tbuckley/cabot-search huggingface dataset:
Abstract 5058: MTHFR and health behaviors: A meta-analysis of epigenetic risks for breast cancer prevention
Authors: Mildred Crisostomo Gonzales, S. Pamela Shiao, Amanda Lie
Journal: Cancer Research (2014)

Abstract Purpose: Breast cancer is the most common malignancy and the second leading cause of cancer death among women worldwide. Methylenetetrahydrofolate reductase (MTHFR) is one of the most studied low penetrant genes that are critical for methylation pathways for deoxyribonucleic acid (DNA) repair and normal cellular development. Methylation pathways are affected by health behaviors such as folate intake, alcohol consumption, and tobacco smoking. While there were several meta-analyses on the associations of MTHFR gene variations and BC, by far, no meta-analysis has been noted on the associations of health behaviors and MTHFR gene variations, with breast cancer. Procedure: PubMed databases were searched by using a combination of key words including “breast cancer”, “MTHFR”, “folate”, “alcohol”, “smoking”, and “health determinants”. Initial search resulted 135 articles from 1999 to 2013. Studies were reviewed for case-control studies, and scored for quality using the standard rating indicators from Quality of Reporting of Meta-analyses. Repeated data from same authors and those with poor quality scores were excluded. Inter-rater reliabilities on data coding and quality scores were established for the selection of studies. Findings: Preliminary results included 55 studies for a total of 22,077 breast cancer cases and 25,419 controls including 27 studies with Whites, 21 studies with Asians, and 7 studies with mixed Euramericans. Twelve studies included MTHFR gene counts with folate intake levels for 8,032 cases and 10,482 controls; 5 studies with alcohol consumption for 3,068 cases and 5,157 controls; and 5 studies with tobacco smoking status for 909 cases and 1233 controls. Preliminary analysis indicated that MTHFR 677CT was associated with increased risk of BC (P &amp;lt; 0.005). The results also suggested that low folate intake, heavy alcohol consumption, and tobacco smoking contributed to increased risks for BC. Conclusion: Investigating the epigenetic risks including healthy life style factors in relation to gene variations has the potential to explain the influence of health behaviors on carcinogenesis. Translating the results from the meta-analysis of health behaviors in relation to epigenetics can provide meaningful insights on the prevention of breast cancer. The findings from the meta-analysis per various race-ethnicity groups can be useful for future development of culturally sensitive and personalized interventions to prevent and reverse breast cancer by promoting the healthy methylation pathways for cancer prevention. Citation Format: Mildred Crisostomo Gonzales, S. Pamela Shiao, Amanda Lie. MTHFR and health behaviors: A meta-analysis of epigenetic risks for breast cancer prevention. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5058. doi:10.1158/1538-7445.AM2014-5058
Altered spectrin association and membrane fragility without abnormal spectrin heat sensitivity in a case of congenital hemolytic anemia
Authors: Yaddanapudi Ravindranath, Robert M. Johnson
Journal: American Journal of Hematology (1985)

Abstract In hereditary pyropoikilocytosis (HPP) and one type of hereditary elliptocytosis (HE), spectrin self‐association is abnormal [5,7]. Spectrin extracted from normal erythro‐cyte membranes at 0°C is nearly all tetrameric, while in HPP and HE (type 1) a substantial amount of the extracted spectrin is dimeric. Abnormal reassociation of spectrin dimers to tetramers can also be demonstrated. We here report the case of a family in which the child has moderately severe hemolysis, with extreme microcytosis and poikilocytosis. The spectrin extracted at 0°C was predominately dimer. Parents had levels of dimer intermediate between patient and control values. The temperature dependence was normal for (a) erythrocyte fragmentation; (b) spectrin extractability; and (c) circular dichroism of purified spectrin. Neither the patient nor either parent had elliptocytic red cells as judged from smears and scanning electron microscopy. The presence of substantial amounts of dimeric spectrin in the parents is consistent with a model in which each parent is heterozygous for a different nonassociating mutant spectrin, while the child has inherited a nonassociating molecule from each parent. In each individual, the degree of mechanical stability of the erythrocyte membrane, determined by ektacytometry, was proportional to the amount of tetramer found in the membrane. The description of this case is consistent with either HPP or a form of homozygous HE which is asymptomatic in the carrier state.
APPARATUS FOR FACILITATING COLOSTOMY IRRIGATION
Authors: Barton McSwain
Journal: JAMA (1952)

