tbuckley/cabot-search huggingface dataset:
P17.71 * ROLE OF ATRX AND TERT EXPRESSION AS DIAGNOSTIC AND PROGNOSTIC FACTORS ON ANAPLASTIC GLIOMAS
Authors: M. Patane, C. Calatozzolo, S. Mazzetti, R. Nunziata, S. Spinello, M. Farinotti, G. Finocchiaro, B. Pollo
Journal: Neuro-Oncology (2014)

Molecular and histological classification of anaplastic gliomas have been recently refined by the elucidation of the role of mutations in alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene and in telomerase reverse transcriptase (TERT) promoter. Loss of ATRX expression and the acquisition of alternative lengthening of telomeres (ALT) phenotype is peculiar of a subtype of astrocytic tumours with p53 and IDH1 mutations and better prognosis, while TERT overexpression, due to its promoter's mutations, is strongly associated to oligodendroglial tumours and 1p/19q codeletion, without a significant correlation with survival. Based on these findings, the aim of our study was to better clarify the role of ATRX and TERT expression in the histological classification of anaplastic gliomas, as diagnostic and prognostic markers of survival and relapse. We performed immunohistochemical and molecular analysis of ATRX and TERT expression on 60 grade III gliomas (astrocytomas, oligoastrocytomas and oligodendrogliomas) and the respective recurrences when they were available. Nuclear accumulation of p53, IDH1 status and LOH of chromosomes 1p, 19q, 9p, 17p and 10q were also evaluated. Our results showed a loss of ATRX expression in 60% of anaplastic oligoastrocytomas and 40% of anaplastic astrocytomas, while ATRX was wild-type in oligodendroglial tumours. We then found a strong positive correlation between loss of ATRX expression and p53 nuclear accumulation, while its strong expression was present mostly in tumours with 1p/19q codeletion. Finally, ATRX loss was correlated with a better prognosis both in anaplastic oligoastrocytomas and in anaplastic astrocytomas according to literature. Regarding TERT expression, we did not find a strictly correlation with 1p/19p codeletion and the oligodendroglial histological pattern, but, surprisingly, we found a possible role in relapse of anaplastic gliomas. In our series, tumours with high TERT expression tend to recur within 25 months, while anaplastic gliomas with low o null expression of TERT tend to recur within 60 months. In conclusion, these set of data could allow us in the future to better classify anaplastic gliomas and their tendency to recur adding immunohistochemistry for ATRX and TERT to other molecular markers in routine diagnostic procedures, and to define new molecular profiles for their therapy.
Dimethylarginine Dimethylaminohydrolase Prevents Progression of Renal Dysfunction by Inhibiting Loss of Peritubular Capillaries and Tubulointerstitial Fibrosis in a Rat Model of Chronic Kidney Disease
Authors: Yuriko Matsumoto, Seiji Ueda, Sho-ichi Yamagishi, Kyoko Matsuguma, Ryo Shibata, Kei Fukami, Hidehiro Matsuoka, Tsutomu Imaizumi, Seiya Okuda
Journal: Journal of the American Society of Nephrology (2007)

