tbuckley/cabot-search huggingface dataset:
Non-voltage-gated Ca2+ entry pathways in the heart: the untold STOrai?
Authors: H. E. Collins, J. C. Chatham
Journal: Cardiovascular Research (2014)

This editorial refers to ‘Emergence of Orai3 activity during cardiac hypertrophy’ by Y. Saliba et al. , doi:10.1093/cvr/cvu207 .

Our understanding of cardiomyocyte Ca2+ handling is primarily based on the regulation of voltage-gated Ca2+ entry, via L-type Ca2+ channels (LTCCs), and the resulting Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR) required for excitation–contraction coupling. Ca2+ is widely recognized as playing a key signalling role in all cells, and in cardiomyocytes the most commonly accepted pathway involves Ca2+ release from intracellular stores such as the endoplasmic reticulum (ER)/SR and the nuclear envelope. However, in non-excitable cells, agonist-mediated increases in intracellular Ca2+ are known to occur as a result of Ca2+ entry across the plasma membrane. The most widely studied of these pathways is store-operated Ca2+ entry (SOCE) as described by Putney1 where Inositol 1, 4, 5 Triphosphate (IP3)-induced release of Ca2+ from ER/SR stores triggered a subsequent influx of extracellular Ca2+, which was required both for subsequent activation of downstream signalling pathways and also for refilling of ER/SR. Such Ca2+ signals have been shown to play a key role in the regulation of diverse cellular responses, including metabolism, transcription, and differentiation. One of the earliest reports demonstrating that SOCE contributed to Ca2+ signalling in cardiomyocytes was in 2002 where Marchase and colleagues2 showed that activation of nuclear factor of activated T-cells …
Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through comparative genomics.
Authors: Nansheng Chen, Allan Mah, Oliver E Blacque, Jeffrey Chu, Kiran Phgora, Mathieu W Bakhoum, C Rebecca Hunt Newbury, Jaswinder Khattra, Susanna Chan, Anne Go, Evgeni Efimenko, Robert Johnsen, Prasad Phirke, Peter Swoboda, Marco Marra, Donald G Moerman, Michel R Leroux, David L Baillie, Lincoln D Stein
Journal: Genome biology (2006)

Abstract Background The recent availability of genome sequences of multiple related Caenorhabditis species has made it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditis elegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C. elegans , some of which may be orthologs of unidentified human ciliopathy genes. Results By screening for genes possessing canonical X-box sequences in promoters of three Caenorhabditis species, namely C. elegans , C. briggsae and C. remanei , we identified 93 genes (including known X-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subject to the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cells was confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative transcriptional profiling of different tissue types and of daf-19(+) and daf-19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5(mn400) animals, which is indicative of compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5. Conclusion Our comparative genomics-based predictions may be useful for identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome (BBS), since the C. elegans orthologs of known human BBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.
Once‐daily mometasone furoate aqueous nasal spray (Nasonex®) in seasonal allergic rhinitis: an active‐ and placebo‐controlled study
Authors: J. R. Hebert, K. Nolop, B. N. Lutsky
Journal: Allergy (1996)

Mometasone furoate aqueous nasal spray (Nasonex®) was compared with beclomethasone dipropionate (BDP) aqueous nasal spray in a double‐blind, randomized, placebo‐controlled, double‐dummy, parallel‐group study of adults with moderate to severe seasonal allergic rhinitis. Patients allergic to at least one tree and/or grass aeroallergen received one of the following regimens for up to 4 weeks: mometasone furoate 100 pg once daily [OD] ( n = 126) or 200 μg OD ( n = 126), BDP 200 μg twice daily ( n = 126), or only placebo spray ( n = 123). Physician‐rated nasal and total symptom scores. and global evaluation of overall condition and therapeutic response by physicians and patients, showed that the three active treatments were equally effective, and all three were significantly superior to placebo at most time points. Overall, mometasone furoate 200 μg OD demonstrated somewhat greater numerical, but not statistical, superiority to mometasone furoate 100 μg OD at the earliest evaluation time poinl. At the end of treatment, complete or marked relief was obtained in 77% of patients with mometasone furoate 100 pg/day, 79% with mometasone furoate 200 pg/day, and 74% with BDP, compared with 54% of placebo vehicle control patients. Mometasone furoate and BDP were equally well tolerated. It was concluded that mometasone furoate adequately controls symptoms of moderate to severe seasonal allergic rhinitis, offers the advantage of OD treatment, and is well tolerated.
The association between primary biliary cirrhosis and coeliac disease: a study of relative prevalences
Authors: J G C Kingham, D R Parker
Journal: Gut (1998)

