[Analysis for the breast cancer screening among urban population in Hebei province, 2018-2019].

From 2018 to 2019, 3 453 cases of high-risk population were screened by the Cancer Screening Program in Urban China (CanSPUC) in Hebei Province, with the age of (53.94±8.00). 147 and 686 cases of breast cancer positive and suspicious positive patients were found, with the positive rate and suspicious positive rate of 4.26% and 19.87% respectively. The suspicious positive rate of 45-49 years old age group was the highest (28.32%), and the positive rate of over 70 years old age group was the highest (7.32%). The positive detection rate of mammography combined with ultrasound was 5.16%, which was higher than that of ultrasound alone (2.46%) (χ²=30.28,P<0.001) or mammography alone (3.06%) (χ²=14.56,P<0.001).

[Association between brain glucose metabolism and cardiac dysfunction in patients with ischemic heart disease undergoing (18)F-FDG PET/CT imaging].

Objective: To evaluate the relationship between the brain glucose metabolism and left ventricular function parameters, and to explore the cerebral glucose metabolism reduction regions in patients with ischemic heart disease (IHD). Methods: A total of 110 consecutive IHD patients who underwent gated (99)Tc(m)-sestamibi (MIBI) SPECT/CT myocardial perfusion imaging, gated (18)F-fluorodeoxyglucose (FDG) PET/CT myocardial and brain glucose metabolic imaging within three days in Beijing Anzhen Hospital from April 2016 to October 2017, were enrolled in this study. Left ventricular functional parameters of SPECT/CT and PET/CT including end-diastolic volume (EDV), end-systolic volume (ESV) and left ventricular ejection fraction (LVEF) were analyzed by QGS software. Viable myocardium and myocardial infarction region were determined by 17-segment and 5 score system, and the ratio of viable myocardium and scar myocardium was calculated. According to the range of viable myocardium, the patients were divided into viable myocardium<10% group (n=44), viable myocardium 10%-<20% group (n=36) and viable myocardium≥20% group (n=30). Pearson correlation analysis was used to analyze the correlation between the range of viable myocardium and scar myocardium and the level of cerebral glucose metabolism. Brain glucose metabolism determined by the mean of standardized uptake value (SUV(mean)) was analyzed by SPM. The ratio of SUV(mean) in whole brain and SUV(mean) in cerebellum were calculated, namely taget/background ratio (TBR). Differences in cerebral glucose metabolism among various groups were analyzed by SPM. Results: There were 101 males, and age was (57±10) years in this cohort. The extent of viable myocardium and the extent of scar, LVEF evaluated by SPECT/CT and PET/CT were significantly correlated with TBR (r=0.280, r=-0.329, r=0.188, r=0.215 respectively,all P<0.05). TBR value was significantly lower in viable myocardium<10% group, compared with viable myocardium 10%-<20% group (1.25±0.97 vs. 1.32±0.17, P<0.05) and viable myocardium≥20% group (1.25±0.97 vs. 1.34±0.16, P<0.05). Furthermore, in comparison with viable myocardium≥20% group, the hypo-metabolic regions of viable myocardium<10% group were located in the precuneus, frontal lobe, postcentral gyrus, parietal lobe, temporal lobe, and so on. Conclusions: There is a correlation between impaired left ventricular function and brain glucose metabolism in IHD patients. In IHD patients with low myocardial viability, the level of glucose metabolism in the whole brain is decreased, especially in the brain functional areas related to cognitive function.

Genome-wide identification and comparison of mRNAs, lncRNAs and circRNAs in porcine intramuscular, subcutaneous, retroperitoneal and mesenteric adipose tissues.

