Community-based Participatory Research: A Practical Guide for Radiologists.

Community-based participatory research (CBPR) is defined by the Kellogg Community Health Scholars Program as a collaborative process that equitably involves all partners in the research process and recognizes the unique strengths that each community member brings. The CBPR process begins with a research topic of importance to the community, with the goal of combining knowledge and action with social change to improve community health and eliminate health disparities. CBPR engages and empowers affected communities to collaborate in defining the research question; sharing the study design process; collecting, analyzing, and disseminating the data; and implementing solutions.

Hepatic expression of GAA results in enhanced enzyme bioavailability in mice and non-human primates.

Pompe disease (PD) is a severe neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). PD is currently treated with enzyme replacement therapy (ERT) with intravenous infusions of recombinant human GAA (rhGAA). Although the introduction of ERT represents a breakthrough in the management of PD, the approach suffers from several shortcomings.

Restoring neuronal chloride homeostasis with anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome.

A common feature of diverse brain disorders is the alteration of GABA-mediated inhibition because of aberrant, intracellular chloride homeostasis induced by changes in the expression and/or function of chloride transporters. Notably, pharmacological inhibition of the chloride importer NKCC1 is able to rescue brain-related core deficits in animal models of these pathologies and in some human clinical studies. Here, we show that reducing NKCC1 expression by RNA interference in the Ts65Dn mouse model of Down syndrome (DS) restores intracellular chloride concentration, efficacy of gamma-aminobutyric acid (GABA)-mediated inhibition, and neuronal network dynamics in vitro and ex vivo.

A Double-Filter Provision for Expanded Red Flag Laws: A Proposal for Balancing Rights and Risks in Preventing Gun Violence.

In response to the continued expansion of "red flag" laws allowing broader classes of people to petition a court for the removal of firearms from individuals who exhibit dangerous conduct, this paper argues that state laws should adopt a double-filter provision that balances individual rights and government public safety interests. The main component of such a provision is a special statutory category - "reporting party" - that enables a broader social network, such as co-workers or school administrators, to request that a law enforcement officer file a petition for an Extreme Risk Protection Order (ERPO). A double-filter provision would not give reporting parties a right to file a court petition directly.

Depletion of LAG-3 T Cells Translated to Pharmacology and Improvement in Psoriasis Disease Activity: A Phase I Randomized Study of mAb GSK2831781.

Activated T cells drive a range of immune-mediated inflammatory diseases. LAG-3 is transiently expressed on recently activated CD4 and CD8 T cells. We describe the engineering and first-in-human clinical study (NCT02195349) of GSK2831781 (an afucosylated humanized IgG1 monoclonal antibody enhanced with high affinity for Fc receptors and LAG-3 and antibody-dependent cellular cytotoxicity capabilities), which depletes LAG-3 expressing cells.

Search for A^{'}→μ^{+}μ^{-} Decays.

Searches are performed for both promptlike and long-lived dark photons, A^{'}, produced in proton-proton collisions at a center-of-mass energy of 13 TeV. These searches look for A^{'}→μ^{+}μ^{-} decays using a data sample corresponding to an integrated luminosity of 5.5  fb^{-1} collected with the LHCb detector.

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with .

Objective: We took advantage of a large multinational recruitment to delineate genotype-phenotype correlations in a large, trans-European multicenter cohort of patients with spastic paraplegia gene 7 ().

Methods: We analyzed clinical and genetic data from 241 patients with , integrating neurologic follow-up data. One case was examined neuropathologically.

Search for Dark Photons Produced in 13 TeV pp Collisions.

Searches are performed for both promptlike and long-lived dark photons, A^{'}, produced in proton-proton collisions at a center-of-mass energy of 13 TeV, using A^{'}→μ^{+}μ^{-} decays and a data sample corresponding to an integrated luminosity of 1.6  fb^{-1} collected with the LHCb detector. The promptlike A^{'} search covers the mass range from near the dimuon threshold up to 70 GeV, while the long-lived A^{'} search is restricted to the low-mass region 214 View Article and Find Full Text PDF

Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase.

Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics analysis and protein engineering, we developed transgenes encoding GAA that could be expressed and secreted by hepatocytes.

Rapid Early Growth May Modulate the Association Between Birth Weight and Blood Pressure at 5 Years in the EDEN Cohort Study.

Physiological evidence suggests that birth weight (BW) and postnatal growth affect blood pressure (BP) level, independently or in interaction. Their respective roles are difficult to disentangle in epidemiological studies, however, especially when adjusting for final weight. We assessed the portion of the effect of BW on BP at 5 years that was not attributable to postnatal growth and investigated potential interactions between BW and postnatal growth velocity at different time points in the EDEN mother-child study.

Accumulation of carbamoylphosphate-synthetase and phosphoenolpyruvate-carboxykinase mRNA in embryonic rat hepatocytes. Evidence for translational control during the initial phases of hepatocyte-specific gene expression in vitro.

The aim of this study was to establish whether the initial accumulation of hepatocyte-specific proteins after hormone induction is regulated at the pretranslational and/or the translational level. To this end, mRNA molar concentrations were determined and compared with rates of protein synthesis from previous studies [van Roon, M.A.