Miracle-dz/UniFAR-FTUs huggingface dataset:
Culture-independent real-time PCR reveals extensive polymicrobial infections in hospitalized diarrhoea cases in Kolkata, India.

Culture-independent identification of diarrhoeal aetiological agents was performed using DNA harvested from diarrhoeal stool specimens with SYBR-Green-based real-time PCR targeting Vibrio cholerae, Vibrio parahaemolyticus, Campylobacter spp. , Shigella spp. and three different pathotypes of diarrhoeagenic Escherichia coli. Conventional culture-dependent methods detected bacterial enteropathogens in 68 of 122 diarrhoeal stool specimens. Of 68 specimens, 59 (86.8%) had a single pathogen and the remaining nine (13.2%) had polymicrobial infections with multiple pathogens. Re-analysis of the 68 specimens by culture-independent real-time PCR methods showed that 25 (36.8%) specimens contained single pathogen and 43 (63.2%) specimens contained mixed infections with multiple pathogens. The prevalence of such high levels of polymicrobial infections would not have been detected without using real-time PCR. Culture-dependent analysis assigned 54 of the 122 selected archived specimens as 'no known aetiology'. However, re-analysis of these samples by real-time PCR showed the presence of single or multiple pathogens among 34 (63%) of these specimens. Estimation of relative pathogen load by real-time PCR in the stool specimens indicated that the inability of conventional culture-dependent methods to detect the pathogens was related to lower colony-forming units of the pathogen, as reflected by lower C(t) values. Detection of high levels of polymicrobial infection by real-time PCR indicates that in the settings like Kolkata and its surroundings, where cholera and other enteric diseases are endemic, the concept of one pathogen one disease might need to be re-evaluated.
Positive Inotropic Effect of Prostaglandin F2&agr; in Rat Ventricular Trabeculae

Abstract: Prostaglandins are ubiquitous signaling molecules in the body that produce autocrine/paracrine effects on target cells in response to mechanical or chemical signals. In the heart, long-term exposure to prostaglandin (PG) F2&agr; has been linked to the development of hypertrophy; however, there is no consensus on the acute effect of PGF2&agr;. Our aim was to determine the response to exogenous PGF2&agr; in isolated trabeculae from rat hearts. PGF2&agr; (1 &mgr;M) increased both the Ca2+ transients and the isometric stress in trabeculae, reaching steady state after 10–15 minutes, without altering the time course of Ca2+ transient decay. The precursor of PGF2&agr;, arachidonic acid, also stimulated a similar response. The positive inotropic effect of PGF2&agr; was mediated through a protein kinase C signaling pathway that involved activation of the sarcolemmal Na+/H+ exchanger. We also found that the slow force response to stretch was attenuated in the presence of PGF2&agr; and by addition of indomethacin, a blocker of prostaglandin synthesis. In conclusion, PGF2&agr; was positively inotropic when acutely applied to trabeculae and contributed to the increased Ca2+ transients during the slow force response to stretch. Together, these data suggest that PGF2&agr; is important in maintaining homeostasis during volume loading in healthy hearts.
N-Methyl-D-Aspartate Receptor Signaling and Function in Cardiovascular Tissues

Abstract: Excellent reviews on central N-methyl-D-aspartate receptor (NMDAR) signaling and function in cardiovascular regulating neuronal pools have been reported. However, much less attention has been given to NMDAR function in peripheral tissues, particularly the heart and vasculature, although a very recent review discusses such function in the kidney. In this short review, we discuss the NMDAR expression and complexity of its function in cardiovascular tissues. In conscious (contrary to anesthetized) rats, activation of the peripheral NMDAR triggers cardiovascular oxidative stress through the PI3K-ERK1/2-NO signaling pathway, which ultimately leads to elevation in blood pressure. Evidence also implicates Ca2+ release, in the peripheral NMDAR-mediated pressor response. Despite evidence of circulating potent ligands (eg, D-aspartate and L-aspartate, L-homocysteic acid, and quinolinic acid) and also their coagonist (eg, glycine or D-serine), the physiological role of peripheral cardiovascular NMDAR remains elusive. Nonetheless, the cardiovascular relevance of the peripheral NMDAR might become apparent when its signaling is altered by drugs, such as alcohol, which interact with the NMDAR or its downstream signaling mechanisms.
Prevalence of bruxism in undergraduate students

