Miracle-dz/UniFAR-FTUs huggingface dataset:
CB1 Receptor Antagonist SR141716A Inhibits Ca2+-Induced Relaxation in CB1 Receptor-Deficient Mice

Mesenteric branch arteries isolated from cannabinoid type 1 receptor knockout (CB1−/−) mice, their wild-type littermates (CB1+/+ mice), and C57BL/J wild-type mice were studied to test the hypothesis that murine arteries undergo high sensitivity Ca2+-induced relaxation that is CB1 receptor dependent. Confocal microscope analysis of mesenteric branch arteries from wild-type mice showed the presence of Ca2+ receptor-positive periadventitial nerves. Arterial segments of C57 control mice mounted on wire myographs contracted in response to 5 &mgr;mol/L norepinephrine and responded to the cumulative addition of extracellular Ca2+ with a concentration-dependent relaxation that reached a maximum of 72.0±6.3% of the prerelaxation tone and had an EC50 for Ca2+ of 2.90±0.54 mmol/L. The relaxation was antagonized by precontraction in buffer containing 100 mmol/L K+ and by pretreatment with 10 mmol/L tetraethylammonium. Arteries from CB1−/− and CB1+/+ mice also relaxed in response to extracellular Ca2+ with no differences being detected between the knockout and their littermate controls. SR141716A, a selective CB1 antagonist, caused concentration-dependent inhibition of Ca2+-induced relaxation in both the knockout and wild-type strains (60% inhibition at 1 &mgr;mol/L). O-1918, a cannabidiol analog, had a similar blocking effect in arteries of both wild-type and CB1−/− mice at 10 &mgr;mol/L. In contrast, 1 &mgr;mol/L SR144538, a cannabinoid type 2 receptor antagonist, or 50 &mgr;mol/L 18&agr;-glycyrrhetinic acid, a gap junction blocker, were without effect. SR141716A (1 to 30 &mgr;mol/L) was also assessed for nonspecific actions on whole-cell K+ currents in isolated vascular smooth muscle cells. SR141716A inhibited macroscopic K+ currents at concentrations higher than those required to inhibit Ca2+-induced relaxation, and appeared to have little effect on currents through large conductance Ca2+-activated K+ channels. These data indicate that arteries of the mouse relax in response to cumulative addition of extracellular Ca2+ in a hyperpolarization-dependent manner and rule out a role for CB1 or CB2 receptors in this effect. The possible role of a nonclassical cannabinoid receptor is discussed.
Molecular-genetic analysis of Hirschsprung's disease in South Africa

Hirschsprung's disease (HSCR) is a common cause of intestinal obstruction in neonates with an incidence of 1 in 5000 live births. The disease occurs due to the absence of parasympathetic neuronal ganglia in the hindgut, resulting in irregular or sustained contraction of the affected segment. DNA samples of 53 unrelated subjects with sporadic HSCR were screened for mutations in the RET proto-oncogene, a major susceptibility gene for HSCR, as well as the endothelin-B receptor (EDNRB) and the endothelin-3 genes (EDN3). Five novel and one previously described mutation were identified in the RET proto-oncogene. Mobility shift aberrations identified in the EDNRB gene represented polymorphisms. No sequence variants were identified in the EDN3 gene. Potential disease-related mutations were identified in the RET proto-oncogene in 19% of individuals and more males (24% representing 9 of 37 males) were affected than females (6% representing 1 of 16 females). This study demonstrated that all the potential disease-related mutations identified in South African patients with sporadic HSCR occur in the RET gene. A mutation in RET was identified in only 2 of 14 patients (14%) presenting with HSCR and Down's syndrome compared to 6 mutations identified in 8 of 39 patients (20.5%) with only HSCR. Stellenbosch University http://scholar.sun.ac.za
Voice hearing within the context of hearers' social worlds: an interpretative phenomenological analysis.

