tbuckley/cabot-search huggingface dataset:
Factors Influencing Glycemic Control in Type 2 Diabetes During Acute- and Maintenance-Phase Treatment of Major Depressive Disorder With Bupropion
Authors: Patrick J. Lustman, Monique M. Williams, Gregory S. Sayuk, Billy D. Nix, Ray E. Clouse
Journal: Diabetes Care (2007)

Depression management in both short- and longer-term treatment studies has been associated with improvement in glycemic control. We used bupropion hydrochloride (Wellbutrin XL) to determine whether this improvement could be attributed to changes in anthropometrics or diabetes self-care.Ninety-three patients with type 2 diabetes and major depressive disorder (MDD) received bupropion hydrochloride in a two-phase, open-label treatment trial. Those who completed the acute phase (10 weeks; n = 75) and whose depression remitted (n = 63) continued bupropion at the remission dose and were followed in the maintenance phase (24 weeks) until attrition (n = 8) or relapse of MDD (n = 0). Self-report scales were used to measure depression symptom severity and diabetes self-care behaviors. Body composition and glycemic control were determined using dual-energy X-ray absorptiometry and serial determinations of A1C.BMI, total fat mass, and A1C decreased and composite diabetes self-care improved over the acute phase (-0.5 kg/m2, -0.7 kg, -0.5%, and +0.4, respectively, P < 0.01 for each), effects that persisted through the maintenance phase for BMI, A1C, and self-care (P < or = 0.01 for each). Reductions in BMI (B = 0.30, P = 0.01) and depression severity (B = 0.04, P = 0.046) independently predicted lower A1C after acute-phase treatment, whereas only reduction in depression severity (B = 0.08, P = 0.001) predicted A1C over the maintenance interval.In the short term, improvement in glycemic control during bupropion treatment is predicted independently by improvements in mood and body composition. Longer-term improvements in glycemic control are predicted primarily by sustained improvement in mood via mechanisms independent of anthropometric and self-care modifications.
The process of truth disclosure: an assessment of the results of information during the diagnostic phase in patients with cancer
Authors: G. Numico, M. Anfossi, G. Bertelli, E. Russi, G. Cento, N. Silvestris, C. Granetto, G. Di Costanzo, M. Occelli, E. Fea, O. Garrone, M. Gasco, I. Colantonio, M. Merlano
Journal: Annals of Oncology (2009)
Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data
Authors: Jennifer C Schymick, Sonja W Scholz, Hon-Chung Fung, Angela Britton, Sampath Arepalli, J Raphael Gibbs, Federica Lombardo, Mar Matarin, Dalia Kasperaviciute, Dena G Hernandez, Cynthia Crews, Lucie Bruijn, Jeffrey Rothstein, Gabriele Mora, Gabriella Restagno, Adriano Chiò, Andrew Singleton, John Hardy, Bryan J Traynor
Journal: The Lancet Neurology (2007)
Xpert MTB/RIF and pulmonary tuberculosis: time to delve deeper?
Authors: Lancelot M Pinto, Zarir F Udwadia
Journal: Thorax (2013)

I find out what the world needs, then proceed to invent it. Thomas Edison.

If Edison, the world’s most prolific inventor, had to get around to creating a new diagnostic test for tuberculosis (TB), he would have considered himself pleased with the Xpert MTB/RIF test. Here is the new diagnostic test for TB that the physician in the developing world has been waiting for. It does two things, and does them both well. It diagnoses TB with a higher sensitivity than a sputum smear examination: a single Xpert MTB/RIF test diagnoses 98% of sputum smear positive cases and around 70% of smear-negative patients.1 More importantly, for the physician practicing in areas with a high prevalence of multi-drug resistant TB (MDR-TB), it diagnoses rifampicin resistance (a surrogate marker for MDR-TB) with around 98% sensitivity and specificity, thus identifying patients who need second-line drugs.2 That it does this with safety, speed and simplicity is what makes this test a ‘game changer’.3 A result is obtained within 90 min, lopping off 6–8 weeks from the time that a traditional culture would take to diagnose MDR-TB. Called a ‘laboratory in a cartridge’, the test comprises of a cartridge-based system using an automated real-time, PCR-based assay with molecular beacon technology. The test, which is easy to learn, can be performed by a technician with 2 days of training. Robust enough to be performed in emergency departments and small laboratories in hospitals across the developing world, it poses substantially less of a biohazard risk and hence obviates the need for bio safety cabinets, which are anyway conspicuous by …
Inhibin and premature ovarian failure
Authors: A.L. Chand, C.A. Harrison, A.N. Shelling
Journal: Human Reproduction Update (2009)

Elucidation of the causes of premature ovarian failure (POF) is difficult due to the heterogeneity of the condition. Inhibin is a potential candidate gene for POF based on its dual actions on FSH secretion by the pituitary and gametogenesis in the gonads. A missense mutation in the inhibin α subunit gene (INHA G769A) is associated with POF in several populations. However, there is phenotypic heterogeneity in INHA G769A mutation carriers. Relevant studies were identified by searching PubMed and mutational frequencies combined for meta-analysis. Meta-analysis of published studies revealed a risk difference of 0.04 (−0.030 to 0.11). The occurrence of asymptomatic carriers in populations suggests incomplete penetrance and/or a multi-genetic cause of POF. We propose that a decline in inhibin bioactivity caused by the mutation could increase FSH levels; and in a susceptible individual, the heightened sensitivity to gonadotrophins causes POF. Impaired paracrine effects of inhibin could impact folliculogenesis due to reduced antagonism of activin, bone morphogenetic protein 15 and growth differentiation factor 9. Functional studies of this mutation indicate normal production of dimeric inhibin A and B and impaired bioactivity of inhibin B. The identification of an autosomal mutation in the inhibin α subunit gene that is significantly linked to POF in certain ethnic populations highlights the role of inhibin in the regulation of ovarian biology and fertility. Although the reduction of inhibin B bioactivity by the INHA G769A mutation is clearly not the only cause, evidence suggests that this change may serve as a susceptibility factor, increasing the likelihood of POF.
MPs agree new financial security pledge for general practice
Authors: A. O'Dowd
Journal: BMJ (2015)

MPs have agreed to a motion that commits the government to securing the financial future of general practice and have voiced strong support for the work done by GPs. However, GP leaders are sceptical about what they called “rhetoric” in the debate, which they fear will lead to little concrete action.

During a three hour debate in the House of Commons on 5 February MPs debated a motion that recognised the vital contribution GPs make to the NHS and acknowledged that there were justified concerns about the strain on services and that they needed better funding.

The motion, sparked by the “Put patients first: back general practice” campaign (www.rcgp.org.uk/campaign-home.aspx) led by the Royal College of General Practitioners and the National Association for Patient Participation, was sponsored by a cross party group of MPs.

Derek Twigg, Labour MP for Halton, proposed the motion, which called on the health secretary to work with NHS England and the royal college to secure the financial future of local GP services “as a matter of urgency.” He said that the vast majority of GPs did an …
Role of early life exposure and environment on neurodegeneration: implications on brain disorders
Authors: Shweta Modgil, Debomoy K Lahiri, Vijay L Sharma, Akshay Anand
Journal: Translational Neurodegeneration (2014)

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and retinal degeneration have been studied extensively and varying molecular mechanisms have been proposed for onset of such diseases. Although genetic analysis of these diseases has also been described, yet the mechanisms governing the extent of vulnerability to such diseases remains unresolved. Recent studies have, therefore, focused on the role of environmental exposure in progression of such diseases especially in the context of prenatal and postnatal life, explaining how molecular mechanisms mediate epigenetic changes leading to degenerative diseases. This review summarizes both the animal and human studies describing various environmental stimuli to which an individual or an animal is exposed during in-utero and postnatal period and mechanisms that promote neurodegeneration. The SNPs mediating gene environment interaction are also described. Further, preventive and therapeutic strategies are suggested for effective intervention.
A randomized trial comparing myocardial salvage achieved by coronary stenting versus balloon angioplasty in patients with acute myocardial infarction considered ineligible for reperfusion therapy
Authors: Adnan Kastrati, Julinda Mehilli, Stefan Nekolla, Hildegard Bollwein, Stefan Martinoff, Jürgen Pache, Helmut Schühlen, Melchior Seyfarth, Meinrad Gawaz, Franz-Josef Neumann, Josef Dirschinger, Markus Schwaiger, Albert Schömig
Journal: Journal of the American College of Cardiology (2004)
Cytotoxic T-cell responses show more restricted specificity for self than for non-self H-2D-coded antigens
Authors: RV Blanden, U Kees
Journal: The Journal of Experimental Medicine (1978)

