tbuckley/cabot-search huggingface dataset:
The Macroeconomic Determinants of Health
Authors: S. V. Subramanian, Paolo Belli, Ichiro Kawachi
Journal: Annual Review of Public Health (2002)

Why are some societies healthier than others? The consensus in development economics is that the health achievement of nations has to do with their levels of economic development. Higher per capita incomes, through steady and stable economic growth, increase a nation's capacity to purchase the necessary economic goods and services that promote health. In this paper, we review the conceptual and empirical linkages between poverty and poor health in both developing and developed countries. The empirical evidence is overwhelming that poverty, measured at the level of societies as well as individuals, is causally related to poor health of societies and individuals, respectively. Recent macroeconomic research has also drawn attention to the role of health as a form of human capital that is vital for achieving economic stability. In particular, attention has been drawn toward the ways in which unhealthy societies impede the process of economic development. However, the reciprocal connection between economic prosperity and improved health is neither automatic nor universal. Other features of society, such as the equality in the distribution of the national wealth, seem to matter as well for improving average population health and especially for reducing inequalities in health. We conclude by arguing for a need to reexamine the way in which health is conceptualized within the macroeconomic development framework.
Ruptured fibular ankle ligament: plaster or Pliton brace?
Authors: R. Cetti, S. E. Christensen, M. T. Corfitzen
Journal: British Journal of Sports Medicine (1984)

A prospective randomised study was performed in order to compare plaster cast with Pliton-80 cast brace with a mobile plastic shoe insert in the treatment of ruptured fibular ankle ligaments. The two treatment groups consisted of 65 patients in each and all were participating in the follow-up sixth months after the accident. There were no statistically significant differences in the overall results between the two treatment groups. Because 1) the mobile Pliton-80 bandage subjectively is more acceptable to the patients and -2) the disability time in the Pliton-80 group was considerably shorter than in the plaster group--it was concluded that the mobile Pliton-80 bandage can be recommended as the treatment of ruptures of the fibular ankle ligaments.
You get what you expect? A critical appraisal of imaging methodology in endosonographic cancer staging
Authors: A Meining
Journal: Gut (2002)

Background and aims: After an initial period of excellent results with newly introduced imaging procedures, the accuracy of most imaging methods declines in later publications. This effect may be due to various methodological factors involved in the research. Using the example of endoscopic ultrasound (EUS), this study aimed to elucidate one of the factors possibly concerned—namely, the extent to which the examiners are adequately blinded. Methods: Well documented videotapes of EUS examinations of 101 patients with resected tumours of the oesophagus (n=32), stomach (n=33), or pancreas (n=36) were evaluated in three different ways: firstly, retrospective analysis under routine clinical conditions; secondly, evaluation of EUS videotapes in a strictly blinded fashion; and thirdly, evaluation of the same videotapes but with additional information from the video endoscopic appearance (oesophageal/gastric cancer) or from computed tomography results (pancreatic cancer). Histopathological T staging was used as the reference method. Results: The accuracy of EUS in T staging was 73% under routine conditions. This value fell significantly to 53% for the blinded evaluation but increased again to 62% for the unblinded evaluation. The sensitivity of staging T1/T2 tumours was 72% (routine EUS), 59% (blinded EUS), and 70% (unblinded EUS). The respective values for advanced tumours were 85%, 74%, and 72%. Conclusions: The accuracy of EUS for T staging in clinical practice appears to be lower than has previously been reported. In addition, blinded analysis produced significantly poorer results, which improved when another test was added. It may be speculated that better results with routine EUS obtained in a clinical setting are due to additional sources of information.
Judgments of Alternatives to Hospitalization
Authors: STEVEN H. LIPSIUS
Journal: American Journal of Psychiatry (1973)

The author compared staff and hospitalized patients' judgments as to the avoidability of hospitalization by means of alternative treatment facilities. There was surprising validity in most patients' opinions concerning their hospitalization, as judged by agreement with staff opinions and experimental findings, except for affective psychotics, who overestimated avoidability. The author compares the specific alternatives selected by patients and staff and identifies factors affecting their judgments.
Mitogen-Activated Protein Kinases in Heart Development and Diseases
Authors: Yibin Wang
Journal: Circulation (2007)