OBJECTIVES Research has found relational qualities of power and intimacy to exist within hearer-voice interactions. The present study aimed to provide a deeper understanding of the interpersonal context of voice hearing by exploring participants' relationships with their voices and other people in their lives. DESIGN This research was designed in consultation with service users and employed a qualitative, phenomenological, and idiographic design using semi-structured interviews. METHOD Ten participants, recruited via mental health services, and who reported hearing voices in the previous week, completed the interviews. These were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS Five themes resulted from the analysis. Theme 1: 'person and voice' demonstrated that participants' voices often reflected the identity, but not always the quality of social acquaintances. Theme 2: 'voices changing and confirming relationship with the self' explored the impact of voice hearing in producing an inferior sense-of-self in comparison to others. Theme 3: 'a battle for control' centred on issues of control and a dilemma of independence within voice relationships. Theme 4: 'friendships facilitating the ability to cope' and theme 5: 'voices creating distance in social relationships' explored experiences of social relationships within the context of voice hearing, and highlighted the impact of social isolation for voice hearers. CONCLUSIONS The study demonstrated the potential role of qualitative research in developing theories of voice hearing. It extended previous research by highlighting the interface between voices and the social world of the hearer, including reciprocal influences of social relationships on voices and coping. Improving voice hearers' sense-of-self may be a key factor in reducing the distress caused by voices.
Family caregivers' attributions about care-recipient behaviour: does caregiver relationship satisfaction mediate the attribution-distress relationship?

OBJECTIVES The relations of caregiver attributions about care-recipient's problem behaviour to caregiving relationship satisfaction and caregiver distress were examined. DESIGN This is a cross sectional study. Seventy-five family caregivers of individuals diagnosed with various disabling health conditions were recruited and interviewed. Caregiver attributions (internality, intentionality, responsibility, and controllability), caregiving relationship satisfaction, and caregiver distress variables were measured. RESULTS Structural equation techniques tested an a priori model of the latent constructs of caregiver attributions and caregiver relationship satisfaction to caregiver distress. Maladaptive caregiver attributions (i.e., more trait, higher intentionality, higher responsibility, and higher controllability) about care-recipients' problem behaviours predicted lower caregiving relationship satisfaction, which in turn was predictive of higher caregiver distress. Unexpectedly, caregiver attributions were not directly related to caregiver distress. However, attributions had an indirect effect on distress through relationship satisfaction. Younger caregivers experienced higher caregiver distress. CONCLUSIONS Caregivers' explanations about care-recipient's problem behaviour are indicative of their satisfaction in the relationship with the care recipient, and poor caregiving relationship satisfaction is predictive of caregiver distress. Caregiver attributions and relationship quality may be considered in interventions with family caregivers.
Factores de riesgo de retraso en el crecimiento linear en niños de 12 a 120 meses de edad en Arandas, Jalisco, México

The purpose was to identify risk factors associated to deficit on linear growth in children from a semi-rural population in Arandas, Jalisco, Mexico. In a cross sectional study 432 children, 12 to 120 months old were included. Social, demographic, economical, dietetic and pathological characteristics and deficit in the height /age index ( 3 children in the family [OR 1.71 (1.01, 2.87)], soft drinks consumption > 4 times a week [OR 2.36 (1.19-4.73)], family's monthly income < 200 USA dollars [OR 3.5 (1.28, 9.76)] and per capita food expenses < 10% of a minimum salary (100 USA dollars a month) [OR 1.81 (1.06,3.09)]; age < 24 months [OR 2.02 (1.09, 3.75)], adding sweeteners to the bottle [OR 8.56 (1.84, 54.9)], diet modification during diarrhea [OR 2.40 (1.02, 5.77)], milk intake < 4 times a week [OR 2.71 (1.55,4.73)] and nearly significant, bean consumption [1.75 (0.98, 3.13). Protection factors: nuclear family [OR 0.28 (0.09, 0.85)] and an adequate infant formula dilution [OR 0.71 (0.60, 0.85)]. In multivariate models associated factors to deficit of height were higher consumption of soft drinks, beans and the addition of sweeteners to the bottle. In addition to socioeconomic variables, lower consumption of high quality food and proteins and higher intake of legumes were important risk factors for mild and moderate deficit height/age.
Adipocinas, tejido adiposo y su relación con células del sistema inmune

