Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathways to marijuana use among adolescents: cultural/ecological, family, peer, and personality influences.

OBJECTIVE To examine the linkages, cultural/ecological factors, and major psychosocial risk factors as they relate to drug use in a sample from Colombia, South America. METHOD The participants were 1.687 adolescents living in mixed urban-rural communities in Colombia, South America. An individual interview was administered to youths in their homes by Colombian interviewers. The scales used were based on item intercorrelations grouped into the following risk categories: (1) adolescent personality, (2) family traits, (3) peer factors, and (4) cultural/ecological variables. RESULTS Pearson correlations were computed for each variable and the frequency of marijuana use. Results show that each of the domains was related to adolescent marijuana use, with some notable gender differences. As regards the interrelation of domains, a mediational model was operative. CONCLUSIONS Findings support a family interactional theory. The domains of family, personality, and peer factors had a direct effect on the adolescents' marijuana use. Implications for prevention are also addressed.
Management and outcome of Ebstein's anomaly in children

Abstract Objectives To assess clinical presentation, treatment, and outcome of children with Ebstein's anomaly. Background Data on long-term outcome of children with Ebstein's anomaly are scarce. Methods Retrospective analysis of all children with Ebstein's anomaly treated between February, 1979 and January, 2009 in a single tertiary institution. Primary outcomes included patient survival and need for intervention, either cardiac surgery or catheter intervention. Results A total of 42 patients were diagnosed with Ebstein's anomaly at a median age of 5 days ranging from 1 day to 11.7 years. Symptoms included cyanosis, heart murmur, and/or dyspnoea. Associated cardiac anomalies occurred in 90% of the patients. Average follow-up was 9.5 plus or minus 7.0 years. The overall mortality rate was 14%. Of the six patients, three died postnatally before treatment. Cardiac surgery and/or catheter-guided interventions were required in 33 patients (79%). Cardiac surgery was performed in 21 (50%) patients at a median age of 9.1 years (range 0.1–16.5 years), including biventricular repair in 13 (62%), one-and-a-half chamber repair in seven (33%), and a staged single-ventricle repair in one. Peri-operative mortality was 4%. Catheter-guided interventions consisted of device closure of an atrial septal defect in three cases and radiofrequency ablation of accessory pathways in nine patients. The estimated 10-year survival was 85.3 plus or minus 5.6%. Conclusion In children, Ebstein's anomaly is usually diagnosed in the first year of age. Even though children with Ebstein's anomaly often require an intervention, their peri-operative mortality is low and long-term survival is good. Symptomatic newborns requiring an intervention may have a worse outcome.
Effect of chromium picolinate and melatonin either in single or in a combination in high carbohydrate diet-fed male Wistar rats.

This study is designed to know the effects of chromium picolinate (CrPic) and melatonin (Mel) each alone and in a combination on high carbohydrate diet-fed (HCD-fed) male Wistar rats that exhibit insulin resistance (IR), hyperglycemia, and oxidative stress. Wistar rats have been categorized into five groups. Each group consisted of six male Wistar rats, control rats (group I), HCD (group II), HCD + CrPic (group III), HCD + Mel (group IV), and HCD + CrPic + Mel (group V). Insignificant differences were observed in serum levels of superoxide dismutase, nitric oxide, and zinc in group III, group IV, and group V when each group was compared with group II rats respectively. Significant differences were observed in group III, group IV, and group V when each group was compared with group II in homeostasis model assessment-estimated IR (P < 0.05, <0.0.05, <0.05), and in the levels of blood glucose (P < 0.05, <0.0.05, <0.05), total cholesterol (P < 0.05, <0.001, <0.001), triacylglycerols (<0.05, <0.001, <0.001), high density lipoprotein cholesterol (P < 0.05, <0.001, <0.001), malondialdehyde (P < 0.05, <0.05, <0.001), catalase (P <0.05, <0.05, <0.05), glutathione (P < 0.05, <0.05, <0.05), Mel (P < 0.05, <0.05, <0.001), and copper (P < 0.05, <0.05, < 0.001). In view of these results, HCD-fed male Wistar rats that are destined to attain IR and T2DM through diet can be prevented by giving CrPic and Mel administration in alone or in a combination.
Properties of the Deoxyribonucleic Acid Contained in the Defective Particle Coliphage 15

