Strong Evidence Of Association Research Articles

Gender diversity, corporate social responsibility and real earnings management for policy management decision: evidence from emerging market

Purpose The study aims to examine whether board gender diversity and corporate social responsibility (CSR) affect real earnings management (REM) practices of public companies in Nigeria. Design/methodology/approach The study analyzes data of public companies for the period of 2011 through 2020. Data on board gender diversity, CSR and REM were collected from audited financial statements. Findings The empirical findings show that companies with greater diverse board are effective in restraining REM, thus supporting the theoretical framework of the study. Also, the result provides strong evidence of association between CSR performance and REM for policy management decision. Research limitations/implications The study is constrained by not considering all public companies in the country. Furthermore, it considered only gender among numerous important board attributes and environmental, social and governance (ESG) among numerous CSR attributes. Hence, future studies should consider other important attributes on REM and important attributes of board diversity and CSR on real earnings management. Originality/value To the best of the authors’ knowledge, this study is the first to investigate the relationship between heterogeneous board gender diversity, CSR via ESG and REM in emerging markets such as Nigeria. Therefore, it provides appropriate treatment of CSR with science and technology via EGS viewpoint of organizational operations and behavior of managing earnings. Therefore, developing better policy management for sustainable development

Different Host-Endogenous Retrovirus Relationships between Mammals and Birds Reflected in Genome-Wide Evolutionary Interaction Patterns.

Mammals and birds differ largely in their average endogenous retrovirus loads, namely the proportion of endogenous retrovirus in the genome. The host-endogenous retrovirus relationships, including conflict and co-option, have been hypothesized among the causes of this difference. However, there has not been studies about the genomic evolutionary signal of constant host-endogenous retrovirus interactions in a long-term scale and how such interactions could lead to the endogenous retrovirus load difference. Through a phylogeny-controlled correlation analysis on ∼5,000 genes between the dN/dS ratio of each gene and the load of endogenous retrovirus in 12 mammals and 21 birds, separately, we detected genes that may have evolved in association with endogenous retrovirus loads. Birds have a higher proportion of genes with strong correlation between dN/dS and the endogenous retrovirus load than mammals. Strong evidence of association is found between the dN/dS of the coding gene for leucine-rich repeat-containing protein 23 and endogenous retrovirus load in birds. Gene set enrichment analysis shows that gene silencing rather than immunity and DNA recombination may have a larger contribution to the association between dN/dS and the endogenous retrovirus load for both mammals and birds. The above results together showing different evolutionary patterns between bird and mammal genes can partially explain the apparently lower endogenous retrovirus loads of birds, while gene silencing may be a universal mechanism that plays a remarkable role in the evolutionary interaction between the host and endogenous retrovirus. In summary, our study presents signals that the host genes might have driven or responded to endogenous retrovirus load changes in long-term evolution.

Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Genetic testing using targeted disease-specific panels that utilize next-generation sequencing (NGS) and include sarcomeric genes with the strongest evidence of association and syndrome-associated genes is highly recommended for every HCM patient to confirm the diagnosis, identify the molecular etiology, and guide screening and management. The yield of genetic testing for a disease-causing variant is 30% in sporadic cases and up to 60% in familial cases and in younger patients with typical asymmetrical septal hypertrophy. Genetic testing remains challenging in the interpretation of results and classification of variants. Therefore, in 2015 the American College of Medical Genetics and Genomics (ACMG) established guidelines to classify and interpret the variants with an emphasis on the necessity of periodic reassessment of variant classification as genetic knowledge rapidly expands. The current guidelines recommend focused cascade genetic testing regardless of age in phenotype-negative first-degree relatives if a variant with decisive evidence of pathogenicity has been identified in the proband. Genetic test results in family members guide longitudinal clinical surveillance. At present, there is emerging evidence for genetic test application in risk stratification and management but its implementation into clinical practice needs further study. Promising fields such as gene therapy and implementation of artificial intelligence in the diagnosis of HCM are emerging and paving the way for more effective screening and management, but many challenges and obstacles need to be overcome before establishing the practical implications of these new methods.

