Assessing the association of the newborn metabolic state with severity of subsequent respiratory tract infection may provide important insights on infection pathogenesis. In this multi-site birth ...cohort study, we identified newborn metabolites associated with lower respiratory tract infection (LRTI) in the first year of life in a discovery cohort and assessed for replication in two independent cohorts. Increased citrulline concentration was associated with decreased odds of LRTI (discovery cohort: aOR 0.83 95% CI 0.70-0.99,
= 0.04; replication cohorts: aOR 0.58 95% CI 0.28-1.22,
= 0.15). While our findings require further replication and investigation of mechanisms of action, they identify a novel target for LRTI prevention and treatment.
Methods Dust samples from the living rooms of children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort were collected at 3 months of age, nasal wash samples were collected ...at 12 months, and atopy determined at 3 years of age. Compared with healthy (non-atopic non-recurrent wheeze) infants, atopic subjects possessed nasal microbiota that were less similar to paired house dust microbiota (linear model β=0.057; p=0.039), following adjustment for site.
Adolescent depression is a serious and debilitating disorder associated with lifelong negative outcomes, including heightened risk for recurrence into adulthood, psychiatric comorbidities, and ...suicide. Among evidence-based treatments for adolescents, psychotherapies for depression have the smallest effect sizes of all psychiatric conditions studied. Advancing care for depression in adolescents is complex due to the heterogeneity in etiology and co-occurring difficulties among youth presenting with depression symptoms. This and a companion paper (Lewandowski et al., 2022) draw on a recent multisite collaboration that focused on implementing depression treatment for adolescents within clinical and research contexts. Specifically, this paper will review our work adapting behavioral activation (BA) as a principle-based framework to improve effectiveness and efficiency of depression treatment used within clinical and research settings in academic medical centers. Piloted adaptations include the use of BA principles to address idiographic drivers of depression and in-session BA "exposures" to illustrate BA principles. Case vignettes illustrate these adaptations of BA to address adolescent depression in the context of co-occurring difficulties.
A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 ...(SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial.
In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 μg or 50 μg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181. Enrolment and randomisation occurred sequentially by group; randomisation was done by an interactive web-based randomisation system and only designated unmasked study personnel had access to the randomisation code. Adults were required to be seronegative and unvaccinated for inclusion. Local and systemic reactogenicity, adverse events, binding and neutralising antibodies, and antigen-specific T-cell responses were quantified. For safety analyses, exact 95% Clopper-Pearson CIs for the probability of any incidence of an unsolicited adverse event was computed for each group. For immunogenicity results, CIs for binary variables were computed using the exact Clopper-Pearson methodology, while CIs for geometric mean titres were based on 10 000 empirical bootstrap samples. Post-hoc, paired one-sample t tests were used to assess the increase in mean log-10 neutralising antibody titres between day 29 and day 43 (after the second vaccination) for the primary SARS-CoV-2 targets of interest. This trial is registered at ClinicalTrials.gov, NCT04784767, and is closed to new participants.
Between April 7, and June 29, 2021, 29 participants were enrolled in the study. 20 individuals were assigned to receive 25 μg SpFN/ALFQ, four to 50 μg SpFN/ALFQ, and five to placebo. Neutralising antibody responses peaked at day 43, 2 weeks after the second dose. Neutralisation activity against multiple omicron subvariants decayed more slowly than against the D614G or beta variants until 5 months after second vaccination for both dose groups. CD4+ T-cell responses were elicited 4 weeks after the first dose and were boosted after a second dose of SpFN/ALFQ for both dose groups. Neutralising antibody titres against early omicron subvariants and clade 1 sarbecoviruses were detectable after two immunisations and peaked after the third immunisation for both dose groups. Neutralising antibody titres against XBB.1.5 were detected after three vaccinations. Passive IgG transfer from vaccinated volunteers into Syrian golden hamsters controlled replication of SARS-CoV-1 after challenge.
SpFN/ALFQ was well tolerated and elicited robust and durable binding antibody and neutralising antibody titres against a broad panel of SARS-CoV-2 variants and other sarbecoviruses.
US Department of Defense, Defense Health Agency.
We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 ...and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that
and
are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the
promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced
promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset,
and
expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (
<1×10
). Larger patient numbers will be needed to convincingly identify any true associations at these loci.
Abstract Disasters have far-reaching and potentially long-lasting effects on youth and families. Research has consistently shown a clear increase in the prevalence of several mental health disorders ...after disasters, including depression and posttraumatic stress disorder. Widely accessible evidence-based interventions are needed to address this unmet need for youth and families, who are underrepresented in disaster research. Rapid growth in Internet and Smartphone access, as well as several Web based evaluation studies with various adult populations has shown that Web-based interventions are likely to be feasible in this context and can improve clinical outcomes. Such interventions also are generally cost-effective, can be targeted or personalized, and can easily be integrated in a stepped care approach to screening and intervention delivery. This is a protocol paper that describes an innovative study design in which we evaluate a self-help Web-based resource, Bounce Back Now , with a population-based sample of disaster affected adolescents and families. The paper includes description and justification for sampling selection and procedures, selection of assessment measures and methods, design of the intervention, and statistical evaluation of critical outcomes. Unique features of this study design include the use of address-based sampling to recruit a population-based sample of disaster-affected adolescents and parents, telephone and Web-based assessments, and development and evaluation of a highly individualized Web intervention for adolescents. Challenges related to large-scale evaluation of technology-delivered interventions with high-risk samples in time-sensitive research are discussed, as well as implications for future research and practice.
PDF