Background —Coexistent primary biliary cirrhosis (PBC) and coeliac disease has been recorded but the association has not been systematically studied. Aims —To determine relative prevalences of PBC and coeliac disease in a defined population over a 12 year period. Patients and methods —All patients with PBC or coeliac disease in a stable population of 250 000 in South Wales were identified from a clinical register and laboratory records. Results —Sixty seven patients with PBC and 143 patients with coeliac disease have been diagnosed and followed over a median of 86 (4–135) months; point prevalences in 1996 were 20 per 100 000 for PBC and 54 per 100 000 for coeliac disease. PBC in patients with coeliac disease was sought by investigating abnormal liver function tests. Ten (7%) had persistent abnormalities and three had PBC. Coeliac disease in patients with PBC was sought by investigating malabsorption, haematinic deficiency, positive antigliadin antibody, or coeliac disease family history. Eleven patients underwent duodenal biopsy revealing one further coeliac disease case. Four patients (three women) have both conditions giving a point prevalence for patients with both conditions of 1.6 per 100 000 (95% confidence limits 0.44 to 4.1 per 100 000). Prevalence of PBC in patients with coeliac disease was 3% and of coeliac disease in patients with PBC was 6%. Conclusion —A 12 year study of a stable 250 000 population revealed a relative prevalence of PBC in 3% of 143 patients with coeliac disease and of coeliac disease in 6% of 67 patients with PBC. PBC and coeliac disease are therefore associated. Screening for PBC in patients with coeliac disease using antimitochondrial antibody testing and screening for coeliac disease in patients with PBC with antigliadin antibody testing or duodenal biopsy are recommended.
Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients
Authors: Jing-Ping Zhang, Jing Yan, Jing Xu, Xiong-Hao Pang, Min-Shan Chen, Li Li, Changyou Wu, Sheng-Ping Li, Limin Zheng
Journal: Journal of Hepatology (2009)
Wood smoke exposure induces a pulmonary and systemic inflammatory response in firefighters
Authors: J. R. Swiston, W. Davidson, S. Attridge, G. T. Li, M. Brauer, S. F. van Eeden
Journal: European Respiratory Journal (2008)

Epidemiological studies report an association between exposure to biomass smoke and cardiopulmonary morbidity. The mechanisms for this association are unclear. The aim of the present study was to characterise the acute pulmonary and systemic inflammatory effects of exposure to forest fire smoke. Seasonal forest firefighters (n = 52) were recruited before and/or after a day of fire-fighting. Exposure was assessed by questionnaires and measurement of carbon monoxide levels (used to estimate respirable particulate matter exposure). The pulmonary response was assessed by questionnaires, spirometry and sputum induction. Peripheral blood cell counts and inflammatory cytokines were measured to define the systemic response. Estimated respirable particulate matter exposure was high (peak levels &gt;2 mg·m −3 ) during fire-fighting activities. Respiratory symptoms were reported by 65% of the firefighters. The percentage sputum granulocytes increased significantly from 6.5 to 10.9% following fire-fighting shifts, with concurrent increases in circulating white blood cells (5.55×10 9 to 7.06×10 9 cells·L −1 ) and band cells (0.11×10 9 to 0.16×10 9 cells·L −1 ). Serum interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 levels significantly increased following fire-fighting. There were no changes in band cells, IL-6, and IL-8 following strenuous physical exertion without fire-fighting. There was a significant association between changes in sputum macrophages containing phagocytosed particles and circulating band cells. In conclusion, acute exposure to air pollution from forest fire smoke elicits inflammation within the lungs, as well as a systemic inflammatory response.
Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy
Authors: J.S. Abramson, T. Feldman, A.R. Kroll-Desrosiers, L.S. Muffly, E. Winer, C.R. Flowers, F. Lansigan, C. Nabhan, L.J. Nastoupil, R. Nath, A. Goy, J.J. Castillo, D. Jagadeesh, B. Woda, S.T. Rosen, S.M. Smith, A.M. Evens
Journal: Annals of Oncology (2014)
Steroid Sidestep: Evading Androgen Ablation by Abiraterone
Authors: Nima Sharifi
Journal: Clinical Cancer Research (2014)

