Exchanging screen for non-screen sitting time or physical activity might attenuate depression and anxiety: A cross-sectional isotemporal analysis during early pandemics in South America

Objectives: To examine the theoretical substitutions of screen exposure, non-screen sitting time, moderate and vigorous physical activity with depressive and anxiety symptoms in South American adults during the COVID-19 pandemic. Design: A cross-sectional study during the first months of the COVID-19 pandemic with data from 1981 adults from Chile, Argentina, and Brazil. Methods: Depressive and anxiety symptoms were assessed using the Beck Depression and Anxiety Inventories. Participants also reported physical activity, sitting time, screen exposure, sociodemographic, and tobacco use data. Isotemporal substitution models were created using multivariable linear regression methods. Results: Vigorous physical activity, moderate physical activity, and screen exposure were independently associated with depression and anxiety symptoms. In adjusted isotemporal substitution models, replacing 10 min/day of either screen exposure or non-screen sitting time with any intensity of physical activity was associated with lower levels of depressive symptoms. Improvements in anxiety symptoms were found when reallocating either screen exposure or non-screen sitting time to moderate physical activity. Furthermore, replacing 10 min/day of screen exposure with non-screen sitting time was beneficially associated with anxiety (B = − 0.033; 95 % CI = − 0.059, − 0.006) and depression (B = − 0.026; 95 % CI = − 0.050, − 0.002). Conclusions: Replacement of screen exposure with any intensity of physical activity or non-screen sitting time could improve mental health symptoms. Strategies aiming to reduce depressive and anxiety symptoms highlight physical activity promotion. However, future interventions should explore specific sedentary behaviors as some will relate positively while others negatively.Fil: Sadarangani, Kabir P.. Universidad Autónoma de Chile; Chile. Universidad Diego Portales; ChileFil: Schuch, Felipe Barreto. Universidade Federal de Santa Maria; Brasil. Universidad Autónoma de Chile; ChileFil: de Roia, Gabriela Fernanda. Universidad de Flores. Laboratorio de Estudios en Actividad Física;Fil: Martínez Gomez, David. Universidad Autónoma de Madrid; España. Consejo Superior de Investigaciones Científicas; España. Consortium for Biomedical Research in Epidemiology and Public Health; EspañaFil: Chávez, Róbinson. Universidad Andrés Bello; ChileFil: Lobo, Pablo Roberto. Universidad de Flores. Laboratorio de Estudios en Actividad Física;Fil: Cristi Montero, Carlos. Pontificia Universidad Católica de Valparaíso; ChileFil: Werneck, André O.. Universidade de Sao Paulo; BrasilFil: Alzahrani, Hosam. Taif University; Arabia SauditaFil: Ferrari, Gerson. Universidad de Santiago de Chile; ChileFil: Ibañez, Agustin Mariano. Universidad de San Andrés; Argentina. University of California; Estados Unidos. Trinity College Dublin; Irlanda. Universidad Adolfo Ibañez; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Silva, Danilo R.. Universidade Federal de Sergipe; Brasil. Universidad Pablo de Olavide; EspañaFil: Von Oetinger, Astrid. Universidad Diego Portales; Chile. Universidad Mayor; ChileFil: Matias, Thiago S.. Universidade Federal de Santa Catarina; BrasilFil: Grabovac, Igor. Universidad de Viena; AustriaFil: Meyer, Jacob. Iowa State University; Estados Unido

Effect of a single nutritional intervention previous to a critical period of fat gain in university students with overweight and obesity: A randomized controlled trial

