tbuckley/cabot-search huggingface dataset:
A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--Part 19
Authors: L M Burke, S J Stear, A Lobb, M Ellison, L M Castell
Journal: British Journal of Sports Medicine (2011)

Glycerol, guarana and the weight-loss agent, hydroxycut, occupy part 19; glycine will appear in part 20. The ubiquitous product, glycerol, is used both orally, for example, as an emulsifier in ice cream and topically, for example, as glycerine in hand cream. In the area of sports nutrition, glycerol plays a role in improving hydration status, as described in detail below. Guarana has been used for centuries as a stimulant in South America, due to its high caffeine content; it also contains xanthine alkaloids, such as theobromine and theophylline, which enhance the effects of caffeine. Further information on caffeine and sports performance can be found in part 6 of this series.1 Unlike glycerol and guarana, hydroxycut is an example of a multi-ingredient supplement with a proprietary formulation that presents special challenges when assessing safety and efficacy, including uncertainty as to which ‘active’ ingredients may provide the desired effects and frequent formulation changes.

### L M Burke

Glycerol is a 3-carbon sugar alcohol that provides the backbone of triglycerides and is naturally found in foods as a component of dietary fats. However, its various physical and chemical properties are valuable in food technology: glycerol is added to manufactured foods and drinks as an emulsifier, humectant, sweetener, filler and thickener. Its viscosity also makes it useful as a component of lotions and creams, explaining its common availability for purchase in purified form under the name of glycerine. Although it has been suggested as a gluconeogenic precursor that could provide a substrate for exercise, the ingestion of glycerol by athletes is best known for its role as an osmolyte. When ingested or released following lipolysis, glycerol contributes to the osmotic pressure of body fluids until it is slowly metabolised. When consumed simultaneously with a substantial volume of fluid, there is a temporary retention of this fluid and …
What happens to patients with pulmonary aspergilloma? Analysis of 23 cases.
Authors: P Rafferty, B A Biggs, G K Crompton, I W Grant
Journal: Thorax (1983)

The problems associated with pulmonary aspergilloma were assessed retrospectively in 23 patients presenting from 1953 to 1982. Haemoptysis occurred in over half the patients and in two it was fatal. Invasive aspergillosis occurred in five patients, a higher proportion than in earlier reports, and two of these died. Amphotericin B in combination with either flucytosine or natamycin and, more recently, ketoconazole have proved useful in the treatment of this condition.
Comparison of Rubella Virus- and Herpes Virus-Associated Anterior Uveitis
Authors: Barbara Wensing, Lia M. Relvas, Laure E. Caspers, Natasa Vidovic Valentincic, Spela Stunf, Jolanda D.F. de Groot-Mijnes, Aniki Rothova
Journal: Ophthalmology (2011)
Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials
Authors: Bodil Als-Nielsen, Lise L Gluud, Christian Gluud
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the effects of non-absorbable disaccharides (lactulose and lactitol) in patients with hepatic encephalopathy. <b>Data sources</b> Cochrane Hepato-Biliary Group controlled trials register, Cochrane Library, Medline, and Embase until March 2003; reference lists of relevant articles; authors and pharmaceutical companies. <b>Review methods</b> Randomised trials that compared non-absorbable disaccharides with placebo, no intervention, or antibiotics for hepatic encephalopathy were included. The primary outcome measures were no improvement of hepatic encephalopathy and all cause mortality. <b>Results</b> 22 trials were included. Compared with placebo or no intervention, non-absorbable disaccharides seemed to reduce the risk of no improvement in patients with hepatic encephalopathy (relative risk 0.62, 95% confidence interval 0.46 to 0.84, six trials). However, high quality trials found no significant effect (0.92, 0.42 to 2.04, two trials). Compared with placebo or no intervention, non-absorbable disaccharides had no significant effect on mortality (0.41, 0.02 to 8.68, four trials). Non-absorbable disaccharides were inferior to antibiotics in reducing the risk of no improvement (1.24, 1.02 to 1.50, 10 trials) and lowering blood ammonia concentration (weighted mean difference 2.35 μmol/l, 0.06 μmol/l to 13.45 μmol/l, 10 trials). There was no significant difference in mortality (0.90, 0.48 to 1.67, five trials). <b>Conclusions</b> There is insufficient evidence to support or refute the use of non-absorbable disaccharides for hepatic encephalopathy. Antibiotics were superior to non-absorbable disaccharides in improving hepatic encephalopathy, but it is unclear whether this difference is clinically important. Non-absorbable disaccharides should not serve as comparator in randomised trials on hepatic encephalopathy.
EXEL-7647 Inhibits Mutant Forms of ErbB2 Associated with Lapatinib Resistance and Neoplastic Transformation
Authors: Torsten Trowe, Sotiria Boukouvala, Keith Calkins, Richard E. Cutler, Ryan Fong, Roel Funke, Steven B. Gendreau, Yong D. Kim, Nicole Miller, John R. Woolfrey, Valentina Vysotskaia, Jing Ping Yang, Mary E. Gerritsen, David J. Matthews, Peter Lamb, Timothy S. Heuer
Journal: Clinical Cancer Research (2008)