Evaluating the implementation of the Primary Health Integrated Care Project for Chronic Conditions: a cohort study from Kenya

IntroductionIn Kenya, non-communicable diseases (NCDs) are estimated to account for almost one-third of all deaths and this is likely to rise by over 50% in the next 10 years. The...

Identification of Coding Variants in 10q22.1 Associated with Vitiligo in the Chinese Han Population.

Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in SLC29A3 and CDH23 and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10-6, OR = 0.84; p = 9.47 × 10-5, OR = 1.18; p = 6.90 × 10-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r2 = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.

'All I do is fight fires': Qualitative exploration of UK veterinarians' attitudes towards and experiences of pre-purchase consultations regarding brachycephalic dogs.

Demand for brachycephalic dogs has dramatically increased over the past decade, despite growing evidence of strong associations between brachycephaly and severe, chronic disease. Positive post-purchase attitudes of owners towards brachycephalic dogs are highly intractable, facilitated by normalisation of breed-related disease and strong dog-owner bonds. Veterinarian-led pre-purchase consultations (PPCs) have been promoted as an opportunity to influence acquisition decisions regarding brachycephalic dogs. Using reflexive thematic analysis, this qualitative study investigated veterinarians' attitudes towards, and experiences of, engaging in PPCs for brachycephalic dogs. Veterinarians described significant structural barriers, such as lack of time and staff, and perceptual barriers, such as perceived futility, negative outcomes of PPCs and public distrust in the profession, that combine to inhibit many veterinarians from offering or delivering brachycephalic PPCs. Some of these barriers are intractable at an individual-veterinarian level and lead to moral distress due to conflicts between veterinarians' responsibilities to animal welfare versus clients' and business needs, with resultant censorship of authentic views on brachycephalic ownership compromising professional integrity and autonomy. Wider views and/or experiences may exist outside of the sampled population. Stronger veterinary leadership, including from the RCVS, BVA and veterinary corporates, is now urgently required to build profession-wide solutions that overcome the barriers identified to create public-facing consensus and innovative solutions to the 'brachycephalic crisis'.

Load and recovery monitoring in Swiss top-level youth soccer players: Exploring the associations of a new web application-based score with recognised load measures

Load and recovery monitoring in Swiss top-level youth soccer players: Exploring the associations of a new web application-based score with recognised load measures

Impact of adult-onset multiple sclerosis on MRI-based intracranial volume: A study in clinically discordant monozygotic twins

ObjectiveIntracranial volume (ICV) represents the maximal brain volume for an individual, attained prior to late adolescence and remaining constant throughout life after. Thus, ICV serves as a surrogate marker for brain growth integrity. To assess the potential impact of adult-onset multiple sclerosis (MS) and its preceding prodromal subclinical changes on ICV in a large cohort of monozygotic twins clinically discordant for MS. MethodsFSL software was used to derive ICV estimates from 3D-T1-weighted-3 T-MRI images by using an atlas scaling factor method. ICV were compared between clinically affected and healthy co-twins. All twins were compared to a large healthy reference cohort using standardized ICV z-scores. Mixed models assessed the impact of age at MS diagnosis on ICV. Results54 twin-pairs (108 individuals/80female/42.45 ± 11.98 years), 731 individuals (375 non-twins, 109/69 monozygotic/dizygotic twin-pairs; 398female/29.18 ± 0.13 years) and 35 healthy local individuals (20male/31.34 ± 1.53 years). In 45/54 (83 %) twin-pairs, both clinically affected and healthy co-twins showed negative ICV z-scores, i.e., ICVs lower than the average of the healthy reference cohort (M = -1.53 ± 0.11, P<10−5). Younger age at MS diagnosis was strongly associated with lower ICVs (t = 3.76, P = 0.0003). Stratification of twin-pairs by age at MS diagnosis of the affected co-twin (≤30 versus > 30 years) yielded lower ICVs in those twin pairs with younger age at diagnosis (P = 0.01). Comparison within individual twin-pairs identified lower ICVs in the MS-affected co-twins with younger age at diagnosis compared to their corresponding healthy co-twins (P = 0.003). ConclusionWe offer for the first-time evidence for strong associations between adult-onset MS and lower ICV, which is more pronounced with younger age at diagnosis. This suggests pre-clinical alterations in early neurodevelopment associated with susceptibility to MS both in individuals with and without clinical manifestation of the disease.

