Dietary intake of branched-chain amino acids (BCAAs), serum BCAAs, and cardiometabolic risk markers among community-dwelling adults.

PURPOSE: To investigate the associations between dietary/serum branched-chain amino acids (BCAAs) and cardiometabolic risk markers. METHODS: In a cohort of 2791 participants, diet and cardiometabolic risk markers were measured twice at baseline in overall participants and after 1-year in a subset of 423 participants. We assessed serum BCAAs at baseline and arterial stiffness after 1-year. The cross-sectional associations between dietary/serum BCAAs and cardiometabolic risk markers were analyzed using baseline measurements by linear regression, while the 1-year longitudinal association were analyzed using repeated measurements by linear mixed-effects regression. RESULTS: Higher BCAA intake from poultry was associated with lower triglycerides (ß=-0.028, P = 0.027) and higher high-density lipoprotein cholesterol (HDL-C, ß = 0.013, P = 0.006), while BCAAs in red and processed meat or fish were inversely associated with low-density lipoprotein cholesterol (ß = 0.025, P = 0.001) and total cholesterol (ß = 0.012, P = 0.033), respectively. BCAAs in whole grains and nuts were associated with higher HDL-C (ß = 0.011, P = 0.016), and lower TG (ß=-0.021, P = 0.041) and diastolic blood pressure (ß=-0.003, P = 0.027). Also, BCAAs from soy or vegetables and fruits were inversely associated with arterial stiffness (ß=-0.018, P = 0.047) and systolic blood pressure (ß=-0.011, P = 0.003), respectively. However, BCAAs in refined grains were positively associated with triglycerides (ß = 0.037, P = 0.014). Total serum BCAAs were unfavorably associated with multiple cardiometabolic risk markers (all P < 0.05). CONCLUSION: Dietary BCAAs in poultry, whole grains and nuts, soy, and vegetables and fruits may be favorably, while BCAAs in red and processed meat, fish, and refined grains were unfavorably associated with cardiometabolic health. Serum BCAAs showed a detrimental association with cardiometabolic risk markers.

Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

'Key skills' building in schools as a possible approach to reducing and preventing challenging behaviour.

BACKGROUND: Building 'key skills' may help prevent the development of challenging behaviour in children with an intellectual disability. The aim of this paper was to extend the current limited evidence in this area. METHOD: We undertook two studies with children with an intellectual disability in school settings: (1) a cross-sectional replication study exploring the relationship between 'key skills' and challenging behaviour. (2) a longitudinal study follow-up exploring change in 'key skill' levels and challenging behaviour. RESULTS: The replication study recruited 74 participants, those scoring lowest in 'key skill' had a 94% chance of having challenging behaviour; those with the highest scores had a 6% chance. The follow-up study recruited 39 participants, we found a significant increase in children's 'key skill' level (p < .001) and a decrease in their challenging behaviour (p = .046). CONCLUSION: Building 'key skills' in children with an intellectual disability may help reduce or prevent challenging behaviour.

[Do drugs have a place in prevention strategies ?] / Les médicaments ont-ils une place dans les stratégies de prévention ?

It's easy to imagine using medicines to treat or even cure an illness. For most people, however, the idea of taking one or more medicines to prevent or delay the onset of an illness or its complications seems less obvious. However, there is indeed a place for using medicines in the field of prevention. Knowing the definition of a medicine means you can immediately understand the role it can play in the field of prevention. What's more, the use of medicines should be based not only on evidence-based medicine, but also on an approach that integrates a collegial discussion with the patient, which will make it possible to discuss the expected benefits of such an approach, as well as explaining any possible side-effects. Only in this way can we expect better compliance of a person still without a disease. This article briefly summarizes the role that medicines can play in a prevention strategy.