Indexación: ScopusBackground: the present study aimed to investigate the effects of a single nutritional preventive session previous to a critical period linked to fat gain in university students with overweightness and obesity, emulating a nutritional session of a public health system. Methods: In this single-blind randomized controlled trial, 23 students met all the criteria to be included (20.91 ± 2.52-year-old; 52.2% women) who were divided into two groups: intervention group (IG) and control group (CG). Fat mass (FM) by dual-energy X-ray absorptiometry (DXA), physical activity by accelerometry, feeding evaluation through three questionnaires, and a set of healthy lifestyle recommendations were evaluated before and after the national holidays (NH). Results: Our findings showed that FM increased significantly in the CG, but not in the IG (CG = 428.1g; IG = 321.9g; ∆ = 106.2g; p = 0.654 [95% CI = −379.57, 591.92]). However, no differences were found during the NH between them (Hedges’ g effect size = 0.19; p = 0.654). In addition, no statistical differences were observed between groups in feeding evaluations, the set of recommendations performed, and physical activity. Conclusion: a single preventive session before a critical period, using a similar counselling approach as used in the public health system, might not be enough to promote changes in eating and physical activity patterns and preventing fat gain in overweight/obese university students. Long-term interventions are a must. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.https://www.mdpi.com/1660-4601/17/14/514

Meningococcal disease in North America: Updates from the Global Meningococcal Initiative

This review summarizes the recent Global Meningococcal Initiative (GMI) regional meeting, which explored meningococcal disease in North America. Invasive meningococcal disease (IMD) cases are documented through both passive and active surveillance networks. IMD appears to be decreasing in many areas, such as the Dominican Republic (2016: 18 cases; 2021: 2 cases) and Panama (2008: 1 case/100,000; 2021: <0.1 cases/100,000); however, there is notable regional and temporal variation. Outbreaks persist in at-risk subpopulations, such as people experiencing homelessness in the US and migrants in Mexico. The recent emergence of β-lactamase-positive and ciprofloxacin-resistant meningococci in the US is a major concern. While vaccination practices vary across North America, vaccine uptake remains relatively high. Monovalent and multivalent conjugate vaccines (which many countries in North America primarily use) can provide herd protection. However, there is no evidence that group B vaccines reduce meningococcal carriage. The coronavirus pandemic illustrates that following public health crises, enhanced surveillance of disease epidemiology and catch-up vaccine schedules is key. Whole genome sequencing is a key epidemiological tool for identifying IMD strain emergence and the evaluation of vaccine strain coverage. The Global Roadmap on Defeating Meningitis by 2030 remains a focus of the GMI.Medical writing support for the development of this manuscript, under the direction of the authors, was provided Matthew Gunther of Ashfield MedComms, an Inizio company. Medical writing support was funded by Sanofi Pasteur. All authors discussed and agreed to the objectives of this manuscript and con- tributed throughout its production. All authors read and approved the final manuscript.S

The Effect of Human Factor H on Immunogenicity of Meningococcal Native Outer Membrane Vesicle Vaccines with Over-Expressed Factor H Binding Protein

The binding of human complement inhibitors to vaccine antigens in vivo could diminish their immunogenicity. A meningococcal ligand for the complement down-regulator, factor H (fH), is fH-binding protein (fHbp), which is specific for human fH. Vaccines containing recombinant fHbp or native outer membrane vesicles (NOMV) from mutant strains with over-expressed fHbp are in clinical development. In a previous study in transgenic mice, the presence of human fH impaired the immunogenicity of a recombinant fHbp vaccine. In the present study, we prepared two NOMV vaccines from mutant group B strains with over-expressed wild-type fHbp or an R41S mutant fHbp with no detectable fH binding. In wild-type mice in which mouse fH did not bind to fHbp in either vaccine, the NOMV vaccine with wild-type fHbp elicited 2-fold higher serum IgG anti-fHbp titers (P = 0.001) and 4-fold higher complement-mediated bactericidal titers against a PorA-heterologous strain than the NOMV with the mutant fHbp (P = 0.003). By adsorption, the bactericidal antibodies were shown to be directed at fHbp. In transgenic mice in which human fH bound to the wild-type fHbp but not to the R41S fHbp, the NOMV vaccine with the mutant fHbp elicited 5-fold higher serum IgG anti-fHbp titers (P = 0.002), and 19-fold higher bactericidal titers than the NOMV vaccine with wild-type fHbp (P = 0.001). Thus, in mice that differed only by the presence of human fH, the respective results with the two vaccines were opposite. The enhanced bactericidal activity elicited by the mutant fHbp vaccine in the presence of human fH far outweighed the loss of immunogenicity of the mutant protein in wild-type animals. Engineering fHbp not to bind to its cognate complement inhibitor, therefore, may increase vaccine immunogenicity in humans

Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial

Four predictors were independently associated with an increased risk of death: acidosis, cerebral manifestations of malaria, elevated blood urea nitrogen, or signs of chronic illness. The standard base deficit was found to be the single most relevant predictor of death

Knockdown of MTDH Sensitizes Endometrial Cancer Cells to Cell Death Induction by Death Receptor Ligand TRAIL and HDAC Inhibitor LBH589 Co-Treatment

Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH correlates with poor clinical outcome in breast cancer, neuroblastoma, hepatocellular carcinoma and prostate cancer. MTDH is also highly expressed in advanced endometrial cancers, a disease for which new therapies are urgently needed. In this present study, we focused on the therapeutic benefit of MTDH depletion in endometrial cancer cells to restore sensitivity to cell death. Cells were treated with a combination of tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL), which promotes death of malignant cells of the human reproductive tract, and histone deacetylase (HDAC) inhibitors, which have been shown to increase the sensitivity of cancer cells to TRAIL-induced apoptosis. Our data indicate that depletion of MTDH in endometrial cancer cells resulted in sensitization of cells that were previously resistant in response to combinatorial treatment with TRAIL and the HDAC inhibitor LBH589. MTDH knockdown reduced the proportion of cells in S and increased cell arrest in G2/M in cells treated with LBH589 alone or LBH589 in combination with TRAIL, suggesting that MTDH functions at the cell cycle checkpoint to accomplish resistance. Using microarray technology, we identified 57 downstream target genes of MTDH, including calbindin 1 and galectin-1, which may contribute to MTDH-mediated therapeutic resistance. On the other hand, in MTDH depleted cells, inhibition of PDK1 and AKT phosphorylation along with increased Bim expression and XIAP degradation correlated with enhanced sensitivity to cell death in response to TRAIL and LBH589. These findings indicate that targeting or depleting MTDH is a potentially novel avenue for reversing therapeutic resistance in patients with endometrial cancer

CEACAM1 Negatively Regulates IL-1β Production in LPS Activated Neutrophils by Recruiting SHP-1 to a SYK-TLR4-CEACAM1 Complex

LPS-activated neutrophils secrete IL-1β by activation of TLR-4. Based on studies in macrophages, it is likely that ROS and lysosomal destabilization regulated by Syk activation may also be involved. Since neutrophils have abundant expression of the ITIM-containing co-receptor CEACAM1 and Gram-negative bacteria such as Neisseria utilize CEACAM1 as a receptor that inhibits inflammation, we hypothesized that the overall production of IL-1β in LPS treated neutrophils may be negatively regulated by CEACAM1. We found that LPS treated neutrophils induced phosphorylation of Syk resulting in the formation of a complex including TLR4, p-Syk, and p-CEACAM1, which in turn, recruited the inhibitory phosphatase SHP-1. LPS treatment leads to ROS production, lysosomal damage, caspase-1 activation and IL-1β secretion in neutrophils. The absence of this regulation in Ceacam1−/− neutrophils led to hyper production of IL-1β in response to LPS. The hyper production of IL-1β was abrogated by in vivo reconstitution of wild type but not ITIM-mutated CEACAM1 bone marrow stem cells. Blocking Syk activation by kinase inhibitors or RNAi reduced Syk phosphorylation, lysosomal destabilization, ROS production, and caspase-1 activation in Ceacam1−/− neutrophils. We conclude that LPS treatment of neutrophils triggers formation of a complex of TLR4 with pSyk and pCEACAM1, which upon recruitment of SHP-1 to the ITIMs of pCEACAM1, inhibits IL-1β production by the inflammasome. Thus, CEACAM1 fine-tunes IL-1β production in LPS treated neutrophils, explaining why the additional utilization of CEACAM1 as a pathogen receptor would further inhibit inflammation

Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres. Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response. Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets

Vaccine value profile for Klebsiella pneumoniae

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91–1.71) and 4.95 million (95% UI: 3.62–6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K. pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A ‘Vaccine Value Profile’ (VVP) for K. pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public–private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K. pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information