Adipokines or adipocytokines are the proteins secreted by the adipose tissue. These bioactive molecules include proteins that modify insulin sensitivity (acylation-stimulating protein (ASP), TNF-alpha IL-6, resistin, leptin and adiponectin), and proteins that have known effects on vascularity (angiotensinogen and the plasminogen inhibitor protein PAI-I). Several studies have found a close relationship between adipocytes and immune cells as a consequence of evolutionary mechanisms that favor metabolic adaptation and survival under adverse conditions. It is known that adipokines contribute to the inflammation and insulin resistance present in obese individuals. The aim of this review is to analyze current information related to the physiology of the adipose tissue, with a special emphasis on the secretion of adipokines and their role in inflammation. We recommend that therapies addressing the treatment of obesity related disorders should focus on modifying the inflammatory process that originates in the adipose tissue.
Reciprocity and social capital in sibling relationships of people with disabilities.

Sibling relationships are some of the longest-lasting relationships people experience, providing ample opportunities to build connections across the life span. For siblings and people with intellectual and developmental disabilities (IDD), these connections take on an increased significance as their families age and parents can no longer provide care. This article presents findings from a qualitative study that addresses the question, "How do siblings support each other after parents no longer can provide care to the person with IDD? " Findings in this study suggest that siblings with and without disabilities experience reciprocity as a transitive exchange, which occurs through the creation of social capital in their families and community, and that nondisabled siblings mobilize their social capital to provide support to their sibling after parents pass away. Implications for future research as well as policy and practice are discussed.
NMDA Antagonism in the treatment of Major Depressive Disorder

With a lifetime prevalence of over 16% and spread over all social classes, major depressive disorder (MDD) is one of the leading causes for psychosocial disability. Although there is no established mechanism for depression most drugs used in pharmacotherapy focus on the monoamine-deficiency hypothesis and inhibit the reuptake or metabolism of serotonin or norepinephrine in order to raise their plasmalevels. With over 20% of patients being resistant to treatment, and very low remission and high relapse rates, new strategies and methods for this treatment-resistant form of depression are warranted. In recent years the use of N-methyl-D-aspartate (NMDA) antagonists, and in particular the well known dissociative drug ketamine, in the treatment of clinical depression has come under increasing interest. This administration is less rigorous than more invasive treatments like deep brain stimulation. Recently the mechanism of action of this acute response, at sub-psychotomimetic doses, has been linked to eukaryotic elongation factor 2 (eEF2) kinase inhibition and desupression of brain-derived neurotrophic factor (BDNF) translation. This supports other research implying synaptic plasticity as an important factor in treating MDD. Chronic administration of ketamine is however linked to impairments of verbal fluency, cognitive processing speed, and verbal learning and its other cognitive effects are associated with potential abuse. In this report we will outline the molecular mechanisms involved in NMDA antagonism, the effects on other neurotransmittersystems and glutamate signaling and how these relate to the positive effects on MDD. The major transduction pathways will be outlined and potential related targets highlighted.
Rigidité artérielle, pression pulsée et risque cardiovasculaire

La rigidite des gros troncs arteriels comporte des modifications de l'organisation structurale des differents composants de la paroi arterielle qui conduisent a la reduction de la distensibilite des gros troncs arteriels. Cette atteinte est distincte de l'atherome, bien que ces deux pathologies puissent coexister [1, 2]. Elle est la consequence majeure [. ]
Early life‐stage toxicity test for copper pyrithione and induction of skeletal anomaly in a teleost, the mummichog (Fundulus heteroclitus)

We used a teleost fish, the mummichog (Fundulus heteroclitus), to conduct early life‐stage toxicity testing for copper pyrithione (CuPT). Fertilized mummichog eggs were exposed to CuPT at various concentrations for 50 d under continuous flow‐through conditions. Hatchability, survival, growth, and morphologic abnormalities were measured. Hatchability did not differ significantly between any experimental group and control groups. Survival and growth were significantly reduced at 50 d in the groups exposed to 2 or 4 μg/L CuPT. During the test, morphologic abnormalities, such as vertebral deformity and formation of inflammatory masses in the lateral muscles, occurred in fish exposed to CuPT. Light and electron microscopic studies indicated that muscle dysfunction played a role in the vertebral deformity and revealed that the inflammatory mass was composed mainly of macrophages and necrotic myocytes. We consider that macrophages infiltrated and phagocytized necrotic cells, thus forming the inflammatory mass. In addition, acetylcholinesterase activity was markedly decreased in the 2‐ and 4‐μg/L exposure groups, suggesting the skeletal deformity was due to mechanisms similar to those proposed for organophosphorous pesticide exposure.
Oxidative DNA damage in CD34+ myelodysplastic cells is associated with intracellular redox changes and elevated plasma tumour necrosis factor‐α concentration