Many types of RNAs, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play crucial roles in regulating fat cell differentiation and tissue development. However, the expression profiles of these RNAs in different adipose tissues are still largely unknown. To shed light on this issue, we performed a transcriptome analysis of mRNAs, lncRNAs and circRNAs obtained from intramuscular adipose tissue, subcutaneous adipose tissue, retroperitoneal adipose tissue and mesenteric adipose tissue of Chinese Erhualian pigs. A number of differentially expressed mRNAs, lncRNAs and circRNAs were identified among the four adipose tissues. Tissue-specific analysis indicated that circRNAs exhibited the highest tissue specificity among mRNAs, lncRNAs and circRNAs, whereas intramuscular adipose tissue had the most tissue-specific genes among the four adipose tissues. Gene Ontology analysis showed that differentially expressed mRNAs among groups were involved mainly in lipid metabolism and immune inflammatory response processes. Furthermore, the co-expression network construction of mRNAs-lncRNAs revealed that several important lncRNAs, such as MSTRG.426159 and MSTRG.604206, might associate with lipid metabolic process. Taken together, these data provide a genome-wide resource of mRNAs, lncRNAs and circRNAs potentially involved in porcine fat metabolism, thus improving understanding of their function in diverse adipose tissues.

[Differences of brain functional alterations between subtypes of Cushing's syndrome patients].

Objective: To compare the differences of brain functional damage of subtypes of patients with Cushing's syndrome (CS). Methods: A total of 11 adrenocorticotropic hormone (ACTH)-dependent CS patients and 29 ACTH-independent CS patients were recruited from Chinese PLA General Hospital between September 2015 and March 2017 with confirmed CS. The psychiatric scales and brain task functional magnetic resonance imaging (fMRI) were evaluated. Results: A total of 40 patients (34 females, 6 males) with a mean age of (39.20±12.10) years and a median education level of 12 (9, 16) years were enrolled. ACTH-dependent patients had significantly worse performance than the ACTH-independent patients in response to the depression evaluation (64.6±6.1 vs 56.2±12.8, P=0.008), positive emotion (17.8±4.2 vs 24.3±7.2, P=0.008) and CS life quality [31(29,33) vs 42(29,51), P=0.040]. In the reaction to positive target pictures, ACTH-dependent CS patients showed stronger activation in left superior temporal gyrus compared with patients in ACTH-independent group, while the activation degree of their bilateral dorsal anterior cingulate cortex, bilateralsuperior frontal gyrus and left middle frontal gyrus was much worse. In the reactions to negative target pictures, ACTH-dependent CS patients had weaker activation in bilateral cerebellum, left superior frontal gyrus, left middle frontal gyrus, left precuneus and right postcentral gyrus, compared with patients in the ACTH-independent CS group (P<0.01, AlphaSim corrected). The activation degree of some regions whose brain function was different between the two groups was correlated to the cortisol level, ACTH level, 24 h urinary free cortisol (UFC) level, depression evaluation and negative emotion assessment (all P<0.05). Conclusions: The severity of the depression and the life quality of patients in ACTH-dependent group are worse than ACTH-independent CS patients. The brain function of ACTH-dependent CS patients is much weaker.

Resting-state brain alteration after a single dose of SSRI administration predicts 8-week remission of patients with major depressive disorder.

BACKGROUND: The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment. METHOD: Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement. RESULTS: Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint. CONCLUSIONS: This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.

