tbuckley/cabot-search huggingface dataset:
Caregiving as a Risk Factor for Mortality
Authors: Richard Schulz, Scott R. Beach
Journal: JAMA (1999)

There is strong consensus that caring for an elderly individual with disability is burdensome and stressful to many family members and contributes to psychiatric morbidity. Researchers have also suggested that the combination of loss, prolonged distress, the physical demands of caregiving, and biological vulnerabilities of older caregivers may compromise their physiological functioning and increase their risk for physical health problems, leading to increased mortality.To examine the relationship between caregiving demands among older spousal caregivers and 4-year all-cause mortality, controlling for sociodemographic factors, prevalent clinical disease, and subclinical disease at baseline.Prospective population-based cohort study, from 1993 through 1998 with an average of 4.5 years of follow-up.Four US communities.A total of 392 caregivers and 427 noncaregivers aged 66 to 96 years who were living with their spouses.Four-year mortality, based on level of caregiving: (1) spouse not disabled; (2) spouse disabled and not helping; (3) spouse disabled and helping with no strain reported; or(4) spouse disabled and helping with mental or emotional strain reported.After 4 years of follow-up, 103 participants (12.6%) died. After adjusting for sociodemographic factors, prevalent disease, and subclinical cardiovascular disease, participants who were providing care and experiencing caregiver strain had mortality risks that were 63% higher than noncaregiving controls (relative risk [RR], 1.63; 95% confidence interval [CI], 1.00-2.65). Participants who were providing care but not experiencing strain (RR, 1.08; 95 % CI, 0.61-1.90) and those with a disabled spouse who were not providing care (RR, 1.37; 95% CI, 0.73-2.58) did not have elevated adjusted mortality rates relative to the noncaregiving controls.Our study suggests that being a caregiver who is experiencing mental or emotional strain is an independent risk factor for mortality among elderly spousal caregivers. Caregivers who report strain associated with caregiving are more likely to die than noncaregiving controls.
Deciphering the Relationship between Mating System and the Molecular Evolution of the Pheromone and Receptor Genes in Neurospora
Authors: Kristiina Nygren, Rebecka Strandberg, Anastasia Gioti, Magnus Karlsson, Hanna Johannesson
Journal: Molecular Biology and Evolution (2012)

Here, we present a study of the molecular evolution of the pheromone receptor genes (pre-1 and pre-2) in Neurospora taxa with different mating systems. We focus on comparisons between heterothallic and homothallic taxa, reproducing sexually by outcrossing and by intrahaploid selfing, respectively. Our general aim was to use a phylogenetic framework to investigate whether the evolutionary trajectory of the pheromone and receptor genes in Neurospora differs between heterothallic and homothallic taxa, and among the homothallic lineages/clades previously indicated to represent independent switches from heterothallism to homothallism in the evolutionary history of the genus. We complemented molecular evolution analyses with an expression study of the pre genes and their upstream regulators, the mating-type (mat) genes, in homothallic taxa. Our analyses suggest that the pheromone receptor gene pre-1 is functionally conserved in both heterothallic and homothallic taxa. Moreover, we found evidence of positive selection for a small fraction of codons in the cytoplasmic signal-transducing C-terminal region of the protein PRE-1. Distribution of positively selected codons differs between heterothallic and homothallic groups, suggesting functional divergence associated with mating system. The gene pre-2 was shown to evolve under high selective constraints, with no strong evidence for positive selection. Although our data suggest that both pre-1 and pre-2 are overall functional in homothallic taxa, individual taxa display frame-shift mutations causing premature stop codons, which might indicate loss of function. Transcriptional patterns of pre and mat genes in six homothallic taxa, selected to represent six different switches from heterothallism to homothallism, do not support a universal pattern of regulation of these genes during reproductive tissue development. Taken together, our analyses suggest that the pheromone receptor genes pre-1 and pre-2 are in general functional in homothallic Neurospora taxa, in contrast with the situation for the mat genes that are generally degenerate in these taxa.
Influence of Rapid Malaria Diagnostic Tests on Treatment and Health Outcome in Fever Patients, Zanzibar—A Crossover Validation Study
Authors: Mwinyi I. Msellem, Andreas Mårtensson, Guida Rotllant, Achuyt Bhattarai, Johan Strömberg, Elizeus Kahigwa, Montse Garcia, Max Petzold, Peter Olumese, Abdullah Ali, Anders Björkman
Journal: PLoS Medicine (2009)

