Laustsenward0515

Hydrodynamic tail vein injection (HTV) is the "gold standard" for delivering naked DNA vectors to mouse liver, thereby transfecting predominately perivenous hepatocytes. While HTV corrects metabolic liver defects such as phenylketonuria or cystathionine β-synthase deficiency, correction of spf ash mice with ornithine transcarbamylase (OTC) deficiency was not possible despite overexpression in the liver, as the OTC enzyme is primarily expressed in periportal hepatocytes. To target periportal hepatocytes, we established hydrodynamic retrograde intrabiliary injection (HRII) in mice and optimized minicircle (MC) vector delivery using luciferase as a marker gene. HRII resulted in a transfection efficiency below 1%, 100-fold lower than HTV. While HRII induced minimal liver toxicity compared with HTV, overexpression of luciferase by both methods, but not of a natural liver-specific enzyme, elicited an immune response that led to the elimination of luciferase expression. Further testing of MC vectors delivered via HRII in spf ash mice did not result in sufficient therapeutic efficacy and needs further optimization and/or selection of the corrected cells. This study reveals that luciferase expression is toxic for the liver. Furthermore, physical delivery of MC vectors via the bile duct has the potential to treat defects restricted to periportal hepatocytes, which opens new doors for non-viral liver-directed gene therapy.Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, NAb prevalence in the target population is vital in designing clinical trials with AAV vectors. Alvespimycin ic50 Hence, updating the seroprevalence of anti-AAV NAbs, herein we analyzed sera from 100 healthy individuals and 216 hemophiliacs in Japan. In both groups, the overall seroprevalence against various AAV serotypes was 20%-30%, and the ratio of the NAb-positive population increased with age. The seroprevalence did not differ between healthy participants and hemophiliacs and was not biased by the concomitant blood-borne viral infections. The high neutralizing activity, which strongly inhibits the transduction with all serotypes in vitro, was mostly found in people in their 60s or of older age. The multivariate analysis suggested that "60s or older age" was the only independent factor related to the high titer of NAbs. Conversely, a large proportion of younger hemophiliacs was seronegative, rendering them eligible for AAV-mediated gene therapy in Japan. Compared with our previous study, the peak of seroprevalences has shifted to older populations, indicating that natural AAV exposure in the elderly occurred in their youth but not during the last decade.This within-subjects experimental study investigated the relative effects of word reading and word meaning instruction (WR+WM) compared to word-reading instruction alone (WR) on the accuracy, fluency, and word meaning knowledge of 4th-5th graders with dyslexia. We matched word lists on syllables, phonemes, frequency, number of definitions, and concreteness. We assigned half the words to WR and half to WR+WM. Word reading accuracy, word reading fluency, and word meaning knowledge were measured at pretest, immediately following each intervention session, and at posttest, administered immediately following the 12, 45-minute, daily instructional sessions. Compared to WR instruction alone, WR+WM significantly improved accuracy (d = 0.65), fluency (d = 0.43), and word meaning knowledge (d = 1.92) immediately following intervention, and significantly improved accuracy (d = 0.74), fluency (d = 0.84), and word meaning knowledge (d = 1.03) at posttest. Findings support the premise that word meaning knowledge facilitates accurate and fluent word reading, and that instruction explicitly integrating word reading and word meaning may be an effective support for upper elementary students with dyslexia.Despite rapid diffusion of Tobacco 21 (T21) laws in the last several years, research examining T21 compliance remains limited. This pilot study examined retailer compliance with carding before and after T21 as well as sales violations after T21 in New Jersey. A 19-year-old buyer made alternating cigar and cigarette purchase attempts in 15 licensed tobacco retailers weekly for five weeks before and 10 weeks following the T21 effective date for a total of 222 visits. We analyzed carding pre and post T21 and sales violations post T21, by store and product type. Failure to card declined post T21 (81.3% to 69.4%), particularly for cigarettes, but not cigars. Overall, 63.3% of retailers sold tobacco to the underage buyer post T21. Following New Jersey's T21 law, compliance with carding improved, but underage sales persisted. Future research examining T21 compliance should consider using a familiarity protocol to mimic real word conditions.

Food allergy (FA) management involves avoiding allergenic foods to prevent an adverse reaction. Affected individuals spend substantial amounts of time thinking about food and the impact it has on their bodies. As such, we posit sustained awareness of food choices may contribute to distorted body image and disordered eating. We performed a narrative review to glean insight into associations between FA, body image and eating disorders.

A literature search of Scopus, PsycINFO, PubMed and Google Scholar was conducted connecting terms for "food allergy" with terms for "body image" and "eating disorders". Title and abstract screening were independently performed by two reviewers, with relevant abstracts carried forward to full text screening.