The specificity of recognition of H-2 antigens by various subsets of Tc cells was investigated with respect to the two separate molecules known to be coded in the H-2D(d) region (a) D which carries the private specificity H-2.4 and (b) D' which carries the public specificity H-2.28. BALB/c.H-2(db) mutant mice express D but not D' on their cell surfaces, whereas wild-type BALB/c mice express both D and D'. H-2 restricted Tc cells specific for viral-plus- H-2D(d)-coded antigens on infected self cells, or minor H-plus-H-2D(d)-coded antigens on H-2-compatible cells apparently recognize D, but do not detectably recognize D. In contrast, BALB/c-H-2(db) anti-BALB/c Tc cell responses do recognize D' (the only known antigen which is not shared by mutant and wild-type); furthermore, D' is also detectably recognized by a significant proportion of the Tc cells that respond in MLR to H-2D(d)-coded antigens. In these latter responses, D' was recognized separately from D, i.e., the response was not "H-2 restricted". These results indicate that H-2 restricted Tc cell responses to modified-self cells are more specific for self H-2D(d)-coded antigens then are allogeneic Tc cell responses directed at the same antigens, in that haplotype-unique (private) specificity recognition (of the D molecule) exclusively occurs only in the former, not the latter case. The implications of this specificity of H-2 restricted responses for possible processes of somatic selection of anti-self recognition structures on progenitor Tc cells are briefly discussed.
The Effects of Free-Living Interval-Walking Training on Glycemic Control, Body Composition, and Physical Fitness in Type 2 Diabetic Patients
Authors: Kristian Karstoft, Kamilla Winding, Sine H. Knudsen, Jens S. Nielsen, Carsten Thomsen, Bente K. Pedersen, Thomas P.J. Solomon
Journal: Diabetes Care (2012)

To evaluate the feasibility of free-living walking training in type 2 diabetic patients and to investigate the effects of interval-walking training versus continuous-walking training upon physical fitness, body composition, and glycemic control.Subjects with type 2 diabetes were randomized to a control (n = 8), continuous-walking (n = 12), or interval-walking group (n = 12). Training groups were prescribed five sessions per week (60 min/session) and were controlled with an accelerometer and a heart-rate monitor. Continuous walkers performed all training at moderate intensity, whereas interval walkers alternated 3-min repetitions at low and high intensity. Before and after the 4-month intervention, the following variables were measured: VO(2)max, body composition, and glycemic control (fasting glucose, HbA(1c), oral glucose tolerance test, and continuous glucose monitoring [CGM]).Training adherence was high (89 ± 4%), and training energy expenditure and mean intensity were comparable. VO(2)max increased 16.1 ± 3.7% in the interval-walking group (P < 0.05), whereas no changes were observed in the continuous-walking or control group. Body mass and adiposity (fat mass and visceral fat) decreased in the interval-walking group only (P < 0.05). Glycemic control (elevated mean CGM glucose levels and increased fasting insulin) worsened in the control group (P < 0.05), whereas mean (P = 0.05) and maximum (P < 0.05) CGM glucose levels decreased in the interval-walking group. The continuous walkers showed no changes in glycemic control.Free-living walking training is feasible in type 2 diabetic patients. Continuous walking offsets the deterioration in glycemia seen in the control group, and interval walking is superior to energy expenditure-matched continuous walking for improving physical fitness, body composition, and glycemic control.
Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial
Authors: Mitsue Saito, Kenjiro Aogi, Ikuo Sekine, Hirohisa Yoshizawa, Yasuhiro Yanagita, Hiroshi Sakai, Kenichi Inoue, Chiyoe Kitagawa, Takashi Ogura, Shoichi Mitsuhashi
Journal: The Lancet Oncology (2009)
HOST-PARASITE INTERACTION IN THE RAT RENAL PELVIS
Authors: Fredric J. Silverblatt
Journal: The Journal of Experimental Medicine (1974)