Background The use of rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria is being suggested to improve diagnostic efficiency in peripheral health care settings in Africa. Such improved diagnostics are critical to minimize overuse and thereby delay development of resistance to artemisinin-based combination therapies (ACTs). Our objective was to study the influence of RDT-aided malaria diagnosis on drug prescriptions, health outcomes, and costs in primary health care settings. Methods and Findings We conducted a cross-over validation clinical trial in four primary health care units in Zanzibar. Patients of all ages with reported fever in the previous 48 hours were eligible and allocated alternate weeks to RDT-aided malaria diagnosis or symptom-based clinical diagnosis (CD) alone. Follow-up was 14 days. ACT was to be prescribed to patients diagnosed with malaria in both groups. Statistical analyses with multilevel modelling were performed. A total of 1,887 patients were enrolled February through August 2005. RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%) (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.03–0.05, p<0.001). Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%) (OR 1.8, 95%CI 1.5–2.2, p<0.001), respectively. Reattendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%) (OR 0.5, 95% CI 0.3–0.9, p = 0.005). Total average cost per patient was similar: USD 2.47 and 2.37 after RDT and CD alone, respectively. Conclusions RDTs resulted in improved adequate treatment and health outcomes without increased cost per patient. RDTs may represent a tool for improved management of patients with fever in peripheral health care settings. Trial Registration Clinicaltrials.gov NCT00549003 Please see later in the article for Editors' Summary
Abstract 4509: Epigallocatechin gallate suppresses tumorigenesis of lung cancer cells by targeting Ras-GTPase-activating protein SH3-domain binding protein 1
Authors: Jung-Hyun Shim, Zheng-Yuan Su, Jung-II Chae, Dong-Joon Kim, Feng Zhu, Wei-Ya Ma, Ann M. Bode, Chung S. Yang, Nam-Pyo Cho, Zigang Dong
Journal: Cancer Research (2010)

Abstract (−)-Epigallocatechin gallate (EGCG) is one of the major green tea catechins that is suggested to have a role as a preventive agent in cancer, obesity, diabetes, and cardiovascular disease. Here we identified Ras-GTPase-activating protein SH3-domain binding protein 1 (G3BP1) as an important and novel molecular target of EGCG in lung cancer. EGCG interacted with the G3BP1 with high binding affinity (Kd = 0.4 μmol/liter). We also showed that EGCG suppressed anchorage-independent growth of H1299 and CL13 lung cancer cells, which contain an abundance of the G3BP1 protein. EGCG was much less effective in suppressing anchorage-independent growth of H460 lung cancer cells in which G3BP1 levels are low. Knockdown shG3BP1-transfected H1299 cells exhibited substantially decreased proliferation and anchorage-independent growth. shG3BP1-H1299 cells were resistant to the inhibitory effect of EGCG on growth and colony formation compared to shMock-transfected H1299 cells. EGCG interfered with the interaction between G3BP1 and Ras-GTPase-activating protein (Ras-GAP) and further suppressed the activation of Ras. Additional results revealed that EGCG effectively attenuated G3BP1-downstream signaling, including extracellular signaling-regulated kinases, and MAPK kinase in wildtype H1299 and shMock-H1299 cells, but had little effect on H460 or shG3BP1- H1299 cells. Overall, these results strongly indicate that EGCG suppresses lung tumorigenesis through its binding with G3BP1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4509.
Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes.
Authors: R L Coffman, D A Lebman, B Shrader
Journal: The Journal of Experimental Medicine (1989)

