bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in COL1A1 of Type I Collagen Genes in Chinese Patients with Osteogenesis Imperfecta
Authors: Wang Zhuo , Yang Zheng , Ke Zunfu , Yang Shicong , Shi Huijuan , Wang Liantang 
Published: May 2016

Background Osteogenesis imperfecta (OI) is an inherited bone disease caused by mutations in collagen genes. Because these mutations occur at a wide variety of sites in the genes and differ among populations, we studied the COL1A1 gene in Chinese with OI and compared the results with findings form other populations. Methods COL1A1 gene mutations were detected by polymerase chain reaction and sequencing from 3 unrelated families and 1 sporadic case in Chinese. Results Four COL1A1 mutations that were novel were found. The patients' clinical characteristics were variable, even within the same family. Notably, some of the novel COL1A1 variants were at the same nucleotide positions as previously described but with different nucleotide changes. In addition, we also found 1 patient with OI with 2 mutations in the same haplotypes. Conclusions We discuss the differences in phenotype related to the specific mutation sites. Although there have been many reports on mutations of COL1A1 and COL1A2, few cases have been reported in Chinese. Our data showed that the COL1A1 gene mutation might also play an important role in OI among Chinese. The Han Chinese represent a quarter of the world's population, and we believe that our new data contributes to fill in the type I collagen mutation map. We thought that the patient with OI could have 2 mutations in the same haplotypes, without limit to 1 mutation.
The Applicability of Lean and Six Sigma Techniques to Clinical and Translational Research
Authors: Schweikhart Sharon A. , Dembe Allard E. 
Published: May 2016

Background Lean and Six Sigma are business management strategies commonly used in production industries to improve process efficiency and quality. During the past decade, these process improvement techniques increasingly have been applied outside the manufacturing sector, for example, in health care and in software development. This article concerns the potential use of Lean and Six Sigma in improving the processes involved in clinical and translational research. Improving quality, avoiding delays and errors, and speeding up the time to implementation of biomedical discoveries are prime objectives of the National Institutes of Health (NIH) Roadmap for Medical Research and the NIH's Clinical and Translational Science Award program. Methods This article presents a description of the main principles, practices, and methods used in Lean and Six Sigma. Available literature involving applications of Lean and Six Sigma to health care, laboratory science, and clinical and translational research is reviewed. Specific issues concerning the use of these techniques in different phases of translational research are identified. Results Examples of Lean and Six Sigma applications that are being planned at a current Clinical and Translational Science Award site are provided, which could potentially be replicated elsewhere. We describe how different process improvement approaches are best adapted for particular translational research phases. Conclusions Lean and Six Sigma process improvement methods are well suited to help achieve NIH's goal of making clinical and translational research more efficient and cost-effective, enhancing the quality of the research, and facilitating the successful adoption of biomedical research findings into practice.
Influence of Nuclear Factor κB Activation on Inflammatory Mediators of Alveolar Macrophages in Rats with Acute Necrotizing Pancreatitis
Authors: Sailai Yalikun , Yu Xiao , Baiheti Paerhati , Tang Huayong , Li Yongguo , Xu Ming 
Published: May 2016

Aim To investigate the potential influence of nuclear factor κB (NF-κB) activation on the inflammatory mediators secreted by alveolar macrophages (AMs) in rats with acute necrotizing pancreatitis (ANP) and to evaluate the effect of an inhibitor of NF-κB- N-acetylcysteine (NAC). Methods Ninety male Sprague-Dawley rats were randomly divided into 3 groups, 30 of each: control, ANP, and ANP plus NAC groups. The ANP rat models were established by a retrograde injection of 5% sodium taurocholate into the pancreatic duct. In addition to sodium taurocholate, the ANP plus NAC group received intravenous infusion of NAC (25 mg/100 g). At the sixth hour after modeling, the protein content of the bronchoalveolar lavage fluid, the myeloperoxidase in the lung tissue, and the transforming growth factor α and the nitric oxide (NO) secreted by AMs were determined. The histopathologic changes of the pancreas and the lung were observed under light microscope, and NF-κB activation of AMs was detected. Results The protein content of the bronchoalveolar lavage fluid and the myeloperoxidase level of the lung tissue showed a significant increase in the ANP group as compared with the NAC-administered group. The levels of transforming growth factor α and NO secreted by AMs in the ANP and the ANP plus NAC group rose significantly over that in the control group, and there was a significant difference between them. Although they were still higher than those in the control group, the pancreas destruction and the lung injury were slighter in the ANP plus NAC group and the activation of NF-κB was lower in the ANP plus NAC group as compared with that in the ANP group. Conclusions The correlation between the NF-κB activation, the up-regulation of the inflammatory mediators secreted by AMs, and the tissue damage suggests a key influence of NF-κB in the pathogenesis of ANP. Inhibition of NF-κB activation may reverse the lung injury of ANP.
Validation of Duruöz Hand Index for Diabetic Hand Dysfunction
Authors: Turan Yasemin , Duruöz Mehmet Tuncay , Aksakalli Elif , Gürgan Alev 
Published: May 2016

