tbuckley/cabot-search huggingface dataset:
Musculoskeletal pain in female asylum seekers and hypovitaminosis D <sub>3</sub>
Authors: Gabrielle de Torrenté de la Jara, Alain Pécoud, Bernard Favrat
Journal: BMJ (2004)

Deficiency of vitamin D, which can lead to osteomalacia, is common in elderly patients in Western countries. However, it is still widely underdiagnosed in young immigrant women, even though the condition has been extensively reported in the immigrant Indo-Asian population in the United Kingdom since the 1960s.1–4 A recent study reports an average 59 months before diagnosis was established,5 and another study found a prevalence of 78% of hypovitaminosis D3 (compared with 58% in controls) in an Indo-Asian population attending a UK rheumatology clinic.6 When recognised, hypovitaminosis D3 is easily treatable. A study on osteomalacic myopathy in veiled Arabic women in Denmark found that muscle strength returned to normal (except in maximal voluntary contraction) after six months' treatment.7

We expected to see this disease in female asylum seekers, especially in those from societies with different customs regarding exposure to sunlight and diet. We report 11 cases of symptomatic hypovitaminosis D3 in female asylum seekers (table 1). We focus on the pathology encountered by the primary care doctors caring for these 11 patients, the length of time between the appearance of symptoms, and the establishment of the diagnosis of hypovitaminosis D3 as well as the women's response to treatment by the improvement of a wide range of clinical symptoms—bone pain, muscular weakness, and fatigue.

View this table:

Table 1. 
Demographic and clinical data for 11 female asylum seekers with hypovitaminosis D3



The primary …
Coordination of Swallowing and Phases of Respiration During Added Respiratory Loads in Awake Subjects
Authors: MASATO KIJIMA, SHIROH ISONO, TAKASHI NISHINO
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

In order to test the hypothesis that different types of respiratory mechanical loads may differently modify the coordination of respiration and swallowing, we investigated the coordination of respiration and swallowing during resistive and elastic loads in 14 healthy subjects. Ventilation was monitored with a pneumotachograph and reflex swallowing was elicited by continuous infusion of distilled water into the pharynx (3 ml/min) and recorded on a submental electromyogram while the subject breathed through a device with a flow-resistive load (180 cm H2O/L/s), an elastic load (70 cm H2O/L), or without any external load. We found that addition of a flow-resistive load did not influence the frequency of swallowing, whereas addition of an elastic load caused a significant increase in swallowing frequency during continuous infusion of water. Analysis of the timing of swallowing in relation to respiratory cycle phase revealed that with flow-resistive loading, swallows occurred preferentially during the inspiratory–expiratory (I–E) transition, whereas with elastic loading, swallows occurred preferentially during the expiratory–inspiratory (E–I) transition. Signs of laryngeal irritation were observed most often during the elastic loading following E–I swallows. These results indicate that different types of respiratory mechanical loads can differently modify this coordination of respiration and swallowing, and suggest that the coordination may be compromised more with elastic loading than with flow-resistive loading.
Cardiovascular Events as a Function of Serum Bilirubin Levels in a Large, Statin-Treated Cohort
Authors: Laura J. Horsfall, Irwin Nazareth, Irene Petersen
Journal: Circulation (2012)