L'usage des médicaments se conçoit aisément pour traiter, voire guérir, une maladie. Dans l'esprit de la population, envisager de prendre un ou des médicaments pour éviter ou retarder l'apparition d'une maladie ou les complications liées à celle-ci semble moins évident. Pourtant, il existe bien une place pour l'usage de médicaments dans le domaine de la prévention. Bien connaître la définition d'un médicament permet de comprendre d'emblée la place que celui-ci peut occuper dans le domaine de la prévention. Cependant, l'utilisation des médicaments devra se baser, non seulement sur la médecine basée sur les preuves, mais aussi en intégrant cette approche dans une discussion collégiale avec le patient. Ce dialogue permettra d'aborder les bénéfices attendus d'une telle approche, mais aussi d'expliquer les éventuelles manifestations indésirables (effets secondaires). Ce n'est que par cette méthode que l'on sera en droit d'attendre une meilleure observance de la part d'une personne non encore malade. Cet article résume brièvement la place que peuvent avoir les médicaments dans une stratégie de prévention.

Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.

Head and neck cancers are a highly complex and heterogeneous group of malignancies that involve very diverse anatomical structures and distinct aetiological factors, treatments and clinical outcomes. Among them, head and neck squamous cell carcinomas (HNSCC) are predominant and the sixth most common cancer worldwide with still low survival rates. Omic technologies have unravelled the intricacies of tumour biology, harbouring a large diversity of genetic and molecular changes to drive the carcinogenesis process. Nonetheless, this remarkable heterogeneity of molecular alterations opens up an immense opportunity to discover novel biomarkers and develop molecular-targeted therapies. Increasing evidence demonstrates that dysregulation of ion channel expression and/or function is frequently and commonly observed in a variety of cancers from different origin. As a consequence, the concept of ion channels as potential membrane therapeutic targets and/or biomarkers for cancer diagnosis and prognosis has attracted growing attention. This chapter intends to comprehensively and critically review the current state-of-art ion channel dysregulation specifically focusing on head and neck cancers and to formulate the major challenges and research needs to translate this knowledge into clinical application. Based on current reported data, various voltage-gated potassium (Kv) channels (i.e. Kv3.4, Kv10.1 and Kv11.1) have been found frequently aberrantly expressed in HNSCC as well as precancerous lesions and are highlighted as clinically and biologically relevant features in both early stages of tumourigenesis and late stages of disease progression. More importantly, they also emerge as promising candidates as cancer risk markers, tumour markers and potential anti-proliferative and anti-metastatic targets for therapeutic interventions; however, the oncogenic properties seem to be independent of their ion-conducting function.

Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort.

RATIONALE & OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a major cause of pediatric nephrotic syndrome, and African Americans exhibit an increased risk for developing FSGS compared with other populations. Predisposing genetic factors have previously been described in adults. Here we performed genomic screening of primary FSGS in a pediatric African American population. STUDY DESIGN: Prospective cohort with case-control genetic association study design. SETTING & PARTICIPANTS: 140 African American children with chronic kidney disease from the Chronic Kidney Disease in Children (CKiD) cohort, including 32 cases with FSGS. PREDICTORS: Over 680,000 common single-nucleotide polymorphisms (SNPs) were tested for association. We also ran a pathway enrichment analysis and a human leucocyte antigen (HLA)-focused association study. OUTCOME: Primary biopsy-proven pediatric FSGS. ANALYTICAL APPROACH: Multivariate logistic regression models. RESULTS: The genome-wide association study revealed 169 SNPs from 14 independent loci significantly associated with FSGS (false discovery rate [FDR]<5%). We observed notable signals for genetic variants within the APOL1 (P=8.6×10-7; OR, 25.8 [95% CI, 7.1-94.0]), ALMS1 (P=1.3×10-7; 13.0% in FSGS cases vs 0% in controls), and FGFR4 (P=4.3×10-6; OR, 24.8 [95% CI, 6.3-97.7]) genes, all of which had previously been associated with adult FSGS, kidney function, or chronic kidney disease. We also highlighted novel, functionally relevant genes, including GRB2 (which encodes a slit diaphragm protein promoting podocyte structure through actin polymerization) and ITGB1 (which is linked to renal injuries). Our results suggest a major role for immune responses and antigen presentation in pediatric FSGS through (1) associations with SNPs in PTPRJ (or CD148, P=3.5×10-7), which plays a role in T-cell receptor signaling, (2) HLA-DRB1∗11:01 association (P=6.1×10-3; OR, 4.5 [95% CI, 1.5-13.0]), and (3) signaling pathway enrichment (P=1.3×10-6). LIMITATIONS: Sample size and no independent replication cohort with genomic data readily available. CONCLUSIONS: Our genetic study has identified functionally relevant risk factors and the importance of immune regulation for pediatric primary FSGS, which contributes to a better description of its molecular pathophysiological mechanisms. PLAIN-LANGUAGE SUMMARY: We assessed the genetic risk factors for primary focal segmental glomerulosclerosis (FSGS) by simultaneously testing over 680,000 genetic markers spread across the genome in 140 children, including 32 with FSGS lesions. Fourteen independent genetic regions were significantly associated with pediatric FSGS, including APOL1 and ALMS1-NAT8, which were previously found to be associated with FSGS and chronic kidney diseases in adults. Novel genes with relevant biological functions were also highlighted, such as GRB2 and FGFR4, which play a role in the kidney filtration barrier and in kidney cell differentiation, respectively. Finally, we revealed the importance of immune regulation in pediatric FSGS through associations involving cell surface proteins presenting antigens to the immune system and interacting with T-cell receptors.