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is mainly degraded by dimethylarginine dimethylaminohydrolase (DDAH). It was recently reported that reduced DDAH expression could contribute to ADMA accumulation and subsequent elevation of BP in an experimental model of chronic kidney disease (CKD). ADMA is a strong predictor of the progression of CKD as well. However, a role for the ADMA-DDAH in the pathogenesis of CKD remains to be elucidated. This study investigated the effects of DDAH-elicited ADMA lowering on renal function and pathology in a rat remnant kidney model. Four weeks after five-sixths subtotal nephrectomy (Nx), the rats were given tail-vein injections of recombinant adenovirus vector encoding DDAH-I (Adv-DDAH) or control vector expressing bacterial beta-galactosidase (Adv-LZ) or orally administered 20 mg/kg per d hydralazine (Hyz), which served as a BP control model. In comparison with Adv-LZ or Hyz administration, Adv-DDAH decreased plasma levels of ADMA and inhibited the deterioration of renal dysfunction. Plasma levels of ADMA were associated with decreased number of peritubular capillaries, increased tubulointerstitial fibrosis, and proteinuria levels in Nx rats. These changes were progressed in Adv-LZ-or Hyz-treated Nx rats, which were ameliorated by DDAH overexpression. In addition, semiquantitative reverse transcriptase-PCR and immunohistochemistry for TGF-beta revealed that Adv-DDAH inhibited upregulation of TGF-beta expression in Nx rats. These data suggest that ADMA may be involved in peritubular capillary loss and tubulointerstitial fibrosis, thereby contributing to the progression of CKD. Substitution of DDAH protein or enhancement of its activity may become a novel therapeutic strategy for the treatment of CKD.
Sirolimus Therapy after Early Cyclosporine Withdrawal Reduces the Risk for Cancer in Adult Renal Transplantation
Authors: Josep M. Campistol, Josette Eris, Rainer Oberbauer, Peter Friend, Brian Hutchison, José M. Morales, Kerstin Claesson, Giovanni Stallone, Graeme Russ, Lionel Rostaing, Henri Kreis, James T. Burke, Yves Brault, Joseph A. Scarola, John F. Neylan
Journal: Journal of the American Society of Nephrology (2006)

Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525 enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to first skin and nonskin malignancies were compared between treatments using a survival analysis. Mean annualized rates of skin malignancy were calculated, and the relative risk was determined using a Poisson model. Malignancy-free survival rates for nonskin malignancies were compared using Kaplan-Meier estimates and the log-rank test. At 5 yr, the median time to a first skin carcinoma was delayed (491 versus 1126 d; log-rank test, P = 0.007), and the risk for an event was significantly lower with SRL-ST therapy (relative risk SRL-ST to SRL-CsA-ST 0.346; 95% confidence interval 0.227 to 0.526; P < 0.001, intention-to-treat analysis). The relative risks for both basal and squamous cell carcinomas were significantly reduced. Kaplan-Meier estimates of nonskin cancer were 9.6 versus 4.0% (SRL-CsA-ST versus SRL-ST; P = 0.032, intention-to-treat analysis). Nonskin cancers included those of the lung, larynx, oropharynx, kidney, gastrointestinal tract, prostate, breast, thyroid, and cervix as well as glioma, liposarcoma, astrocytoma, leukemia, lymphoma, and Kaposi's sarcoma. Patients who received SRL-based, calcineurin inhibitor-free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. Longer follow-up and additional trials are needed to confirm these promising results.
HOW TO IMPROVE OUR ANNIVERSARY MEETINGS
Authors: C. R. Hall
Journal: BMJ (1855)

As one proof", he tels us, "of the obstinay of the Ens mdical department, they would pursue the old Vssm of tretment; notwithading the advice of the French, and the physicians of the country, they would not listn; therefore, not taking into account the climate, many men perished who might have been saved had it not been for this prejudice."We certainly never heard, before Mr. Braeebridge informed us of the fact, that English medicine was at all behind that of France, and we are inclined still seriously to doubt it.Indeed his very next words seem to contradict his conclusions drawn against his countrymen in 0o ex catkedrd a manner; for he tels us that " many of the poor men were completely worn out, and all the medical skill in the world would not have restored them [not perhaps that of his friends the French physicians].Men from twenty to thirty years of age, when brought to the hos- pital, appeared to be seventy or eighty years old.This was caused by bad food, want of clothing, exposure in the trenches, and overwork."So that, after all, the British commanders and the commissariat, rather than the " pre-
BIOAVAILABILITY AND BIOCONVERSION OF CAROTENOIDS
Authors: J. J. M. Castenmiller, C. E. West
Journal: Annual Review of Nutrition (1998)

▪ Abstract Factors that influence the bioavailability of carotenoids and their bioconversion to retinol are species of carotenoids, molecular linkage, amount of carotenoids consumed in a meal, matrix in which the carotenoid is incorporated, effectors of absorption and bioconversion, nutrient status of the host, genetic factors, host-related factors, and mathematical interactions. In this paper, current knowledge of these factors is examined. Although data are not sufficiently comparable to allow an extensive systematic comparison of results, a number of conclusions can be drawn from the information available.
High adherence to a neuromuscular injury prevention programme (FIFA 11+) improves functional balance and reduces injury risk in Canadian youth female football players: a cluster randomised trial
Authors: Kathrin Steffen, Carolyn A Emery, Maria Romiti, Jian Kang, Mario Bizzini, Jiri Dvorak, Caroline F Finch, Willem H Meeuwisse
Journal: British Journal of Sports Medicine (2013)

Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated. However, there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players. Objective The aim of this cluster-randomised controlled trial was to assess whether different delivery methods of an injury prevention programme (FIFA 11+) to coaches could improve player performance, and to examine the effect of player adherence on performance and injury risk. Method During the 2011 football season (May–August), coaches of 31 tiers 1–3 level teams were introduced to the 11+ through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions. Playing exposure, adherence to the 11+, and injuries were recorded for female 13-year-old to 18-year-old players. Performance testing included the Star Excursion Balance Test (SEBT), single-leg balance, triple hop and jumping-over-a-bar tests. Results Complete preseason and postseason performance tests were available for 226 players (66.5%). Compared to the unsupervised group, single-leg balance (OR=2.8; 95% CI 1.1 to 4.6) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players (OR=4.7; 95% CI 2.2 to 7.1), while 2-leg jumping performance decreased (OR=−5.1; 95% CI −9.9 to −0.2). However, significant improvements in 5 of 6 reach distances in the SEBT were found, favouring players who highly adhered to the 11+. Also, injury risk was lower for those players (injury rate ratio, IRR=0.28, 95% CI 0.10 to 0.79). Conclusions Different delivery methods of the FIFA 11+ to coaches influenced players’ physical performance minimally. However, high player adherence to the 11+ resulted in significant improvements in functional balance and reduced injury risk.
Functional effects of DAX-1 mutations identified in patients with X-linked adrenal hypoplasia congenita
Authors: Jin-Ho Choi, Jung-Young Park, Gu-Hwan Kim, Hye Young Jin, Beom Hee Lee, Jae Hyun Kim, Choong Ho Shin, Sei Won Yang, Han-Wook Yoo
Journal: Metabolism (2011)
Polyamines mediate androgenic stimulation of calcium fluxes and membrane transport in rat heart myocytes.
Authors: H Koenig, C C Fan, A D Goldstone, C Y Lu, J J Trout
Journal: Circulation Research (1989)

The androgenic steroid hormone testosterone induced an early (less than 30-60 seconds) stimulation of endocytosis, hexose transport, and amino acid transport, monitored by the temperature-sensitive uptake of horseradish peroxidase, 2-deoxyglucose, and alpha-aminoisobutyrate, respectively, in rat ventricle cubes and acutely isolated ventricular myocytes. This stimulation was time- and concentration-dependent and was maximal at 10(-9) to 10(-8) M testosterone, consistent with androgen-receptor mediation. EGTA (2.5 mM), La3+ (1 mM), and verapamil (100 microM) ablated the hormonal response. The calcium ionophore A23187 (10 microM) induced an acute stimulation of endocytosis, amino acid transport, and hexose transport which was not further increased by testosterone (10(-8) M), suggesting a common effector pathway. Testosterone (10(-8) M) also evoked a rapid (less than 30 seconds) stimulation of 45Ca influx and efflux. Testosterone (10(-8) M) induced a rapid (less than 5 seconds) transient increase in ornithine decarboxylase (ODC) activity peaking (twofold to threefold) at 60 seconds, and an early (15 seconds) transient accumulation of polyamines peaking at 60 seconds in isolated myocytes. The specific, irreversible ODC inhibitor alpha-difluoromethylornithine (DFMO, 5-10 mM) blocked the testosterone-evoked increase in ODC activity and polyamine levels and the stimulation of Ca2+ fluxes, endocytosis, hexose transport, and amino acid transport. Putrescine (0.5-1 mM), the ODC product, reversed DFMO inhibition and restored the increase in polyamines, 45Ca fluxes, and Ca2+-dependent membrane transport processes. These results demonstrate that rapid, transient ODC-regulated polyamine synthesis is essential for androgenic stimulation of Ca2+ fluxes and membrane transport processes in ventricular myocytes. These findings support a model for signal transduction in which newly synthesized polyamines serve as intracellular messengers to regulate transmembrane Ca2+ movements, Ca2+-dependent membrane transport functions, and other Ca2+- and polyamine-sensitive processes in cardiac myocytes.
The Coming Election of Direct Representatives on the General Medical Council
Authors: J. L. Andrew
Journal: BMJ (1891)