The addition of TGF-beta to cultures of LPS-stimulated murine B cells causes a approximately 10-fold enhancement of IgA production, yet causes a 10-fold decrease in total Ig production. IL-2 and, to a lesser extent, IL-5 synergize with TGF-beta to further enhance IgA production and partially reverse the inhibition of total Ig production. IgA constitutes only approximately 0.1% of total Ig in LPS-stimulated cultures, but that percentage rises to 15-25% in cultures to which TGF-beta and IL-2 are added. TGF-beta induces a substantial increase in IgA production from sIgA- B cells but inhibits IgA production by sIgA+ cells. This finding suggests that TGF-beta acts as an isotype-specific switch factor for IgA.
Effects of NO Modulation on Cardiac Arrhythmias in the Rat Isolated Heart
Authors: Ravinder Pabla, Michael J. Curtis
Journal: Circulation Research (1995)

Abstract It has been proposed that NO may function as an endogenous cardioprotectant. We have investigated whether modulation of NO levels (detected in coronary effluent by chemiluminescence) by a blocker of its synthesis, by supplementation of its precursor, and by administration of an NO donor can influence reperfusion arrhythmias in the isolated rat heart. Rat hearts were perfused with modified Krebs’ solution and subjected to 5, 35, or 60 minutes of left regional ischemia followed by 10 minutes of reperfusion. N G -Nitro- l -arginine methyl ester (L-NAME), which blocks NO synthase, increased the incidence of reperfusion-induced ventricular fibrillation (VF) from 5% in the control condition to 35% after 60 minutes of ischemia (n=20, P &lt;.05). The profibrillatory effect of L-NAME was prevented in hearts coperfused with 1 or 10 mmol/L l -arginine (an NO precursor) but persisted in hearts coperfused with d -arginine (1 mmol/L). L-NAME did not increase VF susceptibility in hearts reperfused after 5 or 35 minutes of ischemia. L-NAME caused sinus bradycardia (264±10 versus 309±5 bpm in control groups, P &lt;.05) and reduced coronary flow before ischemia (6.2±0.6 versus 9.2±0.6 mL · min −1 · g −1 tissue in controls, P &lt;.05). L-NAME reduced coronary effluent NO levels after 60 minutes of ischemia; during the first minute of reperfusion, values were reduced from 1457±422 to 812±228 pmol · min −1 · g −1 ( P &lt;.05). This effect was prevented by coperfusion with l -arginine (10 344±1730 pmol · min −1 · g −1 , P &lt;.05). Qualitatively similar changes occurred with other durations of ischemia, but the effects of L-NAME were not significant. L-NAME had no effect on QT interval; eg, values after 5 minutes of ischemia were 76±7 and 85±5 milliseconds in control and L-NAME–treated groups, respectively (n=20, P =NS). The NO donor sodium nitroprusside (10 μmol/L) significantly increased coronary flow 1 minute before ischemia (15.4±1.1 versus 9.2±0.6 mL · min −1 · g −1 tissue and coronary effluent NO levels (from 1122±122 to 4093±1466 pmol · min −1 · g −1 , P &lt;.05). Sodium nitroprusside prevented the proarrhythmic effect of L-NAME and maintained coronary effluent NO levels during reperfusion. NO appears to function as an endogenous cardioprotectant antifibrillatory factor in rat heart during reperfusion following sustained ischemia.
Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Francais d'Etude de la Tetrahydroaminoacridine.
Authors: G Chatellier, L Lacomblez
Journal: BMJ (1990)