The natural history of periodontal disease: The Java study-Origin, implementation, and results 35 years on.

This review describes the origin and results of the prospective longitudinal study to test potential prognostic indicators for periodontal breakdown in a population deprived of regular dental care. Experimental gingivitis studies in individuals highly susceptible or highly resistant to periodontitis showed that bleeding on probing developed quite differently: 50% versus 18% bleeding, respectively, after 18 days of no oral hygiene. This formed, together with other clinical and microbiological parameters, the basis for the 15-year prospective study in the Java tea worker population to test potential prognostic indicators for periodontal breakdown. Evaluation showed that during the 15-year observation period of this population aged 15-25 years at baseline, the number of teeth decreased and the periodontal condition deteriorated. Gingival recession showed no increase during the first 7 years of observation, whereas a sixfold increase had occurred thereafter. Attachment loss doubled during the first 7 years, but almost tripled thereafter. Risk markers for disease onset/progression during the first 7 years of observation were age, the number of sites with subgingival calculus, and the subgingival presence of Aggregatibacter actinomycetemcomitans. Over the full period of 15 years the number of sites with a pocket depth of at least 5 mm and the number of sites with recession were identified as risk markers and male gender as a risk determinant. The prevalence of severe periodontitis amounted to 20% in 2002. Analysis showed that, already at baseline and throughout the study period, the periodontal condition in these individuals was more severe compared with the other participants. In conclusion, characteristics of susceptibility to periodontitis are already apparent in young adulthood.

Emerging Role of Decoy Receptor-2 as a Cancer Risk Predictor in Oral Potentially Malignant Disorders.

The aim of this study was to evaluate the expression of the senescence markers, Decoy Receptor 2 (DcR2) and Differentiated Embryo-Chondrocyte expressed gen 1 (DEC1), in oral potentially malignant disorders (OPMDs) to ascertain their possible association with oral cancer risk. The immunohistochemical analysis of DcR2 and DEC1 expression (along with p16 and Ki67 expression) was carried out in 60 patients with clinically diagnosed oral leukoplakia. Fifteen cases (25%) subsequently developed an invasive carcinoma. Correlations between protein marker expression, histological grade and oral cancer risk were assessed. DcR2, DEC1 and Ki67 protein expressions were found to correlate significantly with increased oral cancer risk, and also with an increased grade of dysplasia. Multivariate analysis demonstrated that DcR2 and Ki67 expression are independent predictors of oral cancer development. Our results evidence for the first time the potential of DcR2 as an early biomarker to assess oral cancer risk in patients with oral leukoplakia (HR = 59.7, p = 0.015), showing a superior predictive value to histology (HR = 4.225, p = 0.08). These findings reveal that the increased expression of DcR2 and DEC1 occurred frequently in OPMDs. In addition, DcR2 expression emerges as a powerful biomarker for oral cancer risk assessment in patients with oral leukoplakia.