Mutations associated with resistance to kinase inhibition are an important mechanism of intrinsic or acquired loss of clinical efficacy for kinase-targeted therapeutics. We report the prospective discovery of ErbB2 mutations that confer resistance to the small-molecule inhibitor lapatinib.We did in vitro screening using a randomly mutagenized ErbB2 expression library in Ba/F3 cells, which were dependent on ErbB2 activity for survival and growth.Lapatinib resistance screens identified mutations at 16 different ErbB2 amino acid residues, with 12 mutated amino acids mapping to the kinase domain. Mutations conferring the greatest lapatinib resistance cluster in the NH2-terminal kinase lobe and hinge region. Structural computer modeling studies suggest that lapatinib resistance is caused by multiple mechanisms; including direct steric interference and restriction of conformational flexibility (the inactive state required for lapatinib binding is energetically unfavorable). ErbB2 T798I imparts the strongest lapatinib resistance effect and is analogous to the epidermal growth factor receptor T790M, ABL T315I, and cKIT T670I gatekeeper mutations that are associated with clinical drug resistance. ErbB2 mutants associated with lapatinib resistance transformed NIH-3T3 cells, including L755S and T733I mutations known to occur in human breast and gastric carcinomas, supporting a direct mechanism for lapatinib resistance in ErbB2-driven human cancers. The epidermal growth factor receptor/ErbB2/vascular endothelial growth factor receptor inhibitor EXEL-7647 was found to inhibit almost all lapatinib resistance-associated mutations. Furthermore, no ErbB2 mutations were found to be associated with EXEL-7647 resistance and lapatinib sensitivity.Taken together, these data suggest potential target-based mechanisms of resistance to lapatinib and suggest that EXEL-7647 may be able to circumvent these effects.
Acute Neuropathic Joint Disease
Authors: Ai Lyn Tan, Adam Greenstein, Stephen J. Jarrett, Dennis McGonagle
Journal: Diabetes Care (2005)

Charcot neuroarthropathy, or, as it is also known, neuropathic joint disease (NJD), is a particularly severe form of osteoarthritis. It is recognized by severe joint damage in the context of relatively little pain in the presence of neuropathy and associated with characteristic radiographic changes in well-established disease. Patients with diabetes are at particular risk of NJD; permanent disability through foot deformity or amputation as a consequence of peripheral neuropathy (1) and diabetes is now the leading cause of NJD. The midfoot or ankle joints are most commonly affected in diabetic patients (2). The limited epidemiologic data on NJD suggest that ∼0.1–0.4% of patients with diabetes develop NJD (3), usually 10–15 years after the onset of diabetes, and up to 16% of diabetic patients with peripheral neuropathy have been reported to be affected by NJD (4), which therefore represents a considerable cause of diabetic ankle- and foot-related morbidity.