Tumor mechanisms of abiraterone resistance in clinical prostate cancer are not well defined. Chen and colleagues report that a T878A androgen receptor mutation occurs in a subset of patients progressing while receiving abiraterone, suggesting that this may be a therapeutically exploitable mechanism of abiraterone resistance in castration-resistant prostate cancer.
Impact of a Community Health Workers–Led Structured Program on Blood Glucose Control Among Latinos With Type 2 Diabetes: The DIALBEST Trial
Authors: Rafael Pérez-Escamilla, Grace Damio, Jyoti Chhabra, Maria L. Fernandez, Sofia Segura-Pérez, Sonia Vega-López, Grace Kollannor-Samuel, Mariana Calle, Fatma M. Shebl, Darrin D’Agostino
Journal: Diabetes Care (2014)

Latinos with type 2 diabetes (T2D) face major healthcare access and disease management disparities. We examined the impact of the Diabetes Among Latinos Best Practices Trial (DIALBEST), a community health worker (CHW)-led structured intervention for improving glycemic control among Latinos with T2D.A total of 211 adult Latinos with poorly controlled T2D were randomly assigned to a standard of healthcare (n = 106) or CHW (n = 105) group. The CHW intervention comprised 17 individual sessions delivered at home by CHWs over a 12-month period. Sessions addressed T2D complications, healthy lifestyles, nutrition, healthy food choices and diet for diabetes, blood glucose self-monitoring, and medication adherence. Demographic, socioeconomic, lifestyle, anthropometric, and biomarker (HbA1c, fasting blood glucose, and lipid profile) data were collected at baseline and 3, 6, 12, and 18 months (6 months postintervention). Groups were equivalent at baseline.Participants had high HbA1c at baseline (mean 9.58% [81.2 mmol/mol]). Relative to participants in the control group, CHWs had a positive impact on net HbA1c improvements at 3 months (-0.42% [-4.62 mmol/mol]), 6 months (-0.47% [-5.10 mmol/mol]), 12 months (-0.57% [-6.18 mmol/mol]), and 18 months (-0.55% [-6.01 mmol/mol]). The overall repeated-measures group effect was statistically significant (mean difference -0.51% [-5.57 mmol/mol], 95% CI -0.83, -0.19% [-9.11, -2.03 mmol/mol], P = 0.002). CHWs had an overall significant effect on fasting glucose concentration that was more pronounced at the 12- and 18-month visits. There was no significant effect on blood lipid levels, hypertension, and weight.DIALBEST is an effective intervention for improving blood glucose control among Latinos with T2D.
Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B
Authors: Mi Sung Park, Beom Kyung Kim, Kyung Sik Kim, Ja Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Oidov Baartarkhuu, Kwang Hyub Han, Chae Yoon Chon, Sang Hoon Ahn
Journal: Clinical and Molecular Hepatology (2013)

