Miracle-dz/UniFAR-FTUs huggingface dataset:
Alcohol-Serving Venues in South Africa as Sites of Risk and Potential Protection for Violence Against Women

This qualitative study explores alcohol-serving venues as sites of risk or protection from violence against women (VAW) in one South African community. In 2010, we conducted in-depth interviews with 31 female patrons, 13 male patrons and 11 venue staff, and conducted structured observations in six alcohol venues. VAW was a common experience and venues contributed to risk through aggression, negative attitudes toward women, risks leaving the venues, and owners tolerating VAW. Concurrently, venues offered potential to avoid VAW through perceived safety and owner protection. Results highlight the influence of the venue environment and importance of addressing the setting of alcohol consumption.
Is Addiction a Failure of Rationality?

This note argues that addiction itself can be seen as a form of double failure, specifically the failure to stick to a predetermined optimal lifetime consumption path for an addictive commodity, which failure might be the result of bad luck, and the failure to adjust the level of consumption of the addictive commodity once the consumer is off their optimal path, which might be seen as a failure of judgment.
Depletion of hnRNP A2/B1 overrides the nuclear retention of the HIV-1 genomic RNA

hnRNP A2 is a cellular protein that is important for nucleocytoplasmic and cytosolic trafficking of the HIV-1 genomic RNA. Both hnRNP A2’s interaction with HIV-1 RNA and its expression levels influence the activities of Rev in mediating nucleocytoplasmic export of the HIV-1 genomic RNA. While the lack of Rev expression during HIV-1 gene expression results in nuclear retention of HIV-1 genomic RNA, we show here by fluorescence in situ hybridization and fractionation studies that the genomic RNA translocates to the cytoplasm when hnRNP A2/B1 are depleted from cells. Polyribosome analyses revealed that the genomic RNA was shunted into a cytoplasmic, dense polyribosomal fraction. This fraction contained several RNA-binding proteins involved in viral gene expression and RNA trafficking but did not contain the translation initiation factor, eIF4G1. Amino acid incorporation into nascent polypeptides in this fraction was also greatly reduced, demonstrating that this fraction contains mRNAs that are poorly translated. These results demonstrate that hnRNP A2/B1 expression plays roles in the nuclear retention of the HIV-1 genomic RNA in the absence of Rev and in the release of the genomic RNA from translationally inactive, cytoplasmic RNP complexes.
Ten lessons with Carl Woese about RNA and comparative analysis

A few years before I started my graduate studies, Carl Woese was establishing a collaboration with his friend, colleague, and my PhD advisor, Harry Noller. Carl was introducing comparative methods to Harry’s lab to determine the secondary structure for the 16S and 23S rRNAs. In addition to an experimental project that had minimal to no success, I was attempting to predict an RNA secondary structure from a single sequence. I determined after a few months that the complexity of RNA folding was much greater than ever anticipated. Ten lessons were learned about the dynamics of RNA folding, the comparative methods used to accurately predict the RNAs secondary structure and the beginnings of its tertiary structure, the use of comparative methods to reveal much more than ever anticipated about RNA structure, other applications beyond RNA structure, and the lessons about the process of scientific discovery.
Drosophila glutamate receptor mRNA expression and mRNP particles

The processes controlling glutamate receptor expression early in synaptogenesis are poorly understood. Here, we examine glutamate receptor (GluR) subunit mRNA expression and localization in Drosophila embryonic/larval neuromuscular junctions (NMJs). We show that postsynaptic GluR subunit gene expression is triggered by contact from the presynaptic nerve, approximately halfway through embryogenesis. After contact, GluRIIA and GluRIIB mRNA abundance rises quickly approximately 20-fold, then falls within a few hours back to very low levels. Protein abundance, however, gradually increases throughout development. At the same time that mRNA levels decrease following their initial spike, GluRIIA, GluRIIB, and GluRIIC subunit mRNA aggregates become visible in the cytoplasm of postsynaptic muscle cells. These mRNA aggregates do not colocalize with eIF4E, but nevertheless presumably represent mRNP particles of unknown function. Multiplex FISH shows that different GluR subunit mRNAs are found in different mRNPs. GluRIIC mRNPs are most common, followed by GluRIIA and then GluRIIB mRNPs. GluR mRNP density is not increased near NMJs, for any subunit; if anything, GluR mRNP density is highest away from NMJs and near nuclei. These results reveal some of the earliest events in postsynaptic development and provide a foundation for future studies of GluR mRNA biology.
Understanding epithelial homeostasis in the intestine

