tbuckley/cabot-search huggingface dataset:
Apparent Trends of Amino Acid Gain and Loss in Protein Evolution Due to Nearly Neutral Variation
Authors: John H. McDonald
Journal: Molecular Biology and Evolution (2005)

It has recently been claimed that certain amino acids have been increasing in frequency in all living organisms for most of the history of life on earth, while other amino acids have been decreasing in frequency. Three lines of evidence have been offered for this assertion, but each has a more plausible alternative interpretation. Here I show that unequal patterns of gains and losses for particular pairs of amino acids (such as more leucine --> phenylalanine than phenylalanine --> leucine substitutions in humans and chimpanzees since they split from a common ancestor) are consistent with a simple neutral model at equilibrium amino acid frequencies. Unequal numbers of gains and losses for particular amino acids (such as more gains than losses of cysteine) are shown by simulations to be consistent with a model of nearly neutral evolution. Unequal numbers of gains and losses for particular amino acids in human polymorphism data are shown by simulations to be explainable by the nearly neutral model as well. In a comparison of protein sequences from four strains of Escherichia coli, polarized by one outgroup strain of Salmonella, the disparity in number of gains and losses for particular amino acids is strong in terminal branches but weaker or nonexistent in internal branches, which is inconsistent with the universal trend model but as expected under the nearly neutral model.
Diagnosis of abdominal tuberculosis: the importance of laparoscopy
Authors: S Rai, W M Thomas
Journal: Journal of the Royal Society of Medicine (2003)

Abdominal tuberculosis (TB) tends to present with non-specific features and can be hard to diagnose. In the University Hospitals of Leicester, which serve a large immigrant population, 36 patients had this diagnosis between 1995 and 2001. We examined their records to identify features, including history, clinical presentation, investigations and diagnostic procedures, that might help with diagnosis of future cases. 32 of the patients were of Asian origin, predominantly from the Indian subcontinent. The most common presenting complaints were abdominal pain and weight loss. On clinical examination the findings were non-specific. Only 2 patients were found to have concurrent pulmonary TB. The most consistent laboratory finding (>90%) was a low haemoglobin with a raised C-reactive protein. The tuberculin test (Mantoux) was positive in only 7 patients (22%), and Ziehl-Neelsen staining of ascitic fluid was negative in all 11 patients in whom it was examined. An ultrasound scan of the abdomen revealed findings consistent with TB in 9/28 patients and a CT scan was helpful in 6/11. Laparoscopy, although usually performed as a last resort, proved the most effective investigation, yielding the diagnosis in 23 (92%) of the 25 patients in whom it was performed. In patients with the relevant background and clinical history, laparoscopy is the investigation of choice.
Serum Uric Acid Levels Predict New-Onset Type 2 Diabetes in Hospitalized Patients With Primary Hypertension: The MAGIC Study
Authors: Francesca Viazzi, Giovanna Leoncini, Marina Vercelli, Giacomo Deferrari, Roberto Pontremoli
Journal: Diabetes Care (2010)

OBJECTIVE Recent studies suggest that uric acid may predict the development of diabetes in the general population. Whether this association holds true in primary hypertension and is independent of renal function and metabolic syndrome is not clear at present. RESEARCH DESIGN AND METHODS In a prospective, observational study, 758 untreated hypertensive patients were evaluated at baseline and followed-up for 11 years. RESULTS A total of 8,332 person-years of follow-up revealed that slightly elevated uric acid levels (i.e., ≥318 μmol/l for women and ≥420 μmol/l for men) at baseline were associated with a significantly higher risk of developing diabetes (hazard ratio 3.65 [95% CI 1.99–6.69], P &amp;lt; 0.0001), even after adjustment for several confounding factors such as metabolic syndrome (2.78 [1.35–5.70], P = 0.0054). CONCLUSIONS Uric acid is an independent predictor of diabetes in primary hypertension.
Long-term treatment with azithromycin is not associated with heart rhythm or QT interval disorders in children
Authors: Marcela Moreno, David Espadas, Silvia Castillo, Carolina Moreno, Elena Martinez, Amparo Escribano
Journal: European Respiratory Journal (2014)

Background: Studies in adults suggest that azithromycin (AZT) use prolongs QT interval, increasing the risk of cardiac arrhythmias and cardiovascular death. There are no studies in children to estimate this risk.