The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development

BackgroundSolute carrier family 13 member 5 (SLC13A5) is a Na+-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the effects of SLC13A5 inhibition in humans, towards prioritizing and informing clinical development efforts.MethodsThe primary Mendelian randomization analyses investigated the effect of SLC13A5 inhibition on measures of kidney function, including creatinine and cystatin C-based measures of estimated glomerular filtration rate (creatinine-eGFR and cystatin C-eGFR), blood urea nitrogen (BUN), urine albumin-creatinine ratio (uACR), and risk of chronic kidney disease and microalbuminuria. Secondary analyses included a paired plasma and urine metabolome-wide association study, investigation of secondary traits related to SLC13A5 biology, a phenome-wide association study (PheWAS), and a proteome-wide association study. All analyses were compared to the effect of genetically predicted plasma citrate levels using variants selected from across the genome, and statistical sensitivity analyses robust to the inclusion of pleiotropic variants were also performed. Data were obtained from large-scale genetic consortia and biobanks, with sample sizes ranging from 5023 to 1,320,016 individuals.ResultsWe found evidence of associations between genetically proxied SLC13A5 inhibition and higher creatinine-eGFR (p = 0.002), cystatin C-eGFR (p = 0.005), and lower BUN (p = 3 × 10−4). Statistical sensitivity analyses robust to the inclusion of pleiotropic variants suggested that these effects may be a consequence of higher plasma citrate levels. There was no strong evidence of associations of genetically proxied SLC13A5 inhibition with uACR or risk of CKD or microalbuminuria. Secondary analyses identified evidence of associations with higher plasma calcium levels (p = 6 × 10−13) and lower fasting glucose (p = 0.02). PheWAS did not identify any safety concerns.ConclusionsThis Mendelian randomization analysis provides human-centric insight to guide clinical development of an SLC13A5 inhibitor. We identify plasma calcium and citrate as biologically plausible biomarkers of target engagement, and plasma citrate as a potential biomarker of mechanism of action. Our human genetic evidence corroborates evidence from various animal models to support effects of SLC13A5 inhibition on improving kidney function.

Interleukins-6 −174G/C (rs1800795) and −572C/G (rs1800796) polymorphisms and prostate cancer risk

Prostate cancer (PCa) is an aggressive cancer influenced by a complex interplay of genetic and environmental factors. Amongst these risk factors, the impact of Interleukin6 (IL6) gene polymorphisms in PCa risk has received a lot of attention. IL-6 is a cytokine that has been implicated in the pathogenesis of several malignancies, including PCa. Two IL-6 gene polymorphisms, − 174 G/C (rs1800795) and − 572 C/G (rs1800796), have received intellectual attention due to their potential role as modulators of prostate cancer risk. The main objective of this research was to comprehensively explore the potential associations between IL-6 rs1800795 and rs1800796 polymorphisms, and their impact on the occurrence of PCa. A case-control study was carried out with a well-defined cohort comprising 110 PCa cases and 110 controls (total n = 220). The genotyping of rs1800795 and rs1800796 was carefully performed using the highly sensitive and accurate Polymerase Chain Reaction-High Resolution Melting Curve (PCR-HRM) technique. The assessment of genetic associations was evaluated using various R packages, such as Haplo-Stats, SNP stat, pheatmap, and LD heatmap. The present study applied odds ratio (OR) analysis to reveal significant evidence of strong associations between the genotypes of rs1800795 and rs1800796 and the susceptibility to PCa. The findings of this study underscore the noteworthy impact of genetic variations in the IL-6 gene on the development of prostate cancer. Specifically, the C/G and G/G genotypes of rs1800795 demonstrated increased PCa risk, with odds ratios (OR) of 1.650 (95% CI = 1.068–2.549, p = 0.032) and 2.475 (95% CI = 1.215–5.043, p < 0.001), respectively. Similarly, the G/C genotype of rs1800796 exhibited an OR of 2.374 (95% CI = 1.363–4.130, p = 0.012) for elevated prostate cancer risk, while the C/C genotype had an OR of 1.81 (95% CI = 1.02–3.22, p = 0.7). Furthermore, our haplotype analysis have revealed an association between haplotype 4 (C-G) and increased risk of PCa (OR = 1.69, 95% CI = 1.05–2.73, p = 0.032). In conclusion, this case-control analysis presents compelling evidence for a significant association between IL-6 variants (rs1800795 and rs1800796) and increased susceptibility to prostate cancer.