The intestinal epithelium constitutes the barrier between the gut lumen and the rest of the body and a very actively renewing cell population. The crypt/villus and crypt/cuff units of the mouse small intestine and colon are its basic functional units. The field is confronted with competing concepts with regard to the nature of the cells that are responsible for all the day-to day cell replacement and those that act to regenerate the tissue upon injury and with two diametrically opposed models for lineage specification. The review revisits groundbreaking pioneering studies to provide non expert readers and crypt watchers with a factual analysis of the origins of the current models deduced from the latest spectacular advances. It also discusses recent progress made by addressing these issues in the crypts of the colon, which need to be better understood, since they are the preferred sites of major pathologies.
Alcohol Use Severity Among Hispanic Emerging Adults in Higher Education: Understanding the Effect of Cultural Congruity

Background: Identifying and understanding determinants of alcohol use behavior among Hispanic college students is an increasingly important public health issue, particularly during emerging adulthood. Studies examining ethnocultural determinants of alcohol use behavior among Hispanic college students have focused on direct associations with cultural orientation (e.g., acculturation and enculturation); yet there is a need for research that accounts for the complex interplay of other culturally relevant sociocultural factors. Objectives: This study examined associations of behavioral acculturation, behavioral enculturation, and cultural congruity (perception of cultural fit between the values of the academic environment and the student's personal values) with alcohol use severity (AUS); and tested if gender moderated those associations. Methods: A hierarchical linear regression and moderation analysis were conducted on a sample of 167 Hispanic emerging adults (ages 18–25) enrolled in college. Results: All predictor variables entered in the regression model accounted for 20.9% of the variance in AUS. After controlling for demographic variables and depressive symptoms, behavioral acculturation and enculturation did not have a statistically significant association with AUS. Further, gender did not moderate either of these associations. Conversely, greater cultural congruity was associated with lower reports of AUS. A moderation analysis suggested that cultural congruity predicted lower reports of AUS among men, but not among women. Conclusions: This was the first known study to examine the association of cultural congruity with alcohol use. Findings highlight the value of examining contextual factors of culture and moving beyond reductive measures of cultural orientation.
No More Waiting Lists

It all began with an unexpected finding in Oregon. We had randomly assigned people with alcohol use disorders to either 10 weeks of immediate outpatient behavioral counseling or what we regarded to be a minimal treatment control condition–-a single session and instructions to keep a diary of alcohol use (Miller, Gribskov, & Mortell, 1981). Both groups also received a self-help book with suggestions based on the same behavioral approach (Miller & Muñoz, 1976). To our surprise, both groups showed marked and equal reduction in drinking at 3-month follow-up. We replicated the study twice in New Mexico with the same finding: no difference between a single session of counseling plus self-help materials and 10 (Miller & Taylor, 1980) or 12 weeks (Miller, Taylor, & West, 1980) of individual or group counseling. The large reductions in alcohol use were maintained in both groups across two years of follow-up (Miller & Baca, 1983). It turned out that we were not alone in this finding. In England, Edwards and colleagues (1977) found no difference in outcomes between clients randomly assigned to state-of-the-art alcoholism treatment or a single session of “brief advice. ” It is now well documented in dozens of trials that brief counseling yields significantly more change in substance use than no treatment at all (e.g., Bernstein et al., 2009; Bernstein et al., 2005; Bien, Miller, & Tonigan, 1993; Miller & Wilbourne, 2002), often equivalent to the impact of more extensive treatment (Project MATCH Research Group, 1998; UKATT Research Team, 2005). Similarly “bibliotherapy” (providing behavioral self-help materials) rather consistently is more beneficial than no treatment, at least in addressing alcohol problems (Apodaca & Miller, 2003). I had not fully considered the implications of these findings until we conducted studies in which clients randomly assigned to a “waiting list” showed no change at all over the same period of time. For example, in Figure 1 both the therapist-directed (dashed line, outpatient counseling) and the self-directed group (dotted line, single session, and self-help material) showed reductions following intake whereas two waiting list groups (solid line) showed no change at all over the same 10 week-period (Harris & Miller, 1990).
Effect of intravenous immunoglobulin on inhibiting peripheral blood lymphocyte apoptosis in acute Kawasaki disease