Escherichia coli strain 15 TAU, which requires thymine, arginine, and uracil for growth and harbors an apparently defective prophage, was induced by exposure to ultraviolet light (580 ergs/mm2) or to mitomycin C (5 μg/ml). Phage particles (coliphage 15) were recovered from the resulting lysate by treatment with deoxyribonuclease, filtration, and several cycles of differential centrifugation. Analysis of the phage particles obtained by using cesium chloride density gradient centrifugation in a preparative ultracentrifuge resulted in the resolution of three components. The major component had a peak density of 1.52 to 1.53 g/cm3 followed by components with densities of 1.5 and 1.49 g/cm3. The guanine plus cytosine content of coliphage 15 deoxyribonucleic acid (DNA) was determined by both analytical ultracentrifugation in cesium chloride and by thermal denaturation in standard saline citrate buffer. Respective values of 46.4 ± 1% and 46.6 ± 1% guanine plus cytosine content were obtained. Coliphage 15 DNA formed molecular hybrids with messenger ribonucleic acid (RNA) from both uninduced and ultraviolet-induced cultures of E. coli 15 TAU, but did not hybridize with E. coli ribosomal RNA. The molecular weight of coliphage 15 DNA was determined by constant velocity sucrose density gradient centrifugation to be about 33 × 106 daltons.
Single-Molecule Analysis Reveals Changes in the DNA Replication Program for the POU5F1 Locus upon Human Embryonic Stem Cell Differentiation

ABSTRACT Human embryonic stem cells (hESCs), due to their pluripotent nature, represent a particularly relevant model system to study the relationship between the replication program and differentiation state. Here, we define the basic properties of the replication program in hESCs and compare them to the programs of hESC-derived multipotent cells (neural rosette cells) and primary differentiated cells (microvascular endothelial cells [MECs]). We characterized three genomic loci: two pluripotency regulatory genes, POU5F1 (OCT4) and NANOG, and the IGH locus, a locus that is transcriptionally active specifically in B-lineage cells. We applied a high-resolution approach to capture images of individual replicated DNA molecules. We demonstrate that for the loci studied, several basic properties of replication, including the average speed of replication forks and the average density of initiation sites, were conserved among the cells analyzed. We also demonstrate, for the first time, the presence of initiation zones in hESCs. However, significant differences were evident in other aspects of replication for the DNA segment containing the POU5F1 gene. Specifically, the locations of centers of initiation zones and the direction of replication fork progression through the POU5F1 gene were conserved in two independent hESC lines but were different in hESC-derived multipotent cells and MECs. Thus, our data identify features of the replication program characteristic of hESCs and define specific changes in replication during hESC differentiation.
Candidate Genes for Nonsyndromic Cleft Palate Detected by Exome Sequencing