MAGE-A is frequently expressed in triple negative breast cancer and associated with epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor metastasis. Triple negative (TN) breast cancer, a high metastasis phenotype, has been verified to be associated with EMT. Melanoma associated antigen-A (MAGE-A) is exclusively expressed in cancers with high aggressiveness as well as unfavorable prognosis and likely to be associated with EMT of triple negative breast cancer (TNBC). The aim of the study is to analyze the expression profile of MAGE-A in breast cancer and the correlation between MAGE-A and EMT of TNBC. Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and ß-catenin in breast cancer tissues and correlate them with clinical pathological parameters. The association between MAGE-A and EMT markers was also evaluated. Scratch assay and transwell invasion assay were carried out to evaluate the impact of MAGE-A down-regulation on migration and invasion of the breast cancer cells. Real-time PCR was also conducted to evaluate alterations in EMT markers with decrease in MAGE-A. The results showed that MAGE-A was absent in normal tissue but expressed in tumor samples with the incidence of 49.17% (P=0.008). MAGE-A staining was higher in TNBC (76.47%, 13/17), followed by HER-2(+) (53.85%, 7/13) and Luminal set (43.33%, 39/90), and it was significantly correlated with ER (-), PR (-), HER-2 (-), lymph nodes involvement and higher histological grade (P<0.05). E-cadherin-positivity was frequent in Luminal set (94.44%, 85/90) and linked to ER (+), negative lymph nodes and lower histological grade (P<0.05). Vimentin expression was often observed in TNBC (70.56%, 12/17) and ER (-), PR (-), lymph nodes (+) groups (P<0.05). Expression of ß-catenin was prevalent in Luminal set (93.33%, 84/90) and correlated with ER (+), PR (+) and lower histological grade (P<0.05). MAGE-A was inversely associated with E-cadherin (P=0.011) and ß-catenin (P=0.048) but expressed in the same trend with vimentin (P=0.000). Migration and invasion of MDA-MB-231 were inhibited when MAGE-A decreased. Increase in epithelial markers and decline in mesenchymal indicators were also seen with MAGE-A reduction. Snail, Slug, ZEB1 and ZEB2 were also down-regulated. In conclusion, MAGE-A may be responsible for high aggressiveness and EMT of TNBC and can be a new choice for targeted therapy.

[Expression of DNA mismatch repair protein in endometrial carcinomas and its correlation with clinicopathologic features].

OBJECTIVE: To study the expression of mismatch repair protein in a series of endometrial carcinomas and its correlation with clinicopathologic features. METHODS: The clinical data of 150 consecutive cases of endometrial carcinoma were collected during the period from December, 2014 to August, 2015 in Fudan University Cancer Center. Morphologic features including tumor infiltrating lymphocytes (TIL), peritumoral lymphocytes and tumor heterogeneity were reviewed. Immunohistochemistry for expression of mismatch repair proteins was performed. The correlation with clinicopathologic features was analyzed. RESULTS: Loss of mismatch repair protein expression was observed in 43 cases (28.7%), including loss of MLH1/PMS2 in 27 cases (18%), loss of MSH2/MSH6 in 7 cases (4.7%), loss of MSH6 in 6 cases (4%) and loss of PMS2 in 3 cases (2%). There were 23.3% and 27.1% of mismatch repair protein-deficient endometrial carcinomas in women under and above 50 years of age, respectively, which was not statistically significant. Amongst the 12 cases with family history of tumors, 4 of the 6 mismatch repair protein-deficient cases were under 50 years of age, which was higher than that in the 6 cases with mismatch repair protein expression (P=0.014). The mismatch repair protein-deficient group showed significantly more prominent TIL and peritumoral lymphocytes than protein-expression group (P=0.033 and <0.001). Moreover, there were also significant differences in depth of myometrial invasion and occurrence of synchronous malignancy (2 cases of ovarian clear cell carcinoma and 1 case of colonic carcinoma) between the two groups (P=0.039 and 0.022). However, there were no significant differences in lymph node metastasis, tumor heterogeneity, lower uterine segment involvement and tumor stage between the two groups. CONCLUSIONS: Prominent TIL and peritumoral lymphocytes characteristically occur in mismatch repair protein-deficient endometrial carcinomas. Patient age does not significantly correlate with the loss of mismatch repair protein expression, but individuals under 50 years of age are more likely to have no expression if there is family history of tumors.

Total hip replacement: a systematic review and meta-analysis on mid-term quality of life.