In order to make irrigation of a colostomy as easy as possible for the patient, a new piece of equipment has been devised. The story of the evolution of the apparatus helps explain its mechanism and value. At first an aluminum stewpot, with a hole in the center, and a piece of metal pipe attached to it, was used; then a stainless steel emesis basin was substituted for the stewpot. A member of the nursing staff suggested the addition of the flange to prevent the return flow from splashing on the patient. A patient suggested moving the hole from the center to an eccentric position, since his colostomy was not in the midline.  Figure 1 is a photograph of the apparatus. The stainless steel basin, 11½ by 5 by 2 in. (31.24 by 12.70 by 5.08 cm.) costs $4.00. The work shop charge for the flange and pipe, both of
Glucosylceramide synthase is an essential regulator of pathogenicity of Cryptococcus neoformans
Authors: P. C. Rittershaus
Journal: Journal of Clinical Investigation (2006)

The pathogenic fungus Cryptococcus neoformans infects humans upon inhalation and causes the most common fungal meningoencephalitis in immunocompromised subjects worldwide. In the host, C. neoformans is found both intracellularly and extracellularly, but how these two components contribute to the development of the disease is largely unknown. Here we show that the glycosphingolipid glucosylceramide (GlcCer), which is present in C. neoformans, was essential for fungal growth in host extracellular environments, such as in alveolar spaces and in the bloodstream, which are characterized by a neutral/alkaline pH, but not in the host intracellular environment, such as in the phagolysosome of macrophages, which is characteristically acidic. Indeed, a C. neoformans mutant strain lacking GlcCer did not grow in vitro at a neutral/alkaline pH, yet it had no growth defect at an acidic pH. The mechanism by which GlcCer regulates alkali tolerance was by allowing the transition of C. neoformans through the cell cycle. This study establishes C. neoformans GlcCer as a key virulence factor of cryptococcal pathogenicity, with important implications for future development of new antifungal strategies.
SYMPTOMATOLOGY AND TREATMENT OF SUMMER COMPLAINT.Lecture delivered at the Fourth Special Course of the Chicago Policlinic.
Authors: W. S. CHRISTOPHER
Journal: JAMA (1892)

The most prominent symptoms in summer complaint are those connected with the bowels. The diarrhoea is characterized by stools which differ from each other greatly, as to number, consistency, color, and odor. Of the several phases of the stools, the odor is the one to which I wish to call particular attention. It is indeed remarkable with what certainty the stools may be divided by their odor into putrid stools and acid stools. Occasionally the stool will be described as having an intensified fecal odor, or smelling like old wood, but it is evident that such odors are but variations of putridity. The acid stools derive their odor from the presence in them of various members of the fatty acid group, all of which have arisen from fermentation of carbo-hydrates. The putrid stools, on the other hand, can only arise from fermentations of albuminous materials. I told you in my
Aspirin and bleeding peptic ulcers in the elderly.
Authors: G. Faulkner, P. Prichard, K. Somerville, M. J. Langman
Journal: BMJ (1988)

A case-control study was performed to determine whether aspirin confers a similar risk of bleeding from gastric or duodenal ulcers in the elderly as non-aspirin, non-steroidal anti-inflammatory drugs. The intake of analgesics in 230 patients with bleeding ulcers aged 60 and over and in hospital and community controls matched for age and sex was examined. Those who had taken aspirin were between two and three times more likely to be admitted to hospital with bleeding ulcers. This increased risk was not accounted for by aspirin taken for indigestion or by concurrent use of non-aspirin, non-steroidal anti-inflammatory drugs. A similar effect was not seen for paracetamol. When aspirin and other non-steroidal anti-inflammatory drugs were considered together the overall risk attributed to the drugs suggested that these drugs may be responsible for over a third of admissions for bleeding peptic ulcers in the elderly.
Cure for Hiccough.
Authors: W. L. Robins
Journal: JAMA (1896)

