tbuckley/cabot-search huggingface dataset:
Letter to the Editor: The Kynurenine Pathway in Hepatic Cirrhosis
Authors: Abdulla Badawy
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: Clària et al.1 reported that cirrhosis activates the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) degradation (Fig. 1) by a systemic inflammation–dependent induction of indoleamine 2,3‐dioxygenase (IDO), leading to increased plasma levels of Kyn and its metabolites kynurenic acid (KA) and quinolinic acid (QA). I propose additional and alternative interpretations of these data.Figure 1: The KP of Trp degradation up to the quinolinic and picolinic acid steps. Abbreviations: ACMS, 2‐amino‐3‐carboxymuconic acid‐semialdehyde; ACMSD, 2‐amino‐3‐carboxymuconic acid‐semialdehyde decarboxylase or picolinate carboxylase; AMS, 2‐amino‐3‐muconic acid‐semialdehyde; 3‐HAAO, 3‐hydroxyanthranilic acid 3,4‐dioxygenase; KMO, kynurenine monooxygenase (hydroxylase).Because the authors determined IDO mRNA expression in only 4 control subjects and 6 patients with acute decompensated cirrhosis, we cannot be sure of the IDO catalytic activity in this and the other patient subgroups, especially those with acute‐on‐chronic liver failure (ACLF) and ACLF‐KF (ACLF with kidney failure). Although the authors1 conclude that the greater plasma levels of Kyn, KA, and QA in ACLF‐KF versus ACLF implies greater KP activation in kidney disease, a more likely explanation is that, in kidney disease, these differences are the result of enhancement of tryptophan 2,3‐dioxygenase (TDO2) and kynurenine aminotransferase, and inhibition of kynureninase and 2‐amino‐3‐carboxymuconic acid‐semialdehyde decarboxylase, with IDO being unchanged.2 I also suggest that an increased flux of plasma‐free Trp through TDO24 is the major mechanism of the increased KP activity in cirrhosis, mediated by decreased circulating albumin and increased non‐esterified fatty acids (NEFAs), both of which are established features of liver cirrhosis. The combination of these two changes leads to maximum elevation of plasma‐free Trp (for example, in fulminant liver failure, free and total Trp can rise to values of 60‐112 µM).5 Although TDO has a much greater capacity for Trp, IDO has a much reduced capacity and is inhibited by Trp of at least 50 µM.4 The increase or the absence of a decrease in total Trp in cirrhosis is due to TDO inhibition. I believe that future development of the important platform provided by Clària et al.1 can be strengthened by extending observations to include measurements of plasma‐free (as well as total) Trp and determinants of Trp binding (albumin and NEFA), direct measurements of IDO activity in peripheral blood cells across patient groups, and whenever possible, liver TDO activity.
Plasma Amino Acids and Incident Type 2 Diabetes in Patients With Coronary Artery Disease
Authors: Adrian McCann, Lasse Melvaer Giil, Arve Ulvik, Reinhard Seifert, Eirik Wilberg Rebnord, Eva Ringdal Pedersen, Gard Frodahl Tveitevåg Svingen, Klaus Meyer, Elin Strand, Simon Dankel, Per Magne Ueland, Ottar Kjell Nygård
Journal: Diabetes Care (2019)

OBJECTIVE Altered plasma amino acid levels have been implicated as markers of risk for incident type 2 diabetes; however, amino acids are also related to established diabetes risk factors. Therefore, potential for confounding and the impact from competing risks require evaluation. RESEARCH DESIGN AND METHODS We prospectively followed 2,519 individuals with coronary artery disease but without diabetes. Mixed Gaussian modeling identified potential for confounding. Confounding, defined as a change in effect estimate (≥10%), was investigated by comparing amino acid–incident diabetes risk in a Cox model containing age and sex with that in models adjusted for potential confounders (BMI, estimated glomerular filtration rate, HDL cholesterol, triacylglycerol, C-reactive protein), which were further adjusted for plasma glucose, competing risks, and multiple comparisons (false discovery rate = 0.05, Benjamini-Hochberg method). Finally, component-wise likelihood-based boosting analysis including amino acids and confounders was performed and adjusted for competing risks in order to identify an optimal submodel for predicting incident diabetes. RESULTS The mean age of the source population was 61.9 years; 72% were men. During a median follow-up of 10.3 years, 267 incident cases of diabetes were identified. In age- and sex-adjusted models, several amino acids, including the branched-chain amino acids, significantly predicted incident diabetes. Adjustment for confounders, however, attenuated associations. Further adjustment for glucose and multiple comparisons rendered only arginine significant (hazard ratio/1 SD 1.21 [95% CI 1.07–1.37]). The optimal submodel included arginine and asparagine. CONCLUSIONS Adjustment for relevant clinical factors attenuated the amino acid–incident diabetes risk. Although these findings do not preclude the potential pathogenic role of other amino acids, they suggest that plasma arginine is independently associated with incident diabetes. Both arginine and asparagine were identified in an optimal model for predicting new-onset type 2 diabetes.
Public information after polonium-210 poisoning: cross sectional survey and qualitative analysis
Authors: Niyi Awofeso
Journal: BMJ (2008)

