Transport poverty meets the digital divide : accessibility and connectivity in rural communities

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Systemic Racism and Health Disparities: A Statement from Editors of Family Medicine Journals

The year 2020 has been marked by historic protests across the United States and the globe sparked by the deaths of George Floyd, Ahmaud Arbery, Breonna Taylor, and so many other Black people. The protests heightened awareness of racism as a public health crisis and triggered an antiracism movement. The editors of several North American family medicine publications have come together to address this call to action and share resources on racism across our readerships.http://deepblue.lib.umich.edu/bitstream/2027.42/163331/1/Final Statement on Systemic Racism- with acknowledgements.pdf-1Description of Final Statement on Systemic Racism- with acknowledgements.pdf : Main ArticleSEL

Using Biologic Markers in Blood to Assess Exposure to Multiple Environmental Chemicals for Inner-City Children 3–6 Years of Age

We assessed concurrent exposure to a mixture of > 50 environmental chemicals by measuring the chemicals or their metabolites in the blood of 43 ethnically diverse children (3–6 years of age) from a socioeconomically disadvantaged neighborhood in Minneapolis. Over a 2-year period, additional samples were collected every 6–12 months from as many children as possible. We analyzed blood samples for 11 volatile organic compounds (VOCs), 2 heavy metals (lead and mercury, 11 organochlorine (OC) pesticides or related compounds, and 30 polychlorinated biphenyl (PCB) congeners. The evidence suggests that numerous VOCs originated from common sources, as did many PCBs. Longitudinal measurements indicate that between-child variance was greater than within-child variance for two VOCs (benzene, toluene), for both heavy metals (Pb, Hg), for all detectable OC pesticides, and for 15 of the measured PCB congeners (74, 99, 101, 118, 138–158, 146, 153, 156, 170, 178, 180, 187, 189, 194, 195). Despite the relatively small sample size, highest measured blood levels of 1,4-dichlorobenzene, styrene, m-/p-xylene, Pb, Hg, heptachlor epoxide, oxychlordane, dichlorodiphenyldichloroethene (p,p′-DDE), trans-nonachlor, and PCB congeners 74, 99, 105, 118, 138, 146, 153, 156, 170, and 180 were comparable with or higher than 95th percentile measurements of older children and adults from national surveys. Results demonstrate that cumulative exposures to multiple environmental carcinogens and neurotoxins can be comparatively high for children from a poor inner-city neighborhood

Outdoor, Indoor, and Personal Exposure to VOCs in Children

We measured volatile organic compound (VOC) exposures in multiple locations for a diverse population of children who attended two inner-city schools in Minneapolis, Minnesota. Fifteen common VOCs were measured at four locations: outdoors (O), indoors at school (S), indoors at home (H), and in personal samples (P). Concentrations of most VOCs followed the general pattern O ≈ S < P ≤ H across the measured microenvironments. The S and O environments had the smallest and H the largest influence on personal exposure to most compounds. A time-weighted model of P exposure using all measured microenvironments and time–activity data provided little additional explanatory power beyond that provided by using the H measurement alone. Although H and P concentrations of most VOCs measured in this study were similar to or lower than levels measured in recent personal monitoring studies of adults and children in the United States, p-dichlorobenzene was the notable exception to this pattern, with upper-bound exposures more than 100 times greater than those found in other studies of children. Median and upper-bound H and P exposures were well above health benchmarks for several compounds, so outdoor measurements likely underestimate long-term health risks from children’s exposure to these compounds

Common DNA Variants Accurately Rank an Individual of Extreme Height

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals

An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men

We examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10–7 for rs4675569, 1.7 × 10–6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P \u3c.05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P \u3c.05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P \u3c.05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection