Miracle-dz/UniFAR-FTUs huggingface dataset:
Emergence of Orai3 activity during cardiac hypertrophy.

AIMS Stromal interaction molecule 1 (STIM1) has been shown to control a calcium (Ca(2+)) influx pathway that emerges during the hypertrophic remodelling of cardiomyocytes. Our aim was to determine the interaction of Orai1 and Orai3 with STIM1 and their role in the constitutive store-independent and the store-operated, STIM1-dependent, Ca(2+) influx in cardiomyocytes. METHODS AND RESULTS We characterized the expression profile of Orai proteins and their interaction with STIM1 in both normal and hypertrophied adult rat ventricular cardiomyocytes. Orai1 and 3 protein levels were unaltered during the hypertrophic process and both proteins co-immunoprecipitated with STIM1. The level of STIM1 and Orai1 were significantly greater in the macromolecular complex precipitated by the Orai3 antibody in hypertrophied cardiomyocytes. We then used a non-viral method to deliver Cy3-tagged siRNAs in vivo to adult ventricular cardiomyocytes and silence Orai channel candidates. Cardiomyocytes were subsequently isolated then the voltage-independent, i.e. store-independent and store-operated Ca(2+) entries were measured on Fura-2 AM loaded Cy3-labelled and control isolated cardiomyocytes. The whole cell patch-clamp technique was used to measure Orai-mediated currents. Specific Orai1 and Orai3 knockdown established Orai3, but not Orai1, as the critical partner of STIM1 carrying these voltage-independent Ca(2+) entries in the adult hypertrophied cardiomyocytes. Orai3 also drove an arachidonic acid-activated inward current. CONCLUSION Cardiac Orai3 is the essential partner of STIM1 and drives voltage-independent Ca(2+) entries in adult cardiomyocytes. Arachidonic acid-activated currents, which are supported by Orai3, are present in adult cardiomyocytes and increased during hypertrophy.
Dispensing practices, attitudes and knowledge of pharmacists towards herbal products in palestine

Background and Objectives: With the global rise in the use of herbal products; pressure is increasing on pharmacists to have more knowledge about herbal medicine. We assessed pharmacists' dispensing practices, attitudes, and knowledge regarding herbal products. Methods: A cross sectional study was carried out among community pharmacists in north Palestine using a questionnaire. A convenience sample of 100 community pharmacists was included in the study. The mean age of participants was 33±11 years. Results: Dispensing of herbal products was common. The majority of participants (91%) believed that herbal products were beneficial and 61% believed these had fewer side effects than conventional medicines. Most participants thought they have good knowledge of herbal preparations. However, their actual knowledge in response to factual questionnaire was low. The lowest score was observed for herbal drug interactions domain. Conclusions: Although herbal products are commonly dispensed in Palestine, community pharmacists have poor knowledge about these medicines. Continuing pharmacy education in general is needed for community pharmacists to qualify them to provide a better pharmaceutical care.
Clinical and laboratory correlates of lung disease and cancer in adults with idiopathic hypogammaglobulinaemia

Idiopathic hypogammaglobulinaemia, including common variable immune deficiency (CVID), has a heterogeneous clinical phenotype. This study used data from the national UK Primary Immune Deficiency (UKPID) registry to examine factors associated with adverse outcomes, particularly lung damage and malignancy. A total of 801 adults labelled with idiopathic hypogammaglobulinaemia and CVID aged 18–96 years from 10 UK cities were recruited using the UKPID registry database. Clinical and laboratory data (leucocyte numbers and serum immunoglobulin concentrations) were collated and analysed using uni‐ and multivariate statistics. Low serum immunoglobulin (Ig)G pre‐immunoglobulin replacement therapy was the key factor associated with lower respiratory tract infections (LRTI) and history of LRTI was the main factor associated with bronchiectasis. History of overt LRTI was also associated with a significantly shorter delay in diagnosis and commencing immunoglobulin replacement therapy [5 (range 1–13 years) versus 9 (range 2–24) years]. Patients with bronchiectasis started immunoglobulin replacement therapy significantly later than those without this complication [7 (range 2–22) years versus 5 (range 1–13) years]. Patients with a history of LRTI had higher serum IgG concentrations on therapy and were twice as likely to be on prophylactic antibiotics. Ensuring prompt commencement of immunoglobulin therapy in patients with idiopathic hypogammaglobulinaemia is likely to help prevent LRTI and subsequent bronchiectasis. Cancer was the only factor associated with mortality. Overt cancer, both haematological and non‐haematological, was associated with significantly lower absolute CD8+ T cell but not natural killer (NK) cell numbers, raising the question as to what extent immune senescence, particularly of CD8+ T cells, might contribute to the increased risk of cancers as individuals age.
Financial payments by orthopedic device makers to orthopedic surgeons.

BACKGROUND There is ongoing concern over potential conflict of interest inherent in physician relationships with industry. However, there are limited empirical data detailing the prevalence and magnitude of these relationships. Our objective was to use data made available by a US Department of Justice (DOJ) lawsuit to describe the extent of orthopedic surgeons' financial relationships with implant manufacturers. METHODS We used data made available by the 2007 DOJ settlement with 5 major joint implant manufacturers to detail the number of orthopedic surgeons receiving payments, the size of these payments, the aggregate dollar amount, and the proportion going to academically affiliated orthopedic surgeons between 2007 and 2010. RESULTS In 2007, 1041 payments totaling in excess of $198 million were made to 939 orthopedic surgeons. In 2008, following the DOJ settlement, the implant makers made 568 payments totaling more than $228 million to 526 orthopedic surgeons (which included $109 million in one-time royalty buyouts by a single firm). The proportion of surgeons receiving payments who had academic affiliations rose from 39.4% in 2007 to 44.9% in 2008. Similar patterns were observed in 2009 and 2010 for 3 firms that continued to disclose by choice. We also noted substantial variation across firms in the details provided in the disclosed data. CONCLUSIONS The impact of the DOJ settlement in the short term appears complex, with an increase in payments, a decline in the number of consultants, and an increase in the proportion of consultants drawn from academia. There is a need for clearer specific requirements for disclosure to allow for meaningful long-term analyses to be performed.
The effect of a structured behavioral intervention on poorly controlled diabetes: a randomized controlled trial.

BACKGROUND Although maintaining nearly normal glycemia delays onset and slows progression of diabetes complications, many patients with diabetes and their physicians struggle to achieve glycemic targets. The best methods to support patients as they follow diabetes prescriptions and recommendations are unclear. METHODS To test the efficacy of a behavioral diabetes intervention in improving glycemia in long-duration, poorly controlled diabetes, we randomized 222 adults with diabetes (49% type 1) (mean [SD] age, 53 [12] years; mean [SD] disease duration 18 [12] years; mean [SD] hemoglobin A(1c) [HbA(1c)] concentration, 9.0% [1.1%]) to attend (1) a 5-session manual-based, educator-led structured group intervention with cognitive behavioral strategies (structured behavioral arm); (2) an educator-led attention control group education program (group attention control); or (3) unlimited individual nurse and dietitian education sessions for 6 months (individual control). Outcomes were baseline and 3-, 6-, and 12-month postintervention HbA(1c) levels (primary) and frequency of diabetes self-care, 3-day pedometer readings, 24-hour diet recalls, average number of glucose checks, physical fitness, depression, coping style, self-efficacy, and quality of life (secondary). RESULTS Linear mixed modeling found that all groups showed improved HbA(1c) levels (P < .001). However, the structured behavioral arm showed greater improvements than the group and individual control arms (3-month HbA(1c) concentration changes: -0.8% vs -0.4% and -0.4%, respectively (P = .04 for group × time interaction). Furthermore, participants with type 2 disease showed greater improvement than those with type 1 (P = .04 for type of diabetes × time interaction). Quality of life, glucose monitoring, and frequency of diabetes self-care did not differ by intervention over time. CONCLUSIONS A structured, cognitive behavioral program is more effective than 2 control interventions in improving glycemia in adults with long-duration diabetes. Educators can successfully use modified psychological and behavioral strategies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT000142922.
Chinese medicine Angelica sinensis suppresses radiation-induced expression of TNF-α and TGF-β1 in mice