Mitogen-activated protein (MAP) kinases belong to a highly conserved family of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological functions. The 4 best-characterized MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, have been implicated in different aspects of cardiac regulation, from development to pathological remodeling. Recent advancements in the development of kinase-specific inhibitors and genetically engineered animal models have revealed significant new insights about MAP kinase pathways in the heart. However, this explosive body of new information also has yielded many controversies about the functional role of specific MAP kinases as either detrimental promoters or critical protectors of the heart during cardiac pathological processes. These uncertainties have raised questions on whether/how MAP kinases can be targeted to develop effective therapies against heart diseases. In this review, recent studies examining the role of MAP kinase subfamilies in cardiac development, hypertrophy, and survival are summarized.
Polychlorinated Biphenyl Levels in Peripheral Blood and Non-Hodgkin's Lymphoma: A Report from Three Cohorts
Authors: Lawrence S. Engel, Francine Laden, Aage Andersen, Paul T. Strickland, Aaron Blair, Larry L. Needham, Dana B. Barr, Mary S. Wolff, Kathy Helzlsouer, David J. Hunter, Qing Lan, Kenneth P. Cantor, George W. Comstock, John W. Brock, David Bush, Robert N. Hoover, Nathaniel Rothman
Journal: Cancer Research (2007)

The incidence of non-Hodgkin's lymphoma (NHL) unrelated to HIV infection has steadily increased over the past several decades and remains substantially unexplained. Limited evidence suggests that increased concentrations of polychlorinated biphenyls (PCB) measured in blood or fat tissue are associated with increased risk of NHL. Although PCB congeners vary in their biological activity, the relation between individual congeners and NHL risk has not been examined previously using prospectively collected biospecimens. We examined congener-specific associations in three prospective cohorts. Prediagnostic serum or plasma concentrations of selected PCB congeners were measured among NHL cases and controls from these cohorts: Janus (190 cases and 190 controls) in Norway and CLUE I (74 cases and 147 controls) and the Nurses' Health Study (30 cases and 78 controls) in the United States. All blood samples were collected in the 1970s or 1980s. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the relations between risk of NHL and lipid-corrected plasma or serum concentrations. Several congeners (i.e., 118, 138, and 153) that were present at higher levels and were moderately to highly correlated with each other showed exposure-response trends with risk of NHL in all three cohorts. These associations were observed primarily among subjects diagnosed closer to the date of blood collection in the two cohorts with sufficient cases to permit stratification by time. Among cases diagnosed within the median years of follow-up (16 years in Janus and 12 years in CLUE I), ORs and 95% CIs for increasing fourths of concentration of congener 118 relative to the lowest fourth were as follows: 2.4 (0.9-6.5), 4.9 (1.6-15.3), and 5.3 (1.5-18.8; P(trend) < 0.005) in Janus and 8.1 (1.0-68.9), 6.6 (0.7-59.0), and 13.0 (1.6-106.8; P(trend) < 0.05) in CLUE I. Similar patterns were seen for congeners 138 and 153 and for total PCBs. Limited evidence of exposure-response trends was also observed for several other congeners. The primary 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane metabolite, p,p'-DDE, was not significantly associated with NHL in most analyses but slightly to moderately confounded the PCB associations. The results from these three cohorts suggest that concentrations of certain PCBs in blood are associated with increased risk of NHL.
Evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D in man.
Authors: P W Lambert, P H Stern, R C Avioli, N C Brackett, R T Turner, A Greene, I Y Fu, N H Bell
Journal: Journal of Clinical Investigation (1982)