Objectives Duruöz Hand Index (DHI) is a functional disability scale that can be used successfully to assess the functional disability with different hand arthropathies. The hands are frequently involved in diabetic patients. We aimed to examine the use of DHI for its accuracy and ease in assessing these patients. Methods Forty patients with diabetes mellitus were recruited in this study. Hand pain was assessed with the visual analog scale. Duruöz Hand Index and Hand Functional Index were applied to assess the disability of hand. We evaluated the grip strength and 3 types of pinch strength (tip pinch, lateral or key pinch, and chuck or 3-finger pinch) for the dominant (D) and nondominant (ND) hands of each patient by 2 different kinds of Jamar dynamometers (JA Preston Corp, Jackson, MI). Results The Jamar dynamometer scores were as follows (mean [SD]): grip strength-D (21.56 [5.86]), grip strength-ND (16.42 [4.26]), tip strength-D (5.14 [1.50]), tip strength-ND (5.13 [1.42]), lateral strength-D (5.15 [1.52]), lateral strength-ND (5.07 [1.19]), chuck strength-D (5.40 [1.40]), chuck strength-ND (5.33 [1.28]). There was a high correlation between DHI and Hand Functional Index ( P < 0.001, ρ = 0.586) showing that DHI has good convergent validity. The DHI had significant correlation with nonfunctional parameters such as visual analog scale-pain ( P < 0.001), restricted hand motion ( P = 0.020), chuck strength-D ( P = 0.006), pins test-D ( P < 0.001), pins test-ND ( P = 0.013), and assembly test ( P = 0.025). Conclusions The DHI is a practical scale that is efficient in accurate assessment of hand dysfunction in diabetic patients.
Allopurinol, Xanthine Oxidase, and Cardiac Ischemia
Authors: Lee Brian E. , Toledo Alexander H. , Anaya-Prado Roberto , Roach Richard R. , Toledo-Pereyra Luis H. 
Published: May 2016

Allopurinol as an effective inhibitor of the enzyme xanthine oxidase (XO) has been used for several decades for the treatment of patients with gout and hyperuricemia. Because the inhibition of XO limits the formation of radical oxygen species as well as uric acid (UA) production, allopurinol has been used experimentally for the treatment of conditions associated with ischemia and reperfusion (I/R) injury. Although there have been many ischemic organs treated in the laboratory with allopurinol, the heart has been of particular interest. Therefore, we emphasize our attention to the administration of XO inhibitors such as allopurinol on cardiac I/R as well as cardiac failure. Experimental data also support allopurinol as a possible consideration for biochemical support after acute myocardial infarction. Anker and associates ( Circulation. 2003;107:1991-1997) have observed a direct correlation between uric acid levels and mortality in treated heart failure patients. Anker and associates showed a 100% mortality rate in patients with UA levels 800 μmol/L or less over a period of 3 years. Comparing this to a 27% mortality rate in patients with UA levels 400 μmol/L or less over a period of 10 years, it seems that the suppression of XO activity ameliorates myocardial inefficiency, and poor vascular flow may present innovative contributions to the future treatment of I/R heart failure patients. Our review focuses on the role of allopurinol on ischemic hearts as well as those with added chronic heart failure.
Ezetimibe Effect on Bone Mineral Density and Markers of Bone Formation and Resorption
Authors: Sertbas Yasar , Ersoy Ugur , Ayter Meltem , Gultekin Tırtıl Filiz , Kucukkaya Belgin 
Published: May 2016