Background— Serum bilirubin is an endogenous antioxidant that is routinely measured before a statin is prescribed primarily to assess liver function, but the association with cardiovascular disease (CVD) in this population has not been explored. Method and Results— We identified patients from a United Kingdom primary care database (The Health Improvement Network) with measurements of serum total bilirubin levels recorded 3 months before the first statin treatment between January 1, 2000, and December 31, 2010, and no history of liver disease or CVD. In total, 130 052 patients met the inclusion criteria, and after a median follow-up of 43 months, there were 7850 CVD events. In men, the incidence of CVD in the lowest decile category of bilirubin (1–6 μmol/L [0.06–0.35 mg/dL]) was 215 per 10 000 person-years compared with 163 per 10 000 person-years in the highest decile (19–40 μmol/L [1.1–2.3 mg/dL]). Similar differences were seen for women. After conventional CVD risk factors were accounted for, the associations with bilirubin were nonlinear (L shaped), and the models predicted that, compared with patients with a bilirubin level of 10 μmol/L (0.6 mg/dL), those with a similar CVD risk profile but a bilirubin level of 5 μmol/L (0.3 mg/dL) had an 18% (95% confidence interval, 9–27) higher risk of any CVD event, a 34% (95% confidence interval, 13–56) higher risk of myocardial infarction, and a 33% (95% confidence interval, 21–46) higher risk of death resulting from any cause. Conclusions— Serum bilirubin level measured before a statin prescription to assess liver function is an independent risk factor for CVD and death in both men and women.
Working Conditions in Primary Care: Physician Reactions and Care Quality
Authors: Mark Linzer, Linda Baier Manwell, Eric S. Williams, James A. Bobula, Roger L. Brown, Anita B. Varkey, Bernice Man, Julia E. McMurray, Ann Maguire, Barbara Horner-Ibler, Mark D. Schwartz
Journal: Annals of Internal Medicine (2009)

Background: Adverse primary care work conditions could lead to a reduction in the primary care workforce and lower-quality patient care. Objective: To assess the relationship among adverse primary care work conditions, adverse physician reactions (stress, burnout, and intent to leave), and patient care. Design: Cross-sectional analysis. Setting: 119 ambulatory clinics in New York, New York, and in the upper Midwest. Participants: 422 family practitioners and general internists and 1795 of their adult patients with diabetes, hypertension, or heart failure. Measurements: Physician perception of clinic workflow (time pressure and pace), work control, and organizational culture (assessed survey); physician satisfaction, stress, burnout, and intent to leave practice (assessed by survey); and health care quality and errors (assessed by chart audits). Results: More than one half of the physicians (53.1%) reported time pressure during office visits, 48.1% said their work pace was chaotic, 78.4% noted low control over their work, and 26.5% reported burnout. Adverse workflow (time pressure and chaotic environments), low work control, and unfavorable organizational culture were strongly associated with low physician satisfaction, high stress, burnout, and intent to leave. Some work conditions were associated with lower quality and more errors, but findings were inconsistent across work conditions and diagnoses. No association was found between adverse physician reactions, such as stress and burnout, and care quality or errors. Limitation: The analyses were cross-sectional, the measures were self-reported, and the sample contained an average of 4 patients per physician. Conclusion: Adverse work conditions are associated with adverse physician reactions, but no consistent associations were found between adverse work conditions and the quality of patient care, and no associations were seen between adverse physician reactions and the quality of patient care. Primary Funding Source: Agency for Healthcare Research and Quality.
H3K9 Histone Methyltransferase G9a Promotes Lung Cancer Invasion and Metastasis by Silencing the Cell Adhesion Molecule Ep-CAM
Authors: Min-Wei Chen, Kuo-Tai Hua, Hsin-Jung Kao, Chia-Chun Chi, Lin-Hung Wei, Gunnar Johansson, Shine-Gwo Shiah, Pai-Sheng Chen, Yung-Ming Jeng, Tsu-Yao Cheng, Tsung-Ching Lai, Jeng-Shou Chang, Yi-Hua Jan, Ming-Hsien Chien, Chih-Jen Yang, Ming-Shyan Huang, Michael Hsiao, Min-Liang Kuo
Journal: Cancer Research (2010)