Recent studies provide evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D [1 alpha ,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha ,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0 +/- 7.6 ng/ml) and was normal in the others (16.4 +/- 0.9 ng/ml, P less than 0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38 +/- 0.27 ng/ml) and was low in the others (0.25 +/- 0.08 ng/ml, P less than 0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r = 0.848, P less than 0.01). Mean serum 1 alpha ,25(OH)2D determined by receptor assay was 5.8 +/- 1.9 pg/ml in patients who were not given vitamin D and was 14.1 +/- 0.6 in those who were given vitamin D (P less than 0.001). Serum 1 alpha ,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P less than 0.01). Mean serum 1 alpha ,25(OH)2D, measured by bioassay, was 8.3 +/- 1.9 pg/ml in patients who were given vitamin D and was 15.9 +/- 2.4 pg/ml in those who were given vitamin D (P less than 0.05). There was a significant correlation between the values for serum 1 alpha ,25(OH)2D obtained with the two methods (r = 0.728, P less than 0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1 alpha , 25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD.
Selective defect in myeloid cell lactoferrin gene expression in neutrophil specific granule deficiency.
Authors: K J Lomax, J I Gallin, D Rotrosen, G D Raphael, M A Kaliner, E J Benz, L A Boxer, H L Malech
Journal: Journal of Clinical Investigation (1989)

Neutrophil specific granule deficiency (SGD) is a congenital disorder associated with an impaired inflammatory response and a deficiency of several granule proteins. The underlying abnormality causing the deficiencies is unknown. We examined mRNA transcription and protein synthesis of two neutrophil granule proteins, lactoferrin and myeloperoxidase in SGD. Metabolically labeled SGD nucleated marrow cells produced normal amounts of myeloperoxidase, but there was no detectable synthesis of lactoferrin. Transcripts of the expected size for lactoferrin were detectable in the nucleated marrow cells of two SGD patients, but were markedly diminished in abundance when compared with normal nucleated marrow cell RNA. Because lactoferrin is secreted by the glandular epithelia of several tissues, we also assessed lactoferrin in the nasal secretions of one SGD patient by ELISA and immunoblotting. Nasal secretory lactoferrin was the same molecular weight as neutrophil lactoferrin and was secreted in normal amounts. From these data, we conclude that lactoferrin deficiency in SGD neutrophils is tissue specific and is secondary to an abnormality of RNA production. We speculate that the deficiency of several granule proteins is due to a common defect in regulation of transcription that is responsible for the abnormal myeloid differentiation seen in SGD patients.
Genetic association studies for complex traits: relevance for the sports medicine practitioner
Authors: William T Gibson
Journal: British Journal of Sports Medicine (2008)

In this issue of BJSM , September et al 1 report DNA variants within the COL5A1 gene among patients with Achilles tendinopathy (the cases) and among controls with no tendinopathy, matched for age and country of origin. Their findings suggest that a common DNA variation in the COL5A1 gene may be a risk factor for Achilles tendinopathy. Replication of their results among larger cohorts will be necessary to validate this finding.

It can be a challenge for the busy sports medicine practitioner to distil the clinical relevance of association studies such as this one. Although genetic testing for mendelian (single-gene) disorders is widely available in many countries, genetic testing for single-nucleotide polymorphisms (SNPs) is generally unavailable outside research laboratories. With certain notable exceptions (eg, the link between apoE variants, cardiovascular and neurological disease),2-4 statistical associations between common SNPs and complex diseases have not been borne out by further study. Numerous pitfalls occur in both the design and interpretation of these studies, which has resulted in a poor track record for independent replication. Thus, a brief summary of these pitfalls may be useful to the BJSM ’s readership.

By way of background, there are just over 14 million SNPs known to exist in the human genome.5 Most of these exist in two possible forms, reflecting variation in the sequence that arose as a new mutation many generations ago. At some loci, any of three or even all four DNA bases (adenine, guanine, cytosine and thymine; A,G, C and T) may occur at measurable frequency in a population. Once a variant’s frequency reaches 1% of all alleles in the population, such a variant is no longer considered a “mutation,” but rather a “polymorphism.” Recent advances in the rapidity and cost-effectiveness of DNA sequencing technologies have enabled the assessment …
2 HIGH SERUM AUTOTAXIN ACTIVITY PREDISPOSES TO SEVERE PRURITUS DURING TREATMENT WITH OBETICHOLIC ACID IN PRIMARY BILIARY CIRRHOSIS
Authors: A.E. Kremer, D.A. Shapiro, G. Rizzo, L. Adorini, R.P. Oude Elferink, U. Beuers
Journal: Journal of Hepatology (2011)
On the pathogenesis of focal nodular hyperplasia of the liver
Authors: Ian R. Wanless, Carolyn Mawdsley, Ronald Adams
Journal: Hepatology (1985)