Background Ezetimibe, as a lipid-lowering agent, inhibits the intestinal absorption of cholesterol and decreases low-density lipoprotein cholesterol (LDL-C) level in serum. It also up-regulates hepatic cholesterol biosynthesis and, by contrast to statins, increases serum mevalonate levels. Statins and biphosphonates decrease osteoclastic activity through the same mechanisms by inhibiting the mevalonate pathway. We therefore tested the effect of ezetimibe on bone turnover in hypercholesterolemic patients. Subject and Methods In an open-label clinical trial, 54 hypercholesterolemic patients included in the study underwent 12 months of treatment with ezetimibe at a dosage of 10 mg/d. Before and after the 1-year ezetimibe treatment, bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry and serum samples taken for measurements of levels of total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol and LDL-C, serum calcium (Ca), serum phosphate, total and bone alkaline phosphatases (ALPs), and carboxyterminal fragment of type 1 collagen in the serum. Results The hypercholesterolemic patients showed a significant reduction with respect to baseline TC and LDL-C serum levels: 20% for TC (270.18 [38.58]−214.46 [38] mg/dL) and 24% for LDL-C (189.57 [38.58]−144 [32.05] mg/dL). Biochemical markers of both bone formations (total ALP level, 65.50 [21.33]−66.27 [21.017] IU/L and bone ALP level, 55.93 [7.92]−56.25 [7.49] IU/L) and bone resorption (β-CTx, 0.44 [0.24]−0.46 [0.21] ng/mL) increased but did not show any significant change for the whole study period. At the end of 1 year, both BMD-lumbar spine (0.90 [0.12]−0.89 [0.08] g/cm2) and BMD-total femur (0.93 [0.12]−0.92 [0.12] g/cm2) showed a negative trend but without reaching statistical significance. Conclusions Our study results showed a negative trend but did not demonstrate statistically significant changes of BMD and metabolic markers with the treatment of ezetimibe.
Can Teaching Research Methodology Influence Students' Attitude toward Science? Cohort Study and Nonrandomized Trial in a Single Medical School
Authors: Vujaklija Ana , Hren Darko , Sambunjak Dario , Vodopivec Ivana , Ivaniš Ana , Marušić Ana , Marušić Matko 
Published: May 2016

Background Medical teaching aims to develop attitudes and behaviors underlying professional competence of future physicians. We investigated whether a mandatory course on scientific methodology in the second study year could affect students' attitudes toward science in medicine. Method In a longitudinal study, students (n = 241) enrolling in 2001-2002 academic year at a single medical school were followed up until graduation in 2006-2007. Each year, they filled out a Likert-type questionnaire of 18 statements evaluating attitude toward science. Direct influence of the course on students' attitudes was tested in a nonrandomized controlled trial with the 2006-2007 second year student cohort. Results Positive students' attitudes toward science increased during study years (mean [SD] score of the maximum score of 90): from 57.6 (6.0) in the first to 69.8 (10.4) in the sixth year. There was a significant trend of increase in attitudes with the years of study (cubic trend by polynomial contrasts analysis, P = 0.011). Attendance of a course on research methodology significantly increased positive attitudes (score, 67.0 [7.0] before and 70.8 [7.5] after course, P = 0.032 vs control group), regardless of grade point average. The intervention had an effect even when the influence of the initial attitude was accounted for (F1,140 = 9.25, P = 0.003; analysis of covariance). The attitude changes after the course was greatest in students with low initial attitude scores (Spearman rinitial score, score difference, −0.44). Conclusions Medical students have positive attitudes toward science and scientific method in medicine. Attendance of a course on research methodology had positive short-term effect on students' attitudes toward science. This positive effect should be maintained by vertical integration of the course in the medical curriculum.
Exchanging Carbohydrate or Protein for Fat Improves Lipid-Related Cardiovascular Risk Profile in Overweight Men and Women When Consumed Ad Libitum
Authors: Kratz Mario , Weigle David S. , Breen Patricia A. , Meeuws Kaatje E. , Burden Verna R. , Callahan Holly S. , Matthys Colleen C. , Purnell Jonathan Q. 
Published: May 2016