This study aimed to explore the therapeutic mechanism of intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) Peripheral blood lymphocytes (PBLs) obtained from 26 children with KD and 20 age‐matched healthy children were stimulated with anti‐CD3 monoclonal antibody (mAb), and the percentage of apoptotic cells and DNA fragmentation were assayed at 0, 12, 24, 48 and 72 h in vitro. The patients were divided into two groups: one treated with aspirin combined with IVIG (n= 16) and one treated with aspirin alone (n= 10). PBLs were stimulated by phytohaemag‐glutinin to evaluate the lymphocyte proliferative response. Compared with normal controls, the apoptotic cell percentage and the DNA fragmentation were markedly decreased (p < 0.001) and delayed in PBLs from KD patients. After IVIG treatment, the decreased percentage of apoptotic cell and delayed DNA fragmentation were restored to the state of the normal controls, accompanied by a fast clinical remission compared with the aspirin‐alone group. The lymphocyte proliferative response was also decreased 3–5 d after IVIG therapy (p < 0.001).
Bullying Perpetration and Victimization as Externalizing and Internalizing Pathways: A Retrospective Study Linking Parenting Styles and Self-Esteem to Depression, Alcohol Use, and Alcohol-Related Problems

ABSTRACT Background: Emerging research suggests significant positive associations between bullying and substance use behaviors. However, these studies typically focused either on the link between substance use and bullying perpetration or victimization, and few have conceptualized bullying perpetration and/or victimization as mediators. Objective: In this study, we simultaneously tested past bullying perpetration and victimization as mediational pathways from retrospective report of parenting styles and global self-esteem to current depressive symptoms, alcohol use, and alcohol-related problems. Methods: Data were collected from a college sample of 419 drinkers. Mediation effects were conducted using a bias-corrected bootstrap technique within a structural equation modeling framework. Results: Two-path mediation analyses indicated that mother and father authoritativeness were protective against bully victimization and depression through higher self-esteem. Conversely, having a permissive or authoritarian mother was positively linked to bullying perpetration, which in turn, was associated with increased alcohol use, and to a lesser degree, more alcohol-related problems. Mother authoritarianism was associated with alcohol-related problems through depressive symptoms. Three-path mediation analyses suggested a trend in which individuals with higher self-esteem were less likely to report alcohol-related problems through lower levels of bullying victimization and depression. Conclusions/Importance: Results suggested that bullying perpetration and victimization may, respectively, serve as externalizing and internalizing pathways through which parenting styles and self-esteem are linked to depression and alcohol-related outcomes. The present study identified multiple modifiable precursors of, and mediational pathways to, alcohol-related problems which could guide the development and implementation of prevention programs targeting problematic alcohol use.
The maternal transfer of bacteria can mediate trans-generational immune priming in insects

