Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania

Journal of NeuroVirology - There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the...     

Identification and characterization of a novel murine allele of Tmprss6

Mutagenesis screens can establish mouse models of utility for the study of critical biological processes such as iron metabolism. Such screens can produce mutations in novel genes or establish novel alleles of known genes, both of which can be useful tools for study. In order to identify genes of relevance to hematologic as well as other phenotypes, we performed N-ethyl-N-nitrosourea mutagenesis in C57BL/6J mice. An anemic mouse was identified and a putative mutation was characterized by mapping, sequencing and in vitro activity analysis. The mouse strain was backcrossed for ten generations then phenotypically characterized with respect to a previously established null mouse strain. Potential modifying loci were identified by quantitative trait locus analysis. Mapping and sequencing in an anemic mouse termed hem8 identified an I286F substitution in Tmprss6, a serine protease essential for iron metabolism; this substitution impaired in vitro protease activity. After backcrossing to C57BL6/J for ten generations, the hem8^−/− strain exhibited a phenotype similar in some but not all aspects to that of Tmprss6^−/− mice. The hem8 and Tmprss6-null mutations were allelic. Both hem8^−/− and Tmprss6^−/− mice responded similarly to pharmacological modulators of bone morphogenetic protein signaling, a key regulator of iron metabolism. Quantitative trait locus analysis in the hem8 strain identified potential modifying loci on chromosomes 2, 4, 7 and 10. In conclusion, the hem8 mouse model carries a novel allele of Tmprss6. Potential uses for this strain in the study of iron metabolism are discussed.     

Unseen Costs: The Direct and Indirect Impact of U.S. Immigration Policies on Child and Adolescent Health and Well-Being

Shifts in migration and border control policies may increase the likelihood of trauma exposure related to child–parent separation and result in costs to the health system and society. In the present study, we estimated direct and indirect costs per child as well as overall cohort costs of border control policies on migrant children and adolescents who were separated from their parents, detained, and placed in the custody of the United States following the implementation of the 2018 Zero Tolerance Policy. Economic modeling techniques, including a Markov process and Monte Carlo simulation, based on data from the National Child Traumatic Stress Network's Core Data Set (N = 458 migrant youth) and published studies were used to estimate economic costs associated with three immigration policies: No Detention, Family Detention, and Zero Tolerance. Clinical evaluation data on mental health symptoms and disorders were used to estimate the initial health state and risks associated with additional trauma exposure for each scenario. The total direct and indirect costs per child were conservatively estimated at $33,008, $33,790, and $34,544 after 5 years for No Detention, Family Detention, and Zero Tolerance, respectively. From a health system perspective, annual estimated spending increases ranged from $1.5 million to $14.9 million for Family Detention and $2.8 million to $29.3 million for Zero Tolerance compared to baseline spending under the No Detention scenario. Border control policies that increase the likelihood of child and adolescent trauma exposure are not only morally troubling but may also create additional economic concerns in the form of direct health care costs and indirect societal costs.