Objective: Evaluate the presence of arrhythmias or prolonged correct QT interval (QTc) in children treated with AZT.

Methods : Children receiving AZT ≥ 1 month were included. Dose 10 mg/kg/day, 3 days/week. Family history (sudden death, cardiac arrhythmias and smoking), personal data (prematurity, syncope), underlying disease, concomitant therapies previous 3 months, AZT treatment duration and adverse effects were collected. Cardiac evaluation (auscultation, pulse, electrocardiogram, QTc and search of arrhythmias) was performed.

Results: 44 children (3-15 years) 7 with cystic fibrosis, 9 asthma, 7 bronchiectasis, 3 persistent atelectasis and 18 other respiratory diseases. More than half had comorbidities. 1 had family history of cardiac death. None arrhythmias. Passive smoking 25%. Six preterm and 1 have history of presyncope. Time with AZT was between 2-72 months. Most (71%) had clinical improved, without adverse effects. All had concomitant treatments for underlying disease. 57% received other antibiotics the previous 3 months. In all cases QTc was < 440 msec. No arrhythmias were detected.

Conclusion: long-term AZT treatment does not cause heart rhythm disturbances or prolonged QTc interval in children with chronic or recurrent respiratory disease.
Human Papillomavirus Testing in the Prevention of Cervical Cancer
Authors: Mark Schiffman, Nicolas Wentzensen, Sholom Wacholder, Walter Kinney, Julia C. Gage, Philip E. Castle
Journal: JNCI Journal of the National Cancer Institute (2011)

Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment.
Efflux of metabolized and nonmetabolized fatty acid from canine myocardium. Implications for quantifying myocardial metabolism tomographically.
Authors: K A Fox, D R Abendschein, H D Ambos, B E Sobel, S R Bergmann
Journal: Circulation Research (1985)

It has generally been assumed, from assessment of myocardial metabolism with [1(-11)C]palmitate and positron emission tomography, that clearance of the radiolabel from the myocardium is attributable solely to efflux of the products of oxidative metabolism. However, interpretations would differ if this assumption were unfulfilled. Furthermore, efflux of metabolized and nonmetabolized tracer has not been quantified. Accordingly, in this study, myocardium was perfused extracorporeally in 21 open-chest anesthetized dogs, and the extraction and clearance of [1(-11)C]palmitate were characterized under baseline conditions (normoxia, n = 21), and, again, with ischemia (n = 6), with hypoxia (n = 9), or under control conditions (n = 6). After intracoronary bolus injection of [1(-11)C]palmitate, myocardial time activity curves were measured with a beta-probe, and the products of oxidative metabolism (11CO2) and efflux of extracted but nonmetabolized fatty acid ("back-diffusion" of [1(-11)C]palmitate) were measured directly from analysis of arterial and regional coronary venous blood. Under control conditions, 45.2 +/- 3.8% (mean +/- SD) of initially extracted [1(-11)C]palmitate was metabolized to 11CO2, whereas 6.2 +/- 2.6% back-diffused in unaltered form in 1-10 minutes. In contrast, with ischemia (perfusion of 26% of baseline), only 16.9 +/- 9.8% of administered tracer evolved as 11CO2 (P less than 0.001 compared with control) but 15.6 +/- 8.9% (i.e., almost half of the total amount cleared) evolved unaltered as [1(-11)C]palmitate (P less than 0.05). Similarly, with hypoxia, 15.1 +/- 8.4% evolved as 11CO2 (P less than 0.0001) and 18.8 +/- 11.7% back-diffused (P less than 0.001). Overall, from 1-40 minutes after intracoronary injection of tracer, back-diffusion of [1(-11)C]palmitate contributed 40.6% of total radioactivity in the effluent with ischemia, 48.7% with hypoxia, but only 8.9% under control conditions. Despite the increased back-diffusion of [1(-11)C]palmitate seen with ischemia and hypoxia, the overall residue of 11C activity in myocardium increased, consistent with the diminished clearance observed in the myocardial time-activity curves and the increase in the tissue content of triglyceride and nonesterified fatty acid. Our results indicate that estimates of oxidative metabolism based upon clearance of radiolabeled fatty acid must take into account the efflux of initially extracted but nonmetabolized fatty acid. The findings apply to external determination of oxidative metabolism of the heart with any imaging modality that delineates retention and clearance of labeled fatty acids or their analogs.
The classics in perspective
Authors: J. Panes, S. Ghosh
Journal: Gut (2007)