Washington, D. C., Feb. 3,1896. <h3>To the Editor:</h3> —I have found the following method a positive cure for<i>hiccough</i>without the use of drugs. Immediately after the paroxysm of hiccough, close the mouth and inflate the lungs to their utmost capacity by breathing the air in through the nose; then hold the breath as long as possible; when finally compelled to expel the air from the lungs we do so and to our astonishment find that we are no longer troubled with hiccough. Once usually suffices, but it may be necessary to repeat the process the second time for the reason that during the first trial at thorough inflation of the lungs there may come a slight spasm of the glottis, when we find it necessary to quickly exhale. Immediately after this sudden exhalation take a long, full breath (mouth closed) and hold it from twenty to thirty seconds. There
Management of raised blood pressure in New Zealand: a discussion document.
Authors: R Jackson, P Barham, J Bills, T Birch, L McLennan, S MacMahon, T Maling
Journal: BMJ (1993)

A report to the National Advisory Committee on Core Health and Disability Support Services, New Zealand, on the management of raised blood pressure recommends that decisions to treat raised blood pressure should be based primarily on the estimated absolute risk of cardiovascular disease rather than on blood pressure alone. In general, patients with a blood pressure of 150-170 mm Hg systolic or 90-100 mm Hg diastolic, or both, should be given treatment to lower blood pressure if the risk of a major cardiovascular disease event in 10 years is more than about 20%. The results of clinical trials indicate that, at this level of absolute risk, 150 people would require treatment to reduce the annual number of cardiovascular events by about one. Implementation of these recommendations may result in a smaller proportion of people aged under 60, particularly women, receiving treatment but an increased proportion of older people treated. In the absence of specific contraindications, low dose diuretics and low dose beta blockers should be considered for first line treatment, since for only these drug groups is there direct evidence of reduced risk of stroke and coronary disease in people with raised blood pressure.
A Low-Power View
Authors: Charles D. Aring
Journal: JAMA (1970)

In an article entitled "The World Through Myopic Eyes," Trevor-Roper' endeavors to show how certain poets, writers, and painters were influenced by the shortness of their sight. Lord Byron might well have agreed. It was he who observed that Lord Russell's essays on London society were too microscopic for his mind, and advised, "He who would take a just view of the world must neither examine it through a microscope nor a magnifying glass." Perspective is prejudiced by unduly close proximity, as Byron said. The technique that defines by refining does little to encourage<i>Weltanschauung</i>. That a few are able, nevertheless to maintain a steady view of microcosm and macrocosm is one of those exceptions that illustrate the rule. Low-power and high-power viewing are extremes; there are of course many positions in between. But microscopical contemplation has been a favored method of science for a long, long time. While serving
Cross-linked Cytokeratin Polypeptides in Liver and Hepatoma Cells: Possible Association with the Process of Cell Degeneration and Death
Authors: Kazunori Fukuda, Masamichi Kojiro, Jen-Fu Chiu
Journal: Hepatology (1993)

We investigated transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells. To overcome the difficulties in the biochemical analysis of highly cross-linked polymers and aggregates of cytokeratins, cross-linked cytokeratin dimers were analyzed by immunoblotting to evaluate the degree of cross-linking of cytokeratins. Covalently cross-linked cytokeratin dimers were not detectable in normal rat liver cells. However, cytokeratin dimers and high-molecular-weight cytokeratin polymers were detected in liver tissue with histological evidence of coagulative necrosis induced by ischemia or carbon tetrachloride. Treatment of cultured hepatoma cells with the Ca2+ ionophore A23187 showed a dose-dependent, time-dependent decrease of cell viability. The appearance of cytokeratin dimers was shown to be correlated with cell death. These results suggest that the transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells is closely associated with the process of cell degeneration and death.
ABC of emergency radiology. The shoulder.
Authors: D A Nicholson, I Lang, P Hughes, P A Driscoll
Journal: BMJ (1993)