Prognostic factors to identify resolution of small bowel obstruction without need for operative management: systematic review.

To identify imaging, clinical, and laboratory variables potentially prognostic for surgical management of small bowel obstruction. Two researchers systematically reviewed indexed literature 2001-2021 inclusive for imaging, clinical, and laboratory variables potentially predictive of surgical management of small bowl obstruction and/or ischaemia at surgery, where performed. Risk of bias was assessed. Contingency tables for variables reported in at least 5 studies were extracted and meta-analysed to identify strong evidence of association with clinical outcomes, across studies. Thirty-one studies were ultimately included, reporting 4638 patients (44 to 313 per study). 11 (35%) studies raised no risk of bias concerns. CT was the modality reported most (29 studies, 94%). Meta-analysis of 21 predictors identified 5 strongly associated with surgical intervention, 3 derived from CT (peritoneal free fluid, odds ratio [OR] 3.24, 95%CI 2.45 to 4.29; high grade obstruction, OR 3.58, 95%CI 2.46 to 5.20; mesenteric inflammation, OR 2.61, 95%CI 1.94 to 3.50; abdominal distension, OR 2.43, 95%CI 1.34 to 4.42; peritonism, OR 3.97, 95%CI 2.67 to 5.90) and one with conservative management (previous abdominopelvic surgery, OR 0.58, 95%CI 0.40 to 0.85). Meta-analysis of 10 predictors identified 3 strongly associated with ischaemia at surgery, 2 derived from CT (peritoneal free fluid, OR 3.49, 95%CI 2.28 to 5.35; bowel thickening, OR 3.26 95%CI 1.91 to 5.55; white cell count, OR 4.76, 95%CI 2.71 to 8.36). Systematic review of patients with small bowel obstruction identified four imaging, three clinical, and one laboratory predictors associated strongly with surgical intervention and/or ischaemia at surgery. Via systematic review and meta-analysis, we identified imaging, clinical, and laboratory predictors strongly associated with surgical management of small bowel obstruction and/or ischaemia. Multivariable model development to guide management should incorporate these since they display strong evidence of potential utility. • While multivariable models incorporating clinical, laboratory, and imaging factors could predict surgical management of small bowel obstruction, none are used widely. • Via systematic review and meta-analysis we identified imaging, clinical, and laboratory variables strongly associated with surgical management and/or ischaemia at surgery. • Development of multivariable models to guide management should incorporate these predictors, notably CT scanning, since they display strong evidence of potential utility.

Epidemiology and etiology of diffuse large B-cell lymphoma

As the most common non-Hodgkin lymphoma subtype, diffuse large B-cell lymphoma (DLBCL) incidence patterns generally parallel that for NHL overall. Globally, DLBCL accounts for a third of all NHLs, ranging between 20% and 50% by country. Based on United States (U.S.) cancer registry data, age-standardized incidence rate for DLBCL was 7.2 per 100,000. DLBCL incidence rises with age and is generally higher in males than females; in the U.S., incidence is highest among non-Hispanic whites (9.2/100,000). Like NHL incidence, DLBCL incidence rose in the first half of the 20th century but has largely plateaued. However, there is some evidence that incidence rates are rising in areas of historically low rates, such as Asia; there are also estimates for rising DLBCL incidence in the near future due to the changing demographics in developed countries whose aging population is growing. Established risk factors for DLBCL include those that result in severe immune deficiency such as HIV/AIDS, inherited immunodeficiency syndromes, and organ transplant recipients. Factors that lead to chronic immune dysregulations are also established risk factors, and include a number of autoimmune conditions (eg, Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis), viral infections (eg, HIV, KSHV/HHV8, HCV, EBV), and obesity. Family history of NHL/DLBCL, personal history of cancer, and multiple genetic susceptibility loci are also well-established risk factors for DLBCL. There is strong evidence for multiple environmental exposures in DLBCL etiology, including exposure to trichloroethylene, benzene, and pesticides and herbicides, with recent associations noted with glyphosate. There is also strong evidence for associations with other viruses, such as HBV. Recent estimates suggest that obesity accounts for nearly a quarter of DLBCLs that develop, but despite recent gains in the understanding of DLBCL etiology, the majority of disease remain unexplained. An understanding of the host and environmental contributions to disease etiology, and concerted efforts to expand our understanding to multiple race/ethnic groups, will be essential for constructing clinically relevant risk prediction models and develop effective strategies for disease prevention.