CHWs used WhatsApp with their supervisors to document their work, spurring healthy competition and team building between CHWs in the 2 pilot sites. While there was considerable variation in the number of times each participant posted messages—from 1 message to 270 messages—in total they posted nearly 2,000 messages over 6 months. 88% of messages corresponded to at least 1 of 3 defined supervisory objectives of (1) creating a social environment, (2) sharing communication and information, or (3) promoting quality of services.
An acquired hemorrhagic disorder of fibrin crosslinking due to LgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide
Authors: Alberto Tosetto, Francesco Rodeghiero, Elisabetta Gatto, Cesare Manotti, Tullio Poli
Journal: American Journal of Hematology (1995)

Abstract We report a new case of severe bleeding diathesis due to an acquired inhibitor of fibrin crosslinking. The patient, an 80‐year‐old woman, was admitted to the hospital for a massive subcutaneous hematoma, with severe anemia requiring red cell transfusion; a subsequent retroperitoneal hematoma developed 2 weeks later. Coagulation studies were normal except for a thromboelastographic pattern suggestive of FXIII deficiency. Clot solubility test was abnormal even after 1: 1 mix with normal plasma. Immunochemical studies confirmed the presence of a monoclonal IgG lambda inhibitor directed against FXIII activity (type II FXIII inhibitor). The patient IgG fraction selectively inhibited FXIII transamidating activity but did not inhibit the thrombin‐mediated activation of FXIII. The patient was treated with high doses of FXIII concentrate to overcome the inhibitor and immunosuppressive therapy with cyclophosphamide and discharged in good conditions. High doses of commercially available FXIII appear to be a safe and effective method of controlling acute episodes of bleeding in patients with acquired FXIII deficiency. ©1995 Wiley‐Liss, Inc.
Importance of Pattern of Alcohol Consumption
Authors: R. Curtis Ellison
Journal: Circulation (2005)

ver the last several decades, prospective epidemiological studies have consistently shown that moderate alcohol consumers have a lower risk than abstainers of an initial myocardial infarction (MI) 1,2 or of recurrent cardiovascular disease. 3,46][7] For developed nations, epidemiological studies estimate that a population with more moderate drinkers and fewer abstainers will have lower rates of cardiovascular disease and total mortality. 5,6,8In fact, guidelines for sensible drinking developed in the United Kingdom suggest that "middle aged or elderly men and post-menopausal women who drink infrequently or not at all may wish to consider the possibility that light drinking might benefit their health." 9Still, the absence of a clinical trial for the effects of alcohol on cardiovascular disease and mortality forces us to use observational data and studies of the effects of alcohol on risk factors to make recommendations encouraging alcohol use, a condition some physicians remain reluctant to accept.In addition, the adverse health and societal effects of heavy or inappropriate drinking are well known to all.
Tuberculosis in immunocompromised hosts: Pathogenetic and pathologic peculiarities
Authors: Maryna Dziusmikeyeva, Dzmitry Gorenok
Journal: European Respiratory Journal (2012)

Fast spreading of HIV-infection is one of the leading reasons of TB incidence increase. HIV-associated immunodeficiency leads to transition TB from infection to disease. Active TB strengthens HIV replication due to rapid synthesis of proinflammatory cytokines. In Belarus, the annual tendency to HIV-associated TB increase is observed. In 2002, a total of 35 HIV/TB patients was registered, whereas 265 in 2009.

The purpose of study: to investigate pathogenetic and pathologic peculiarities of pulmonary TB in patients with HIV/AIDS.

Methods: Morphological study of HIV/AIDS-associated TB was carried out on autopsy material of 11 patients died in center clinic in 2006-2010. The control group was 10 not HIV-infected TB patients.