Plasma mannose as a novel marker of myocardial infarction across different glycaemic states: a case control study.

BACKGROUND: Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. METHODS: Fasting plasma mannose concentrations were analysed in 777 patients 6-10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. RESULTS: Mannose levels increased across the glycaemic states (p < 0.0001) and were significantly associated with a first MI in the whole study population (odds ratio, OR: 2.2; 95% CI 1.4 to - 3.5). Considering the different subgroups separately, the association persisted only in subjects with NGT (adjusted OR: 2.0; 95% CI 1.2-3.6), but not in subgroups with glucose perturbations (adjusted OR: 1.8, 95% CI 0.8-3.7). CONCLUSIONS: Mannose concentrations increased across worsening levels of glucose perturbations but were independently associated with a first MI only in NGT individuals. Thus, mannose might be a novel, independent risk marker for MI, possibly targeted for the early management of previously unidentified patients at high cardiovascular risk.

Impact of Ankle Brachial Index Calculations on Peripheral Arterial Disease Prevalence and as a Predictor of Cardiovascular Risk.

OBJECTIVE: The aim of this study was to estimate the prevalence and predictive accuracy for cardiovascular (CV) morbidity by using different ankle brachial index (ABI) calculation methods in the general population. METHODS: ABI measurements and questionnaire data were collected from 5 080 randomly selected citizens aged 60 - 90 years. A 10 year follow up with data from Swedish national health registries was carried out. ABI was calculated using as numerator the highest (ABI-HI) or the lowest (ABI-LO) ankle BP obtained in each leg. Subjects were defined as references or having peripheral arterial disease (PAD) based on ABI-LO (Group 1) or ABI-HI (Group 2). Prevalence, mortality, CV events and risk were then analysed for these three groups, and their predictive power by using the area under the curve (AUC). RESULTS: A total of 4 909 inhabitants were included in the cohort (References: 83.8%, Group 1: 6.7% and Group 2: 9.6%). The prevalence of PAD was 16% using ABI-LO, and 9.6% using ABI-HI. The 10 year all cause mortality for references and Groups 1 and 2 was 27.6%, 48.8%, and 67.2%, respectively. The overall age adjusted hazard ratio (95% confidence interval) for the composite outcome of CV mortality and a non-fatal CV event was 1.25 (1.06 - 1.49) for Group 1 and 2.11 (1.85 - 2.39) for Group 2. The prediction accuracy for ABI < 0.9 in predicting CV event measured with AUC was 0.60 for ABI-HI and 0.62 for ABI-LO. CONCLUSION: An ABI < 0.9 should be considered a strong risk marker for future CV morbidity. Applying the traditional ABI calculation method of using the highest measured ankle BP, a group of subjects with high CV risk may be overlooked for intervention, and this why the lowest ankle BP should be the preferred for risk stratification. However, as a single predictive tool an ABI < 0.9 cannot adequately discriminate which individual will have a future CV event regardless of calculation method used.

Effectiveness of vitamin D2 supplementation on high-sensitivity C-reactive protein and other metabolic indices in menopausal Thai women: a randomized-controlled trial.

OBJECTIVE: To investigate the effectiveness of vitamin D2 supplementation with ergocalciferol on high-sensitivity C-reactive protein (hsCRP) level and other cardio-metabolic indices in menopausal Thai women. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted at the menopause clinic of a university hospital in Thailand from May 2017 to 2018. Participants were 80 postmenopausal women randomly assigned to treatment (N = 40, receiving vitamin D2 40,000 IU/week) or control (N = 40, receiving placebo) for 12 weeks. The primary outcome was hsCRP level, and secondary outcomes were cardio-metabolic profiles and 10-year risk of developing cardiovascular disease using the Framingham risk score. The changes from baseline to week-12 (Δ) of all outcomes were analyzed using a modified intention-to-treat (ITT) population. RESULTS: The vitamin D2 (N = 39) and placebo (N = 37) groups were comparable in all baseline characteristics. The hsCRP level was significantly reduced in the vitamin D2 group (Δ of -0.39 ± 1.30 mg/L, p = .024) but not in the placebo group (Δ of -0.15 ± 1.15 mg/L, p = .521). However, the Δ of hsCRP had no statistical difference between groups; neither did the Δ of other cardio-metabolic parameters. CONCLUSION: In menopausal Thai women, vitamin D2 supplementation with ergocalciferol 40,000 IU/week for 12 weeks can reduce hsCRP level; and the treatment might be superior to placebo. However, the hsCRP levels after 12 weeks between both groups were not statistically different. Clinical Trial Registration: Thai Clinical Trials Registry (TCTR20161216001).