Trauma to the shoulder is common, although the type of injury varies considerably in different age ,. ~~~~~~~g roups.Clavicular fractures are common in childhood and early adulthood, glenohumeral dislocation and acromioclavicular disruption are M-~~~~~~~~~~~~~~frequent between the ages of 15 and 40 years, and Normal m se n o| T sue fracture of the humeral head is often seen in elderly people.This chapter describes the features f ~~~~*~~~J' ~of these types of injury and a system of radiological interpretation to ensure that many of the subtle signs associated with them are not missed. FIG 1Diagram of shoulder ligamentsImportant anatomical considerations Adult Normal measurements of The shoulder consists of three bones and three joints.The acromion, acromioclavicular joint coracoid process, and clavicle are linked by the shoulder ligaments.The Joint distance <8mm coracoclavicular ligament is important as it is the main ligamentous Differece beteen sids <3mmattachment of the upper limb to the trunk.The acromioclavicular ligament is of secondary importance, but it is where radiographic evidence of injury is initially sought.FIG 2-Anteroposterior radiograph of normal shoulder with line diagram.
RAPID PROVISIONAL MICROSCOPIC DIAGNOSES OF MALIGNANCY WITHOUT A MICROTOME
Authors: BENJAMIN TAYLOR TERRY
Journal: JAMA (1924)

The method here described is the result of my having missed a small area of malignancy in an examination I was called on to make a year and a half ago. A middle aged fleshy white woman had, in the upper and outer quadrant of her right breast, a small rounded mass about 1.5 cm. in diameter. In removing this mass the surgeon cut well around it and turned it over to me for microscopic examination. Two sections from this tumor were cut on the freezing microtome, and appeared benign. The surgeon was satisfied, and the patient was sent back to her room. About two weeks later, I was not quite so busy and sectioned very carefully the rest of the mass. Much to my surprise, I found, in a part not previously examined, a small area that I believed was malignant. After careful study, I reported my findings to
Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of clinical study reports, trial registries, and publications
Authors: E. Maund, B. Tendal, A. Hrobjartsson, K. J. Jorgensen, A. Lundh, J. Schroll, P. C. Gotzsche
Journal: BMJ (2014)

<b>Objective</b> To determine, using research on duloxetine for major depressive disorder as an example, if there are inconsistencies between protocols, clinical study reports, and main publicly available sources (journal articles and trial registries), and within clinical study reports themselves, with respect to benefits and major harms. <b>Design</b> Data on primary efficacy analysis and major harms extracted from each data source and compared. <b>Setting</b> Nine randomised placebo controlled trials of duloxetine (total 2878 patients) submitted to the European Medicines Agency (EMA) for marketing approval for major depressive disorder. <b>Data sources</b> Clinical study reports, including protocols as appendices (total 13 729 pages), were obtained from the EMA in May 2011. Journal articles were identified through relevant literature databases and contacting the manufacturer, Eli Lilly. Clinicaltrials.gov and the manufacturer's online clinical trial registry were searched for trial results. <b>Results</b> Clinical study reports fully described the primary efficacy analysis and major harms (deaths (including suicides), suicide attempts, serious adverse events, and discontinuations because of adverse events). There were minor inconsistencies in the population in the primary efficacy analysis between the protocol and clinical study report and within the clinical study report for one trial. Furthermore, we found contradictory information within the reports for seven serious adverse events and eight adverse events that led to discontinuation but with no apparent bias. In each trial, a median of 406 (range 177-645) and 166 (100-241) treatment emergent adverse events (adverse events that emerged or worsened after study drug was started) in the randomised phase were not reported in journal articles and Lilly trial registry reports, respectively. We also found publication bias in relation to beneficial effects. <b>Conclusion</b> Clinical study reports contained extensive data on major harms that were unavailable in journal articles and in trial registry reports. There were inconsistencies between protocols and clinical study reports and within clinical study reports. Clinical study reports should be used as the data source for systematic reviews of drugs, but they should first be checked against protocols and within themselves for accuracy and consistency.
Nitric oxide synthase in post-ischaemic remodelling: new pathways and mechanisms
Authors: B. Manoury, V. Montiel, J.-L. Balligand
Journal: Cardiovascular Research (2012)