### This month's paper

“Public information needs after the poisoning of Alexander Litvinenko with polonium-210 in London: cross sectional telephone survey and qualitative analysis” by Rubin GJ and colleagues ( BMJ 2007;335:1143 doi: 10.1136/bmj.39367.455243.BE). See bmj.com for rapid responses to this paper.

#### Abstract

Objectives —To identify public perceptions of the risk to health after the poisoning of Alexander Litvinenko with polonium-210 (210Po) in London and to assess the impact of public health communications.

Design —Cross sectional telephone survey and qualitative interviews.

Setting —London, United Kingdom.

Participants —1000 people completed the cross sectional survey and 86 potentially exposed people completed the qualitative interviews.

Main outcome measures —Perception of risk to personal health after the 210Po incident. Qualitative interviews were analysed with an emphasis on information needs.

Results —11.7% of the survey sample (n=117) perceived their health to be at risk. Aside from personal variables the main predictors of perceived risk to health were believing that the incident was related to terrorism (odds ratio 2.7, 95% confidence interval 1.5 to 4.6) rather than to espionage, that it was targeted at the wider public rather than one person (5.9, 3.2 to 10.9), and that it could affect people who had not been in the contaminated area (3.2, 2.1 to 5.1). Participants in the qualitative interviews were generally satisfied with the information they had received, although they would have preferred more information about their individual risk of exposure, the results of their urine tests, and the health implications of the incident.

Conclusions —Perceptions of the public that the 210Po incident in London in 2006 was related to espionage helped to reassure them that the risks to personal health were low. In the event of future incidents it is important to ensure that detailed, comprehensible information about the risks of any exposure is available.

Possible radiological terrorism or …
Equity effects of parenting interventions for child conduct problems: a pan-European individual participant data meta-analysis
Authors: Frances Gardner, Patty Leijten, Victoria Harris, Joanna Mann, Judy Hutchings, Jennifer Beecham, Eva-Maria Bonin, Vashti Berry, Sinead McGilloway, Maria Gaspar, Maria João Seabra-Santos, Bram Orobio de Castro, Ankie Menting, Margiad Williams, Ulf Axberg, Willy-Tore Morch, Stephen Scott, Sabine Landau
Journal: The Lancet Psychiatry (2019)
In it for the money
Authors: Shikha Singh
Journal: BMJ (2007)

It might sound eccentric when I say that clearing out old drawers is a great way to spend a Sunday, but I have found that it can give rise to some delectable memories. I recently found a primary school magazine with a “what I want to be when I'm older” spread. I located my own entry-pop star-illustrated by a triangular shaped, microphone bearing woman. (I was never a great artist.)



How GPs' soaring salaries made front page news



Although I was laughing at my ridiculous pipedream, I realised that before cynicism develops children aim …
Abstract P231: Alcohol Consumption and Hospitalization Risk: Prospective Results From the Moli-sani Study
Authors: Simona Costanzo, Kenneth J Mukamal, Augusto Di Castelnuovo, Marco Olivieri, Marialaura Bonaccio, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria B Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2018)