Parents invest in their offspring by preparing them for defense against pathogens and parasites that only the parents have encountered, a phenomenon known as trans-generational immune priming. We investigated the underlying mechanism using the established lepidopteran model host Galleria mellonella. When larvae were fed with non-pathogenic bacteria, or the entomopathogenic species Pseudomonas entomophila and Serratia entomophila, the activity of lysozyme and phenoloxidase increased in the hemolymph, and immunity-related genes encoding antibacterial proteins such as gloverin were induced. Remarkably, the ingestion of bacteria by female larvae resulted in the differential expression of immunity-related genes in the eggs subsequently laid by the same females, providing evidence for trans-generational immune priming in G. mellonella. To determine the fate of these ingested microbes, the larval diet was supplemented with bacteria carrying a fluorescent label. We observed these bacteria crossing the midgut epithelium, their entrapment within nodules in the hemocoel, their accumulation within the ovary, and ultimately their deposition in the eggs. Therefore, we propose that trans-generational immune priming in Lepidoptera can be mediated by the maternal transfer of bacteria or bacterial fragments to the developing eggs.
P147 Outcomes of pulmonary rehabilitation in severe asthma

Objectives Structured physical training programmes are a key component of pulmonary rehabilitation (PR) and have consistently been shown to be of significant benefit to patients with COPD. It is unclear whether the application of similar principles provides similar health improvements in patients with severe asthma. We aimed to assess this by studying the effects of pulmonary rehabilitation in a group of patients with severe asthma and significant disability who have completed our standard 7 week PR programme. Methods 111 patients with a physician diagnosis of severe asthma who have completed our standard PR programme were studied. Assessments including spirometry, chronic respiratory questionnaire (CRQ), hospital anxiety and depression scores (HAD) and incremental and endurance shuttle walk testing (ISWT, ESWT) were performed at baseline and completion to determine the effect of PR. Baseline demographic and spirometric data were compared with a larger population of patients with severe asthma attending our difficult asthma clinic (DAC). Results Following rehabilitation, statistically significant improvements were seen in MRC dyspnoea score (mean (95% CI) improvement −0.35 (−0.13 to −0.57), p=0.003); HADS anxiety (−1.4 (−0.4 to −2.3), p=0.007); HADS depression (−1.2 (−0.2 to −2.2), p=0.026); CRQ dyspnoea (+0.72 (+0.33 to +1.1), p=0.001); CRQ fatigue (+0.92 (+0.65 to +1.2), p<0.001); CRQ Emotion (+0.64 (+0.36 to +0.92), p<0.001); CRQ mastery (+0.47 (+0.13 to +0.81), p=0.007); Incremental shuttle walk test (ISWT) (+63 m (49.5 to 76.5), p<0.001); and Endurance shuttle walk test (ESWT) (+339.7 m, (249.7 to 429.7), p<0.001). Interestingly however, patients with severe asthma who completed pulmonary rehabilitation were older (66 vs 48 yrs p<0.01), more likely to have smoked (69.5% vs 43.5%, p<0.01), and tended to have more severe fixed airflow obstruction (FEV1% predicted 55.9 vs 71.9, p=0.28) than our DAC population. This may be because clinicians were more likely to refer patients with asthma who had a COPD-like phenotype or because patients with severe asthma were more likely to drop-out of the programme. Conclusion Pulmonary rehabilitation may offer significant benefit to patients with severe asthma though further work is needed to identify the patients mostly likely to benefit and the optimum training required.
An active film-coating approach to enhance chemical stability of a potent drug molecule

Peliglitazar, a PPAR α/γ agonist, was found to undergo acid as well as base catalyzed degradation. The acid catalyzed degradation led to the formation of benzylic alcohol and glycine carbamate and the base catalyzed degradation led to formation of p-hydroxyanisole and an amine degradant. In capsule formulations, the capsules with the lowest drug-loading exhibited maximum instability even at 25°C/60% RH storage condition. Incorporation of pH-modifiers to maintain ‘micro-environmental pH’ acidic did not prevent the formation of the base-catalyzed degradants. Traditional dry granulated tablet formulation which is qualitatively similar to the capsule formulations showed the presence of acid-catalyzed degradants even without the presence of an acidifying agent. On the other hand, traditional wet granulated tablet formulation showed mainly base-catalyzed degradants. Stability problems of the tablet formulation were aggravated because the potent molecule required low tablet strengths which resulted in low drug to excipient ratio. To stabilize the molecule, an active film-coating approach was explored. In this approach, the drug was sprayed with the coating material onto non-active containing tablet cores. This approach of trapping the drug particles into the coating material provided tablets with satisfactory chemical stability. The stability enhancement observed in the active coating approach is attributed to the higher drug to excipient ratio in the film coat of non-reactive coating material compared to that in the traditional dry or wet granulated formulations.
Comparison of spray congealing and melt emulsification methods for the incorporation of the water-soluble salbutamol sulphate in lipid microparticles