SYNOPSISVitamin D2 supplementation in menopausal Thai women can reduce hsCRP level and might be superior to placebo.

Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction.

Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case-control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CIcorr) 1.02-3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CIcorr 1.06-3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.

Cardiovascular risk unawareness is common in individuals admitting to cardiology outpatient clinics in Turkey: the CVSCORE-TR study.

OBJECTIVES: Cardiovascular "risk" is an abstract concept that is frequently misunderstood by the general public. However, correct estimation of one's own cardiovascular risk is important as risk unawareness is associated with noncompliance with interventions aimed to reduce risk burden. Knowing the prevalence and factors linked with an increased probability of risk unawareness are therefore important to develop strategies aimed to increase risk awareness. Aims. To study prevalence of risk unawareness and to understand risk markers associated with risk underestimation and overestimation. Design. A total of 1716 participants were enrolled to the study in 33 centers across Turkey. Relevant demographic and clinical data were collected by direct interview. Cardiovascular risk of the participants was calculated using SCORE risk charts. Results. Ten-year risk for a fatal cardiovascular event was calculated as low in 633 (36.8%), intermediate in 513 (29.9%) and high-very high in 570 (33.2%) participants, respectively. According to these findings, 34.6% (n = 593) of the participants estimated their risk correctly, whereas 22.7% (n = 390) of the participants overestimated and 42.7% (n = 733) of the participants underestimated their risk. Male gender was the sole factor that was associated with an increased risk of underestimation, while having hypertension, significant valve disease or atrial fibrillation was associated with increased odds for risk overestimation. Conclusions. Only one-thirds of the sample was aware of their calculated risk for cardiovascular mortality and risk underestimation was the most common mode of risk unawareness, prompting concerns on the possible impact of the latter on adherence to the strategies aimed to reduce cardiovascular risk.

Aborted sudden cardiac death due to ventricular fibrillation in a female patient with mitral valve prolapse.

BACKGROUND: Mitral valve prolapse is the most frequent valvular defect associated with a wide range of electro-hemodynamic abnormalities, leading to heart failure, arrhythmias and sudden cardiac death. Mitral valve prolapse, first described from Barlow in the 1960s, is defined as displacement of mitral leaflet tissue into the left atrium past the mitral annular plane during systole. The correlation between mitral valve prolapse and sudden cardiac death has been investigated and clarified by various studies in recent years. However, identifying patients at risk and applying measures to prevent those from sudden cardiac death is challenging. CASE PRESENTATION: We report on a 61-year-old female patient who had undergone an aborted sudden cardiac death. An arrythmogenic mitral valve prolapse was diagnosed. In addition, electrocardiographically and morphologically risk markers for sudden cardiac death were found in this case. We performed an ICD implantation as secondary prophylaxis and intended to reconstruct the mitral valve. CONCLUSION: This article examines the association of mitral valve prolapse with sudden cardiac death, the underlying pathophysiological mechanisms and the strategies leading to identify the risk group.

New insights from the MESA study: increased high-sensitivity troponins as a cardiovascular risk factor.