Background The impact of low-fat diets on the plasma lipoprotein profile is incompletely understood. Methods We conducted two 16-week dietary studies to compare the effects of a moderate-fat (mod-FAT) baseline diet with isocaloric and ad libitum low-fat diets rich in either carbohydrates (high-CHO, n = 16) or protein (high-PRO, n = 19) on plasma lipids, post-heparin lipase activities, cholesteryl ester transfer protein, and phospholipid transfer protein. Results Switching from the mod-FAT to the isocaloric high-CHO diet lowered plasma high-density lipoprotein cholesterol concentrations ( P < 0.001) and tended to increase triglyceride levels ( P = 0.087). Cholesterol content in the larger, buoyant low-density lipoprotein (LDL) fractions decreased, whereas those of the very-low-density lipoprotein, intermediate-density lipoprotein, and smaller, denser LDL fractions tended to increase. These changes were largely reversed when subjects lost weight by consuming this high-CHO diet ad libitum. Switching from the mod-FAT diet to the isocaloric high-PRO diet did not increase cholesterol content in the small-dense LDL fraction and led to decreases in both LDL and high-density lipoprotein cholesterol in plasma ( P < 0.001 for both). Consumption of the high-protein ad libitum diet accompanied by weight loss did not change plasma lipids further, except for a shift of cholesterol from dense low-density lipoprotein fractions to more buoyant low-density lipoprotein fractions. Cholesteryl ester transfer protein concentrations decreased with high-cholesterol feeding, whereas cholesteryl ester transfer protein concentrations and hepatic lipase and phospholipid transfer protein activities all decreased during high-protein feeding. Conclusions Both high-CHO and high-PRO diets improve plasma lipid-related risk of cardiovascular disease when consumed ad libitum.
A Novel Missense Mutation in Cathepsin K (CTSK) Gene in a Consanguineous Pakistani Family with Pycnodysostosis
Authors: Khan Bushra , Ahmed Zahoor , Ahmad Wasim 
Published: May 2016

Background Deficiency of cathepsin K ( CTSK), a lysosomal cysteine protease, has been shown earlier as a cause of an autosomal recessive osteosclerotic skeletal dysplasia pycnodysostosis. The objective of the present study was to identify the potential sequence variants in CTSK gene in a large consanguineous Pakistani family with pycnodysostosis. Methods Genotyping of 4 affected and 6 unaffected members of the family was performed using polymorphic microsatellite markers linked to CTSK gene on chromosome 1q21. To screen for pathogenic mutation, exons and splice junctions of CTSK gene were polymerase chain reaction amplified from genomic DNA and sequenced directly in an automated DNA sequencer. Results Microsatellite analysis showed linkage of the family to CTSK gene on chromosome 1q21. Sequence analysis revealed a novel missense mutation c.728G>A (p.G243E) in exon 6 of the CTSK gene. Conclusions A novel missense mutation was identified in CTSK gene in a Pakistani family with 5 individuals affected with autosomal recessive pycnodysostosis
Acetaminophen Dose Does Not Predict Outcome in Acetaminophen-Induced Acute Liver Failure
Authors:   The Acute Liver Failure Study Group, Gregory Blake , Larson Anne M. , Reisch Joan , Lee William M. 
Published: May 2016

Background Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator. Methods Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and χ2 tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested. Results Multivariate and χ2 analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators. Conclusions Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients.
Effects of Dantrolene on Ischemia-Reperfusion Injury in Animal Models: A Review of Outcomes in Heart, Brain, Liver, and Kidney
Authors: Boys Joshua A. , Toledo Alexander H. , Anaya-Prado Roberto , Lopez-Neblina Fernando , Toledo-Pereyra Luis H. 
Published: May 2016