Context: Salbutamol sulphate is widely used as bronchodilator for the treatment of asthma. Its use is limited by the relatively short duration of action and hence sustained delivery of salbutamol sulphate offers potential benefits to patients. Objective: This study explores the preparation of lipid microparticles (LMs) as biocompatible carrier for the prolonged release of salbutamol sulphate. Materials and methods: The LMs were produced using different lipidic materials and surfactants, by classical melt emulsification-based methods (oil-in-water and water-in-oil-in-water emulsions) and the spray congealing technique. Results: For the LMs obtained by melt emulsification a lack of release modulation was observed. On the other hand, the sustained release of salbutamol sulphate was achieved with glyceryl behenate microparticles prepared by spray congealing. These LMs were characterized by scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry. The drug loading was 4.72% (w/w). The particle size distribution measured by laser diffraction and electrical zone sensing was represented by a volume median diameter (Dv50) of 51.7–71.4 µm. Increasing the atomization air pressure from 4 to 8 bar produced a decrease of the Dv50 to 12.7–17.5 µm. Conclusions: Incorporation of the hydrophilic salbutamol sulphate into LMs with sustained release characteristics was achieved by spray congealing.
Absolute Continuity of a Function and Uniform Integrability of Its Divided Differences

Abstract We describe a proof of the fundamental theorem of calculus for the Lebesgue integral, based on the following result: A real-valued function f on a compact interval is absolutely continuous if and only if its family of divided difference functions, {x ↦ [f(x + h) − f(x)]/h}0<h≤1, is uniformly integrable. The Vitali convergence theorem states that, for a sequence of uniformly integrable functions, pointwise convergence implies integrability of the limit function and convergence of the integrals. Our characterization of absolute continuity, together with Vitali's theorem, shows that the fundamental theorem for absolutely continuous functions follows simply by passing to the limit in its discrete formulation.
Curcumin amorphous solid dispersions: the influence of intra and intermolecular bonding on physical stability

Abstract We have investigated the physical stability of amorphous curcumin dispersions and the role of curcumin–polymer intermolecular interactions in delaying crystallization. Curcumin is an interesting model compound as it forms both intra and intermolecular hydrogen bonds in the crystal. A structurally diverse set of amorphous dispersion polymers was investigated; poly(vinylpyrrolidone), Eudragit E100, carboxymethyl cellulose acetate butyrate, hydroxypropyl methyl cellulose (HPMC) and HPMC-acetate succinate. Mid-infrared spectroscopy was used to determine and quantify the extent of curcumin–polymer interactions. Physical stability under different environmental conditions was monitored by powder X-ray diffraction. Curcumin chemical stability was monitored by UV-Vis spectroscopy. Isolation of stable amorphous curcumin was difficult in the absence of polymers. Polymers proved to be effective curcumin crystallization inhibitors enabling the production of amorphous solid dispersions; however, the polymers showed very different abilities to inhibit crystallization during long-term storage. Curcumin intramolecular hydrogen bonding reduced the extent of its hydrogen bonding with polymers; hence most polymers were not highly effective crystallization inhibitors. Overall, polymers proved to be crystallization inhibitors, but inhibition was limited due to the intramolecular hydrogen bonding in curcumin, which leads to a decrease in the ability of the polymers to interact at a molecular level.