The most recent high-sensitivity assays for troponins I and T (hs-TnI and hs-TnT) have made it possible to detect blood concentrations up to 10 times lower than previous assays, making troponins detectable even in asymptomatic subjects without manifest cardiovascular disease. For this reason, hs-Tn, initially introduced as markers of myocardial damage in an acute setting, have also become possible markers of subclinical myocardial damage in baseline conditions. In fact, recent evidence suggests that hs-TnT and hs-TnI predict the risk of future cardiovascular events also in the context of primary prevention, and offer incremental information when added to current risk stratification models. The different association highlighted with different outcome measures, such as coronary heart disease, atherosclerotic cardiovascular disease, heart failure, and death from all causes, seems to indicate that the risk observed in asymptomatic subjects with high levels of hs-Tn is an expression of subclinical damage secondary to multiple pathophysiological mechanisms, and not only to atherothrombosis. However, the ability of hs-TnT and hs-TnI (until now used interchangeably), to provide differential predictive information, and not redundant with respect to more traditional factors, remains to be definitively clarified, both for the purpose of predicting specific outcomes and for the implementation of specific preventive strategies. To date, evidences available allow us to hypothesize their role more as markers than as risk factors.

Association of cyclin-dependent kinase inhibitor 2A/B with increased risk of developing breast cancer.

There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real-time polymerase chain reaction (RT-PCR) method and gene expression analysis was ran by RT-PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4-5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.

Anticardiolipin antibody and anti-ß2 glycoprotein I antibody are potential risk markers of ischaemic stroke in Chinese adults.

OBJECTIVES: aCL and anti-ß2 glycoprotein I antibody (aß2GPI) are autoantibodies associated with thromboembolic diseases. Here we investigated whether they are correlated with ischaemic cardiovascular disease in a Chinese population. METHODS: Serum total aCL and aß2GPI isotypes (IgA, IgG or IgM, separately) were measured in 11 015 Chinese adults. Differences of antibody level between disease and non-disease groups were examined by t-test. The correlation between antibody and ischaemic cardiovascular disease was determined by logistic regression analysis. Performance of risk prediction models employed aCL or aß2GPI isotypes was evaluated by C statistic, net reclassification improvement index and integrated discrimination improvement. RESULTS: Total aCL and aß2GPI isotypes maintained low levels and increased with increasing age except total aCL and aß2GPI IgG in participants older than 70 years. When distinguishing ischaemic cardiovascular disease by coronary heart disease (CHD) and ischaemic stroke, the stroke group had higher levels of aCL and aß2GPI isotypes than the non-stroke group, while the CHD group only had a slightly higher aß2GPI IgG than non-CHD groups. aCL and aß2GPI were positively correlated with stroke but not with CHD, and improved the performance of conventional risk factors for stroke risk prediction, with C statistic from 0.769 (95% CI 0.744, 0.793) to 0.777 (95% CI 0.754, 0.800) (aß2GPI IgG, P = 0.0091), and 0.778 (95% CI 0.754, 0.801) (aß2GPI IgA, P = 0.0793). Stroke risk could be better reclassified by aCL and aß2GPI, in association with both net reclassification improvement and integrated discrimination improvement statistics (P < 0.05). CONCLUSION: aCL and aß2GPI are associated with ischaemic stroke and have added value for stroke risk prediction.

Cervical ribs in human early life: morphological variability and first identification as a morbidity criterion in a past population.

Despite the medical literature on supernumerary cervical ribs in extant adult samples, little is known about their development and occurrence in early infancy. The documentation of cervical ribs in modern samples of fetuses and neonates is indeed affected by ethical as well as technical limitations. The aim of the present study was to investigate their frequencies and morphological variability in the first known archaeological collection of very young children with this anatomical variant. The study sample comes from the 8B-51 necropolis on the Saï island (Sudan) and dates to the Classic Kerma Period (XVIIIe-XVIe centuries BC). It consists of 64 individuals deceased between 24 weeks of amenorrhoea and 2 years of age. Bilateral or unilateral cervical ribs were found in 27 individuals. A total of 43 cervical ribs were identified, 38 of which are fully preserved. According to these observations, at least 42% of the individuals have unilateral or bilateral cervical ribs, with an average maximum length of < 1 cm. This frequency is very high compared to those observed in contemporary adult samples (up to 3%). First, the comparison of our results with biological and genetic research demonstrating the link between the occurrence of cervical ribs and a reduced chance of survival during infancy allows the first identification of this trait as an indicator of morbidity in an archaeological collection, a morbidity to which a genetic homogeneity or even endogamy could contribute. Second, the number of ribs studied makes it possible to propose a morphological classification based on the general shape and the shape of the articular facets, classification that can be used tos refine the analyses of the trait in future samples.

Drugs linked to plasma homoarginine in chronic kidney disease patients-a cross-sectional analysis of the German Chronic Kidney Disease cohort.

BACKGROUND: Elevated plasma concentrations of symmetric and asymmetric dimethylarginine (SDMA and ADMA, respectively) and a lower plasma concentration of the structurally related homoarginine are commonly observed in patients with chronic kidney disease (CKD) and independently predict total mortality as well as progression of renal disease. We aimed to identify drugs that may alter this adverse metabolite pattern in a favourable fashion. METHODS: Plasma ADMA, SDMA, homoarginine and l-arginine were determined by liquid chromatography-tandem mass spectrometry in 4756 CKD patients ages 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 and overt proteinuria who were enrolled in the German Chronic Kidney Disease (GCKD) study. Associations between laboratory, clinical and medication data were assessed. RESULTS: Intake of several commonly used drugs was independently associated with plasma concentrations of homoarginine and/or related metabolites. Among these, the peroxisome proliferator-activated receptor alpha (PPAR-α) agonist fenofibrate was associated with the most profound differences in ADMA, SDMA and homoarginine plasma concentrations: 66 patients taking fenofibrate had a multivariable adjusted odds ratio (OR) of 5.83 [95% confidence interval (CI) 2.82-12.03, P < 0.001] to have a plasma homoarginine concentration above the median. The median homoarginine plasma concentration in patients taking fenofibrate was 2.30 µmol/L versus 1.55 in patients not taking the drug (P < 0.001). In addition, fibrates were significantly associated with lower plasma SDMA and higher l-arginine concentrations. In contrast, glucocorticoids were associated with lower plasma homoarginine, with adjusted ORs of 0.52 (95% CI 0.40-0.67, P < 0.001) and 0.53 (95% CI 0.31-0.90, P = 0.018) for prednisolone and methylprednisolone, respectively. CONCLUSIONS: In a large cohort of CKD patients, intake of fenofibrate and glucocorticoids were independently associated with higher and lower plasma homoarginine concentrations, respectively. Effects on plasma homoarginine and methylarginines warrant further investigation as potential mechanisms mediating beneficial or adverse drug effects.

Spatial peak and mean QRS-T angles: A comparison of similar but different emerging risk factors for cardiac death.

BACKGROUND: The spatial peak and mean QRS-T angles are scientifically but not clinically established risk factors for cardiovascular events including cardiac death. The study aims were to compare these angles, assess their association with hypertension (HT) and diabetes mellitus (DM), and explore the relation between the mean QRS-T angle and the ventricular gradient (VG; reflecting electrical heterogeneity), which both are derived from the QRSarea and Tarea vectors. METHODS: Altogether 1094 participants (aged 50-65 years, 550 women) from the pilot of the population-based Swedish CArdioPulmonary bioImage Study with Frank vectorcardiographic recordings were included and divided into 5 subgroups: apparently healthy n = 320; HT n = 311; DM n = 33; DM + HT n = 53; miscellaneous conditions n = 377. Abnormal peak and mean QRS-T angles were defined as >95th percentile. RESULTS: Peak QRS-T angles were generally narrower than the mean QRS-T angles; both were narrower in women than in men. Abnormal peak (>124°) and/or mean (>119°) QRS-T angles were found in 73 participants (6.7%). The concordance regarding abnormal versus normal-borderline QRS-T angles was good (Cohen's kappa 0.61). The prevalence of abnormal angles varied from 2.5% in healthy to 21.2% in DM. There was an inverse logarithmical relation between the mean QRS-T angle and the VG. CONCLUSIONS: The peak and mean QRS-T angles are not interchangeable but complementary. DM, HT, sex and absence of disease are important determinants of both QRS-T angles. The mean QRS-T angle and the VG relationship is complex. All three VCG derived measures reflect related but differing electrophysiological properties and have potential prognostic value vis-à-vis cardiovascular events.