Abstract G9a is a mammalian histone methyltransferase that contributes to the epigenetic silencing of tumor suppressor genes. Emerging evidence suggests that G9a is required to maintain the malignant phenotype, but the role of G9a function in mediating tumor metastasis has not been explored. Here, we show that G9a is expressed in aggressive lung cancer cells, and its elevated expression correlates with poor prognosis. RNAi-mediated knockdown of G9a in highly invasive lung cancer cells inhibited cell migration and invasion in vitro and metastasis in vivo. Conversely, ectopic G9a expression in weakly invasive lung cancer cells increased motility and metastasis. Mechanistic investigations suggested that repression of the cell adhesion molecule Ep-CAM mediated the effects of G9a. First, RNAi-mediated knockdown of Ep-CAM partially relieved metastasis suppression imposed by G9a suppression. Second, an inverse correlation between G9a and Ep-CAM expression existed in primary lung cancer. Third, Ep-CAM repression was associated with promoter methylation and an enrichment for dimethylated histone H3K9. G9a knockdown reduced the levels of H3K9 dimethylation and decreased the recruitment of the transcriptional cofactors HP1, DNMT1, and HDAC1 to the Ep-CAM promoter. Our findings establish a functional contribution of G9a overexpression with concomitant dysregulation of epigenetic pathways in lung cancer progression. Cancer Res; 70(20); 7830–40. ©2010 AACR.
Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies
Authors: G Espinosa
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL). <b>Methods:</b> A computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002. <b>Results:</b> 46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients. <b>Conclusions:</b> The results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL.
Chylous ascites after an H-graft interposition mesocaval shunt.
Authors: J Reichen, J W Schaefer
Journal: Gut (1982)

A case of chylous ascites occurring after an emergency mesocaval shunt is reported. After an attempt at conservative management had failed, the patient was surgically explored. Although a lymphatic leak could not be identified, oversewing the retroperitoneum in the area of previous dissection and reinforcement with an omental pedicle was successful in preventing postoperative reaccumulation of chylous ascites. A review of the 26 reported cases of postoperative chylous ascites indicates a spontaneous resolution rate of 41% with non-operative management including low fat diet, paracenteses, and total parenteral nutrition. If conservative measures fail, surgical repair of the traumatised lymphatic bed has been successful.
Determination of smoking status of rheumatoid arthritis patients by means of a self-reported questionnaire and serum cotinine assay: a cross-sectional study
Authors: K. Naraghi, M. Booth, A. J. Russell, J. M. van Laar
Journal: Annals of the Rheumatic Diseases (2011)

Rheumatoid arthritis (RA) is characterised by a chronic, destructive and debilitating arthritis.1 Smoking may adversely influence the severity of RA as well as its response to treatment in a dose-dependent manner.1,–,4 Furthermore, the link between passive smoking and RA has been suggested by some researchers.5 Self-reporting is commonly used to identify the smoking status of RA patients. In the general population, self-reporting underestimates the true rate of smoking.6 7 To what extent this issue affects RA patients in particular is unreported. Unless we correctly ascertain RA patients in terms of smoking status, it will remain difficult to investigate the true impact of smoking, or smoking cessation, on signs and symptoms associated with the disease.