Introduction: To evaluate the broad impact of alcohol on health and healthcare utilization, the dose-response relationship of alcohol intake with all-cause and cause-specific hospitalizations was examined. Methods: In the Moli-sani study, an Italian population-based cohort, we followed 20,682 initially healthy individuals (48% men, age ≥35 y) free of CVD or cancer. Alcohol intake in the year before enrolment was assessed by the Italian EPIC-FFQ and classified as: abstainers (referent), ex-drinkers, occasional drinkers (&lt;1 gr/day), 1-12, 12.1-24, 24.1-48 and &gt;48 gr/day. We identified hospitalizations by linkage to the regional hospitalization registry. Cause-specific hospitalizations were assigned by the ICD9 code of the primary admission diagnosis. We estimated incidence rate ratios (IRR) for admission by Poisson regression, accounting for repeated hospitalizations. Results: At baseline, 27% of participants were abstainers, 3% ex-drinkers, 6% occasional drinkers and 64% regular current drinkers. During a median follow-up of 6.3 y, 12,996 hospital admissions occurred. In multivariable analyses, occasional consumption and intake up to 48 gr/day were associated with a lower risk of all-cause hospitalization than was abstention. There was a roughly dose-dependent association with lower risk of hospitalization for vascular disease. Excessive alcohol consumption was associated with a higher risk of hospitalization for alcohol-related diseases (IRR: 1.92, 95% CI: 1.43-2.59) and for cancer (IRR: 1.33, 95% CI: 1.08-1.63). Former drinkers were at higher risk for vascular and alcohol-related hospitalization. No association was observed with hospitalization for trauma. Conclusions: Heavy alcohol consumption is associated with higher risk of hospitalization for alcohol-attributable conditions and cancer, but intake up to 48 gr/day is associated with lower risk of all-cause and vascular hospitalization. These estimates highlight the different healthcare burden imposed by varying levels of alcohol intake.
Women in medicine: are they succeeding?
Authors: Anja Spindler, Barbara Buddeberg-Fischer, Victoria Reed
Journal: BMJ (2001)

Women in medicine: are they succeeding? Women are still underrepresented in many areas of medicine

Despite the sex distribution in today's medical school classes, we have not reached the age of equal representation of the sexes in medicine. Western industrialised countries have seen an increase in the percentage of women enrolling in medical school, and in some countries women entrants outnumber men. The large proportion of women applying to and being accepted by medical schools provides evidence of equal access. Yet once they are out of medical school, men and women differ in their choices and career paths. As a result, women are still underrepresented in several disciplines such as hospital surgical and medical specialties. Women are more likely to work in general specialties or primary care and tend to specialise in disciplines that are ranked lower in terms of prestige and earnings.

This breakdown of the sexes by medical specialty is similar to other gender schemas. “Since gender schemas represent women as more nurturant and expressive …
Surgery may be better than drugs in epilepsy
Authors: Samena Chaudhry
Journal: BMJ (2001)

Surgery is more effective than drugs for treating epilepsy and should no longer be considered the treatment of last resort, according to the first clinical trial to compare the two approaches published recently in the New England Journal of Medicine (2001;345:315-8). Sixty four per cent of the patients who underwent the surgery were free of disabling seizures for the year after surgery, compared with only 8% of those receiving drug treatment. In addition, they were better able to participate in social activities, hold jobs, and lead satisfying lives.

However, four of the patients who had surgery had adverse effects. One developed a sensory abnormality in the thigh, one had …
What's on the web? Medical errors
Authors: Susmita Barman
Journal: BMJ (2003)

To err is human, the old adage goes, but when an error leads to death, the ancient wisdom is difficult to digest. Medical mistakes are nearly impossible to forgive or forget. Although everyone involved in the tragedy feels it, often the doctor has to bear the brunt.

Visit www.wrongdiagnosis.com for one of the most comprehensive guides to medical mistakes on the web. It focuses on common medical errors of more than 1200 diseases and 300 symptoms. The site includes a quick …
A beginner's guide to genetics: the basics
Authors: Adrién J Gonzélez, Heidy R Arrieta, Osvaldo M Mutchinick
Journal: BMJ (2004)

In the first of our new series about clinical genetics, <b>Adrién J Gonzélez</b>, <b>Heidy R Arrieta</b>, and <b>Osvaldo M Mutchinick</b> explain the fundamental principles of medical genetics, which provide the basis of prevention and treatment of genetic diseases
Abstract 164: Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms using Transluminal Attenuation Gradient Analysis
Authors: Noelia Grande Gutierrez, Andrew M Kahn, Olga Shirinsky, Galina A Lyskina, Ryuji Fukazawa, Shunichi Ogawa, Jane C Burns, Alison L Marsden
Journal: Circulation (2015)