Ineffective haemopoiesis in the myelodysplastic syndromes (MDS) is mediated, at least in part, by apoptosis, though the mechanisms of apoptotic induction are unclear. Tumour necrosis factor‐α (TNF‐α) promotes apoptosis via intracellular oxygen free radical production, oxidation of DNA and proteins, and is increasingly implicated in the pathogenesis of MDS. Using single‐cell gel electrophoresis, we have identified oxidized pyrimidine nucleotides in the progenitor‐enriched bone marrow CD34+ compartment from MDS patients (P = 0.039), which are absent in both CD34− MDS cells (P = 0.53) and also CD34+ cells from normal subjects (P = 0.55). MDS CD34+ blood cells also showed oxidized pyrimidine nucleotides compared with CD34− cells (P = 0.029). Within normal subjects no differences were seen between CD34+ and CD34− bone marrow cell compartments. CD34+ bone marrow cell oxidized pyrimidines were strongly associated with elevated plasma TNF‐α and low bone marrow mononuclear cell glutathione concentrations (5/6 patients) and the inverse relationship was also found (3/4 patients). This data implies a role for intracellular oxygen free radical production, perhaps mediated by TNF‐α, in the pathogenesis of ineffective haemopoiesis in MDS and provides a rationale for the bone marrow stimulatory effects of antioxidants such as Amifostine in MDS.
Raman Spectroscopy of Atherosclerosis

Raman spectroscopy can provide detailed, quantitative information about the chemical composition of an atherosclerotic plaque. Recent development of compact clinical Raman systems and specially developed Raman catheters allow the remote, intravascular application of the technique. This shows prospects for the detection of coronary plaques that are prone to rupture and for the quantitative study of atherosclerosis in terms of chemical composition. This review discusses the basic principles and advances of Raman spectroscopy in the field of atherosclerosis, and its future directions in cardiovascular medicine.
Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers in Galapagos Sea Lions (Zalophus wollebaeki)

Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzo‐p‐dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) were measured in muscle‐blubber biopsy samples from 21 Galapagos sea lion (Zalophus wollebaeki) pups that were live captured in the Galapagos Islands (Ecuador) using gas chromatography/high‐resolution mass spectrometry. Only traces of PBDEs were detected in one male pup, whereas PCDDs and PCDFs were not detected in any sample. The total concentration of PCBs (σPCB) in the pups averaged 104 μg/kg lipid (range, 49–384 μg/kg). No statistically significant differences in σPCB were observed among the four study sites in the Galapagos Islands. Concentrations of PCB congeners in Galapagos sea lion pups were dominated by low‐molecular‐weight congeners. These results suggest that global transport is the main source for PCBs in Galapagos sea lions. The σPCB levels were below immunotoxic and endocrine‐disruption thresholds in pinnipeds, suggesting a limited risk of adverse health effects. The present study indicates that Galapagos sea lions can serve as a useful sentinel of pollutants with a long‐range transport capacity and that Galapagos Islands are not exempt from the threats of global pollutants despite its remote locale.
Application of a stable isotope technique to determine the simultaneous uptake of cadmium, copper, nickel, lead, and zinc by the water flea Daphnia Magna from water and the green algae Pseudokirchneriella Subcapitata