The three isoforms of nitric oxide synthase (NOS), spatially confined in specific intracellular compartments in cardiac cells, have distinct roles in the regulation of contractility in pathophysiological situations. Recently, evidence has emerged that implicates NOS in modulating myocardial remodelling during cardiac stress, including after ischaemic insults. As long as they remain in a coupled state the NOS mostly attenuate hypertrophic remodelling through both cGMP-dependent and independent mechanisms. We review the evidence provided from the phenotype of genetic mouse models as well as from in vitro cell experiments dissecting the signalling effectors involved in the NOS-mediated regulation that justify new therapeutic interventions on the NOS–cGMP axis to attenuate the development of heart failure.
Systemic steroids in chronic severe asthma.
Authors: A Banerjee, S Virdee
Journal: BMJ (1986)

referenced with a colleague or senior member of the nursing staff.Further evidence of incom- petence must be presented to senior colleagues.The options open to them will be explained by the personnel officer of the district and may include secondment to a more supervised post for the remainder of this man's contract.It is most important for the registrar to realise that he is not alone in this dilemma.Many of us have faced it and I have had to persuade both doctors and paramedical staff to reconsider their career plans in the light of such findings of incompetence.
The Nature of Bell's Palsy
Authors: R. Wyburn-Mason
Journal: BMJ (1954)

<h3>Objectives</h3> The enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analysing population-scale datasets in real time to monitor and better understand the evolving pandemic. The objectives of this study were to examine the relationship of risk factors to COVID-19 susceptibility and severity and to develop risk models to accurately predict COVID-19 outcomes using rapidly obtained self-reported data. <h3>Design</h3> A cross-sectional study. <h3>Setting</h3> AncestryDNA customers in the USA who consented to research. <h3>Participants</h3> The AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors and exposures for over 563 000 adult individuals in the USA in just under 4 months, including over 4700 COVID-19 cases as measured by a self-reported positive test. <h3>Results</h3> We replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for men even after adjusting for known exposures and age (adjusted OR=1.36, 95% CI=1.19 to 1.55). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualised COVID-19 susceptibility (area under the curve (AUC)=0.84) and severity outcomes including hospitalisation and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex and genetic ancestry groups within the study. <h3>Conclusions</h3> The results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic.
Psychology in Medical Education
Authors: J. Rickman
Journal: BMJ (1947)

MEDICAL 6URNAL 3 recommends that no part of a final or qualifying examination should be taken before the end of thirty months of clinical study, and that the examination should not be completed before the end of the period of clinical studies of thirty-three months.(5) It has abandoned the recom- mendation of 1933 that candidates should be required to complete the three portions (medicine, surgery, and mid- wifery) of the final or qualifying examination within a period of nineteen months.It would be less than frank not to add that the Council's decision on the last point was not inspired by sympathy with the chronic student but by confidence that examiners can be trusted to guard the public against candidates in- capable of passing at a reasonable standard.In short, the aim of the General Medical Council is to ensure that the medical practitioner will not (to borrow from H. A. L. Fisher) have to navigate the sea of knowledge without the charts and compass of an adequate education.
An hereditary syndrome of lumpy scalp, odd ears, and rudimentary nipples
Authors: A.Y. FINLY, R. MARKS
Journal: British Journal of Dermatology (1978)

A syndrome, consisting of a congenital abnormality of the scalp, ears and nipples inherited as an autosomal dominant trait, is reported. Ten affected members of a family over five generations are recorded and the four living affected members are described in detail. A review of congenital localized aplasias of skin suggests that this may be a new syndrome.