Background: Coronary artery aneurysms (CAA) put patients (pts) at risk for thrombosis and myocardial infarction. Clinical guidelines recommend systemic anticoagulation for giant CAA, diameter ≥ 8mm. Pt-specific modeling and computer simulations in KD pts suggest that hemodynamic data can predict regions with increased risk of thrombus formation and may be superior to simple assessment of the geometry of the aneurysm. Specifically, regions with high Particle Residence Time gradients (PRTg) have correlated with regions of thrombus formation. Methods: Transluminal Attenuation Gradient (TAG) is determined from the change in radiological attenuation on CT angiography (CTA) images in Hounsfield units per vessel length. TAG analysis has been used for characterizing coronary artery stenoses; however this approach has not been used for CAA. We analyzed the correlation between TAG and PRTg in KD pts with CAA and evaluated TAG for prediction of thrombotic risk. Results: Pt-specific anatomic models for flow simulations were constructed from CTA image data from 6 KD pts with CAA and one normal control. TAG was calculated for all aneurysmal vessels and one control vessel. TAG values for the CAA were markedly lower than for the non-aneurysmal vessel (mean -23.76 vs. -2.21). In addition, TAG values were compared to PRTg and other hemodynamic data obtained for each pt. Conclusion: TAG analysis is a new technique that can be applied to pt data obtained non-invasively through CTA. Thrombotic risk stratification for CAA and decisions about whether to start systemic anticoagulation may be improved by incorporating TAG and should be evaluated in future prospective studies.
Computerised admission test used in London
Authors: Clare Hughes
Journal: BMJ (2002)

A computerised university admission test for medical students has been used in London for the first time. The pilot evaluated the feasibility of replacing the written medical college admission test (MCAT) with a computerised version. Scores from the computerised entrance exam can be processed twice as quickly as scores from the written test, and candidates preferred the computerised version, which they could complete faster.

Most applicants to medical, veterinary, and healthcare university courses in America and Canada routinely complete the MCAT. The test is designed …
The Torres Strait: an ancient yet modern Australia
Authors: Vibhore Prasad, Hariharan Raju
Journal: BMJ (2002)

The Torres Strait contains a group of 70 islands between mainland Australia and Papua New Guinea, 17 of which are inhabited. Politics, geography, and, most importantly, imposed religion have all affected the delivery of health care to the people of these Australian governed islands.1

The Torres Strait islanders are Melanesians whose ancestors migrated to the region from Papua New Guinea 70 000 years ago.23 Their first contact with westerners was in 1871 when the London Missionary Society arrived on Darnley Island.2 The main pastimes of the islanders were hunting, fishing, and agriculture. The people had a sophisticated system of kinship groups, systems of trade with nearby Papua New Guinea, and social behaviour that was reinforced by rituals and tribal customs. Their religion centred around “cultural heroes” or religious figures, ceremonies, and traditional worship objects--for example, turtle shell masks.4 Gardening was important on certain islands and was related to prestige.3

After 1871, the traditional way of life--called the “old ways” by the islanders--gave way to practices more acceptable to the missionaries. Traditional rituals and customs were forbidden leading to a loss of traditional skills and knowledge that would have been passed down through the generations.2 The London Missionary Society had a mixed reception. In 1873, two teachers were killed. But by the 1880s, islands that did not have resident missionaries were requesting them.5

The society stayed in the region until 1915, when they handed over to the Church of England and regulations were …
New hopes for diabetes cure
Authors: Sian Knight
Journal: BMJ (2000)

New research into cell differentiation has raised hopes of finding a cure for insulin-dependent diabetes mellitis. A study published in the Proceedings of the National Academy of Sciences last month has shown that in vitro, duct tissue from the human pancreas can be expanded and then reverted back into pancreatic stem cells. By culturing these cells under the correct conditions, they can be directed towards …
Clinical research on Mount Everest
Authors: Golnar Aref-Adib, Tracie Plant
Journal: BMJ (2007)