OBJECTIVE--To see whether combined treatment with oral tacrine (tetrahydroaminoacridine; THA) and lecithin improves the symptoms of patients with Alzheimer9s disease. DESIGN--Multicentre double blind, placebo controlled, random order crossover trial with individual determination of maximum tolerated dosage and four month follow up. SETTING--Outpatient departments at six university neurological centres. PATIENTS--67 Outpatients (24 men, 43 women) aged 53-81 (mean 66 (SD 7.3)) selected according to the following criteria: probable Alzheimer9s disease as defined by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer9s Disease and Related Disorders Association; absence of mood disorder; mini mental state score lower than 26; availability of a close relative able to complete questionnaires; and informed consent of the patient or his or her closest relative, or both. INTERVENTIONS--Mean of 114 mg tacrine or placebo daily plus 1200 mg lecithin daily given in three divided doses for one four week active treatment period and one four week control period without washout at crossover. MAIN OUTCOME MEASURES--Cognitive state as assessed by Folstein9s mini mental state rating scale, behavioural state as assessed by the Stockton geriatric rating scale, and overall state as assessed with a visual analogue scale rated by both the relative and the physician. RESULTS--Compared with placebo tacrine did not improve either the mini mental state score (mean 14.9 (SD 7.3) v 14.8 (7.3)) or the Stockton geriatric score (28.2 (15.7) v 28.7 (17.8)), but a slight and statistically significant improvement occurred in the physician9s score on the visual analogue scale (6.3 (10.2) v 11.6 (17.9)). Seven patients dropped out. Six patients were excluded because of acute hepatitis and one withdrew for personal reasons not related to treatment. Two other patients developed acute hepatitis at the end of the eight week crossover trial and another during the follow up study. Twenty patients complained of gastrointestinal side effects. CONCLUSIONS--Neither short term nor long term treatment with oral tacrine at dosages lower than 125 mg/day improves the symptoms of Alzheimer9s disease. Moreover, these dosages may induce hepatitis (nine of 67 patients in this series).
Safety and side effects of sustained-release niacin
Authors: J. M. Keenan
Journal: JAMA (1994)

To the Editor.  —The study by Dr McKenney and colleagues 1 is described by the authors as a well-designed clinical trial. We would concur with that description if the authors would make more explicit the intention of the study, namely, that it was clearly designed to maximize the potential for niacin intolerance and toxicity. Despite their obvious familiarity with the clinical literature, they chose a peculiarly unphysiologic twice-daily dosing schedule. Similarly, they intentionally escalated both the immediate-release (IR) nicotinic acid and sustained-release (SR) nicotinic acid to a total dose of 3000 mg (1500 mg twice daily), whether or not the patient had demonstrated an adequate lipid response at a lower dose.
Independent Adoptions; A Follow-Up Study
Authors: Arthur G. King
Journal: JAMA (1963)

This intensive (and discursive) work is of value primarily to doctors, lawyers, and social workers involved in infant adoptions, and to any doctor whose opinion might be asked on whether a child should be "given up" for adoption or placed in a given home. Although the investigation reported was limited to Florida, the results are not dissimilar from those found in other states. The original placements had been made independently rather than through qualified agencies. Ten years later a study of home conditions and child development revealed that 30% of homes failed to offer a favorable setting for healthy growth, and only 46% were rated good to excellent. Maladjustment of children was found in 23% of the "unfavorable" homes, compared with only 1% of children in homes rated "favorable." Factors related to favorable outcomes were: placement before 30 days of age, study of the child and the home before placement,
The splenic microenvironment is a source of proangiogenesis/inflammatory mediators accelerating the expansion of murine erythroleukemic cells
Authors: Yuval Shaked, Dave Cervi, Manuela Neuman, Limor Chen, Giannoula Klement, Crystal R. Michaud, Mehran Haeri, Brian J. Pak, Robert S. Kerbel, Yaacov Ben-David
Journal: Blood (2005)
Use of the Selective Oral Neuraminidase Inhibitor Oseltamivir to Prevent Influenza
Authors: Frederick G. Hayden, Robert L. Atmar, Margo Schilling, Casey Johnson, Donald Poretz, David Paar, Les Huson, Penelope Ward, Roger G. Mills
Journal: New England Journal of Medicine (1999)

Safe and effective antiviral agents are needed to prevent infection with influenza A and B viruses. Oseltamivir (GS4104), which can be administered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for long-term prophylaxis against influenza in two placebo-controlled, double-blind trials at different U.S. sites during the winter of 1997–1998.
Long term results of alpha-interferon monotherapy
Authors: Z. Kaymakoglu, Y. Cakaloglu, A. Danalioglu, K. Demir, F. Akyuz, N. Aksoy, D. Oner, S. Badur, F. Besisik, Z. Mungan, U. Cevikbas, A. Okten
Journal: Journal of Hepatology (2003)
The Walker Resolutions.
Authors: Jabez N. Jackson
Journal: JAMA (1906)