The initial interaction between bacteria and the renal pelvic epithelium may determine whether intrarenal infection occurs. A model of retrograde pyelonephritis was employed to study these events by electron microscopy. Female rats received an intravesicular inoculation of a 0.5-ml suspension of Proteus mirabilis containing 10(8) organisms. At intervals after inoculation, the kidneys were fixed by intravascular perfusion and the tissues were prepared for electron microscopy. During the first 24 h, increasing numbers of bacteria were seen to be attached by pili to the renal pelvic epithelial cells. The organism appeared to cross the mucosal barrier by several mechanisms: (a) penetration into the cytoplasm of intact epithelial cells, (b) passage between epithelial cells that were separated by excessive hydrostatic pressure generated during bladder inoculation, (c) passage across necrotic regions of the pelvis, and (d) translocation to the cortex by calicotubular backflow. Whereas at inoculation bacteria possessed pili 40 A in diameter (type III pili) 24 h after reflux, the predominant type of pili measured 70 A in thickness (type IV pili). Repetitive subculture induced a similar transition in vitro. To assess the influence of pili type on virulence in this model, 80 rats were challenged with either type III or type IV pilated organisms and the frequency of rats with cortical abscesses were compared at 1 wk. A significantly greater number of rats inoculated with type IV pilated Proteus manifested macroscopic evidence of infection. These results suggest that pili play a role in the pathogenesis of ascending pyelonephritis.
Chronic Obstructive Pulmonary Disease Is Associated with Lung Cancer Mortality in a Prospective Study of Never Smokers
Authors: Michelle C. Turner, Yue Chen, Daniel Krewski, Eugenia E. Calle, Michael J. Thun
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Several studies have suggested that previous lung disease may increase the risk of lung cancer. It is important to clarify the association between previous lung disease and lung cancer risk in the general population.The association between self-reported physician-diagnosed chronic bronchitis and emphysema and lung cancer mortality was examined in a U.S. prospective study of 448,600 lifelong nonsmokers who were cancer-free at baseline.During the 20-year follow-up period from 1982 to 2002, 1,759 lung cancer deaths occurred. Cox proportional hazards models were used to obtain adjusted hazard ratios (HRs) for lung cancer mortality associated with chronic bronchitis and emphysema as well as for both of these diseases together.Lung cancer mortality was significantly associated with both emphysema (HR, 1.66; 95% confidence interval [CI], 1.06, 2.59) and with the combined endpoint of emphysema and chronic bronchitis (HR, 2.44; 95% CI, 1.22, 4.90) in analyses that combined men and women. No association was observed with chronic bronchitis alone (HR, 0.96; 95% CI, 0.72, 1.28) in the overall analysis, although the association was stronger in men (HR, 1.59; 95% CI, 0.95, 2.66) than women (HR, 0.82; 95% CI, 0.58, 1.16; p for interaction, 0.04). The association between emphysema and lung cancer was stronger in analyses that excluded early years of follow-up.This large prospective study strengthens the evidence that increased lung cancer risk is associated with nonmalignant pulmonary conditions, especially emphysema, even in lifelong nonsmokers.
Effect of scaling up women's groups on birth outcomes in three rural districts in Bangladesh: a cluster-randomised controlled trial
Authors: Kishwar Azad, Sarah Barnett, Biplob Banerjee, Sanjit Shaha, Kasmin Khan, Arati Roselyn Rego, Shampa Barua, Dorothy Flatman, Christina Pagel, Audrey Prost, Matthew Ellis, Anthony Costello
Journal: The Lancet (2010)
Iron Excretion in Thalassaemia Major After Administration of Chelating Agents
Authors: R. S. Smith
Journal: BMJ (1962)

The excretion of iron in the urine has been studied before and during treatment with a new chelating agent for iron, desferrioxamine.Three male subjects with presumably normal iron stores showed an increased iron excretion of 1 to 1.5 mg. of iron after 600 mg. of the chelate.Patients with various types of iron overload all showed a marked increase in iron excretion when the material was given parenterally (8 to 33 mg./g. of chelate).A similar effect was noted in one subject with siderosis given D.T.P.A.The possible therapeutic uses of such chelating agents are discussed.We are grateful to the Geigy Company for supplies of D.T.P.A. and to Ciba Ltd., of Horsham and Basle, for a generous supply of desferrioxamine B and for unpublished information about this material.
Phase II Study of Dasatinib in Patients with Metastatic Castration-Resistant Prostate Cancer
Authors: Evan Y. Yu, George Wilding, Edwin Posadas, Mitchell Gross, Stephane Culine, Christophe Massard, Michael J. Morris, Gary Hudes, Fabio Calabrò, Shinta Cheng, Géralyn C. Trudel, Prashni Paliwal, Cora N. Sternberg
Journal: Clinical Cancer Research (2009)