Abstract Objective: The aim of this study was to determine the prevalence of bruxism in students at the Federal University of the Jequitinhonha and Mucuri Valleys in Brazil. The secondary objectives were to identify the factors associated with bruxism; prevalence of dental wear; and to distinguish the signs and symptoms of temporomandibular dysfunction when present, and verify its relationship with bruxism. Methods: Two hundred fifty-three students (106 males, 147 females) were clinically examined and answered a questionnaire. Trained researchers performed the dental wear evaluation. The incisal edge and occlusal surface were classified as follows: no wear, wear into enamel, wear into dentin, and extensive wear into dentin. Demographic data and factors related to bruxism were obtained by a questionnaire. The participants who presented dental wear and habit of clenching/grinding teeth were classified as bruxers. The data were analyzed by the SPSS program (p < 0.05). Results: The results showed that 31.6% of the students had bruxism. Of the 7084 teeth evaluated, 376 (5.3%) had some type of facet wear. The teeth that had the highest prevalence of wear facets were the canines. Stress, muscle pain, temporomandibular joint (TMJ) pain, and TMJ noise were significantly associated with bruxism (p < 0.001). Conclusion: The prevalence of bruxism was 31.6% in this population. The factors most associated with bruxism were stress, muscle pain, TMJ pain, and TMJ noise.
Large‐scale Molecular Analysis of a 34 Mb Interval on Chromosome 6q: Major Refinement of the RP25 Interval

A large scale bioinformatics and molecular analysis of a 34 Mb interval on chromosome 6q12 was undertaken as part of our ongoing study to identify the gene responsible for an autosomal recessive retinitis pigmentosa (arRP) locus, RP25. Extensive bioinformatics analysis indicated in excess of 110 genes within the region and we also noted unfinished sequence on chromosome 6q in the Human Genome Database, between 58 and 61.2 Mb. Forty three genes within the RP25 interval were considered as good candidates for mutation screening. Direct sequence analysis of the selected genes in 7 Spanish families with arRP revealed a total of 244 sequence variants, of which 67 were novel but none were pathogenic. This, together with previous reports, excludes 60 genes within the interval (∼55%) as disease causing for RP. To investigate if copy number variation (CNV) exists within RP25, a comparative genomic hybridization (CGH) analysis was performed on a consanguineous family. A clone from the tiling path array, chr6tp‐19C7, spanning ∼100‐Kb was found to be deleted in all affected members of the family, leading to a major refinement of the interval. This will eventually have a significant impact on cloning of the RP25 gene.
Significance Levels in Genome‐Wide Interaction Analysis (GWIA)

Interaction between genetic variants is hypothesized to be one of several putative explanations for the ‘case of missing heritability. ’ Therefore, Genome‐Wide Interaction Analysis (GWIA) has recently gained substantial interest. GWIA is computationally challenging and respective power type I error studies are particularly difficult. Therefore, an accepted significance level for GWIA studies does not currently exist. It has been shown that for a GWAS single‐marker analysis with n SNPs a correction for multiple testing with 1/2 ·n is appropriate for populations of European ancestry. We speculated that for GWIA, correction by 1/4 ·m should be appropriate, where m=n· (n− 1)/2 is the number of SNP pairs. We tried to verify this hypothesis using the INTERSNP program that implements interaction analysis and genome‐wide Monte‐Carlo (MC) simulation. Using a type I error study based on Illumina® HumanHap 550 data, we were able to reproduce the published result for single‐marker analysis. For GWIA using a test for allelic interaction, we show that correction with roughly 0.4 ·m is appropriate, a number that is somewhat larger than that of our hypothesis. In summary, it can be stated that for an Illumina®‐type marker panel with 500,000 SNPs, an uncorrected P‐value of 1.0 × 10−12 is needed to establish genome‐wide significance at the 0.05 level.
Can dietary intervention alter prostate cancer progression