NJD often presents acutely, resulting in misdiagnosis and inappropriate treatment and consequently leading to disastrous damage and possible loss of the affected limb (3). Typically, in the acute phase, NJD presents as a warm, edematous, and erythematous joint (5,6). As a result of sensory neuropathy, there may be little pain or tenderness, and the patient may not even seek medical assistance. During examination, a bounding pedal pulse compared with the other limb is found (7). The radiographic changes of chronic NJD include florid new bone formation, joint space loss, and severe joint destruction and deformity, but these characteristic changes are usually absent in early NJD. In this clinical context, cellulitis, osteomyelitis, or infection may be diagnosed instead and treated accordingly, and the window of opportunity for the initiation of treatment designed to minimize subsequent NJD joint …
Predictors of Autosomal Dominant Polycystic Kidney Disease Progression
Authors: Robert W. Schrier, Godela Brosnahan, Melissa A. Cadnapaphornchai, Michel Chonchol, Keith Friend, Berenice Gitomer, Sandro Rossetti
Journal: Journal of the American Society of Nephrology (2014)

Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
British athletics muscle injury classification: a new grading system
Authors: Noel Pollock, Steven L J James, Justin C Lee, Robin Chakraverty
Journal: British Journal of Sports Medicine (2014)

The commonly used muscle injury grading systems based on three grades of injury, representing minor, moderate and complete injuries to the muscle, are lacking in diagnostic accuracy and provide limited prognostic information to the clinician. In recent years, there have been a number of proposals for alternative grading systems. While there is recent evidence regarding the prognostic features of muscle injuries, this evidence has not often been incorporated into the grading proposals. The British Athletics Muscle Injury Classification proposes a new system, based on the available evidence, which should provide a sound diagnostic base for therapeutic decision-making and prognostication. Injuries are graded 0-4 based on MRI features, with Grades 1-4 including an additional suffix 'a', 'b' or 'c' if the injury is 'myofascial', 'musculo-tendinous' or 'intratendinous'. Retrospective and prospective studies in elite track and field athletes are underway to validate the classification for use in hamstring muscle injury management. It is intended that this grading system can provide a suitable diagnostic framework for enhanced clinical decision-making in the management of muscle injuries and assist with future research to inform the development of improved prevention and management strategies.
Lack of improvement after audit assessing the management of voiding dysfunction in patients with spinal cord injury: Necessity for institutional guidelines
Authors: Syed Johar Raza, Muhammad Shahzad Shamim, Saniya Siraj Godil, S. Raziuddin Biyabani, Muhammad Ehsan Bari, Rajesh Kumar, Atta ul Aleem Bhatti, Saeed Soomro
Journal: International Journal of Surgery (2011)
Increased Intratumor Vα24-Positive Natural Killer T Cells: A Prognostic Factor for Primary Colorectal Carcinomas
Authors: Tsuyoshi Tachibana, Hisashi Onodera, Tatsuaki Tsuruyama, Akira Mori, Satoshi Nagayama, Hiroshi Hiai, Masayuki Imamura
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Vα24-Vβ11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Vα24+ NKT cells in colorectal carcinomas and their clinicopathologic significance. Experimental Design: Vα24+ NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (&amp;lt;7 NKT cells/5 HPF) or high (≥7 NKT cells/5 HPF). The correlation between the degree of infiltrated Vα24+ NKT cells and clinicopathologic variables was studied statistically. Results: A small number of Vα24+ NKT cells were found in the normal colorectal mucosa (2.6 ± 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 ± 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates. Conclusions: Increased infiltration of Vα24+ NKT cells was observed in colorectal carcinomas. Higher Vα24+ NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.
Expression of Insulin Receptor Isoform A and Insulin-like Growth Factor-1 Receptor in Human Acute Myelogenous Leukemia: Effect of the Dual-Receptor Inhibitor BMS-536924 <i>In vitro</i>
Authors: Andrea E. Wahner Hendrickson, Paul Haluska, Paula A. Schneider, David A. Loegering, Kevin L. Peterson, Ricardo Attar, B. Douglas Smith, Charles Erlichman, Marco Gottardis, Judith E. Karp, Joan M. Carboni, Scott H. Kaufmann
Journal: Cancer Research (2009)