With the development and introduction of anti-cytokine therapies as biological agents, our therapeutic approach to Crohn disease and inflammatory diseases in general has dramatically expanded within the past few years. Biological agents technically mean a molecule that is the product of a biological system and functionally that is an agent that targets a specific biological molecule. Gastroenterologists are facing a remarkable wave of new biological therapies for inflammatory bowel diseases (IBD), including anti-tumour necrosis factor (TNF) antibodies (infliximab, adalimumab, certolizumab pegol), an anti-CD3 antibody (visilizumab), an anti-integrin antibody (natalizumab), and an anti-IL-12p40 and anti-IL6 receptor antibody (tocilizumab). Several biological therapies have also proven to be ineffective in large clinical trials, despite good initial promise, such as antibodies against soluble TNF receptors (etanercept, onercept), interleukin-10 and granulocyte–macrophage colony-stimulating factor (sargramostim).

Infliximab, an intravenously administered chimeric monoclonal antibody to TNF, has been for some years the only biological molecule approved for the treatment of Crohn disease, and more recently ulcerative colitis. Currently, two new subcutaneously administered anti-TNF molecules are in the process of being incorporated into the therapeutic armamentarium, including a fully human antibody (adalimumab) and a humanised pegylated Fab fragment (certolizumab pegol). The efficacy of adalimumab for induction of remission in patients with active Crohn disease not previously exposed to anti-TNF therapy was assessed in the CLASSIC (CLinical assessment of Adalimumab Safety and efficacy Studied as an Induction therapy in Crohn’s) I trial,1 showing that remission rates at week 4 in patients receiving two injections of 160 mg and 80 mg of adalimumab (the highest dose tested) at weeks 0 and 2 were significantly higher than in placebo-treated patients (36 vs. 9%). The CLASSIC II study, reported in this issue of Gut ( see page 1232 ),2 is a continuation trial assessing the efficacy and safety of adalimumab 40 mg …
Immediate post-injury considerations in rugby football [proceedings]
Authors: L. Walkden
Journal: British Journal of Sports Medicine (1978)

This paper discusses the circumstances, diagnosis, management and treatment of some Rugby injuries on the field and for 48 h post match.Relevant aspects of injury prevention are also considered.Ideally from a medical viewpoint a team is covered by a doctor, a physiotherapist skilled in sports medicine and an enlightened coach.The pitch is inspected regularly while first aid facilities at hand include stretchers, inflatable splints and a treatment room easily accessible from the field of play.This room should have strip lighting, running water, couch, steriliser, ice etc.In reality facilities at the majority of clubs do not extend beyond the proverbial bucket and sponge.The R.F.U.encourage repeatedly the presence of trained personnel at all Rugby grounds though the situation is still unsatisfactory.
Characterization of an amyloid fibril protein from senile cardiac amyloid.
Authors: P Westermark, J B Natvig, B Johansson
Journal: The Journal of Experimental Medicine (1977)

A protein, ASCA, is isolated from amyloid fibrils extracted from heart tissue of five different patients with senile cardiac amyloidosis (SCA). The proteins of all five patients showed immunological identity when reacted with an antiserum raised against one of the proteins. In contrast, no reaction was obtained with antisera against a variety of other amyloid proteins. The antiserum against the subunit protein of senile cardiac amyloid did not react with any other amyloid preparations tested, nor with extracts of normal heart tissue. Thus, the subunit protein appeared to be unique to senile heart amyloid. The protein could form fibrils in vitro, had a mol wt of about 6,000 daltons and the amino acid compositions investigated in two cases showed extensive similarities but were clearly different from that of protein AA of secondary amyloid fibrils.
Effects of prior concentric training on eccentric exercise induced muscle damage
Authors: N Gleeson, R Eston, V Marginson, M McHugh
Journal: British Journal of Sports Medicine (2003)