Fifty-one focal nodular hyperplasia lesions from 36 patients were examined histologically. Serial sections and three-dimensional models were studied in selected cases. Lesions were multiple in 19% of patients. Thirty-four patients were female. One case had 11 focal nodular hyperplasia lesions and 7 hemangiomata in the liver. Three had astrocytoma and one had anomalous pulmonary venous drainage. Morphometric analysis revealed that the lesions were supplied by an anomalous artery larger than expected for the locale in the liver. This artery branched to form a spider-like structure and was usually not accompanied by a portal vein or duct. Each terminal arterial branch supplied a separate nodule 1 mm in diameter; adjacent nodules coalesced to form the focal nodular hyperplasia lesion. The arterial blood appeared to drain directly into the sinusoids of the nodule. We propose that focal nodular hyperplasia is an hyperplastic response of the hepatic parenchyma to a preexisting arterial spider-like malformation. The frequent coexistence of focal nodular hyperplasia with other vascular and neuroendocrine anomalies suggest that the malformations are developmental in origin. The basic requirement for development of hepatic hyperplasia may be greater blood flow to a region compared to the adjacent parenchyma. This requirement appears to be met in the other forms of nodular transformation of the liver, i.e., nodular regenerative hyperplasia and partial nodular transformation.
Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt
Authors: Samer S El-Kamary, Mohamed Hashem, Doa'a A Saleh, Mohamed Ehab, Sahar A Sharaf, Fatma El-Mougy, Lobna Abdelsalam, Ravi Jhaveri, Ahmed Aboulnasr, Hesham El-Ghazaly
Journal: Journal of Infection (2015)
The Cytophaga hutchinsonii ChTPSP: First Characterized Bifunctional TPS–TPP Protein as Putative Ancestor of All Eukaryotic Trehalose Biosynthesis Proteins
Authors: Nelson Avonce, Jan Wuyts, Katrien Verschooten, Lies Vandesteene, Patrick Van Dijck
Journal: Molecular Biology and Evolution (2009)

The most widely distributed pathway to synthesize trehalose in nature consists of two consecutive enzymatic reactions with a trehalose-6-P (T6P)-synthase (TPS) enzyme, producing the intermediate T6P, and a T6P-phosphatase (TPP) enzyme, which dephosphorylates T6P to produce trehalose and inorganic phosphate. In plants, these enzymes are called Class I and Class II proteins, respectively, with some Class I proteins being active enzymes. The Class II proteins possess both TPS and TPP consensus regions but appear to have lost enzymatic activity during evolution. Plants also contain an extra group of enzymes of small protein size, of which some members have been characterized as functional TPPs. These Class III proteins have less sequence similarity with the Class I and Class II proteins. Here, we characterize for the first time, by using biochemical analysis and yeast growth complementation assays, the existence of a natural TPS–TPP bifunctional enzyme found in the bacterial species Cytophaga hutchinsonii. Through phylogenetic analysis, we show that prokaryotic genes such as ChTPSP might be the ancestor of the eukaryotic trehalose biosynthesis genes. Second, we show that plants have recruited during evolution, possibly by horizontal transfer from bacteria such as Rhodoferax ferrireducens, a new type of small protein, encoding TPP activity, which have been named Class III proteins. RfTPP has very high TPP activity upon expression in yeast. Finally, we demonstrate that TPS gene duplication, the recruitment of the Class III enzymes, and recruitment of an N-terminal regulatory element, which regulates the Class I enzyme activity in higher plants, were initiated very early in eukaryan evolution as the three classes of trehalose biosynthesis genes are already present in the alga Ostreococcus tauri.
The role of Kupffer cells in the differentiation process of hepatic natural killer cells
Authors: Karin Vanderkerken, Luc Bouwens, Nico Van Rooijen, Kit Van Den Berg, Marijke Baekeland, Eddie Wisse
Journal: Hepatology (1995)