Radiotherapy of thoracic cancer often causes pulmonary inflammation leading to pneumonitis and fibrosis. We favor the hypothesis that cytokine-mediated multicellular interactions may result in the overexpression of proinflammatory cytokines such as TNF-alpha and TGF-beta1, which promotes progressive radiation-induced lung injury. The root of Angelica sinensis, known as 'Danggui' in Chinese medicine, is widely used to treat radiation-induced pneumonitis in humans and shows clinical efficacy and low/no toxicity with an unclear mechanism. Using quantitative RT-PCR and immunohistochemistry (IHC) methods, we investigated radiation-induced lung injury in a mouse model. C57BL/6 mice were assigned to 4 groups: no treatment (NT), Angelica Sinensis treatment only (AS), X-ray irradiation only (XRT, single fraction of 12 Gy irradiation to the thoraces) and AS treatment plus XRT (AS/XRT). Mice in NT and AS groups exhibited low TNF-alpha and TGF-beta1 mRNA levels and few positive cell counts for TNF-alpha (8-17 cells per field, x400 magnification) and TGF-beta1 (9-31 cells per field), respectively. In XRT mice, there were increased inflammatory cells positive for TNF-alpha and TGF-beta1 in lung tissue compared with NT mice (P<0.01). However, when XRT mice received AS treatment (AS/XRT), the number of inflammatory cells in lung tissue positive for both TNF-alpha and TGF-beta1 was decreased compared with XRT-only mice (P<0.01) accompanied by moderately decreased mRNA levels of TNF-alpha and TGF-beta1. We conclude that radiation induces expression of TNF-alpha and TGF-beta1 in the inflammatory cells of irradiated lung tissue during the pneumonic phase. The predominant localization of TNF-alpha and TGF-beta1 in inflammatory cell infiltrates suggests these cytokines' involvement in the process of radiation-induced pneumonitis. Moreover, effective down-regulation of TNF-alpha and TGF-beta1 in irradiated lung tissue by Angelica Sinensis is, at least in part, indicative of its clinical efficacy in treating radiation-induced pneumonitis.
Phenotypical characterization of regulatory T cells in humans and rodents

Regulatory T cells (Tregs) constitute a fascinating subpopulation of CD4+ T cells due to their ability to limit the immune response against self and non‐self antigens. Murine models and antibodies directed against surface and intracellular molecules have allowed elucidation of the mechanisms that govern their development and function. However, these markers used to their classification lack of specificity, as they can be expressed by activated T cells. Similarly, there are slight differences between animal models, in steady state and pathological conditions, anatomical localization and strategy of analysis by flow cytometry. Here, we revised the most common markers utilized for Treg typification by flow cytometry such as CD25, forkhead box protein 3 (FoxP3) and CD127, along with our data obtained in different body compartments of humans, mice and rats. Furthermore, we revised and determined the expression of other molecules important for the phenotypical characterization of Treg cells. We draw attention to the drawbacks of those markers used in chronic states of inflammation. However, until a specific marker for the identification of Tregs is discovered, the best combination of markers will depend upon the tissue or the degree of inflammation from which Tregs derive.
An observation on the bias in clinic-based estimates of malnutrition rates

Clinic-based data on malnutrition are the most readily available for following malnutrition levels and trends in most countries, but there is a bias inherent in clinic-based estimates of malnutrition rates. The authors compare annual clinic-based malnutrition data and those from four household surveys in Jamaica. The clinic data give lower estimates of malnutrition than the survey data in all four cases - significantly so in three. The size of the bias was variable over time, so the clinic data were not a good indicator of either levels of trends in nutrition status.
Lack of evidence of rotavirus‐dependent molecular mimicry as a trigger of coeliac disease