Food Is Medicine: A Presidential Advisory From the American Heart Association.

Unhealthy diets are a major impediment to achieving a healthier population in the United States. Although there is a relatively clear sense of what constitutes a healthy diet, most of the US population does not eat healthy food at rates consistent with the recommended clinical guidelines. An abundance of barriers, including food and nutrition insecurity, how food is marketed and advertised, access to and affordability of healthy foods, and behavioral challenges such as a focus on immediate versus delayed gratification, stand in the way of healthier dietary patterns for many Americans. Food Is Medicine may be defined as the provision of healthy food resources to prevent, manage, or treat specific clinical conditions in coordination with the health care sector. Although the field has promise, relatively few studies have been conducted with designs that provide strong evidence of associations between Food Is Medicine interventions and health outcomes or health costs. Much work needs to be done to create a stronger body of evidence that convincingly demonstrates the effectiveness and cost-effectiveness of different types of Food Is Medicine interventions. An estimated 90% of the $4.3 trillion annual cost of health care in the United States is spent on medical care for chronic disease. For many of these diseases, diet is a major risk factor, so even modest improvements in diet could have a significant impact. This presidential advisory offers an overview of the state of the field of Food Is Medicine and a road map for a new research initiative that strategically approaches the outstanding questions in the field while prioritizing a human-centered design approach to achieve high rates of patient engagement and sustained behavior change. This will ideally happen in the context of broader efforts to use a health equity-centered approach to enhance the ways in which our food system and related policies support improvements in health.

Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer

Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence is limited for some genes currently included in panel testing, gene panels are also likely to be incomplete and missing genes that influence PCa risk and aggressive disease. To identify genes associated with aggressive PCa. A 2-stage exome sequencing case-only genetic association study was conducted including men of European ancestry from 18 international studies. Data analysis was performed from January 2021 to March 2023. Participants were 9185 men with aggressive PCa (including 6033 who died of PCa and 2397 with confirmed metastasis) and 8361 men with nonaggressive PCa. Sequencing data were evaluated exome-wide and in a focused investigation of 29 DNA repair pathway and cancer susceptibility genes, many of which are included on gene panels. The primary study outcomes were aggressive (category T4 or both T3 and Gleason score ≥8 tumors, metastatic PCa, or PCa death) vs nonaggressive PCa (category T1 or T2 and Gleason score ≤6 tumors without known recurrence), and metastatic vs nonaggressive PCa. A total of 17 546 men of European ancestry were included in the analyses; mean (SD) age at diagnosis was 65.1 (9.2) years in patients with aggressive PCa and 63.7 (8.0) years in those with nonaggressive disease. The strongest evidence of association with aggressive or metastatic PCa was noted for rare deleterious variants in known PCa risk genes BRCA2 and ATM (P ≤ 1.9 × 10-6), followed by NBN (P = 1.7 × 10-4). This study found nominal evidence (P < .05) of association with rare deleterious variants in MSH2, XRCC2, and MRE11A. Five other genes had evidence of greater risk (OR≥2) but carrier frequency differences between aggressive and nonaggressive PCa were not statistically significant: TP53, RAD51D, BARD1, GEN1, and SLX4. Deleterious variants in these 11 candidate genes were carried by 2.3% of patients with nonaggressive, 5.6% with aggressive, and 7.0% with metastatic PCa. The findings of this study provide further support for DNA repair and cancer susceptibility genes to better inform disease management in men with PCa and for extending testing to men with nonaggressive disease, as men carrying deleterious alleles in these genes are likely to develop more advanced disease.