Purpose – Research has shown that dietary factors can mediate the transformation of latent prostate cancer into clinically apparent cancers. This paper aims to review the evidence from studies on nutrition and prostate cancer.Design/methodology/approach – A literature review of studies on nutrition and cancer was undertaken.Findings – The data showed that deficiencies in trace elements and vitamins may lead to an increased risk of prostate cancer.Originality/value – The paper shows that there appears to be a clear link with aspects of vitamin and mineral deficiencies and prostate cancer and the area merits more work.
Glucuronic Acid Epimerase is Associated with Plasma Triglyceride and High‐Density Lipoprotein Cholesterol Levels in Turks

We narrowed chromosome 15q21–23 linkage to plasma high‐density lipoprotein cholesterol (HDL‐C) levels in Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with HDL‐C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, and rs3865014) were associated with triglyceride and HDL‐C levels in males (nonpermuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple‐testing significance (p < 0.05) in both males and females (n= 2612). Similar results were obtained in the second cohort (n= 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions resembled the European pattern. Studies of glce+/−apoe−/− mice fed a chow or high‐fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL‐C levels in Turks, and mouse studies support a role for glce in lipid metabolism.
Selection and Mutation for α Thalassemia in Nonmalarial and Malarial Environments

α thalassemia is the result of the loss of one or both copies of the two human α globin genes. α thalassemia appears to be the most common monogenic disease in the world and is in high frequency where malaria is, or has been, endemic. In nonmalarial environments, α thalassemia is rare and its frequency can be explained by a balance of deletional mutation and purifying selection. In malarial environments, the loss of one or two copies of the four α globin genes in normal diploid genotypes confers resistance (lower mortality) to malaria. Fitness estimates from data from Kenyan and Papua New Guinea populations are used to predict the increase in the −α haplotype (with one deleted gene). The frequency of double deletions (−− haplotypes) is higher in some Asian populations than that of single deletions. In this case, heterozygotes with normal αα haplotypes are expected to have the highest fitness. Overall, this population genetic examination provides an evolutionary framework for understanding the worldwide frequency of α thalassemia and the deletions that cause it in both nonmalarial and malarial environments.
An In-depth Analysis of Vasodilation in the Management of Hypertension: Focus on Adrenergic Blockade

Sustained activation of the sympathetic nervous system leads not only to elevated blood pressure but also to vascular remodeling, microvascular complications, and target organ damage. Although β-blocking agents, which act directly on the adrenergic receptors of the sympathetic nervous system, have been used in the treatment of hypertension for almost 40 years, questions have recently arisen about their effectiveness as first-step treatment. Lack of consistent outcome data may relate to the failure of traditional β-blockers (eg, atenolol, metoprolol, and propranolol) to positively affect peripheral vascular resistance; instead, these agents rely on reduction of cardiac output to lower blood pressure. Accumulating evidence points to reductions in vascular resistance as an important component in hypertension treatment, especially with regard to improving vascular remodeling and reducing target organ damage. The vasodilating β-blockers carvedilol, labetalol, and nebivolol block β-adrenergic receptors and vasodilate through diverse mechanisms, allowing for the possibility of better tolerability and adherence and translating into a more favorable effect on the vasculature compared with traditional β-blockers.
The psychometric properties of the Greek version of the State-Trait Anxiety Inventory in cancer patients receiving palliative care

Objectives: To validate the Greek version of the State-Trait Anxiety Inventory (STAI) in a sample of cancer patients. Design: The scale was administered twice, with a 3-day interval, to 99 eligible patients with cancer. Together with the Greek version of STAI scale, the patients also completed the anxiety subscale from the Hospital Anxiety and Depression scale (HAD). Observations: Factor analysis yielded a three-factor solution, explaining 47.143% of the variance. Cronbach α for three scales was between 0.729 and 0.852. Inter-scale correlations were moderate-to-high and ranged from 0.282 to 0.563 (p < 0.0005, p < 0.005). The assessment of the relationships among the Greek STAI scales and HAD-Anxiety showed statistically significant correlations between them (r ranged between 0.428 and 0.596, p < 0.0005). The test/retest reliability of scale (Pearson's ‘r’), showed that the coefficient agreement ranged between 0.85 and 0.90 (p < 0.0005). Univariate analysis revealed significant correlations between female gender, metastasis, performance status, chemotherapy, mild opioids and low education level with increased anxiety. Conclusions: These results support that the Greek version of STAI is an instrument with satisfactory psychometric properties, and is a valid research tool for Greek cancer patients.
TRC4186, a Novel AGE-breaker, Improves Diabetic Cardiomyopathy and Nephropathy in Ob-ZSF1 Model of Type 2 Diabetes