New data suggest the involvement of rotavirus (RV) in triggering autoimmunity in coeliac disease (CD) by molecular mimicry between the human‐transglutaminase protein and the dodecapeptide (260‐271 aa) of the RV protein VP7 (pVP7). To assess the role of RV in the onset of CD, we measured anti‐pVP7 antibodies in the sera of children with CD and of control groups. We analysed serum samples of 118 biopsy‐proven CD patients and 46 patients with potential CD; 32 children with other gastrointestinal diseases; 107 no‐CD children and 107 blood donors. Using enzyme‐linked immunosorbent assay (ELISA) assay, we measured immunoglobulin (Ig)A–IgG antibodies against the synthetic peptides pVP7, the human transglutaminase‐derived peptide (476–487 aa) which shows a homology with VP7 protein and a control peptide. The triple‐layered RV particles (TLPs) containing the VP7 protein and the double‐layered RV‐particles (DLPs) lacking the VP7 protein were also used as antigens in ELISA assay. Antibody reactivity to the RV‐TLPs was positive in 22 of 118 (18%) CD patients and in both paediatric (17 of 107, 16%) and adult (29 of 107, 27%) control groups, without showing a statistically significant difference among them (P = 0·6, P = 0·1). Biopsy‐proven CD patients as well as the adult control group demonstrated a high positive antibody reactivity against both pVP7 (34 of 118, 29% CD patients; 66 of 107, 62% adult controls) and control synthetic peptides (35 of 118, 30% CD patients; 56 of 107, 52% adult controls), suggesting a non‐specific response against RV pVP7. We show that children with CD do not have higher immune reactivity to RV, thus questioning the molecular mimicry mechanism as a triggering factor of CD.
Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis

The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non‐invasive diagnosis, follow‐up and more appropriate use of treatment. The aim of this study was to explore the role of serum high‐mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti‐NCS), complement factor C1q (anti‐C1q) and glomerular basement membrane (anti‐GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme‐linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti‐NCS, anti‐GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without renal involvement. The anti‐C1q and the HMGB1 serum levels were correlated positively with pSLE activity. The HMGB1 serum levels were also correlated positively with pLN activity. These findings suggest that serum anti‐NCS, anti‐GBM and HMGB1 may serve as biomarkers specific for the presence of nephritis in pSLE. HMGB1 emerged as a useful biomarker for the assessment of pLN and pSLE activity, whereas anti‐C1q only of pSLE activity.
Down-regulation of Fibulin-5 is associated with aortic dilation: role of inflammation and epigenetics.

AIMS Destructive remodelling of extracellular matrix (ECM) and inflammation lead to dilation and ultimately abdominal aortic aneurysm (AAA). Fibulin-5 (FBLN5) mediates cell-ECM interactions and elastic fibre assembly and is critical for ECM remodelling. We aimed to characterize FBLN5 regulation in human AAA and analyse the underlying mechanisms. METHODS AND RESULTS FBLN5 expression was significantly decreased in human aneurysmatic aortas compared with healthy vessels. Local FBLN5 knockdown promoted aortic dilation and enhanced vascular expression of inflammatory markers in Ang II-infused C57BL/6J mice. Inflammatory stimuli down-regulated FBLN5 expression and transcriptional activity in human aortic vascular smooth muscle cells (VSMC). Further, aortic FBLN5 expression was reduced in LPS-challenged mice. A SOX response element was critical for FBLN5 promoter activity. The SOX9 expression pattern in human AAA parallels that of FBLN5, and like FBLN5, it was reduced in TNFα-stimulated VSMC. Interestingly, SOX9 over-expression prevented the cytokine-mediated reduction of FBLN5 expression and transcription. The inhibition of Class I histone deacetylases (HDACs) by MS-275 or gene silencing attenuated the inflammation-mediated decrease of FBLN5 expression in VSMC and in the vascular wall. Consistently, HDAC inhibition counteracted the reduction of SOX9 expression induced by inflammatory stimuli and prevented the TNFα-mediated decrease in the binding of SOX9 to FBLN5 promoter normalizing FBLN5 expression. CONCLUSION We evidence the deregulation of FBLN5 in human AAA and identify a SOX9/HDAC-dependent mechanism involved in the down-regulation of FBLN5 by inflammation. HDAC inhibitors or pharmacological approaches that aimed to preserve FBLN5 could be useful to prevent the disorganization of ECM induced by inflammation in AAA.
Emergency Room High Index of Suspicion in Apparently Innocent Wounds Can Encounter Missed Tendon Injuries