Clinical potential of automated convolutional neural network-based hematoma volumetry after aneurysmal subarachnoid hemorrhage

ObjectivesCerebrospinal fluid hemoglobin has been positioned as a potential biomarker and drug target for aneurysmal subarachnoid hemorrhage-related secondary brain injury (SAH-SBI). The maximum amount of hemoglobin, which may be released into the cerebrospinal fluid, is defined by the initial subarachnoid hematoma volume (ISHV). In patients without external ventricular or lumbar drain, there remains an unmet clinical need to predict the risk for SAH-SBI. The aim of this study was to explore automated segmentation of ISHV as a potential surrogate for cerebrospinal fluid hemoglobin to predict SAH-SBI. MethodsThis study is based on a retrospective analysis of imaging and clinical data from 220 consecutive patients with aneurysmal subarachnoid hemorrhage collected over a five-year period. 127 annotated initial non-contrast CT scans were used to train and test a convolutional neural network to automatically segment the ISHV in the remaining cohort. Performance was reported in terms of Dice score and intraclass correlation. We characterized the associations between ISHV and baseline cohort characteristics, SAH-SBI, ventriculoperitoneal shunt dependence, functional outcome, and survival. Established clinical (World Federation of Neurosurgical Societies, Hunt & Hess) and radiological (modified Fisher, Barrow Neurological Institute) scores served as references. ResultsA strong volume agreement (0.73 Dice, range 0.43 - 0.93) and intraclass correlation (0.89, 95% CI, 0.81-0.94) were shown. While ISHV was not associated with the use of antithrombotics or cardiovascular risk factors, there was strong evidence for an association with a lower Glasgow Coma Scale at hospital admission. Aneurysm size and location were not associated with ISHV, but the presence of intracerebral or intraventricular hemorrhage were independently associated with higher ISHV. Despite strong evidence for a positive association between ISHV and SAH-SBI, the discriminatory ability of ISHV for SAH-SBI was insufficient. The discriminatory ability of ISHV was, however, higher regarding ventriculoperitoneal shunt dependence and functional outcome at three-months follow-up. Multivariate survival analysis provided strong evidence for an independent negative association between survival probability and both ISHV and intraventricular hemorrhage. ConclusionsThe proposed algorithm demonstrates strong performance in volumetric segmentation of the ISHV on the admission CT. While the discriminatory ability of ISHV for SAH-SBI was similar to established clinical and radiological scores, it showed a high discriminatory ability for ventriculoperitoneal shunt dependence and functional outcome at three-months follow-up.

Genomic profile of diabetic retinopathy in a north indian cohort.

Diabetic Retinopathy (DR) is one of the major microvascular complications of diabetes. Being a complex disease, it is important to delineate the genetic and environmental factors that influence the susceptibility to DR in a population. Therefore, the present study was designed to investigate the role of genetic and lifestyle risk factors associated with DR susceptibility in a North-Indian population. A total of 848 subjects were enrolled, comprising of DR cases (n = 414) and healthy controls (n = 434). The Sequenom MassARRAY technology was used to perform target genome analysis of 111 SNPs across 57 candidate genes and 14 intergenic region SNPs that are involved in the metabolic pathways associated with type 2 diabetes (T2D) and DR. Allele, genotype and haplotype frequencies were determined and compared among cases and controls. Logistic regression models were used to determine genotype-phenotype and phenotype-phenotype correlations. The strongest association was observed with TCF7L2 rs12255372 T allele [p < 0.0001; odds ratio (OR) = 1.81 (1.44-2.27)] and rs11196205 C allele [p < 0.0008; OR = 1.62 (1.32-1.99)]. Genotype-phenotype and phenotype-phenotype correlations were found in the present study. Our study provides strong evidence of association between the TCF7L2variants and DR susceptibility.