Nonsyndromic cleft palate only (nsCPO) is a facial malformation that has a livebirth prevalence of 1 in 2,500. Research suggests that the etiology of nsCPO is multifactorial, with a clear genetic component. To date, genome-wide association studies have identified only 1 conclusive common variant for nsCPO, that is, a missense variant in the gene grainyhead-like-3 (GRHL3). Thus, the underlying genetic causes of nsCPO remain largely unknown. The present study aimed at identifying rare variants that might contribute to nsCPO risk, via whole-exome sequencing (WES), in multiply affected Central European nsCPO pedigrees. WES was performed in 2 affected first-degree relatives from each family. Variants shared between both individuals were analyzed for their potential deleterious nature and a low frequency in the general population. Genes carrying promising variants were annotated for 1) reported associations with facial development, 2) multiple occurrence of variants, and 3) expression in mouse embryonic palatal shelves. This strategy resulted in the identification of a set of 26 candidate genes that were resequenced in 132 independent nsCPO cases and 623 independent controls of 2 different ethnicities, using molecular inversion probes. No rare loss-of-function mutation was identified in either WES or resequencing step. However, we identified 2 or more missense variants predicted to be deleterious in each of 3 genes (ACACB, PTPRS, MIB1) in individuals from independent families. In addition, the analyses identified a novel variant in GRHL3 in 1 patient and a variant in CREBBP in 2 siblings. Both genes underlie different syndromic forms of CPO. A plausible hypothesis is that the apparently nonsyndromic clefts in these 3 patients might represent hypomorphic forms of the respective syndromes. In summary, the present study identified rare variants that might contribute to nsCPO risk and suggests candidate genes for further investigation.
Events and the Means of Attention

Events and the Means of Attention In the contemporary network society, attracting public attention has become more challenging as the supply of information increases. Events arguably play an essential role in synchronizing personal, social and political agendas, helping to focus attention and frame places, objects and people. The event audience justifies the event by paying attention to it, but the event also has to reciprocate by paying attention to the audience. This paper looks at how contemporary rituals that are designed to focus attention and generate ‘emotional energy’ through shared co-presence and a mutual focus of attention, as suggested by Collins in 2004. The event itself, therefore, arguably mirrors practices in the wider network society, where sociality increasingly depends on generating and exchanging attention. The extent to which events and event places successfully create the conditions for successful event rituals by developing the means of attention is examined through examples of cultural and sporting events, focusing on the creative interplay between consumers and producers and their cocreation of event experiences.
Internalization and Recycling of the CB1 Cannabinoid Receptor

Abstract : Tolerance develops rapidly to cannabis, cannabinoids, and related drugs acting at the CB1 cannabinoid receptor. However, little is known about what happens to the receptor as tolerance is developing. In this study, we have found that CB1 receptors are rapidly internalized following agonist binding and receptor activation. Efficacious cannabinoid agonists (WIN 55,212‐2, CP 55,940, and HU 210) caused rapid internalization. Methanandamide (an analogue of an endogenous cannabinoid, anandamide) was less effective, causing internalization only at high concentration, whereas Δ9‐tetrahydrocannabinol caused little internalization, even at 3 μM. CB1 internalized via clathrin‐coated pits as sequestration was inhibited by hypertonic sucrose. Internalization did not require activated G protein αi, αo, or αs subunits. A region of the extreme carboxy terminus of the receptor was necessary for internalization, as a mutant CB1 receptor lacking the last 14 residues did not internalize, whereas a mutant lacking the last 10 residues did. Steps involved in the recycling of sequestered receptor were also investigated. Recovery of CB1 to the cell surface after short (20 min) but not long (90 min) agonist treatment was independent of new protein synthesis. Recycling also required endosomal acidification and dephosphorylation. These results show that CB1 receptor trafficking is dynamically regulated by cannabimimetic drugs.
Immunohistochemical and cytogenetic findings in malignant rhabdoid tumor.

BACKGROUND The histogenesis of malignant rhabdoid tumor (RT) remains a matter of controversy. From published reports it appears that some extrarenal RT (ERRT) exhibit neural or neuroectodermal features. Systematic investigation of renal RT (RRT) for neural differentiation has not yet been published. In this study, two RRT and two ERRT were investigated by light and electron microscopy, immunocytochemistry, and cytogenetic analysis. RESULTS All four cases exhibited similar morphology and a largely consistent immunohistochemical staining profile. Both tumor types showed immunoreactivity for various cytokeratins, epithelial membrane antigen (EMA), vimentin, neurofilaments, S100 protein, neuron specific enolase, Leu7, CD34, p53, MB2, MIC2, VS38c, laminin and fibronectin. Reactivity was usually confined to a small proportion of the tumor cells, especially in the case of antibodies against neurofilaments, NSE, S100 proteins Leu7, CD34 and p53. Only a few of the antibodies (anti-vimentin, MB2, MIC2, anti-EMA, and VS38c) stained the majority of the tumor cells. Chromosome analysis revealed a discrete aberration in 11p (most probably a paracentric inversion in 11p15) in the one RRT investigated. One ERRT had a normal karyotype, but the other one exhibited various structural abnormalities on chromosomes 18 and 22. CONCLUSIONS The immunohistochemical investigations revealed many similarities between RRT and ERRT, and all four tumors investigated exhibited neuroectodermal differentiation. As far as histogenetic classification is concerned, our findings point in the direction of the group of tumors that includes Ewing's sarcoma and primitive neuroectodermal tumors.
Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery

Significance Many therapeutic peptides suffer from short plasma half-lives and, as a consequence, require frequent injections to be therapeutically effective; this in turn can adversely affect patient compliance. Here, we describe the development of a novel peptide engineering strategy that incorporates a serum protein binding motif into a covalent side-chain staple. This approach was used to generate stapled long-acting glucagon-like peptide-1 analogs with potency comparable to exendin-4 and significantly enhanced pharmacokinetic properties. Administration by a dissolvable microstructure-based transdermal system resulted in sustained therapeutic blood concentrations with glucose lowering activity in guinea pigs. This approach likely provides a general, straightforward platform for generating stapled long-acting peptide hormones for a range of therapeutic applications. Antidiabetic treatments aiming to reduce body weight are currently gaining increased interest. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist administered twice daily via s.c. injection, improves glycemic control, often with associated weight reduction. To further improve the therapeutic efficacy of exendin-4, we have developed a novel peptide engineering strategy that incorporates a serum protein binding motif onto a covalent side-chain staple and applied to the peptide to enhance its helicity and, as a consequence, its potency and serum half-life. We demonstrated that one of the resulting peptides, E6, has significantly improved half-life and glucose tolerance in an oral glucose tolerance test in rodents. Chronic treatment of E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism, and also reduced hepatic steatosis in diet-induced obese mice. Moreover, the high potency of E6 allowed us to administer this peptide using a dissolvable microstructure-based transdermal delivery system. Pharmacokinetic and pharmacodynamic studies in guinea pigs showed that a single 5-min application of a microstructure system containing E6 significantly improved glucose tolerance for 96 h. This delivery strategy may offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables and can likely be extended to other peptide hormones.
Obesity and Hospitalization over the Adult Life Course: Does Duration of Exposure Increase Use?∗

Consistent with a new genre of research on life-course analyses of health-service use, this study explores the consequences of long-term exposure to a risk factor. Drawing from cumulative-disadvantage theory, the study examines whether obesity, especially chronic obesity, increases hospitalization admission and length of stay. Analyses make use of hospital records abstracted over 20 years from a national survey of adults 41 to 77 years of age at baseline (n = 4,574). Multiple measures of body weight are used to calculate adult obesity duration. Results reveal that obesity increased hospital admissions and length of stay over the 20 years studied. Among persons obese at any time during the study, years of obesity also led to longer stays. The findings highlight the utility of measures of the duration of risk exposure for both life-course studies of health and tests of cumulative-disadvantage theory.
Systematic review of N‐acetylcysteine in cystic fibrosis