Background/Aims The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment. Methods Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks. Results The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log10 IU/mL, week 96: -4.27 log10 IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P=0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm. Conclusions There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available. Keywords: Hepatitis B virus; Multidrug resistance; Hepatitis B; Entecavir; Adefovir
Mental Health Service Delivery and Suicide Risk: The Role of Individual Patient and Facility Factors
Authors: Rani A Desai, David J Dausey, Robert A Rosenheck
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study explores suicide rates as a quality measure and identifies risk factors for suicide among psychiatric inpatients. METHOD: Data from a prospective mortality study of psychiatric inpatients from 128 U.S. Department of Veterans Affairs hospitals throughout the United States were utilized to examine the relationship of death by suicide to patient-level sociodemographic, clinical, and mental health service delivery characteristics, as well as to facility-level measures of service delivery. Data were collected on all patients discharged with a diagnosis of schizophrenia, major depression, posttraumatic stress disorder, or bipolar disorder (N=121,933) between 1994 and 1998. RESULTS: There were 481 suicides in the study sample. Several variables were associated with higher risk for suicide risk, including length of stay less than 14 days, poorer continuity of care, and lack of readmission within 6 months. These variables were significant even after adjustment for state suicide rates, the proportion of members of racial minority groups in the state population, and state-level social capital. CONCLUSIONS: Suicide rates are not likely to be a useful indicator of the quality of mental health care because of the instability of suicide rates, difficulty collecting data, and the lack of association between suicide and facility quality of care. The lack of association with facility-level variables suggests that systemic changes in these performance measures would be unlikely to significantly reduce suicide rates.
Polymorphism in the beta subunit and Na+ transport.
Authors: D G Warnock
Journal: Journal of the American Society of Nephrology (1996)

Primary dysregulation of the epithelial sodium channel, manifested by continuing Na+ channel activity despite dietary salt excess, would cause inappropriate renal sodium reabsorption, blunted sodium excretion, and low-renin hypertension. There are now well-characterized genetic causes of hypertension in human pedigrees, which are explained by inappropriate and/or constitutive activation of the epithelial Na+ channel. Although Liddle's syndrome has been the most thoroughly investigated, the incidence of such activating mutations in the subunits of the Na+ channel appears to be relatively rare. Of continuing interest is the possibility that polymorphisms in the channel subunits could result in activation of the channel in response to normal regulatory influences. One such example is provided by a provocative report by Su et al. In this issue of the journal (J Am Soc Nephrol 1996;7:2543-2549). Despite several important technical limitations of the findings presented in the article, the suggestion that polymorphisms found in defined human populations would affect the regulation of sodium channel activity in response to environmental variables is worthy of serious consideration, and serves as a further stimulus to defining the functional significance of the various polymorphisms described in the subunits of the amiloride-sensitive sodium channel.
P225 First national survey of the respiratory physiotherapy workforce
Authors: C. Mikelsons, M. Buxton
Journal: Thorax (2010)

In 2008, the RCP/BTS COPD Audit reviewed the multidisciplinary workforce provided by acute Trusts in managing the care of patients with COPD: the results showed that nationally, the median number of respiratory specialist physiotherapists employed in each hospital was 1 (Abstract P225 Table 1), highlighting that the understanding of the number and speciality level of this workforce is poorly recognised by other professionals. In conjunction with the BTS, and to complement the recently published BTS/ACPRC Physiotherapy Guidelines on the Spontaneously Breathing Adult Medical Patient (2009), a survey of the respiratory physiotherapy workforce was carried out in October 2009. An electronic questionnaire was sent to all ACPRC members and circulated to members of the Chartered Society of Physiotherapy, with a request for a response from each institution, providing information on the number of respiratory physiotherapists, their grading and the estimated percentages of various diagnostic respiratory cases seen on a daily basis. 149 responses were received: 70% (n=105) from acute trusts, 24% (n=36) from primary care organisations. 73% (n=110) of respiratory physiotherapists were employed by physiotherapy departments: 59% (n=89) as dedicated medical respiratory physiotherapy teams, the rest providing cross speciality respiratory physiotherapy cover. The results highlight the model of staffing most often seen in respiratory physiotherapy, with the team consisting of a range of staffing grades but no standard team structure nationally. The level of physiotherapy clinician leading the team varied from Band 7 to a Consultant Respiratory Physiotherapist (8A – 8D): the average was less than 1 at Band 8 nationally. 54% (n=81) of responders were ACPRC members, 19% (n=28) both ACPRC and BTS members. The survey identified that largely the respiratory physiotherapy workforce is not embedded within respiratory medicine departments which means that appreciation of multidisciplinary team membership is of even greater importance. Despite the survey identifying a higher number of respiratory physiotherapists compared to earlier audit results, it also highlighted a workforce capacity shortfall, leaving some respiratory patients untreated on a daily basis. In addition, there is a need to encourage membership of special interest groups such as the ACPRC and BTS to promote exchange and dissemination of good practice.
Bioavailability of inhaled fluticasone propionate via chambers/masks in young children
Authors: K. Blake, R. Mehta, T. Spencer, R.L. Kunka, L. Hendeles
Journal: European Respiratory Journal (2011)