Accumulation and toxicological effects of water and dietary metals in aquatic organisms can potentially be very different. Therefore, it is important to know the relative contribution of these different sources to metal exposure, availability, and accumulation. In the present study, a stable isotope technique was applied to investigate the uptake of Cd, Cu, Ni, Pb, and Zn by the green alga Pseudokirchneriella subcapitata and the water flea Daphnia magna during simultaneous exposure to the five metals at environmentally realistic concentrations from separate water and dietary routes. Green algae take up Cu faster compared to Cd, Ni, Pb, and Zn, and the distribution of metals between the external and internal compartments is dependent on metal and population growth stage. The metal accumulation reached a steady state within 24 to 48 h for all metals. Metal uptake rate constants from water were highest for Cu and lowest for Ni. Metal assimilation efficiencies from the food source varied with metal, ranging from approximately 80% in the case of Cd to near 0% in the case of Ni. Because the data for the different metals were obtained on the same multimetal‐exposed organisms, the results are directly comparable among the metals. For all five metals studied, water appeared to be the most important route of uptake by D. magna.
Orientation to learning and previous learning experiences: Are they factors that affect learning in the distance mode?

This paper is an attempt to investigate whether the outcome of learning advanced language skills through the distance mode is affected by students' orientation to learning and by their previous learning experiences. Motivation or orientation to learning is a factor often used to explain variation in student performance. Motivation is of fundamental importance particularly to Open University students since a) they have chosen to engage in post-compulsory education and, b) because the nature of distance education requires the student to be responsible for steering and maintaining her own learning. Orientation to learning, following Morgan (1993) is broadly categorised as ‘vocational', ‘academic' or ‘personal' and used in conjunction with motivation in language learning defined as ‘instrumental' or ‘integrative' (Gardner and Lambert 1972). Prior learning was established on the basis of formal education/examinations taken before enrolling at the Open University. doi: 10.4038/ouslj.v2i0. 366 OUSL Journal (1999) Vol.2, (pp.94-124)
Prevalence of mental morbidity amongst prisoners

Jails and prisons hold many people that society does not want to have around and it would be wise to keep them there, despite the fact that the legal and correctional system have failed to bring any positive changes in them. Prisoners with mental illness frequently endure violence, exploitation and extortion at the hands of other inmates and neglect and mistreatment by jail staff. To know the prevalence of mental morbidity among prisoners. The study was carried out in the district jail, Rohtak. A study sample of 150 male prisoners above sixteen was selected by random sampling technique ensuring proportionate representation to convicts as well as the non-convicts. Indian Psychiatric Interview Schedule (IPIS) was used for the purpose of screening the subjects suspected for psychiatric disorders and those who screened positive were administered Structured Clinical Interview for DSM-IV AXIS-I disorder (SCID-I) and AXIS-II disorder (SCID-II). 56% convicts belong to the age group of 30 to 50 years while 52% non-convicts were in the age group of 21 to 30 years. Prevalence of mental morbidity was 70% among convicts and 93% among non-convicts. 20% of convicts and 80% of non-convicts had AXIS-1 disorders while 24.6% of convicts and 75.4% of non-convicts had AXIS-11 disorders. Key words: Mental morbidity, prisoners.
WHO working group on population levels of alcohol consumption

: Target 17 of the Health Policy for Europe calls for the health-damaging consumption of dependence-producing substances such as alcohol, tobacco and psychoactive substances to be significantly reduced in all Member States between the year 1980 and the year 2000. With regard to alcohol, it is suggested that alcohol consumption be reduced by 25%, with particular attention to reducing harmful use. A question posed by a number of Member States is what is the level of per capita alcohol consumption of lowest risk to physical, psychological and social harm. A working group was convened to consider population levels of alcohol consumption with particular reference to the Member States of the European Region of WHO. A basis for understanding population problem experience can be established through the interaction between individual risk and distribution of consumption levels within the population. The working group concluded that public health policy within the European Region should continue to advise decreases of per capita consumption. Even when taking into account coronary heart disease, it can be concluded at the population level, across all ranges of alcohol consumption found in almost all countries of Europe, that a reduction in consumption is linked to better health. However, public health policy concerning alcohol should not be based solely on mortality. All outcomes of drinking, that is mortality, morbidity, social and criminal consequences, as well as quality of life, should be considered. The existing data relating alcohol consumption to health originates from countries primarily with a cultural experience of consuming alcohol. In those countries, where there is a cultural or religious tradition of not consuming alcohol, there can be no public health grounds for recommending alcohol consumption.