To address this issue, we recently determined the smoking status of RA patients attending the Rheumatology Department of a large university …
Cholesteryl ester transfer protein and lecithin: Cholesterol acyltransferase activities in hispanic and anglo postmenopausal women: Associations with total and regional body fat
Authors: Kathryn A. Greaves, Scott B. Going, Maria Luz Fernandez, Laura A. Milliken, Timothy G. Lohman, Tamsen Bassford, Donald J. McNamara
Journal: Metabolism (2003)
CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice
Authors: Daniel Turnberg, Marina Botto, Joanna Warren, B. Paul Morgan, Mark. J. Walport, H. Terence Cook
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. CD59 is a complement regulatory protein that inhibits the terminal part of the complement system, the membrane attack complex (MAC), a mediator of renal injury. Mice deficient in the <i>Cd59a</i> gene (<i>mCd59a</i>−/−) were used to investigate the role of CD59 in experimentally induced accelerated nephrotoxic nephritis, a model of immune complex–mediated glomerulonephritis. After accelerated nephrotoxic nephritis was induced by administration of sheep nephrotoxic globulin, <i>mCd59a</i>−/− mice and strain-matched controls on two genetic backgrounds, 129/Sv × C57BL/6 and 129/Sv, were examined. For both, <i>mCd59a</i>−/− mice developed significantly greater glomerular cellularity than wild-type (WT) mice at day 5 after administration. At day 10 post-administration, <i>mCd59a</i>−/− mice exhibited more glomerular thrombosis than WT mice (thrombosis score, 1.8 [range, 1.4 to 4.0] <i>versus</i> 0.8 [range, 0.2 to 1.5] quadrants thrombosed per glomerulus, respectively; <i>P</i> = 0.0006). In the majority of experiments, <i>mCd59a</i>−/− mice also had significantly more proteinuria than controls; however, there was no difference in serum creatinine or albumin. Quantitative immunofluorescence of kidney sections revealed significantly more C9 (as a marker of MAC) deposition within glomeruli of <i>mCd59a</i>−/− mice than WT controls (<i>P</i> &lt; 0.001). There was no difference in deposition of C3 and sheep IgG between the two experimental groups. The lack of CD59a, by allowing unregulated MAC deposition, exacerbates the renal injury in this model of immune complex–mediated glomerulonephritis. E-mail: t.h.cook@ic.ac.uk
Adult Psychiatric Outcomes of Bullying and Being Bullied by Peers in Childhood and Adolescence
Authors: William E. Copeland, Dieter Wolke, Adrian Angold, E. Jane Costello
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3>Both bullies and victims of bullying are at risk for psychiatric problems in childhood, but it is unclear if this elevated risk extends into early adulthood.<h3>Objective</h3>To test whether bullying and/or being bullied in childhood predicts psychiatric problems and suicidality in young adulthood after accounting for childhood psychiatric problems and family hardships.<h3>Design</h3>Prospective, population-based study.<h3>Setting</h3>Community sample from 11 counties in Western North Carolina.<h3>Participants</h3>A total of 1420 participants who had being bullied and bullying assessed 4 to 6 times between the ages of 9 and 16 years. Participants were categorized as bullies only, victims only, bullies and victims (hereafter referred to as bullies/victims), or neither.<h3>Main Outcome Measure</h3>Psychiatric outcomes, which included depression, anxiety, antisocial personality disorder, substance use disorders, and suicidality (including recurrent thoughts of death, suicidal ideation, or a suicide attempt), were assessed in young adulthood (19, 21, and 24-26 years) by use of structured diagnostic interviews.<h3>Results</h3>Victims and bullies/victims had elevated rates of young adult psychiatric disorders, but also elevated rates of childhood psychiatric disorders and family hardships. After controlling for childhood psychiatric problems or family hardships, we found that victims continued to have a higher prevalence of agoraphobia (odds ratio [OR], 4.6 [95% CI, 1.7-12.5]; P &lt; .01), generalized anxiety (OR, 2.7 [95% CI, 1.1-6.3]; P &lt; .001), and panic disorder (OR, 3.1 [95% CI, 1.5-6.5]; P &lt; .01) and that bullies/victims were at increased risk of young adult depression (OR, 4.8 [95% CI, 1.2-19.4]; P &lt; .05), panic disorder (OR, 14.5 [95% CI, 5.7-36.6]; P &lt; .001), agoraphobia (females only; OR, 26.7 [95% CI, 4.3-52.5]; P &lt; .001), and suicidality (males only; OR, 18.5 [95% CI, 6.2-55.1]; P &lt; .001). Bullies were at risk for antisocial personality disorder only (OR, 4.1 [95% CI, 1.1-15.8]; P &lt; .04).<h3>Conclusions and Relevance</h3>The effects of being bullied are direct, pleiotropic, and long-lasting, with the worst effects for those who are both victims and bullies.
Electron Transfer in Ferredoxin: Are Tunneling Pathways Evolutionarily Conserved?
Authors: Iraj Daizadeh, Dmitry M. Medvedev, Alexei A. Stuchebrukhov
Journal: Molecular Biology and Evolution (2002)

