Perceived social support: Its impact on length of sobriety

This study examined the relationship between perceived social support and length of sobriety. In particular this study investigated whether higher reports of perceived social support had an effect on an individual\u27s length of sobriety. Sixty-seven male and female residents of an inpatient alcohol and drug treatment center participated in this study

A simple microbiological tool to evaluate the effect of environmental health interventions on hand contamination.

The effects of interventions such as sanitation or hand hygiene on hand contamination are difficult to evaluate. We explored the ability of a simple microbiological test to: (1) detect recontamination after handwashing; (2) reflect risk factors for microbial contamination and (3) be applicable to large populations. The study was done in rural Andhra Pradesh, India, and Maputo, Mozambique. Participants placed all 10 fingertips on a chromogenic agar that stains Enterococcus spp. and E. coli spp. Outcomes were the number of colonies and the number of fingertips with colonies. In the recontamination study, participants were randomised to handwashing with soap and no handwashing, and tested at 30 min intervals afterwards. In two cross sectional studies, risk factors for hand contamination were explored. Recontamination of hands after washing with soap was fast, with baseline levels reached after 1 h. Child care was associated with higher Enterococcus spp. counts, whereas agricultural activities increased E. coli spp. counts. Food preparation was associated with higher counts for both organisms. In Maputo, counts were not strongly associated with water access, latrine type, education or diarrhoea. The method seems unsuitable for the evaluation of handwashing promotion. It may reflect immediately preceding risk practices but not household-level risk factors

Epilepsy, identity, and the experience of the body

© 2018 Elsevier Inc. Living with a chronic condition can challenge a person\u27s identity, yet there is a paucity of research exploring this experience for people with epilepsy and particularly for those diagnosed in adulthood. Consequently, through an interpretative phenomenological approach, the current study aimed to explore what the experience of adult-onset epilepsy meant for a person\u27s identity. Thirty-nine people with adult-onset epilepsy from across the UK took part in up to two semi-structured interviews. A modified form of interpretative phenomenological analysis was conducted and identified three themes: 1) disarming the impact of seizures considered strategies used to control seizure occurrence and regain a sense of control over the body; 2) distinguishing the self from the body highlighted participants’ attempts to separate their sense of self from the unpredictability of their bodies; 3) separating epilepsy from themselves demonstrated how participants externalized epilepsy from themselves in order to reject it as part of their identity. The findings highlighted that living with adult-onset epilepsy can challenge a person\u27s sense of self and trust in their body, resulting in the adoption of various strategies to manage the threat to their identity. As such, practitioners must pay attention to the impact that adult-onset epilepsy can have on a person\u27s identity and faith in their body

The experience of living with adult-onset epilepsy.

© 2017 Elsevier Inc. The incidence and prevalence of adults diagnosed with epilepsy is higher compared to those diagnosed in childhood, yet the experience of living with adult-onset epilepsy has rarely been examined. Hence, the current study took a phenomenological approach to examining the experience of living with epilepsy following diagnosis in adulthood. Semi-structured interviews were conducted with 39 people from across the UK, diagnosed with epilepsy between the ages of eighteen and sixty, at two points in time, six months apart. Phenomenological analysis identified three central themes: the unpredictability of seizure occurrence; the ripple effect; and re-evaluating the future. Despite the accepted consensus in the epilepsy literature that living and coping with epilepsy becomes more difficult the older a person is diagnosed, the current findings indicated that this is inadequate. Rather, it is more suitable to consider that those living with adult-onset epilepsy have a specific experience of the condition and particular support needs, given that they once lived their lives as people without epilepsy

Learning about Street Harassment on Transit: A Survey Instrument for Transit Agencies

This study was conducted in accordance with California Senate Bill 1161 (2022), legislation that directed the Mineta Transportation Institute to develop a reliable, easy-to-use survey instrument for collecting information from public transit passengers about the extent, location, and characteristics of any street harassment they experience. Although the legislation is focused on large California transit agencies, the study findings are equally relevant to smaller agencies and agencies outside the state. To develop the recommended questionnaire, we reviewed literature about street harassment, analyzed transit passenger surveys to explore the questions asked about safety and harassment, received feedback on iterative drafts of the questionnaire from numerous transit riders and experts, and pilot-tested the survey with 329 bus and train riders. The recommended questionnaire is available on the MTI website in fourteen languages, including English, Spanish, and Chinese

An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis

Adsorbents designed with porosity which allows the removal of protein bound and high molecular weight uraemic toxins may improve the effectiveness of haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated carbon monolith prototype designed for direct blood contact was first assessed for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p-cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked healthy donor studies. Haemodialysis patient blood samples were then used to measure the presence of these markers in pre- and post-dialysis blood and their removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20–100 nm) were necessary for marker uraemic toxin removal during in vitro studies. Limited removal of IS and p-CS occurred during haemodialysis, whereas almost complete removal occurred following perfusion through the carbon monoliths suggesting a key role for such adsorbent therapies in CKD patient care

Caspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in a mouse model of retinal vein occlusion