The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are receptor tyrosine kinases that participate in mitogenic and antiapoptotic signaling in normal and neoplastic epithelia. In the present study, immunoblotting and reverse transcription-PCR demonstrated expression of IGF1R and IR isoform A in acute myelogenous leukemia (AML) cell lines as well as in >80% of clinical AML isolates. Treatment with insulin enhanced signaling through the Akt and MEK1/2 pathways as well as survival of serum-starved AML cell lines. Conversely, treatment with BMS-536924, a dual IGF1R/IR kinase inhibitor that is undergoing preclinical testing, inhibited constitutive receptor phosphorylation as well as downstream signaling through MEK1/2 and Akt. These changes inhibited proliferation and, in some AML cell lines, induced apoptosis at submicromolar concentrations. Likewise, BMS-536924 inhibited leukemic colony formation in CD34+ clinical AML samples in vitro. Collectively, these results not only indicate that expression of IGF1R and IR isoform A is common in AML but also show that interruption of signaling from these receptors inhibits proliferation in clinical AML isolates. Accordingly, further investigation of IGF1R/IR axis as a potential therapeutic target in AML appears warranted.
High genetic diversity including potential new subtypes of hepatitis C virus genotype 6 in Lao People's Democratic Republic
Authors: J.M. Hübschen, P. Jutavijittum, T. Thammavong, B. Samountry, A. Yousukh, K. Toriyama, A. Sausy, C.P. Muller
Journal: Clinical Microbiology and Infection (2011)
SHP2 Is Overexpressed and Inhibits pSTAT1-Mediated APM Component Expression, T-cell Attracting Chemokine Secretion, and CTL Recognition in Head and Neck Cancer Cells
Authors: Michael S. Leibowitz, Raghvendra M. Srivastava, Pedro A. Andrade Filho, Ann Marie Egloff, Lin Wang, Raja R. Seethala, Soldano Ferrone, Robert L. Ferris
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Human leukocyte antigen (HLA) class I antigen processing machinery (APM) component downregulation permits escape of malignant cells from recognition by cytotoxic T lymphocytes (CTL) and correlates with poor prognosis in patients with head and neck cancer (HNC). Activated STAT1 (pSTAT1) is necessary for APM component expression in HNC cells. We investigated whether an overexpressed phosphatase was responsible for basal suppression of pSTAT1 and subsequent APM component-mediated immune escape in HNC cells. Experimental Design: Immunohistochemical staining and reverse transcription PCR of paired HNC tumors was performed for the phosphatases src homology domain-containing phosphatase (SHP)–1 and SHP2. Depletion of phosphatase activity in HNC and STAT1−/− tumor cells was achieved by siRNA knockdown. HLA class I–restricted, tumor antigen-specific CTL were used in IFN-γ ELISPOT assays against HNC cells. Chemokine secretion was measured after SHP2 depletion in HNC cells. Results: SHP2, but not SHP1, was significantly upregulated in HNC tissues. In HNC cells, SHP2 depletion significantly upregulated expression of pSTAT1 and HLA class I APM components. Overexpression of SHP2 in nonmalignant keratinocytes inhibited IFN-γ–mediated STAT1 phosphorylation, and SHP2 depletion in STAT1−/− tumor cells did not significantly induce IFN-γ–mediated APM component expression, verifying STAT1 dependence of SHP2 activity. SHP2 depletion induced recognition of HNC cells by HLA class I–restricted CTL and secretion of inflammatory, T-cell attracting chemokines, RANTES and IP10. Conclusion: These findings suggest for the first time an important role for SHP2 in APM-mediated escape of HNC cells from CTL recognition. Targeting SHP2 could enhance T-cell–based cancer immunotherapy. Clin Cancer Res; 19(4); 798–808. ©2012 AACR.
Neural models of development and learning
Authors: Stephen Grossberg
Journal: Behavioral and Brain Sciences (1997)