Advanced glycation end products (AGEs) contribute significantly to diabetic complications, both macro- and microvascular. TRC4186 is an AGE-breaker that has been evaluated in vitro and in vivo and shown to reduce AGE burden. The aim of this study was to determine the effect of TRC4186 on diabetic cardiomyopathy and nephropathy in obese Zucker spontaneously hypertensive fatty rats (Ob-ZSF1), an animal model of diabetes with progressive cardiac and renal dysfunction. Ob-ZSF1 rats loaded with 0.5% salt were treated with TRC4186, 9 or 27 mg/kg twice daily intraperitoneally or vehicle control and monitored telemetrically throughout the study. Cardiac function was assessed terminally by Millar catheter. Markers of cardiac and renal dysfunction were measured and changes evaluated histopathologically. TRC4186 at 27 mg/kg prevented rise in blood pressure (BP) and also improved cardiac output (CO) secondary to better diastolic relaxation as well as systolic emptying in association with the reduction in afterload. At 9 mg/kg, CO was improved by compensatory increase in pre-load however afterload reduction was not adequate to allow efficient systolic emptying. Brain natriuretic peptide (BNP) and interleukin-6 (IL-6) expression was reduced with treatment. Deterioration in renal function was retarded as evident from albumin to creatinine ratio and renal histopathology. TRC4186, an AGE-breaker, clearly preserved cardiac function and reduced the severity of renal dysfunction in Ob-ZSF1, an animal model with persistent severe hyperglycemia leading to diabetic heart failure and renal failure.
mtDNA Lineages Reveal Coronary Artery Disease‐Associated Structures in the Lebanese Population

Population origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS‐1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P= 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50–35.30, P= 0.026) among Lebanese samples. Haplogroup A was only found in controls (P= 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r= 0.316, P < 0.001) than between haplogroup A and CAD (r= 0.149, P < 0.001). HVS‐1 phylogenetic network of haplogroup W shows controls are restricted to European clusters while cases belong mostly to Middle Eastern natives. The network of haplogroup A shows that the controls belong to a cluster dominated by Central Asians. Our results show evidence of a gene flow into Lebanon, creating CAD‐associated population structures that are similar to those in the source populations, maintained by limited admixture, and probably encompassing variations on the nuclear and/or the mitochondrial genome that are correlated with the disease.
Moving beyond the function of the health behaviour: The effect of message frame on behavioural decision-making

Health messages that provide gain- or loss-framed arguments have a differential impact on behavioural decision-making (Rothman & Salovey, 1997). Typically, gain-framed messages more effectively promote preventive health behaviours, which maintain health and minimise the risk of a health problem, whereas loss-framed messages more effectively promote detection behaviours, which involve the risk of finding a health problem. Two experiments tested the thesis that the risk implications of the behaviour are an important determinant of the persuasive impact of gain- and loss-framed appeals. Results revealed that when the risk associated with a health behaviour (either a prevention behaviour in Experiment 1 or a detection behaviour in Experiment 2) was low, participants responded more favourably to gain-framed messages. However, when the risk associated with the health behaviour (either prevention or detection) was high, participants responded more favourably to loss-framed messages. Discussion focuses on the importance of taking into account how individuals construe a behaviour when constructing framed appeals.
Epidemiology, Aetiology and Prognosis of Hypertension

