High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Consumption of Lactobacillus casei fermented milk prevents Salmonella reactive arthritis by modulating IL-23/IL-17 expression.

Reactive arthritis is the development of sterile joint inflammation as a sequel to a remote infection, often in the gut. We have previously shown that a low dose of S. enteritidis inoculated to streptomycin-pretreated mice generates a self-limiting enterocolitis suitable for studying reactive arthritis. Here we show that consumption of Lactobacillus casei prior to infection abolishes intestinal and joint inflammation triggered by Salmonella. BALB/c mice were sacrificed after infection; intestinal and joint samples were analyzed for histological changes and expression of cytokines. TNF-α was measured by ELISA and the expression of IL-1β, IL-6, IL-10, IL-17, IL-23 and TGF-β was assessed by qPCR. L. casei consumption prevented Salmonella-induced synovitis, the increment of TNF-α in knees and the increase of IL-17 expression in popliteal and inguinal lymph nodes. At intestinal level consumption of L. casei drastically diminished S. enteritidis invasiveness and shortened splenic persistence of the pathogen. Bacterial loads recovered at days 2 and 5 from Peyer's patches were 10-fold lower in mice fed with L. casei. In accordance, we found that the augment in gut permeability induced during enterocolitis was decreased in those animals. Consumption of L. casei prior to infection failed to increase anti- inflammatory molecules such as IL-10 and TGF-β in the intestine. On the other hand, consumption of L. casei abrogated the expression of TNF-α, IL-17, IL-23, IL-1β and IL-6 in cecum and mesenteric lymph nodes. These cytokines are needed for differentiation of immune cells involved in the development of reactive arthritis such as Th17 and γδ T cells. Trafficking of these inflammatory cells from the gut to the joints has been proposed as a mechanism of generation of reactive arthritis. Our results suggest that L. casei consumption prevents Salmonella-induced synovitis by altering the intestinal milieu necessary for differentiation of cells involved in the generation of joint inflammation

Vaccine hesitancy among communities in ten countries in Asia, Africa, and South America during the COVID-19 pandemic

Vaccine hesitancy is considered one of the greatest threats to the ongoing coronavirus disease 2019 (COVID-19) vaccination programs. Lack of trust in vaccine benefits, along with concerns about side effects of the newly developed COVID-19 vaccine, might significantly contribute to COVID-19 vaccine hesitancy. The objective of this study was to determine the level of vaccine hesitancy among communities in particular their belief in vaccination benefits and perceived risks of new vaccines. An online cross-sectional study was conducted in 10 countries in Asia, Africa, and South America from February to May 2021. Seven items from the WHO SAGE Vaccine Hesitancy Scale were used to measure a construct of belief in vaccination benefit, and one item measured perceived riskiness of new vaccines. A logistic regression was used to determine which sociodemographic factors were associated with both vaccine hesitancy constructs. A total of 1,832 respondents were included in the final analysis of which 36.2% (range 5.6–52.2%) and 77.6% (range 38.3–91.2%) of them were classified as vaccine hesitant in terms of beliefs in vaccination benefits and concerns about new vaccines, respectively. Respondents from Pakistan had the highest vaccine hesitancy while those from Chile had the lowest. Being females, Muslim, having a non-healthcare-related job and not receiving a flu vaccination during the past 12 months were associated with poor beliefs of vaccination benefits. Those who were living in rural areas, Muslim, and those who did not received a flu vaccination during the past 12 months had relatively higher beliefs that new vaccines are riskier. High prevalence of vaccine hesitancy in some countries during the COVID-19 pandemic might hamper COVID-19 vaccination programs worldwide. Programs should be developed to promote vaccination in those sociodemographic groups with relatively high vaccine hesitancy

Tratamientos Psicológicos Empíricamente Apoyados Para la Infancia y Adolescencia: : Estado de la Cuestión

Background: The empirical evidence accumulated on the effi cacy, effectiveness, and effi ciency of psychotherapeutic treatments in children and adolescents calls for an update. The main goal of this paper objective was to carry out a selective review of empirically supported psychological treatments for a variety of common psychological disorders and problems in childhood and adolescence. Method: A review was carried out of the psychological treatments for different psychological disorders and problems in socialemotional or behavioral adjustment in the child-adolescent population according to the Spanish National Health System (Clinical Practice Guidelines) levels of evidence and degrees of recommendation. Results: The fi ndings suggest that psychological treatments have empirical support for addressing a wide range of psychological problems in these developmental stages. The degree of empirical support ranges from low to high depending on the phenomenon analyzed. The review suggests unequal progress in the different fi elds of intervention. Conclusions: From this update, psychologists will be able to make informed decisions when implementing those empirically supported treatments to address the problems that occur in childhood and adolescence.Antecedentes: la evidencia empírica acumulada en los últimos años sobre la efi cacia, efectividad y efi ciencia de los tratamientos psicológicos en la infancia y adolescencia reclama una actualización. El principal objetivo de este artículo es el de llevar a cabo una revisión de los tratamientos psicológicos empíricamente apoyados para una diversidad de problemas psicológicos habituales en la infancia y la adolescencia. Método: se revisan los tratamientos psicológicos para diferentes trastornos psicológicos y problemas en el ajuste socioemocional o conductual en población infanto-juvenil en función de los niveles de evidencia y grados de recomendación del Sistema Nacional de Salud de España (Guías de Práctica Clínica). Resultados: los hallazgos sugieren que los tratamientos psicológicos específi camente dirigidos a niños, niñas y adolescentes disponen de apoyo empírico para el abordaje de un amplio elenco de problemas psicológicos. Este grado de apoyo empírico oscila de bajo a alto en función del problema analizado. La revisión muestra un avance desigual en los diferentes campos de intervención. Conclusiones: a partir de esta actualización, los profesionales de la psicología podrán tomar decisiones informadas a la hora de implementar aquellas intervenciones psicológicas con apoyo empírico para el abordaje de los problemas en la infancia y la adolescenci

Role of Ectonucleotidases in the Synapse Formation During Brain Development: Physiological and Pathological Implications

Extracellular adenine nucleotides and nucleosides, such as ATP and adenosine, are among the most recently identified and least investigated diffusible signaling factors that contribute to the structural and functional remodeling of the brain, both during embryonic and postnatal development. Their levels in the extracellular milieu are tightly controlled by various ectonucleotidases: ectonucleotide pyrophosphatase/phosphodiesterases (E-NPP), alkaline phosphatases (AP), ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) and ecto-5&#039;-nucleotidase (eN). During central nervous system development and in adulthood all ectonucleotidases have diverse expression pattern, cell specific localization and function. Formation, maturation, and refinement of synaptic contacts are influenced by neurotransmitters and neuromodulators, and control of extracellular adenine nucleotide levels by ectonucleotidases are important for understanding the role of purinergic signaling in developing tissues and potential targets in developmental disorders such as autism