The causes of death in HIV-infected patients were generalized TB with extrapulmonary manifestations in 6 cases, caseous pneumonia in 2 cases, acute progressing disseminated TB in 3 patients. We distinguished following pathogenetic variants of associated HIV/TB pathology: HIV was primary, duration of observation before TB revealing 5-7 years; TB was primary, duration of observation before HIV revealing 1-3 years; HIV/TB were revealed simultaneously. Peculiarities of TB coursing in AIDS patients compared with non HIV-associated TB were: loss of wavy TB coursing signs and specific inflammation features; monomorphy of TB inflammation foci; prevalence of necrotic suppurative foci; absence of productive inflammation elements on foci periphery; absence of localization and organizations signs of TB foci.

Morphological peculiarities of HIV/TB determine diagnostics complexity and require histobacteriological study with Ziehl-Nielsen staining.
Defining the Scope of Implied Consent in the Emergency Department
Authors: Raul B. Easton, Mark A. Graber, Jay Monnahan, Jason Hughes
Journal: The American Journal of Bioethics (2007)

To determine the relative value that patients place on consent for procedures in the emergency department (ED) and to define a set of procedures that fall in the realm of implied consent.A questionnaire was administered to a convenience sample 134 of 174 patients who were seen in the ED of a Midwestern teaching hospital. The questionnaire asked how much time they believed was necessary to give consent for various procedures. Procedures ranged from simple (venipuncture) to complex (procedural sedation).Participants valued a simple blood draw at a low mean of 1.02 minutes of extra time and a lumbar puncture at a high mean of 7.78 minutes. Of all participants 52% and 48% noted a time-value of "0" time on blood draw and intravenous line starts, respectively, indicating that they desire no additional consent for these procedures.Defining a set of ED procedures covered under implied consent will be difficult because many patients value formal consent for even the simplest procedure.
Coexisting type III hyperlipoproteinemia and familial hypercholesterolemia: A case report
Authors: Nagahiko Sakuma, Seiji Iwata, Reiko Ikeuchi, Takayoshi Ichikawa, Takeshi Hibino, Yoshinobu Kamiya, Nobuyuki Ohte, Masanobu Kawaguchi, Mitoshi Kunimatsu, Hirohisa Kawahara, Takao Fujinami
Journal: Metabolism (1995)
Hospitalization Costs for Radical Prostatectomy Attributable to Robotic Surgery
Authors: Simon P. Kim, Nilay D. Shah, R. Jeffrey Karnes, Christopher J. Weight, Nathan D. Shippee, Leona C. Han, Stephen A. Boorjian, Marc C. Smaldone, Igor Frank, Matthew T. Gettman, Matthew K. Tollefson, R. Houston Thompson
Journal: European Urology (2012)
Validation and Extension of the Endophenotype Model in ADHD Patterns of Inheritance in a Family Study of Inhibitory Control
Authors: Lisa M. Goos, Jennifer Crosbie, Shalaine Payne, Russell Schachar
Journal: American Journal of Psychiatry (2009)

Objective: Endophenotypes, markers of underlying liability to psychiatric disorders, can improve the power to detect genetic risks relative to a complex clinical endpoint. Motor response inhibition is a prime candidate endophenotype in ADHD. In this study, the authors sought to extend the endophenotype model and further demonstrate its utility by investigating the parental origin of shared genetic risk in ADHD. Method: Inhibitory control was studied in children with ADHD, unaffected siblings, and their biological parents. Covariation in inhibitory control within families was investigated. Differential covariation as a function of parental sex was also studied. A number of validity criteria for inhibitory control as an endophenotype were assessed, including sensitivity to the disorder and presence in unaffected relatives. Results: The results confirmed an inhibitory control deficit in children with ADHD as well as in their parents, independent of symptom severity in both generations. Inhibitory control ability in children was significantly predicted by the ability of their parents, particularly their fathers. Conclusions: These findings indicate that an inhibitory control deficit is a cognitive marker of genetic risk shared by parents and offspring. The endophenotype model is also extended by evidence of differential parental contributions to this risk, consistent with findings of parent-of-origin effects in the transmission of certain risk alleles observed in molecular analyses. The identification of these effects at the endophenotype level and their incorporation in genetic modeling can improve both linkage detection and localization of quantitative trait loci.