The Influence of Sexual Assault and Fear of Crime on Judgments of Rational Discrimination

Female undergraduates rated the rationality of using gender stereotypes in several potentially dangerous situations. We tested whether sexual assault history and fear of crime moderated perceptions of the use of gender stereotypes in public and private settings. Primary results revealed differences in ratings among victims and nonvictims of sexual assault as a function of type of setting. Additionally, fear of crime increased ratings of rationality in nighttime public situations. The implications of these results are discussed in the context of the “rational discrimination” phenomenon (Khan & Lambert, 2001)

Relative persistence of AAV serotype 1 vector genomes in dystrophic muscle

The purpose of this study was to assess the behavior of pseudotyped recombinant adeno-associated virus type 1 (rAAV2/1) vector genomes in dystrophic skeletal muscle. A comparison was made between a therapeutic vector and a reporter vector by injecting the hindlimb in a mouse model of Limb Girdle Muscular Dystrophy Type 2D (LGMD-2D) prior to disease onset. We hypothesized that the therapeutic vector would establish long-term persistence through prevention of myofiber turnover. In contrast, the reporter vector genome copy number would diminish over time due to disease-associated muscle degradation

Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice

The AAV9 capsid displays a high natural affinity for the heart following a single intravenous (IV) administration in both newborn and adult mice. It also results in substantial albeit relatively lower expression levels in many other tissues. To increase the overall safety of this gene delivery method we sought to identify which one of a group of promoters is able to confer the highest level of cardiac specific expression and concurrently, which is able to provide a broad biodistribution of expression across both cardiac and skeletal muscle. The in vivo behavior of five different promoters was compared: CMV, desmin (Des), alpha-myosin heavy chain (α-MHC), myosin light chain 2 (MLC-2) and cardiac troponin C (cTnC). Following IV administration to newborn mice, LacZ expression was measured by enzyme activity assays. Results showed that rAAV2/9-mediated gene delivery using the α-MHC promoter is effective for focal transgene expression in the heart and the Des promoter is highly suitable for achieving gene expression in cardiac and skeletal muscle following systemic vector administration. Importantly, these promoters provide an added layer of control over transgene activity following systemic gene delivery

The activity of cAMP-Phosphodiesterase 4D7 (PDE4D7) is regulated by protein kinase A-dependent phosphorylation within its unique N-terminus

The cyclic AMP phosphodiesterases type 4 (PDE4s) are expressed in a cell specific manner, with intracellular targeting directed by unique N-terminal anchor domains. All long form PDE4s are phosphorylated and activated by PKA phosphorylation within their upstream conserved region 1 (UCR1). Here, we identify and characterise a novel PKA site (serine 42) within the N-terminal region of PDE4D7, an isoform whose activity is known to be important in prostate cancer progression and ischemic stroke. In contrast to the UCR1 site, PKA phosphorylation of the PDE4D7 N-terminus appears to occur constitutively and inhibits PDE4 activity to allow cAMP signalling under basal conditions

The Etiology of Individual Differences in Second Language Acquisition in Australian School Students: A Behavior‐Genetic Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93553/1/j.1467-9922.2012.00718.x.pd

Elevated liver glycogenolysis mediates higher blood glucose during acute exercise in Barth syndrome

UNLABELLED: Barth syndrome (BTHS) is an X-linked recessive genetic disorder due to mutations in the Tafazzin (TAFAZZIN) gene that lead to cardiac and skeletal muscle mitochondrial dysfunction. Previous studies in humans with BTHS demonstrate that the defects in muscle mitochondrial oxidative metabolism result in an enhanced reliance on anaerobic metabolism during exercise to meet energy demands of muscular work. During exercise, the liver normally increases glucose production via glycogenolysis and gluconeogenesis to match the elevated rate of muscle glucose uptake and meet the ATP requirements of working muscle. However, the impact of Tafazzin deficiency on hepatic glucose production and the pathways contributing to hepatic glucose production during exercise is unknown. Therefore, the purpose of this study was to quantify in vivo liver gluconeogenesis and glycogenolysis in Tafazzin knockdown mice at rest and during acute exercise. METHODS: Male TAFAZZIN shRNA transgenic (TG) and wild-type (WT) mice completed exhaustive treadmill running protocols to test exercise tolerance. Mice underwent 2H- and 13C-stable isotope infusions at rest and during a 30-minute treadmill running bout to quantify hepatic glucose production and associated nutrient fluxes under sedentary conditions and during acute exercise. Circulating and tissue (skeletal muscle and liver) samples were obtained during and following exercise to assess static metabolite levels. RESULTS: TG mice reached exhaustion sooner during exhaustive treadmill running protocols and exhibited higher plasma lactate concentrations after exhaustive exercise compared to WT mice. Arterial glucose levels were comparable between genotypes at rest, but higher in TG mice compared to WT mice during exercise. Consistent with the higher blood glucose, TG mice showed increased endogenous glucose production owing to elevated glycogenolysis compared to WT mice during exercise. Total gluconeogenesis, gluconeogenesis from glycerol, gluconeogenesis from phosphoenolpyruvate, pyruvate cycling, total cataplerosis, and anaplerotic fluxes were similar between TG and WT mice at rest and during exercise. However, lactate dehydrogenase flux and TCA cycle fluxes trended higher in TG mice during exercise. Liver glycogen content in TG was higher in TG vs. controls. CONCLUSION: Our data in the Tafazzin knockdown mouse suggest that elevated anaerobic metabolism during rest and exercise previously reported in humans with BTHS are supported by the finding of higher hepatic glycogenolysis