Antiproliferative and antiosteoclastic activity from preclinical models show potential for dasatinib, an oral SRC and SRC family kinase inhibitor, as a targeted therapy for patients with prostate cancer. This phase II study investigated the activity of dasatinib in patients with metastatic castration-resistant prostate cancer (CRPC).Chemotherapy-naive men with CRPC and increasing prostate-specific antigen were treated with dasatinib 100 or 70 mg twice daily. Endpoints included changes in prostate-specific antigen, bone scans, measurable disease (Response Evaluation Criteria in Solid Tumor), and markers of bone metabolism. Following Prostate Cancer Working Group 2 guidelines, lack of progression according to Response Evaluation Criteria in Solid Tumor and bone scan was determined and reported at 12 and 24 weeks.Forty-seven patients were enrolled and received dasatinib (initial dose 100 mg twice daily, n = 25; 70 mg twice daily, n = 22), of whom 41 (87%) had bone disease. Lack of progression was achieved in 20 (43%) patients at week 12 and in 9 (19%) patients at week 24. Of 41 evaluable patients, 21 (51%) patients achieved > or =40% reduction in urinary N-telopeptide by week 12, with 33 (80%) achieving some level of reduction anytime on study. Of 15 patients with elevated urinary N-telopeptide at baseline, 8 (53%) normalized on study. Of 40 evaluable patients, 24 (60%) had reduction in bone alkaline phosphatase at week 12 and 25 (63%) achieved some reduction on study. Dasatinib was generally well tolerated and treatment-related adverse events were moderate.This study provides encouraging evidence of dasatinib activity in bone and reasonable tolerability in chemotherapy-naive patients with metastatic CRPC.
Build A Braveheart: The Missing Linc (RNA)
Authors: Masaharu Kataoka, Zhan-Peng Huang, Da-Zhi Wang
Journal: Circulation Research (2013)

A novel long noncoding RNA (lncRNA), Braveheart (Bvht), has been defined as a critical regulator of commitment of the embryonic stem cells (ESCs) to cardiovascular lineages.Bvht activates a cardiovascular gene network and functions upstream of mesoderm posterior 1 (MESP1), a master regulator of a common multipotent cardiovascular progenitor.Bvht mediates epigenetic regulation of commitment to a cardiac lineage by interacting with suppressor of zeste12 (SUZ12), a component of polycomb repressive complex 2 (PRC2).Bvht represents the first lncRNA that defines cardiac cell fate and lineage specificity, linking lncRNAs to cardiac development and disease.
Impact of intranasal budesonide on immune inflammatory responses and epithelial remodeling in chronic upper airway inflammation
Authors: Claudio Mastruzzo, Lucia Roberta Greco, Koichi Nakano, Atsuko Nakano, Filippo Palermo, Maria Provvidenza Pistorio, Elisa Trovato Salinaro, Manel Jordana, Jerry Dolovich, †Nunzio Crimi, Carlo Vancheri
Journal: Journal of Allergy and Clinical Immunology (2003)
Adverse effects of moxifloxacin during tuberculosis treatment
Authors: Erik Schmok, Graham Bothamley
Journal: European Respiratory Journal (2012)

Aim: Prolonged use of moxifloxacin in tuberculosis (TB) may have adverse effects, particularly prolongation of the QT interval and arrhythmias.

Methods: All TB patients treated with moxifloxacin from 2003-2011 were identified. Concurrent medication and history of drug abuse were noted. Charts noted adverse effects. ECGs were obtained on and off treatment and the longest QTc was used for the study.

Results: 93 patients treated with moxifloxacin for at least one month were identified. Adverse effects included: nausea (2), palpitations (1) and photosensitivity (1); itching, arthralgia, flushing amd depression were probably due to concurrent medication. 60 patients had ECGs, mostly taken during treatment and none had a QTc >500 ms. Variability in QTc was high (standard deviation 31 ms). One male had a QTc > 450 and 3 females >470 ms but none had arrhythmias; one patient developed right bundle branch block during treatment, but this persisted when not taking moxifloxacin. All 4 used opiates.

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28 patients had paired ECGs on and off treatment showing a QTc interval increase of 6,4 msec (95 % CI -4,2 to 17,0 msec). Five increased by 69, 51, 48, 44 and 40 ms of whom four had limited access to opiates while in prison during their pre-treatment ECGs. Only one of the 28 had a QTc >450 ms after a normal interval (413 to 482 ms).

Conclusions: Moxifloxacin is well tolerated in treating TB. ECGs should be performed at a standard time after ingestion and with concurrent urine drug screens.
What Is the Greatest Regulatory Challenge in the Translation of Biomaterials to the Clinic?
Authors: Glenn D. Prestwich, Sangeeta Bhatia, Christopher K. Breuer, Shannon L. M. Dahl, Chris Mason, Richard McFarland, David J. McQuillan, Jonathan Sackner-Bernstein, Jeffrey Schox, William E. Tente, Alan Trounson
Journal: Science Translational Medicine (2012)

Leaders in the field comment on what they perceive to be the greatest barriers to biomaterial translation.