ASSOCIATION OF ORAL MICROBIOTA AND PERIODONTAL DISEASE WITH LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Evidence of oral microbiota perturbations has been accumulated for lung cancers. This review focused on the oral microbiota alterations in population suffering from lung cancer. In addition, we also discussed conflicting data about the association between oral microbiota dysbiosis and risk of lung cancer. A systematic search was conducted in Medline, Embase, PubMed, and Cochrane Library databases. The studies evaluated diversity and abundance of oral microbes in healthy and lung cancer individuals as well as association of periodontal disease and pathogens with lung cancer. Of 3559 studies, 28 included studies were performed in qualitative analysis, and 25 studies were used in meta-analyses for quantitative assessment. Heterogeneity was analyzed by using I² and chi-squared Q test statistics. Statistical analyses were performed by using the RevMan 5.4 software. Compared with the control, lung cancer patients had lower alpha diversity (Shannon: SMD = -0.54; 95% CI, -0.90 to -0.19; P < .01, I2 = 71%). In nested case-control studies, individuals with decreased alpha diversity tended to have an increased risk of lung cancer (observed species: HR = 0.90; 95% CI, 0.85-0.96; P < .01, I2 = 0%; Shannon: HR = 0.89; 95% CI, 0.83-0.95; P < .01, I2 = 0%). Overall, no strong evidence of association of relative abundance with specific oral microbes with lung cancers was found because of inconsistent data. No associations were found between periodontal pathogens and lung cancer risk (red complex: HR = 1.12, 95% CI: 0.42-3.02, P = .82, I2 = 62%; orange complex: HR =1.77, 95% CI: 0.78-3.98, P = .17, I2 = 36%), expect for Fusobacterium nucleatum (HR = 2.27, 95% CI: 1.13-4.58, P = .02, I2 = 0%). The positive association of periodontal disease with lung cancer risk was found (HR = 1.58, 95% CI: 1.25-2.00, P < .001, I2= 0%) with increase of periodontal diseases severity (HR = 2.39, 95% CI: 1.57-3.66, P < .001, I2 = 0%). However, such association was not found in never-smoker participants (HR = 1.00, 95% CI: 0.76-1.31, P = .37, I2= 7%). Lower alpha diversity of oral microbiome may be associated with a greater risk of lung cancer and might serve as a predictive signal of lung cancer risk. There was no strong evidence of relative abundance of oral microbial taxa and periodontal pathogens in lung cancer patients. Fusobacterium nucleatum might be a potential microbial candidate of biomarkers in lung cancer. Periodontal disease may be positively associated with lung cancer risk by confounding of smoking, but not an independent risk factor.

Association between socioeconomic status with pregnancy and neonatal outcomes: An international multicenter cohort.

Previous evidence examining the association between socioeconomic status and pregnancy complications are conflicted and often limited to using area-based measures of socioeconomic status. In this study, we aimed to examine the association between individual-level socioeconomic factors and a wide range of adverse pregnancy and neonatal outcomes using data from the IMPROvED birth cohort conducted in Sweden, the Netherlands and Republic of Ireland. The study cohort consisted of women who participated in the IMPROvED birth cohort between 2013 and 2017. Data on socioeconomic factors were self-reported and obtained at 15 weeks' gestation, and included level of education, employment status, relationship status, and income. Data on pregnancy and neonatal outcomes included gestational hypertension, pre-eclampsia, gestational diabetes mellitus, emergency cesarean section, preterm birth, post term delivery, small for gestational age and Apgar score at 1 min. These data were obtained within 72 h following delivery and confirmed using medical records. Multivariable logistic regression examined the association between each socioeconomic variable and each outcome separately adjusting for maternal age, maternal body mass index, maternal smoking, maternal alcohol consumption and cohort center. We also examined the effect of exposure to any ≥2 risk factors compared to none. A total of 2879 participants were included. Adjusted results suggested that those with less than third level of education had an increased odds of gestational hypertension (OR: 1.74, 95% CI: 1.23-2.46), while those on a middle level of income had a reduced odds of emergency cesarean section (OR: 0.59, 95% CI: 0.42-0.84). No significant associations were observed between socioeconomic variables and neonatal outcomes. Exposure to any ≥2 socioeconomic risk factors was associated with an increased risk of preterm birth (OR: 1.75, 95% CI: 1.06-2.89). We did not find strong evidence of associations between individual-level socioeconomic factors and pregnancy and neonatal outcomes in high-income settings overall, with only few significant associations observed among pregnancy outcomes.