Etiology and management of hospitalized and outpatient diarrhea among children less than 5 years of age in Lambaréné, Gabon

Objectives: Diarrhea remains a significant cause of global under-5 mortality, particularly in SubSaharan Africa (SSA). To reduce morbidity and mortality, the World Health Organization (WHO) recommends oral rehydration salts (ORS), zinc supplementation, and continued feeding or breastfeeding for all children with diarrhea to prevent dehydration and malnutrition; antibiotics only for bloody diarrhea (i.e. probable shigellosis), suspected cholera, or severe non-intestinal infections (e.g. pneumonia or sepsis); and avoidance of antidiarrheals and antiemetics owing to lack of benefit and potential for harm in young children. Gabon is an upper-middle income country in SSA for which there is a lack of recent, high quality data on the etiology and management of childhood diarrhea. This prospective study aimed to describe the etiology and management of hospitalized and outpatient cases of diarrhea in Gabonese children under five years of age. Methods: Children ≤ 59 months presenting to the Albert Schweitzer or George Rawiri Regional hospitals (February-July 2017) in Lambaréné, Gabon were included if they had ≥ 3 liquid stools per day within the past 3 days. Data was obtained via medical records and standardized questionnaires with caregivers. Diarrheaogenic Escherichia coli, Salmonella enterica, and Shigella spp. were detected using conventional culture techniques. Rotavirus, adenovirus, and Cryptosporidium spp. antigens were detected with commercial rapid immunoassays. Multiplex PCR was used for Cryptosporidium spp., Giardia intestinalis, and Cyclospora cayetanensis detection. Results: Forty-five children were included, 34 of whom were hospitalized. Mean age was 12.2 months; 58% were female. 49% were infected with one or more sought-for pathogens, most commonly with Giardia intestinalis (28.9%) or Cryptosporidium spp. (24.4%). 33% and 36% of hospitalized and outpatient children, respectively, received ORS. Zinc was given to one (3%) hospitalized patient and zero outpatients. Antidiarrheals were frequently given to hospitalized (48%) and outpatient (73%) children. Antibiotics were prescribed in 85% and 36% of hospitalized and outpatient cases, respectively, while only 8 children (18%) presented with bloody stools. 79% of children presented with severe acute malnutrition; 21% had never been breastfed. Conclusions: Ongoing education of healthcare workers and communities regarding WHO-recommended management of childhood diarrhea is needed. The overuse of antibiotics observed in this study is consistent with previous reports and is concerning given high levels of antimicrobial resistance in SSA. Strategies to increase provider awareness of indicated uses of antimicrobials in the setting of childhood diarrhea may help limit the spread of resistance

Qualitative analysis of community pharmacists' opinions on their involvement in reducing potentially inappropriate prescribing

Purpose: Older people are at risk of potentially inappropriate prescribing (PIP) due to polypharmacy arising from multi-morbidity. Despite available explicit criteria to reduce PIP, it is highly prevalent. Whilst community pharmacists have the required knowledge to help reduce PIP, they are not currently engaged with the problem. This study explores the views of community pharmacists on their potential involvement in reducing PIP and determines the challenges to its implementation. Methods: Semi-structured interviews with pharmacists working in community pharmacies in Ireland. The theoretical domains framework (TDF) was used to develop the topic guide and to analyse the transcripts. Domains of highest relevance for PIP reduction were identified based on their frequency or whether the participants emphasised the impact of constructs within a domain. Local ethical approval was obtained. Results: Of 18 participants, 12 were female, median age was 30 years (IQR, 27–35) with a median of 6 years (IQR, 3–8) of experience. Seven TDF domains were identified as relevant to PIP reduction. Pharmacists were uncertain about their role in reducing PIP and reluctant to challenge physicians’ prescribing decisions. Challenges pertained to the environment, knowledge, social influences, professional role and identity. Conclusions: Pharmacists welcomed new responsibilities in reducing PIP as part of their daily practice but expressed a need for removal of social and environmental barriers as well as, provision of relevant guidelines and education about PIP. This study provides useful insights into the target domains for overcoming barriers of pharmacist involvement in reducing PIP