Exercise induced muscle damage (EIMD) from strenuous unaccustomed eccentric exercise is well documented. So too is the observation that a prior bout of eccentric exercise reduces the severity of symptoms of EIMD. This has been attributed to an increase in sarcomeres in series. Recent studies have suggested that prior concentric training increases the susceptibility of muscle to EIMD following eccentric exercise. This has been attributed to a reduction of sarcomeres in series, which decreases muscle compliance and changes the length-tension relation of muscle contraction.To assess the effects of prior concentric training on the severity of EIMD.Four men and four women (mean (SD) age 21.1 (0.8) years) followed a four week concentric training programme. The elbow flexor musculature of the non-dominant arm was trained at 60% of one repetition maximum dynamic concentric strength performance, three times a week, increasing to 70% by week 3. After three days of rest, participants performed 50 maximal isokinetic eccentric contractions on both arms. All participants gave written informed consent before taking part in this study, which was approved by the school ethics committee. Strength, relaxed arm angle (RAA), arm circumference, and soreness on active extension and flexion were recorded immediately before eccentric exercise, one hour after, and at 24 hour intervals for three days. Data were analysed with fully repeated measures analyses of variance.Strength retention was significantly (p<0.01) greater in the control arm than the trained arm (84.0 (13.7)%, 90.4 (14.7)%, 95.2 (10.5)%, 103.5 (7.6)% v 75.5 (11.3)%, 77.6 (15.3)%, 80.1 (13.9)%, 80.9 (12.5)%) at one, 24, 48, and 72 hours respectively. Similarly, soreness was greater in the trained arm (0.7 (0.6), 3.1 (1.4), 3.0 (1.5), 1.9 (2.3)) than in the untrained arm (0 (0.2), 1.6 (1.3), 1.4 (0.6), 0.6 (0.4)) at one, 24, 48, and 72 hours respectively (p<0.05). Concentric training induced a significant reduction in RAA (165.2 (6.7) degrees v 157.3 (4.9) degrees ) before the eccentric exercise bout (p<0.01). This was further reduced and remained lower in the trained arm at all time points after the eccentric exercise (p<0.01). The arm circumference of the concentrically trained arm was significantly greater than baseline (p<0.05) at 72 hours (30.3 (2.9) v 29.8 (3.3) cm).These findings extend the understanding of the effects of prior concentric training in increasing the severity of EIMD to an upper limb exercise model. The inclusion of concentric conditioning in rehabilitation programmes tends to exacerbate the severity of EIMD in subsequent unaccustomed exercise. However, where concentric conditioning is indicated clinically, the net effect of conditioning outcome and EIMD may still confer enhanced strength performance and capability to dynamically stabilise a joint system.
Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice
Authors: David E.G. McNay, Nadege Briançon, Maia V. Kokoeva, Eleftheria Maratos-Flier, Jeffrey S. Flier
Journal: Journal of Clinical Investigation (2011)