I agree with Quartz &amp; Sejnowski's (Q&amp;S's) points, which are familiar to many scientists. A number of models with the sought-after properties, however, are overlooked, while models without them are highlighted. I will review nonstationary learning, links between development and learning, locality, stability, learning throughout life, hypothesis testing that models the learner's problem domain, and active dendritic processes.
Second-line chemotherapy with weekly oxaliplatin and high-dose 5-fluorouracil with folinic acid in metastatic colorectal carcinoma: A Hellenic Cooperative Oncology Group (HeCOG) phase II feasibility study
Authors: J. Janinis, P. Papakostas, G. Samelis, D. Skarlos, P. Papagianopoulos, G. Fountzilas
Journal: Annals of Oncology (2000)
More than a million people signed petition against polyclinics
Authors: A. O'Dowd
Journal: BMJ (2008)

Around 1.2 million people signed a petition calling for existing general practices in England to be protected in the face of government plans to create large health centres known as polyclinics.

Relations between the government and the BMA have grown increasingly bitter over the issue of polyclinics, prompting the health secretary to accuse doctors’ leaders of lying and scaremongering ( BMJ 2008;336:1328, 14 Jun, doi: 10.1136/bmj.39608.577639.DB).

The BMA handed in the petition to the prime minister last week as part of its “support your surgery” campaign. The petition asks Gordon Brown to continue to support …
Mechanism of Syncope in Patients With Isolated Syncope and in Patients With Tilt-Positive Syncope
Authors: Angel Moya, Michele Brignole, Carlo Menozzi, Roberto Garcia-Civera, Stefano Tognarini, Luis Mont, Gianluca Botto, Franco Giada, Daniele Cornacchia
Journal: Circulation (2001)

Because of its episodic behavior, the correlation of spontaneous syncope with an abnormal finding can be considered a reference standard.We inserted an implantable loop recorder in 111 patients with syncope, absence of significant structural heart disease, and a normal ECG; tilt-testing was negative in 82 (isolated syncope) and positive in 29 (tilt-positive). The patients had had >/=3 episodes of syncope in the previous 2 years and were followed up for 3 to 15 months. Results were similar in the isolated syncope group and the tilt-positive group: syncope recurred in 28 (34%) and 10 patients (34%), respectively, and electrocardiographic correlation was found in 24 (23%) and 8 (28%) patients, respectively. The most frequent finding, which was recorded in 46% and 62% of patients, respectively, was one or more prolonged asystolic pauses, mainly due to sinus arrest, preceded for a few minutes by progressive bradycardia or progressive tachycardia-bradycardia. Bradycardia without pauses was observed in 8% and 12% of cases, respectively. The remaining patients had normal sinus rhythm or sinus tachycardia, except for one, who had ectopic atrial tachycardia. In the tilt-positive group, an asystolic syncope was also recorded when the type of response to tilt-testing was vasodepressor or mixed. Presyncopal episodes were never characterized by asystolic pauses; normal sinus rhythm was the most frequent finding.Homogeneous findings were observed during syncope. In most patients, the likely cause was neurally-mediated, and the most frequent mechanism was a bradycardic reflex. In the other cases, a normal sinus rhythm was frequently recorded. Presyncope was not an accurate surrogate for syncope in establishing a diagnosis.
Promoting Healthy Outcomes Among Youth with Multiple Risks: Innovative Approaches
Authors: Mark T. Greenberg, Melissa A. Lippold
Journal: Annual Review of Public Health (2013)

Adolescent behavior problems such as substance use, antisocial behavior problems, and mental health problems have extremely high social costs and lead to overburdened mental health and juvenile justice systems in the United States and Europe. The prevalence of these problems is substantial, and at-risk youth often present with a combination of concerns. An understanding of risk and protective factors at multiple levels, including the child, family, peer, school, and community, has influenced intervention development. At the individual and family levels, the most effective and cost-effective programs work intensively with youth and their families or use individual and group cognitive-behavioral approaches. However, there is a paucity of careful studies of effective policies and programs in the juvenile justice system. Research is needed that focuses on adoption, financing, implementation, and sustainable use of evidence-based programs in public service systems. In addition, the field needs to understand better for whom current programs are most effective to create the next generation of more effective and efficient programs.