PurposeRetinal vein occlusion (RVO) is a sight-threatening condition typically treated with intravitreal injection of vascular endothelial growth factor (VEGF) antagonists. Treatment response to anti-VEGF therapies is highly variable, with poor visual outcomes and treatment response in patients with significant retinal nonperfusion following RVO. Recently, caspase-9 has been identified as a potent regulator of edema, gliosis, and neuronal dysfunction during acute retinal hypoxia. The purpose of this study was to compare the therapeutic effect of caspase-9 inhibition against VEGF-neutralization in an established mouse model of RVO.MethodsAdult male C57Bl/6 J mice were randomized to induction of RVO and treatment with either vehicle, intravitreal injection of anti-VEGF antibody, topical administration of a selective caspase-9 inhibitor (Pen1-XBir3), or a combination therapy. Animals were followed on days 1, 2, and 8 after RVO with fundus retinal imaging, and with optical coherence tomography (OCT) to capture retinal swelling, capillary nonperfusion (measured by disorganization of retinal inner layers, DRIL), hyperreflective foci (HRF), and retinal atrophy. Focal electroretinography (ERG) measurements were performed on day 7. Histology was performed on retinal sections from day 8.ResultsBoth VEGF neutralization and caspase-9 inhibition showed significant retinal protection from RVO compared to vehicle treatment arm. Retinal reperfusion of occluded veins was accelerated in eyes receiving caspase-9 inhibitor, but not significantly different from vehicle in the anti-VEGF group. Retinal edema was suppressed in all treatment groups, with approximately 2-fold greater edema reduction with caspase-9 inhibition compared to VEGF neutralization. HRF were reduced similarly across all treatment groups compared to vehicle. Retinal detachment was reduced only in eyes treated with caspase-9 inhibitor monotherapy. Caspase-9 inhibition reduced retinal atrophy and preserved ERG response; VEGF neutralization did not prevent neurodegeneration following RVO.ConclusionCaspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in the mouse laser-induced model of RVO

Hypothalamic AMP-Activated Protein Kinase Regulates Glucose Production

OBJECTIVE—The fuel sensor AMP-activated protein kinase (AMPK) in the hypothalamus regulates energy homeostasis by sensing nutritional and hormonal signals. However, the role of hypothalamic AMPK in glucose production regulation remains to be elucidated. We hypothesize that bidirectional changes in hypothalamic AMPK activity alter glucose production. RESEARCH DESIGN AND METHODS—To introduce bidirec-tional changes in hypothalamic AMPK activity in vivo, we first knocked down hypothalamic AMPK activity in male Sprague-Dawley rats by either injecting an adenovirus expressing the dominant-negative form of AMPK (Ad-DN AMPK2 [D157A]) or infusing AMPK inhibitor compound C directly into the medio-basal hypothalamus. Next, we independently activated hypotha-lamic AMPK by delivering either an adenovirus expressing the constitutive active form of AMPK (Ad-CA AMPK1312 [T172D]

Intrinsic Disorder in PRAME and Its Role in Uveal Melanoma

Introduction The PReferentially expressed Antigen in MElanoma (PRAME) protein has been shown to be an independent biomarker for increased risk of metastasis in Class 1 uveal melanomas (UM). Intrinsically disordered proteins and regions of proteins (IDPs/IDPRs) are proteins that do not have a well-defined three-dimensional structure and have been linked to neoplastic development. Our study aimed to evaluate the presence of intrinsic disorder in PRAME and the role these structureless regions have in PRAME( +) Class 1 UM. Methods A bioinformatics study to characterize PRAME’s propensity for the intrinsic disorder. We first used the AlphaFold tool to qualitatively assess the protein structure of PRAME. Then we used the Compositional Profiler and a set of per-residue intrinsic disorder predictors to quantify the intrinsic disorder. The Database of Disordered Protein Prediction (D2P2) platform, IUPred, FuzDrop, fIDPnn, AUCpred, SPOT-Disorder2, and metapredict V2 allowed us to evaluate the potential functional disorder of PRAME. Additionally, we used the Search Tool for the Retrieval of Interacting Genes (STRING) to analyze PRAME\u27s potential interactions with other proteins. Results Our structural analysis showed that PRAME contains intrinsically disordered protein regions (IDPRs), which are structureless and flexible. We found that PRAME is significantly enriched with serine (p-value \u3c 0.05), a disorder-promoting amino acid. PRAME was found to have an average disorder score of 16.49% (i.e., moderately disordered) across six per-residue intrinsic disorder predictors. Our IUPred analysis revealed the presence of disorder-to-order transition (DOT) regions in PRAME near the C-terminus of the protein (residues 475–509). The D2P2 platform predicted a region from approximately 140 and 175 to be highly concentrated with post-translational modifications (PTMs). FuzDrop predicted the PTM hot spot of PRAME to be a droplet-promoting region and an aggregation hotspot. Finally, our analysis using the STRING tool revealed that PRAME has significantly more interactions with other proteins than expected for randomly selected proteins of the same size, with the ability to interact with 84 different partners (STRING analysis result: p-value \u3c 1.0 × 10–16; model confidence: 0.400). Conclusion Our study revealed that PRAME has IDPRs that are possibly linked to its functionality in the context of Class 1 UM. The regions of functionality (i.e., DOT regions, PTM sites, droplet-promoting regions, and aggregation hotspots) are localized to regions of high levels of disorder. PRAME has a complex protein–protein interaction (PPI) network that may be secondary to the structureless features of the polypeptide. Our findings contribute to our understanding of UM and suggest that IDPRs and DOT regions in PRAME may be targeted in developing new therapies for this aggressive cancer