Association between spill-related exposure to fine particulate matter and peripheral motor and sensory nerve function among oil spill response and cleanup workers following the Deepwater Horizon oil spill.

Burning/flaring of oil/gas during the Deepwater Horizon oil spill response and cleanup (OSRC) generated high concentrations of fine particulate matter (PM2.5). Personnel working on the water during these activities may have inhaled combustion products. Neurologic effects of PM2.5 have been reported previously but few studies have examined lasting effects following disaster exposures. The association of brief, high exposures and adverse effects on sensory and motor nerve function in the years following exposure have not been examined for OSRC workers. We assessed the relationship between exposure to burning/flaring-related PM2.5 and measures of sensory and motor nerve function among OSRC workers. PM2.5 concentrations were estimated from Gaussian plume dispersion models and linked to self-reported work histories. Quantitative measures of sensory and motor nerve function were obtained 4-6 years after the disaster during a clinical exam restricted to those living close to two clinics in Mobile, AL or New Orleans, LA (n = 3401). We obtained covariate data from a baseline enrollment survey and a home visit, both in 2011-2013. The analytic sample included 1186 participants. We did not find strong evidence of associations between exposure to PM2.5 and sensory or motor nerve function, although there was a suggestion of impairment based on single leg stance among individuals with high exposure to PM2.5. Results were generally consistent whether we examined average or cumulative maximum exposures or removed individuals with the highest crude oil exposures to account for co-pollutant confounding. There was no evidence of exposure-response trends. Remediating environmental disasters is essential for long-term human and environmental health. During the Deepwater Horizon oil spill disaster, burning and flaring of oil and gas were used to remove these pollutants from the environment, but led to potentially high fine particulate matter exposures for spill response workers working on the water. We investigate the potential adverse effects of these exposures on peripheral nerve function; understanding the potential health harm of remediation tactics is necessary to inform future clean up approaches and protect human health.

Xanthine oxidoreductase gene polymorphisms are associated with high risk of sepsis and organ failure

BackgroundSepsis and associated organ failures confer substantial morbidity and mortality. Xanthine oxidoreductase (XOR) is implicated in the development of tissue oxidative damage in a wide variety of respiratory and cardiovascular disorders including sepsis and sepsis-associated acute respiratory distress syndrome (ARDS). We examined whether single nucleotide polymorphisms (SNPs) in the XDH gene (encoding XOR) might influence susceptibility to and outcome in patients with sepsis.MethodsWe genotyped 28 tag SNPs in XDH gene in the CELEG cohort, including 621 European American (EA) and 353 African American (AA) sepsis patients. Serum XOR activity was measured in a subset of CELEG subjects. Additionally, we assessed the functional effects of XDH variants utilizing empirical data from different integrated software tools and datasets.ResultsAmong AA patients, six intronic variants (rs206805, rs513311, rs185925, rs561525, rs2163059, rs13387204), in a region enriched with regulatory elements, were associated with risk of sepsis (P < 0.008–0.049). Two out of six SNPs (rs561525 and rs2163059) were associated with risk of sepsis-associated ARDS in an independent validation cohort (GEN-SEP) of 590 sepsis patients of European descent. Two common SNPs (rs1884725 and rs4952085) in tight linkage disequilibrium (LD) provided strong evidence for association with increased levels of serum creatinine (Padjusted<0.0005 and 0.0006, respectively), suggesting a role in increased risk of renal dysfunction. In contrast, among EA ARDS patients, the missense variant rs17011368 (I703V) was associated with enhanced mortality at 60-days (P < 0.038). We found higher serum XOR activity in 143 sepsis patients (54.5 ± 57.1 mU/mL) compared to 31 controls (20.9 ± 12.4 mU/mL, P = 1.96 × 10− 13). XOR activity was associated with the lead variant rs185925 among AA sepsis patients with ARDS (P < 0.005 and Padjusted<0.01). Multifaceted functions of prioritized XDH variants, as suggested by various functional annotation tools, support their potential causality in sepsis.ConclusionsOur findings suggest that XOR is a novel combined genetic and biochemical marker for risk and outcome in patients with sepsis and ARDS.