Abstract Hypertension is a common disorder. In fewer than 5% of cases there is an identifiable cause (secondary hypertension) but the great majority of patients have ‘primary' or ‘essential' hypertension because there is no clearly identifiable underlying cause. A number of genetic and environmental factors are known to be contributory to the development of an elevated blood pressure but a clearly defined cause is seldom identified. Irrespective of the cause, uncontrolled hypertension increases cardiovascular (CV) risk but there is now clear evidence that antihypertensive drug treatment improves patient outcome across the whole spectrum of CV risk.
PRENATAL DIAGNOSIS OF β‐THALASSAEMIA AND SICKLE CELL ANAEMIA IN TURKEY

This paper reports our experience of molecular analysis and diagnosis of β‐thalassaemia and sickle cell anaemia (HbS) in 70 prospective parents of Turkish descent and their fetuses. Molecular screening was carried out by allele‐specific oligonucleotide (ASO) hybridization of amplified DNA to the 12 most common mutations in the Turkish population. By using this approach, we were able to define the mutation in 95 per cent of chromosomes investigated. Genomic sequencing led to the additional detection of three rare mutations: Cd 44 (−C), IVS‐I‐5 (G–C), and IVS‐I‐116 (T–G). All diagnoses were successfully accomplished and no misdiagnosis occurred. Consanguineous marriage appears to contribute significantly to the frequency of affected births in Turkey. Out of the 14 homozygous fetuses, six were the result of close consanguinity. This study indicates that fetal diagnosis of β‐thalassaemia and HbS may be obtained in practically all cases, even in a heterogeneous population like the Turkish population, when early methods of fetal sampling are combined with polymerase chain reaction (PCR)‐based techniques. Until gene therapy becomes a reality, the only approaches to the control of haemoglobinopathies are prevention and avoidance. The most relevant and common aspects of the programmes, which have been very effective in reducing the birth rate of β‐thalassaemia major in several at‐risk areas of the Mediterranean basin, are the continuous educational campaigns directed at the population at large, the voluntary basis, and non‐directive counselling. The most important challenge for the eradication of the haemoglobinopathies in Turkey is the organization of a nation‐wide and comprehensive genetic preventive programme based on DNA technology.
Anesthesia and Arrhythmogenesis in the Chronic Atrioventricular Block Dog Model

Background: Drug-induced torsade de pointes (TdP) arrhythmias can readily be induced in anesthetized dogs with remodeled hearts [chronic complete atrioventricular block (CAVB) dogs]. Similar studies in conscious CAVB dogs reveal lower TdP incidences. Regulations forced us to reconsider our anesthetic regimen, which consist of pentobarbital followed by halothane (P + H). We investigated the relevance of anesthesia for this enhanced susceptibility (part 1) and compared 3 anesthetic regimens (part 2). Methods: Part 1-Ten CAVB dogs paced from the high septum at 1000 milliseconds were challenged with dofetilide (25 μg·kg−1·5 min−1) twice: once under anesthesia and once awake. Anesthesia consisted of P + H (n = 5) and thiopental maintained by isoflurane (T + I). Part 2-In CAVB dogs (n = 6) with spontaneous idioventricular rhythm, the electrophysiological and arrhythmogenic consequences of different anesthetic regimens (P + H, T + I, and P + I) were serially compared. Results: Part 1-In paced dogs, dofetilide-induced TdP was higher under anesthetized than in conscious circumstances, with the more severe outcome seen after T + I as compared with P + H or control (2×): 5/5, 2/5, 0/5, and 0/5, respectively; P < 0.05. Part 2-Electrophysiologically, T accelerated idioventricular rhythm, increased QTc, and transiently induced polymorphic ventricular tachycardias in 2 of 6 dogs. This was not seen after P. At 120 minutes (end of the preparation), QTc increase was highest after T + I, intermediate with P + I, and the smallest after P + H. Dofetilide in combination with T + I induced the most severe arrhythmogenic outcome. Conclusions: Thiopental anesthesia causes arrhythmias sec, whereas anesthesia in general predisposes for drug-induced TdP in the CAVB dog. In combination with dofetilide, T + I has a more arrhythmic outcome than P + I or P + H.