159 articles were eligible for full text screening and a total of 12 publications were ultimately included in this narrative review, and 1 article from the grey literature. Adolescents and adults both reported feeling as though their bodies were "defective" and were found to have integrated their FA as a stable facet of their identities. In addition, FA was overwhelmingly associated with prevalence of eating disorders and eating disorder-like symptoms. Disturbed body image was found to be a mediating variable for the development of disordered patterns of eating in food allergic individuals.

Few studies appeared to consider comorbidities as confounders. Also, many studies employed convenience sampling, which does limit generalizability of conclusions.

Based on a small body of literature, there appears to be a potential association between FA and distorted body image and disordered eating.

Based on a small body of literature, there appears to be a potential association between FA and distorted body image and disordered eating.How a society relates to nature is shaped by the dominant social paradigm (DSP) a society's collective view on social, economic, political, and environmental issues. The characteristics of the DSP have important consequences for natural systems and their conservation. Based on a synthesis of academic literature, we provide a new gradient of 12 types of human-nature relationships synthesized from scientific literature, and an analysis of where the DSP of industrialized, and more specifically, neoliberal societies fit on that gradient. We aim to answer how the industrialized DSP relates to nature, i.e., what types of human-nature relationships this DSP incorporates, and what the consequences of these relationships are for nature conservation and a sustainable future. The gradient of human-nature relationships is based on three defining characteristics (1) a nature-culture divide, (2) core values, and (3) being anthropocentric or ecocentric. We argue that the industrialized DSP includes elements of the anthropocentric relationships of mastery, utilization, detachment, and stewardship. It therefore regards nature and culture as separate, is mainly driven by instrumental values, and drives detachment from and commodification of nature. Consequently, most green initiatives and policies driven by an industrialized and neoliberal DSP are based on economic incentives and economic growth, without recognition of the needs and limits of natural systems. This leads to environmental degradation and social inequality, obstructing the path to a truly sustainable society. To reach a more ecocentric DSP, systemic changes, in addition to individual changes, in the political and economic structures of the industrialized DSP are needed, along with a change in values and approach toward nature, long-term sustainability, and conservation.Physical activity (PA) has many benefits; however, groups facing barriers to health-promoting behaviors are less likely to be physically active. This may be addressed through workplace interventions. The current study employs objective (accelerometry) and perceived (International Physical Activity Questionnaire [IPAQ]) measures of PA among a subset of participants from the "Working for You" study, which tests a multi-level (work group and individual) workplace intervention targeted at workers with low-incomes. Linear mixed and hierarchical logistic regression models are used to determine the intervention's impact on moderate- to vigorous-PA (MVPA) and achieving the PA Guideline for Americans (≥150 minutes MVPA/week), respectively from baseline to 6- and 24-months, relative to a control group. Correlations (Spearman Rho) between perceived and objective PA are assessed. Of the 140 workers (69 control, 71 intervention) in the sub-study, 131 (94%) have valid data at baseline, 88 (63%) at 6-months, and 77 (55%) at 24-months. Changes in MVPA are not significantly different among intervention relative to control participants assessed by accelerometer or IPAQ at 6- or 24-months follow-up. The percent achieving the PA Guideline for Americans does not vary by treatment group by any measure at any time point (e.g., baseline accelerometry [control n=37 (57%); intervention n=35 (53%)]). This study identifies limited agreement (correlation range 0.04 to 0.42, all p>.05) between perceived and objective measures. Results suggest the intervention did not improve PA among the sub-study participants. Though agreement between objective and perceived MVPA is low, similar conclusions regarding intervention effectiveness are drawn.Patients with pulmonary hypertension (PH) are happy to perform simple exercise capacity tests at home and believe this is feasible. A proportion of patients are able to use an electronic form to complete quality of life questionnaires. These findings are being used to build a telemedicine strategy for PH patients.Upon diagnosis of pulmonary hypertension in pediatrics, standard practice often involves acute vasoreactivity testing (AVT) in the cardiac catheterization laboratory. However, the importance of repeated AVT testing in a given patient thereafter remains unclear. This study sought to describe serial AVT results in pediatric patients and understand the prognostic significance of longitudinal AVT results in pediatric pulmonary hypertension. A retrospective chart review was performed for pediatric pulmonary hypertension patients diagnosed between 2008 and 2021. Patients were included if they had two or more catheterizations with AVT. The study cohorts were patients who were AVT negative upon initial catheterization then AVT positive at any subsequent catheterization (AVT-/+) compared to those were AVT negative upon initial and all subsequent catheterizations (AVT-/-). A positive AVT was defined by Sitbon criteria. The analyzed outcome was event-free survival. The relationship between study cohorts and event-free survival was analyzed by log-rank Kaplan-Meier survival as well as Cox proportional hazard regression to control for confounders.