Introduction: Limb inju ries by sharp objects commonly result in tendon or neurovascular damage. The aim of this study is (1) to determine the incidence of significant neurological, musculotendinous or vascular injury; (2) to explore the cause of such wounds; (3) to determine the incidence of missed injuries; and (4) to assess the prognosis of neurological, vascular and musculotendinous injuries. Methods: Fifty eight adult patients were evaluated in the Emergency Department of our institution for incised wounds sustained to upper and lower extremities. Major trauma with obvious Original Research Article
Who Cares? An Exploration, using Q methodology, of Young Carers' and Professionals' Viewpoints.

This research used Q methodology to explore the shared viewpoints of N=20 children and young people identified as young carers, within the context of looking after a family member with a disability, and of N=20 professionals working with children and young people. A literature search revealed a layer of complex, multi-faceted discourse and social constructions around the subject of young carers in terms of their definition, identification, and circumstances, and the way in which professionals intervene in their lives. A gap in research identified that Q methodology had not before been used to elicit young carers‟ views, nor were there any published papers within the field of educational psychology relating to young carers‟ or professionals‟ viewpoints on the topic. The aim of the study was twofold: to explore young carers‟ shared viewpoints about their roles, responsibilities and experiences, including intervention and support processes from professionals, and explore the shared viewpoints of professionals about young carers and the intervention and support mechanisms available to them. A Q sort, using 50 statements, was used to elicit participant views, which were analysed using by-person factor analysis. Results revealed four distinct factors (shared viewpoints) within young carer participants: (Factor 1: “We‟re proud and positive. We feel included and well supported but don‟t like being singled out”; Factor 2: “Caring‟s just what we do. We feel mature, but are unsupported and misunderstood”; Factor 3: “„Parentified‟ and wanting to care, but we need people to recognise that we‟re struggling and worried”; Factor 4: “Being mature doesn‟t stop us from worrying, although we‟re supported, especially in school”), and two distinct factors within professionals: (Factor 1: “Young carers worry and struggle. They are unsupported and neglected by professionals”; Factor 2: “Young carers are mature and resilient, and want to be treated like every other young person. Professionals could do more, but are getting there”). These factors were interpreted and discussed, and the implications for professional practice explored.
Spirituality among Physicians and Nurses in Metropolitan Cities

Purpose: This study was a descriptive survey research to investigate physicians and nurses' spirituality and to determine thegeneral characteristicsof physicians and nurses and the differencesintheir spiritualityaccording to characteristicsrelated to their works. Methods:Theparticipants were 120 physicians and120nurses working in general hospitals with more than 500 beds located in metropolitan cities. The study data were collected from Nov. 15, 2009 to Dec. 30, 2009. Spirituality was measured using 'The scale for Koreans' spirituality' developed byLee et al (2003). The scale has 30questions answered ona five-point scale. Descriptive statistics, ANCOVA, t-test and one-wayANOVA werealsoused withtheSPSS/WIN 170.0 programto analyze the data. Results:The spiritualityof physiciansandnurseswas slightlyhigher than 3points, a theoreticalmean, which wasat mid-level. Thenurseshada significantlyhigher level than thephysiciansin 6dimensions ofspiritualityandinthe dimension of awareness. For differencesof spiritualityaccording to generalcharacteristicsand work relatedcharacteristics, there were significant differences according to the importance of religion in life, religion and age. Conclusion: Interest in spiritualityisanimportant for medical professionals if they wereto meet variouspatient demandswithin diverse cultures and beliefs. Medical science and nursing science should be sensitive to the spiritual demands of medical professionalsthemselvesandtheirpatientsbydevelopingeducationalprogramstoincreasespirituality in education and practical affairs.