CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro

Body composition in male elite athletes, comparison of bioelectrical impedance spectroscopy with dual energy X-ray absorptiometry

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare body composition results from bioelectrical spectroscopy (BIS) with results from dual energy X-ray absorptiometry (DXA) in a population of male elite athletes. Body composition was assessed using DXA (Lunar Prodigy, GE Lunar Corp., Madison, USA) and BIS (Hydra 4200, Xitron Technologies Inc, San Diego, California, USA) at the same occasion. Agreement between methods was assessed using paired t-tests and agreement-plots.</p> <p>Results</p> <p>Thirty-three male elite athletes (soccer and ice hockey) were included in the study. The results showed that BIS underestimates the proportion of fat mass by 4.6% points in the ice hockey players. In soccer players the BIS resulted in a lower mean fat mass by 1.1% points. Agreement between the methods at the individual level was highly variable.</p> <p>Conclusion</p> <p>Body composition results assessed by BIS in elite athletes should be interpreted with caution, especially in individual subjects. BIS may present values of fat mass that is either higher or lower than fat mass assessed by DXA, independent of true fat content of the individual.</p

Treatment of Periodontitis by Local Administration of Minocycline Microspheres: A Controlled Trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141491/1/jper1535.pd

Vaccination with M2e-Based Multiple Antigenic Peptides: Characterization of the B Cell Response and Protection Efficacy in Inbred and Outbred Mice

The extracellular domain of the influenza A virus protein matrix protein 2 (M2e) is remarkably conserved between various human isolates and thus is a viable target antigen for a universal influenza vaccine. With the goal of inducing protection in multiple mouse haplotypes, M2e-based multiple antigenic peptides (M2e-MAP) were synthesized to contain promiscuous T helper determinants from the Plasmodium falciparum circumsporozoite protein, the hepatitis B virus antigen and the influenza virus hemagglutinin. Here, we investigated the nature of the M2e-MAP-induced B cell response in terms of the distribution of antibody (Ab) secreting cells (ASCs) and Ab isotypes, and tested the protective efficacy in various mouse strains.Immunization of BALB/c mice with M2e-MAPs together with potent adjuvants, CpG 1826 oligonucleotides (ODN) and cholera toxin (CT) elicited high M2e-specific serum Ab titers that protected mice against viral challenge. Subcutaneous (s.c.) and intranasal (i.n.) delivery of M2e-MAPs resulted in the induction of IgG in serum and airway secretions, however only i.n. immunization induced anti-M2e IgA ASCs locally in the lungs, correlating with M2-specific IgA in the bronchio-alveolar lavage (BAL). Interestingly, both routes of vaccination resulted in equal protection against viral challenge. Moreover, M2e-MAPs induced cross-reactive and protective responses to diverse M2e peptides and variant influenza viruses. However, in contrast to BALB/c mice, immunization of other inbred and outbred mouse strains did not induce protective Abs. This correlated with a defect in T cell but not B cell responsiveness to the M2e-MAPs.Anti-M2e Abs induced by M2e-MAPs are highly cross-reactive and can mediate protection to variant viruses. Although synthetic MAPs are promising designs for vaccines, future constructs will need to be optimized for use in the genetically heterogeneous human population

A Longitudinal Analysis of Violence and Housing Insecurity

Violence and housing insecurity are horrible events that may be intertwined, with violence possibly forcing victims to abandon their accommodations and housing insecurity depriving people of the safety of a home or placing them in compromised circumstances. This study uses national, prospective, longitudinal data from the Journeys Home Survey to examine how violence, housing insecurity, and other characteristics in one period affect disadvantaged Australian men's and women's chances of experiencing violence and housing insecurity in subsequent periods. The study is one of the first to investigate these relationships prospectively and unusual in considering how violence among adult men contributes to their housing insecurity. We estimate dynamic multivariate models that control for observed and time-invariant unobserved characteristics and find that men's chances of being housing secure without experiencing violence are 24-45 percent lower and women's chances are 12- 20 percent lower if they experienced housing insecurity, violence or both in the previous period. Heavy drinking, marijuana use, psychological distress, and a history of childhood abuse and neglect also increase the risks of violence and housing insecurity for both genders, while the presence of children reduces these risks. Women who are bisexual or lesbian and women with homeless friends also face elevated risks of housing insecurity, while men's sexual orientation and friend networks seem less relevant

Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study

BACKGROUND: A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. METHODS: Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. RESULTS: About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95–100) to 100% and specificity from 99% (95% CI 97–100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76–87) to 94% (95% CI 89–98) and specificity ranging from 76% (95% CI 70–82) to 92% (95% CI 88–96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. CONCLUSIONS: People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people. Trial Registration NCT04509713 (clinicaltrials.gov)

Megadroughts in the Common Era and the Anthropocene

Exceptional drought events, known as megadroughts, have occurred on every continent outside Antarctica over the past ~2,000 years, causing major ecological and societal disturbances. In this Review, we discuss shared causes and features of Common Era (Year 1–present) and future megadroughts. Decadal variations in sea surface temperatures are the primary driver of megadroughts, with secondary contributions from radiative forcing and land–atmosphere interactions. Anthropogenic climate change has intensified ongoing megadroughts in south-western North America and across Chile and Argentina. Future megadroughts will be substantially warmer than past events, with this warming driving projected increases in megadrought risk and severity across many regions, including western North America, Central America, Europe and the Mediterranean, extratropical South America, and Australia. However, several knowledge gaps currently undermine confidence in understanding past and future megadroughts. These gaps include a paucity of high-resolution palaeoclimate information over Africa, tropical South America and other regions; incomplete representations of internal variability and land surface processes in climate models; and the undetermined capacity of water-resource management systems to mitigate megadrought impacts. Addressing these deficiencies will be crucial for increasing confidence in projections of future megadrought risk and for resiliency planning

Developing healthy food preferences in preschool children through taste exposure, sensory learning and nutrition education

Purpose of Review: The present review was undertaken in order to summarize and evaluate recent research investigating taste exposure, sensory learning, and nutrition education interventions for promoting vegetable intake in preschool children. Recent Findings: Overall, taste exposure interventions yielded the best outcomes for increasing vegetable intake in early childhood. Evidence from sensory learning strategies such as visual exposure and experiential learning also show some success. While nutrition education remains the most common approach used in preschool settings, additional elements are needed to strengthen the educational program for increasing vegetable intake. There is a substantial gap in the evidence base to promote vegetable intake in food fussy children. Summary: The present review reveals the relative importance of different intervention strategies for promoting vegetable intake. To strengthen intervention effects for improving vegetable intake in preschool children, future research could consider integrating taste exposure and sensory learning strategies with nutrition education within the preschool curriculum