Pit cells, or hepatic natural killer (NK) cells, present in rat liver sinusoids, represent an organ-associated NK cell population, with a higher level of activation and a different morphology when compared with peripheral blood NK cells. These cells are the result of an influx of peripheral blood NK cells in the liver microenvironment, followed by an activation or differentiation process toward the highly activated phenotype. In this work we investigated the role of Kupffer cells in this differentiation process of NK cells in the liver sinusoids. In vivo elimination of Kupffer cells with the macrophage cytotoxic drug dichloromethylene diphosphonate induced a decrease in number of hepatic NK cells that paralleled that of Kupffer cells. This effect was further investigated in vitro. Kupffer cell-conditioned medium appeared to enhance the viability, tumor-cytotoxic activity, and adherence of hepatic NK cells to liver endothelial cells in vitro. We conclude therefore that Kupffer cells, present in the microenvironment of the liver sinusoids, play an essential role in the differentiation process of peripheral blood NK cells to the highly activated hepatic NK cell population. (HEPATOLOGY 1995; 22:283–290.)
The Use of Packed Red Blood Cells
Authors: David L. Barrett
Journal: JAMA (1976)

<h3>To the Editor.—</h3> I think that Dr Grindon's commentary (235:389, 1976), in which he expressed reservations about the emphasis on the use of packed red blood cells (PRBC), is timely and pertinent. Being in general agreement with his remarks, I would like only to add that some consideration must be given to the increased cost of the transfusion of PRBC, especially when used with plasma substitutes to replace surgical blood volume loss. At a recent blood bank seminar, a New York City-based blood bank technologist told me that his hospital was spending $250,000 annually on plasma substitutes, because he could obtain<i>only</i>PRBC from his regional source (and the blood bank was being criticized for this expenditure). Theirs is a cost consideration of magnitude, but even in smaller hospitals, the added technologist time, materials, equipment, and use of plasma substitutes significantly raise the already high price for transfusion. Also, the plasma
Molecular Epidemiology of <i>EGFR</i> and <i>KRAS</i> Mutations in 3,026 Lung Adenocarcinomas: Higher Susceptibility of Women to Smoking-Related <i>KRAS</i>-Mutant Cancers
Authors: Snjezana Dogan, Ronglai Shen, Daphne C. Ang, Melissa L. Johnson, Sandra P. D'Angelo, Paul K. Paik, Edyta B. Brzostowski, Gregory J. Riely, Mark G. Kris, Maureen F. Zakowski, Marc Ladanyi
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear. Experimental Design: We genotyped 3,026 lung adenocarcinomas for the major EGFR (exon 19 deletions and L858R) and KRAS (G12, G13) mutations and examined correlations with demographic, clinical, and smoking history data. Results: EGFR mutations were found in 43% of never smokers and in 11% of smokers. KRAS mutations occurred in 34% of smokers and in 6% of never smokers. In patients with smoking histories up to 10 pack-years, EGFR predominated over KRAS. Among former smokers with lung cancer, multivariate analysis showed that, independent of pack-years, increasing smoking-free years raise the likelihood of EGFR mutation. Never smokers were more likely than smokers to have KRAS G &amp;gt; A transition mutation (mostly G12D; 58% vs. 20%, P = 0.0001). KRAS G12C, the most common G &amp;gt; T transversion mutation in smokers, was more frequent in women (P = 0.007) and these women were younger than men with the same mutation (median 65 vs. 69, P = 0.0008) and had smoked less. Conclusions: The distinct types of KRAS mutations in smokers versus never smokers suggest that most KRAS-mutant lung cancers in never smokers are not due to second-hand smoke exposure. The higher frequency of KRAS G12C in women, their younger age, and lesser smoking history together support a heightened susceptibility to tobacco carcinogens. Clin Cancer Res; 18(22); 6169–77. ©2012 AACR.