We determined lung bioavailability of a fluticasone propionate (FP) pressurised metred-dose inhaler (Flovent HFA; GlaxoSmithKline, Research Triangle Park, NC, USA) administered via AeroChamber Plus (Monaghan Medical, Plattsburgh, NY, USA) with Facemask and Babyhaler (GlaxoSmithKline) valved holding chambers (VHCs) using a population pharmacokinetic approach. Children from 1 to <4 yrs of age with stable asthma but a clinical need for inhaled corticosteroid therapy were administered 88 μg FP hydrofluoroalkane (2 × 44 μg) twice daily delivered through the two devices in an open-label, randomised crossover manner for 8 days each. Patients were randomised to one of three sparse sampling schedules for blood collection throughout the 12-h dosing interval on the 8th day of each treatment for pharmacokinetic analysis. The area under the FP plasma concentration-time curve (AUC) was determined for each regimen. 17 children completed the study. The population mean AUC following FP with AeroChamber Plus with Facemask was 97.45 pg·h·mL(-1) (95% CI 85.49-113.32 pg·h·mL(-1)) and with Babyhaler was 51.55 pg·h·mL(-1) (95% CI 34.45-64.46 pg·h·mL(-1)). The relative bioavailability (Babyhaler/AeroChamber Plus) was 0.53 (95% CI 0.30-0.75). Clinically significant differences in lung bioavailability were observed between the devices. VHCs are not interchangeable, as differences in drug delivery to the lung may occur. A population pharmacokinetic approach can be used to determine lung bioavailability of FP.
Comparison of Anthropometric Characteristics in Predicting the Incidence of Type 2 Diabetes in the EPIC-Potsdam Study
Authors: Matthias B. Schulze, Christin Heidemann, Anja Schienkiewitz, Manuela M. Bergmann, Kurt Hoffmann, Heiner Boeing
Journal: Diabetes Care (2006)

Obesity is a well-established risk factor for type 2 diabetes (1–3). However, while several studies (4–10) suggest that anthropometric measurements that describe central fat distribution are superior in predicting type 2 diabetes compared with measurements of general adiposity, this issue remains controversial (11–14). The aim of this study was to compare different anthropometric measurements and derived estimates of body composition, in particular BMI, waist-to-height ratio, waist-to-hip ratio (WHR), metric index, and percentage body fat, in their ability to predict risk of type 2 diabetes in a large prospective cohort study of men and women.

The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study includes 27,548 subjects, 16,644 women aged mainly 35–65 years and 10,904 men aged mainly 40–65 years, from the general population of Potsdam, Germany, recruited between 1994 and 1998 (15). The baseline examination included anthropometric measurements (16,17) as well as a personal interview and a questionnaire on prevalent diseases and sociodemographic and lifestyle characteristics. Follow-up questionnaires have been administered every 2–3 years. Response rates for follow-up rounds 1, 2, 3, and 4 were 96, 95, 91, and 90% (31 August 2005), respectively. All potential incident cases of diabetes were verified by the diagnosing physician using …