A systematic review was carried out to evaluate whether the use of N‐acetylcysteine to improve lung function in patients with cystic fibrosis is supported by published evidence. Medline and the Cochrane Library were searched and the reference lists of all retrieved papers and of relevant chapters of three major textbooks were scanned. Data on lung function (forced expiratory volume in one second (FEV1)) were extracted from controlled clinical trials and pooled as weighted mean differences for analysis. Twenty‐three studies, mostly uncontrolled clinical observations, were retrieved. Only three randomized controlled clinical trials on nebulized N‐acetylcysteine in cystic fibrosis were found, not showing any beneficial effect on lung function. Six randomized controlled clinical trials on oral N‐acetylcysteine in cystic fibrosis were found, with a total number of 181 patients. There was a tendency towards a beneficial effect on lung function of oral N‐acetylcysteine therapy on FEV1 but it was small (2.3%, 95% CI from (−0.3 to 4.9% of predicted) and of doubtful clinical relevance. In all studies, follow‐up was 3 months or shorter. In conclusion, at present there is no evidence supporting the use of N‐acetylcysteine in cystic fibrosis, although a beneficial effect with long‐term use of N‐acetylcysteine in cystic fibrosis cannot be excluded.
Inflammatory bowel disease in individuals seropositive for the human immunodeficiency virus

Objective: CD4 lymphocytes mediate disease expression in both human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD). Analysis of the clinical course of IBD in HIV-seropositive individuals may elucidate aspects of the role of CD4 lymphocytes in the pathogenesis of these conditions. Design: A retrospective case series study. Patients: Diagnostic coding for IBD and pharmacy records for 5-aminosalicylic acid compounds and rectal steroid preparations were examined for all HIV-seropositive subjects attending the Chelsea and Westminster Hospitals between January 1988 and December 1993. Eight HIV-seropositive individuals with a confirmed diagnosis of IBD were identified. Setting: HIV/Genitourinary medicine (GUM) units. Main outcome measures: Change in CD4 count. Results: Four subjects with an intact colon had a decline in CD4 count of 85 cells/mm3/year, four patients undergoing colectomy had a subsequent rise of four cells/mm3/year and eight case matched controls had a decline of 47cells/mm3/year. Acute exacerbations of IBD did not cause a significant change in CD4 count. There were no exacerbations of IBD in patients with a CD4 count below 200 cells/mm3. Conclusion: HIV infection may influence the pathogenesis of IBD. A chronically inflamed colon may accelerate CD4 cell depletion which is reversed by colectomy.
The Geography of spina bifida in England and Wales

Spina bifida is a generic term describing malformations of the central nervous system in infants. Over 1000 cases of spina bifida were notified in England and Wales in 1971, but this had declined to 360 in 1985, partly due to maternal screening and the acceptance of therapeutic abortion. This paper reviews hypotheses about the causes of spina bifida and uses Poisson probabilities and regression techniques to examine spatial variations in the prevalence of spina bifida between 1983 and 1985. Differences in the maternal screening policies of health authorities are highlighted as an important factor, indicating that the study of 'geographical epidemiology' cannot be divorced from issues of health care.
Understanding the impact of interprofessional collaboration on the quality of care: a case report from a small-scale resource limited health care environment

Background A critical assessment of current health care practices, as well as the training needs of various health care providers, is crucial for improving patient care. Several approaches have been proposed for defining these needs with attention on communication as a key competency for effective collaboration. Taking our cultural context, resource limitations, and small-scale setting into account, we researched the applicability of a mixed focus group approach for analysis of the communication between doctors and nurses, as well as the measures for improvement. Study objective Assessment of nurse-physician communication perception in patient care in a Caribbean setting. Methods Focus group sessions consisting of nurses, interns, and medical specialists were conducted using an ethnographic approach, paying attention to existing communication, risk evaluation, and recommendations for improvement. Data derived from the focus group sessions were analyzed by thematic synthesis method with descriptive themes and development of analytic themes. Results The initial focus group sessions produced an extensive list of key recommendations which could be clustered into three domains (standardization, sustainment, and collaboration). Further discussion of these domains in focus groups showed nurses’ and physicians’ domain perspectives and effects on patient care to be broadly similar. Risks related to lack of information, knowledge sharing, and professional respect were clearly described by the participants. Conclusion The described mixed focus group session approach for effectively determining current interprofessional communication and key improvement areas seems suitable for our small-scale, limited resource setting. The impact of the cultural context should be further evaluated by a similar study in a different cultural context.