<b>Monty Mythen</b> has been working in anaesthetics and critical care for over 20 years. He is Smiths medical professor at University College London and heads the academic department at the Institute of Child Health. He recently spent three months in Nepal helping with the largest ever medical research project at altitude, the Caudwell Xtreme Everest study. He attracted considerable media attention when his children, aged between 6 and 13, took part in a similar study, the Smiths Medical Young Everest study. <b>Golnar Aref-Adib</b> and <b>Tracie Plant</b> spoke to him on the foothills of Everest, Namche Bazaar
Gpnmb secreted from liver promotes lipogenesis in white adipose tissue and aggravates obesity and insulin resistance
Authors: Xue-Min Gong, Yun-Feng Li, Jie Luo, Ji-Qiu Wang, Jian Wei, Ju-Qiong Wang, Ting Xiao, Chang Xie, Jie Hong, Guang Ning, Xiong-Jie Shi, Bo-Liang Li, Wei Qi, Bao-Liang Song
Journal: Nature Metabolism (2019)
Sitting on an interview panel is a privilege
Authors: Bing-Chiu Pang
Journal: BMJ (2005)

I had an opportunity to be on the panel for interviewing prospective medical students. I have always thought it would be interesting to see how it might be from the other side and how different things would be if I were doing the questioning. I remember quite vividly the interviews I had to endure before being accepted by a medical school several years ago, and how daunting the whole event was to a relatively inexperienced student. Now that I am in the fourth year, I felt I had some opinions about what would make a good doctor.

The …
An unusual cause of breathlessness: part 2
Authors: James S Dawson, Jonathan Corne
Journal: BMJ (2005)

A72 year old man was referred to the respiratory team by the cardiologists. He had been operated on for a cardiac myxoma in the past, and was now complaining of shortness of breath. The patient had worked in the postal industry all his life, had never smoked, and consumed 10 units of alcohol a week. He had been investigated for breathlessness about 18 months previously, when a left atrial myxoma had been diagnosed and surgically excised. At this time, benign pleural thickening had been noted, which was thought to be secondary to asbestos exposure. The patient reported that since his operation he had experienced breathlessness on minimal exertion, which was more pronounced when lying flat. He denied any swelling of his ankles. The cardiology team had repeated his echocardiogram, which was normal with no recurrence of his atrial myxoma and with normal left ventricular function. Physical examination was unremarkable. ### Box 1: Causes of unilateral diaphragmatic paralysis 1. What difference between the two radiographs could account for this patient's breathlessness? 2. What are the common causes for this finding, and what is the cause in this patient's case? 3. What simple scheme can you use to study chest radiographs to ensure all the salient aspects are noted?
A systematic review of existing peripheral biomarkers of cognitive aging: Is there enough evidence for biomarker proxies in behavioral modification interventions?
Authors: Alexandra J. Fiocco, Laura Krieger, Danielle D’Amico, Matthew D. Parrott, Danielle Laurin, Pierrette Gaudreau, Carol Greenwood, Guylaine Ferland
Journal: Ageing Research Reviews (2019)
Slice of life
Authors: Chris Callaghan, Ayyaz Ali, Gavin Pettigrew
Journal: BMJ (2004)

For budding surgeons with an interest in complex surgery that is both ethically and technically challenging, transplant surgery may be the ideal career choice. <b>Chris Callaghan</b>, <b>Ayyaz Ali</b>, and <b>Gavin Pettigrew</b> offer a practical guide
Glucocorticoids for Croup in Children
Authors: Allison Gates, David W. Johnson, Terry P. Klassen
Journal: JAMA Pediatrics (2019)

For children with croup, do glucocorticoids reduce clinical symptoms, minimize return visits and/or (re)admissions to the hospital, shorten lengths of stay, or reduce the need for additional treatments?Glucocorticoids reduce symptoms of croup at 2 hours and for at least 24 hours, reduce return visits to care, and shorten hospital stays by about 15 hours. Serious adverse events are infrequent.
Ireland: state pays maximum of £124 a week for elderly care
Authors: Muiris Houston
Journal: BMJ (2002)

Long term care for elderly people who are incapacitated is provided in several different ways in Ireland.

If a 74 year old woman had a stroke, for example, and required nursing home care, several options are available. She could be placed in the long stay ward of a geriatric hospital, in a welfare home, or in a district (cottage) …