Background/Objectives Ischemia-reperfusion (IR) is the restoration of blood flow to a tissue that was formerly deficient of blood flow. Tissue damage after IR is considered an IR injury (IRI). During IR, there is an increased level of cytosolic calcium ([Ca2+]i) due to the release of calcium from mitochondrial, sarcoendoplasmic reticulum, and nuclear organelles. Dantrolene sodium (dantrolene) is a 1-[[[5-(4-nitrophenol)-2-furanyl]methylene]amino]-2, 4-imidazolidinedione sodium salt with a nonspecific mechanism, inhibiting organelle release of Ca2+ into the cytosol. This work reviews the outcomes of administering dantrolene in brain, heart, liver, and kidney animal models of IRI. Methods An extensive PubMed, MEDLINE, and MEDLAR literature review during the last 30 years on the effect of dantrolene in IRI in animal models was analyzed to determine the clinical implications of this important study. Particular attention was given to dantrolene in heart, brain, liver, and kidney IRI. Results Heart: Nine studies of heart IRI were reviewed and include an in vivo dog model (n = 1), in vivo rabbit model (n = 1), isolated dog myocardial fibers (n = 1), and isolated rat hearts (n = 6). Four studies showed decreased infarct size and increased cardiac function after IRI. One in vivo rabbit study found no difference in infarct size or cardiac function after IRI versus controls. Dantrolene may be protective or inductive of post-IRI arrhythmias depending on preestablished myocyte cycling times. Brain: Nine studies of brain IRI were reviewed and include an in vivo dog model (n = 1), in vivo gerbil model (n = 2), and in vivo rat models (n = 6). Dantrolene shows protective decreases in apoptotic markers in 6 studies, but it shows no effect on the necrotic core and mixed effects on reduction of infarct volume. One study found increased mortality in the dantrolene group. Liver: One study of in vivo rat liver IRI found that dantrolene decreased liver function tests, tissue necrosis factor α, tissue necrosis, and increased interleukin 10. Kidney: One study of in vivo rat kidney IRI showed that dantrolene had no effect. Conclusions Dantrolene shows protective effects in animal models of heart, brain, and potentially liver IRI, reinforcing the importance of calcium homeostasis during IRI. Variations of dose, timing of administration, route of administration, and outcomes between studies make definitive conclusions difficult. The nonspecific mechanism of action of dantrolene may also account for the variation among studies. Lack of studies in the liver and kidney makes any consensus in these organs premature, and thus, emphasis for this review was put on studies of the heart and brain.
Apolipoprotein C-III Gene Polymorphism and Several Environmental Factors with Serum Lipid Levels in the Guangxi Hei Yi Zhuang and Han Populations
Authors: Yiyang Li , Ruixing Yin , Meng Li , Kela Li , Xingjiang Long , Lin Zhang , Wanying Liu , Shangling Pan , Dezhai Yang , Weixiong Lin 
Published: May 2016

Background Apolipoprotein (apo) C-III gene polymorphisms have been associated with increased plasma triglycerides (TGs) and coronary artery disease, but the results have not always been concordant among diverse populations. The present study was undertaken to detect the association of the apoC-III 3238C>G polymorphism and several environmental factors with serum lipid profiles in the Guangxi Hei Yi Zhuang and Han populations. Methods A total of 490 subjects of Hei Yi Zhuang and 540 participants of Han Chinese aged 15 to 89 years were randomly selected from our previous stratified randomized cluster samples. Genotyping of the apoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis and then confirmed by direct sequencing. Results There was no difference in the genotype and allele frequencies between the 2 ethnic groups ( P > 0.05), but G allele and GG genotype frequencies were higher in females than in males, or in high TG than in normal TG individuals in Hei Yi Zhuang ( P < 0.01); and in high total cholesterol than in normal total cholesterol subgroups, in high low-density lipoprotein cholesterol (LDL-C) than in normal LDL-C subgroups, or in high apoB than in normal apoB subgroups in Han ( P < 0.05). There were also differences in the genotypic frequencies between normal apoA-I and low apoA-I subjects in Hei Yi Zhuang, and between males and females or between normal TG and high TG subgroups in Han ( P < 0.05). Serum TG and apoA-I levels were correlated with genotype or allele in Hei Yi Zhuang, and TG, LDL-C, and apoB levels were associated with genotype in Han ( P < 0.05). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index. Conclusions There were no significant differences in genotypic and allelic frequencies between the Hei Yi Zhuang and Han populations. But the 3238G carriers have unfavorable serum lipid profiles. The differences in the serum lipid profiles between the 2 ethnic groups might result from different gene-environmental interactions.