A theoretical study of electron transfer (ET) pathways in a recently crystallized Clostridium acidurici ferredoxin is reported. The electronic structure of the protein complex is treated at the semiempirical extended Hückel level, and the tunneling pathways are calculated with the rigorous quantum mechanical method of tunneling currents. The model predicts two pathways between the two [4Fe-4S] cubanes: a strong one running directly from Cys(14) to Cys(43) and a weaker one from Cys(14) via Ile(23) to Cys(18), whereas other amino acids do not play a significant role in the electron tunneling. The cysteine ligands conduct almost all of the current when Ile(23) is mutated to valine in silico, so that there is no appreciable change in the ET rate. The calculated value of the transfer matrix element is consistent with the experimentally determined rate of transfer. Results of the sequence analysis performed on this ferredoxin reveal that Ile(23) is a highly variable amino acid compared with the cubane-ligating cysteine amino acids, even though Ile(23) lies directly between the donor and acceptor complexes. We further argue that the homologous proteins with a [3Fe-4S] cofactor, which does not have one of the four cysteine ligands, use the same tunneling pathways as those in this ferredoxin, on the basis of the high homology as well as the absolute conservation of Cys(14) and Cys(43) which serve as the main tunneling conduit. Our results explain why mutation of amino acids around and between the donor and acceptor cubane clusters, including that of Ile(23), does not appreciably affect the rate of transfer and add support to the proposal that there exist evolutionarily conserved electron tunneling pathways in biological ET reactions.
Vaccination leads to an aberrant FOXP3 T-cell response in non-remitting juvenile idiopathic arthritis
Authors: A. Ronaghy, W. de Jager, E. Zonneveld-Huijssoon, M. R. Klein, F. van Wijk, G. T. Rijkers, W. Kuis, N. M. Wulffraat, B. J. Prakken
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To investigate how meningococcal C vaccination in patients with remitting (oligoarticular) or progressive (polyarticular) juvenile idiopathic arthritis (JIA) influences the specific T-cell response to both the vaccine and heat shock protein 60, a regulatory auto-antigen in JIA. <h3>Methods</h3> Twenty six oligoarticular, 28 polyarticular JIA patients and 20 healthy adults were studied before and after MenC vaccination in a prospective follow-up study. T-cell proliferation assay, flow cytometry, carboxyfluorescein diacetate succinimidyl ester staining and multiplex immunoassay were performed to quantify and qualify the antigen-specific immune responses. <h3>Results</h3> Peripheral blood mononuclear cells (PBMC) from polyarticular JIA exemplified higher antigen-specific CD4 T-cell proliferation, interleukin 2 (IL-2) and tumour necrosis factor alpha (TNFα) production when compared with oligoarticular JIA or healthy individuals after vaccination. Furthermore, in polyarticular JIA antigen-induced CD4+CD25<sup>bright</sup> or CD4+FOXP3+ T cells did not increase upon vaccination. <h3>Conclusion</h3> Polyarticular JIA CD4+FOXP3+ T cells did not respond to vaccination and demonstrated a higher percentage of cells irrespective of vaccination when compared with oligoarticular JIA. These cells are either activated T cells and/or regulatory cells unable to regulate the antigen-specific immune response after vaccination. When compared with oligoarticular JIA, the increased IL-2 and TNFα production underline the immune hyperresponsiveness of polyarticular JIA PBMC to an antigenic trigger. As this may hold a risk for derailment, these findings could provide a cellular basis for the presumed relationship between environmental triggers and disease in human autoimmune diseases.
Importance of Achieving Stringent Complete Response After Autologous Stem-Cell Transplantation in Multiple Myeloma
Authors: Prashant Kapoor, Shaji K. Kumar, Angela Dispenzieri, Martha Q. Lacy, Francis Buadi, David Dingli, Stephen J. Russell, Suzanne R. Hayman, Thomas E. Witzig, John A. Lust, Nelson Leung, Yi Lin, Steven R. Zeldenrust, Arleigh McCurdy, Philip R. Greipp, Robert A. Kyle, S. Vincent Rajkumar, Morie A. Gertz
Journal: Journal of Clinical Oncology (2013)

To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM).Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study.One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007).Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories.