandemic, while 23.1% reported being less willing. Trust in 11 selected sources of vaccine information each averaged less than 7 on a 10-point scale with one's own doctor or nurse and the World Health Organization, averaging a 6.9 and 6.5, respectively. Our findings emphasize that vaccine hesitancy and trust challenges remain for public health practitioners, underscoring the need for targeted, culturally sensitive health communication strategies.

Kinin B1 receptor gene ablation affects hypothalamic CART productionb.

A role for the kinin B1 receptor in energy-homeostatic processes was implicated in previous studies; notably, the studies where kinin B1 receptor knockout mice (B1-/-) were shown to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet-induced obesity when fed a high fat diet (HFD). In particular, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of cocaine and amphetamine related transcript (CART) in the (lateral hypothalamic area (LHA) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Furthermore, it seems to indicate that the mechanism underlying the 'lean' phenotype of B1-/- mice does not stem solely from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes.

Natural occurrence of White spot syndrome virus and Infectious hypodermal and hematopoietic necrosis virus in Neohelice granulata crab.

White spot syndrome virus (WSSV) and Infectious hypodermal and hematopoietic necrosis virus (IHHNV) are two infectious agents associated to economic losses in shrimp aquaculture. As virus spread occurs through vectors and hosts, this study sought to verify the presence of WSSV and IHHNV in Neohelice granulata crab from Lagoa dos Patos estuary in Brazil and nearby shrimp farms. DNA extractions were performed with phenol/chloroform protocol. Molecular diagnosis was carried out by nested PCR for WSSV and one-step PCR for IHHNV. Results showed the presence of WSSV on crabs of both Lagoa dos Patos and farms, while IHHNV was found only on crabs collected in estuary. This is the first study to report IHHNV presence in N. granulata. Moreover, as analyzed crabs had no clinical symptoms or showed in situ mortality, we suggest its use as a bioindicator for virus occurrence in aquatic environments.

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.

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.