In the CNS, the hypothalamic arcuate nucleus (ARN) energy-balance circuit plays a key role in regulating body weight. Recent studies have shown that neurogenesis occurs in the adult hypothalamus, revealing that the ARN energy-balance circuit is more plastic than originally believed. Changes in diet result in altered gene expression and neuronal activity in the ARN, some of which may reflect hypothalamic plasticity. To explore this possibility, we examined the turnover of hypothalamic neurons in mice with obesity secondary to either high-fat diet (HFD) consumption or leptin deficiency. We found substantial turnover of neurons in the ARN that resulted in ongoing cellular remodeling. Feeding mice HFD suppressed neurogenesis, as demonstrated by the observation that these mice both generated fewer new neurons and retained more old neurons. This suppression of neuronal turnover was associated with increased apoptosis of newborn neurons. Leptin-deficient mice also generated fewer new neurons, an observation that was explained in part by a loss of hypothalamic neural stem cells. These data demonstrate that there is substantial postnatal turnover of the arcuate neuronal circuitry in the mouse and reveal the unexpected capacity of diet and leptin deficiency to inhibit this neuronal remodeling. This insight has important implications for our understanding of nutritional regulation of energy balance and brain function.
Informed Consent for Clinical Trials: a Comparative Study of Standard Versus Simplified Forms
Authors: T. C. Davis, H. J. Berkel, R. F. Holcombe, S. Pramanik, S. G. Divers
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: A high level of reading skill and comprehension is necessary to understand and complete most consent forms that are required for participation in clinical research studies. This study was conducted to test the hypothesis that a simplified consent form would be less intimidating and more easily understood by individuals with low-to-marginal reading skills. Methods: During July 1996, 183 adults (53 patients with cancer or another medical condition and 130 apparently healthy participants) were tested for reading ability and then asked to read either the standard Southwestern Oncology Group (SWOG) consent form (16th grade level) or a simplified form (7th grade level) developed at Louisiana State University Medical Center—Shreveport (LSU). Participants were interviewed to assess their attitudes toward and comprehension of the form read. Then they were given the alternate consent form and asked which one they preferred and why. Results: Overall, participants preferred the LSU form (62%; 95% confidence interval [CI] = 54.8%- 69.2%) over the SWOG form (38%; 95% CI = 30.8%- 45.2%) (P = .0033). Nearly all participants thought that the LSU form was easier to read (97%; 95% CI = 93.1%-99.9%) than the SWOG form (75%; 95% CI = 65.1%-85.7%) (P<.0001). However, the degree to which the participants understood the forms was essentially the same for the LSU form (58%; 95% CI = 48.6%-67.0%) and the SWOG form (56%; 95% CI = 43.8%-66.8%). Implications: These findings raise serious questions regarding the adequacy of the design of written informed consent documents for the substantial proportion of Americans with low-to-marginal literacy skills.
Oral domperidone: double blind comparison with placebo in irritable bowel syndrome.
Authors: P A Cann, N W Read, C D Holdsworth
Journal: Gut (1983)

Symptom scores, stool data, and the transit of a standard, solid meal were measured in 25 patients with irritable bowel syndrome during baseline conditions and after four weeks treatment with placebo and domperidone in the form of a double-blind cross-over trial. All patients had previously undergone a comprehensive series of diagnostic investigations and had failed to respond to dietary supplementation with coarse wheat bran (10-30 g daily). Compared with placebo treatment, domperidone had no significant effect on gastric emptying, small bowel or whole gut transit times, stool weight, frequency, or consistency. Most symptoms improved significantly with both placebo and domperidone treatments, compared with the baseline period, but there was no significant difference between placebo and domperidone for any of the symptoms. Abdominal distension, however, was reported on more days per week during domperidone treatment (p = 0.02). The findings in this study do not support the use of domperidone in the management of irritable bowel syndrome.
Prognostic Value of Health Status in Patients With Heart Failure After Acute Myocardial Infarction
Authors: Gabriel E. Soto, Philip Jones, William S. Weintraub, Harlan M. Krumholz, John A. Spertus
Journal: Circulation (2004)

Disease-specific health status instruments such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) can quantify symptoms, functional limitations, and quality of life in patients with heart failure. Understanding the relationship between KCCQ scores and prognosis may assist clinicians in both interpreting KCCQ scores and stratifying risk in patients.We examined the prognostic value of the KCCQ in a prospective, international cohort of 1516 patients with heart failure after a recent acute myocardial infarction. We focused on the relationship between the KCCQ overall score (KCCQ-os), measured at the first outpatient visit (4 weeks after enrollment), and subsequent 1-year cardiovascular mortality or hospitalization (n=258, 20.3%). KCCQ-os was strongly associated with subsequent cardiovascular events in that those with a score > or =75 had an 84% 1-year event-free survival compared with 59% for those with a score <25 (P<0.001). After demographic and other clinical characteristics were controlled for in multivariable models, KCCQ-os remained strongly associated with outcome (hazard ratio, 2.02; 95% CI, 1.24 to 3.27 for KCCQ-os <25; P<0.001).In outpatients with heart failure complicating an acute myocardial infarction, KCCQ-os is strongly associated with subsequent 1-year cardiovascular mortality and hospitalization. Use of the KCCQ in outpatient clinical practice can both quantify patients' health status and provide insight into their prognosis.