Kansas City, Sept. 6, 1906. <h3>To the Editor:</h3> —After reading Dr. Carstens' letter inThe Journal, September 1, I desire, as the mover of the motion to lay the Walker resolutions on the table, to correct some erroneous impressions that have gained circulation regarding the reasons for tabling these resolutions. In the first place, I had no knowledge that such resolutions were to be introduced, nor had I been asked by any one to take any position relative thereto. When they were read, however, they at once impressed me as a covert attack on the honesty of the members of the Board of Trustees, and of the officers of the Association. I consider it necessary in any organization that a few men of capacity should have the main work fall on their shoulders. Such an organization would always be called by others a "machine." I do not object to this
Book Review Family Support for the Elderly: The International Experience Edited by Hal Kendig, Akiko Hashimoto, and Larry C. Coppard. 323 pp. New York, Oxford University Press, 1992. $70. 0-19-262173-4 Ethics in an Aging Society By Harry R. Moody. 288 pp. Baltimore, Johns Hopkins University Press, 1992. $40. 0-8018-4323-5
Authors: Katherine A. Hesse
Journal: New England Journal of Medicine (1993)
Organisation of bank of raw and pasteurised human milk for neonatal intensive care.
Authors: S Williamson, J H Hewitt, E Finucane, H R Gamsu
Journal: BMJ (1978)

In 1976 a human-milk bank was established at King's College Hospital to serve the neonatal intensive care unit. The bank is staffed by two part-time nurses, who interview prospective donors, organise collections, prepare samples for bacteriological screening, and process the milk. On average 25 litres a month may be collected from about 15 donors, of which at least two-thirds is free enough of bacteria to be fed raw (unheated) to sick and low-birth-weight infants. Most of the remainder may be used after holder pasteurisation. The bank provides an adequate supply of milk of consistent nutritional quality and permits a more informed approach to the dietary management of infants of low birth weight.
Setting priorities for research and development in the NHS: a case study on the interface between primary and secondary care
Authors: R. Jones, T. Lamont, A. Haines
Journal: BMJ (1995)

Since 1991 the NHS has attempted to identify and prioritise its needs for research and development in a systematic manner. This has not been done before and there is little evidence on which to draw. Multidisciplinary expert groups have identified priorities in different topics using explicit criteria and after widespread consultation within the NHS and research community to identify pressing problems and opportunities for research. This paper focuses on a review completed in 1993 to identify research and development priorities for the NHS in relation to the interface between primary and secondary care. The review covered several recent developments which require evaluation. The authors describe the process used to identify research and development priorities in this complex subject and examine the strengths and weaknesses of the approach. This case study should help to stimulate a wider debate on methods of identifying priorities, particularly those using participatory approaches, in research and non-research contexts.
How to attract, retain and nurture young academic clinicians
Authors: Jeffrey K Aronson
Journal: Journal of the Royal Society of Medicine (2011)

The announcement of a new UK Centre for Medical Research and Innovation (UKCMRI), which will concentrate on attracting scientists in their mid-30s who are eager to try new ideas,1 recognizes, although it may be too late for some, the need to make academic careers more attractive and to ensure that trainees, the specialists of the future, are bred in such a way as to be able to practise their discipline most efficiently. We therefore need to consider how those young scientists should best be encouraged.

For at least 15 years there has been a crisis in academic medicine, which has been extensively discussed in the UK and the USA.2,3 For example, the number of academic clinicians in the UK has been falling. Since this trend was first highlighted,4 there have been various initiatives to try to reverse it. Here I review the measures that have been instituted in the UK, enumerate the problems that handicap academic recruitment and retention, and suggest remedies, inspired by Peter Medawar's Advice to a Young Scientist and James Watson's Avoid Boring People. Although my comments are formulated from a UK perspective, the problems that I discuss, of how to attract, retain and nurture academic clinicians, are universal, and recent UK initiatives are relevant to academic medicine wherever it is practised.