OBJECTIVE: Total hip replacement (THR) is one of the most successful and frequently performed operations worldwide. Health-related quality of life (HRQOL) is a key outcome measure of surgery. We investigated mid-term HRQOL after THR in patients with osteoarthritis (OA). DESIGN: A systematic review of clinical studies published after January 2000 was performed using strict eligibility criteria. Quality appraisal and data tabulation were performed using pre-determined forms. Data were synthesised by narrative review and random-effects meta-analysis using standardised response means. Tau(2) and I(2) values and Funnel plots were analysed. RESULTS: 20 studies were included. Mid-term post-operative HRQOL is superior compared to pre-operative status on qualitative and quantitative analysis. Pooled response means of total Harris Hip Score (HHS) (P < 0.00001) and combined pain (P = 0.00001) and physical function (P < 0.00001) domains of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and HHS improved markedly up to 7 years. Medical Outcomes Survey Short Form 36 shows physical functioning (PF) (P < 0.00001), bodily pain (BP) (P < 0.00001), role physical (P = 0.001), role emotional (P = 0.04), and social functioning (SF) (P = 0.03) were improved up to 7 years. General health (GH) (P = 0.29), mental health (MH) (P = 0.43), and vitality (P = 0.17) was similar. HRQOL is at least as good as reference populations in the first few years and subsequently plateaus or declines. Patient satisfaction and functional status was favourable. There was significant heterogeneity amongst all studies, but publication bias was low in pooled analysis. CONCLUSION: THR confers significant mid-term HRQOL benefits across a broad range of health domains. Further studies based on consistent guidelines provided in this review are required.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

Introduction: This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Curcumin acts anti-proliferative and pro-apoptotic in human meningiomas.

Meningiomas, the most frequent benign intracranial and intraspinal types of tumors are normally removed by surgery. Complications can occur when the tumor is critically localized and cannot be completely removed or when comorbidities of the mostly elder patients increase the general surgical risk. Thus, alternate medical treatment concepts for the therapy of meningiomas would be desirable. Curcumin, the active ingredient of the spice plant Curcuma longa has shown anti-tumorigenic actions in many different types of tumors and therefore, its effect on growth and apoptosis of meningioma cells was studied in the present paper. In vitro, treatment of the human Ben-Men-1 meningioma cell line and of a series of 21 primary human meningioma cell cultures with curcumin (1-20 µM) strongly reduced the proliferation in all cases in a dose dependent manner. Cell cycle analysis by fluorescence-activated cell sorting showed growth arrest at G2/M phase, which was confirmed by demonstrating the corresponding modulation of proteins involved in G2/M arrest by immunoblotting and/or confocal laser microscopy. High dosages (20, 50 µM) of curcumin induced a significant increase of apoptosis in Ben-Men-1 and primary meningioma cell cultures as demonstrated by morphological changes of cell nuclei, DNA fragmentation, translocation of cell membrane associated phosphatidyl serine and the induction of apoptotic-acting cleaved caspase-3. Our results suggest that the multi-targeting drug curcumin has potent anti-tumorigenic actions in meningioma cells and might therefore be a putative candidate for the pharmacological treatment of meningiomas.

An efficient multi-level pre-processing algorithm for the enhancement of dermoscopy images in melanoma detection.

In this paper, a multi-level algorithm for pre-processing of dermoscopy images is proposed, which helps in improving the quality of the raw images, making it suitable for skin lesion detection. This multi-level pre-processing method has a positive impact on automated skin lesion segmentation using Regularized Extreme Learning Machine. Raw images are subjected to de-noising, illumination correction, contrast enhancement, sharpening, reflection removal, and virtual shaving before the skin lesion segmentation. The Non-Local Means (NLM) filter with lowest Blind Reference less Image Spatial Quality Evaluator (BRISQUE) score exhibits better de-noising of dermoscopy images. To suppress uneven illumination, gamma correction is subjected to the denoised image. The Robust Image Contrast Enhancement (RICE) algorithm is used for contrast enhancement, and produces enhanced images with better structural preservation and negligible loss of information. Unsharp masking for sharpening exhibits low BRISQUE scores for better sharpening of fine details in an image. Output images produced by the phase congruency-based method in virtual shaving show high similarity with ground truth images as the hair is removed completely from the input images. Obtained scores at each stage of pre-processing framework show that the performance is superior compared to all the existing methods, both qualitatively and quantitatively, in terms of uniform contrast, preservation of information content, removal of undesired information, and elimination of artifacts in melanoma images. The output of the proposed system is assessed qualitatively and quantitatively with and without pre-processing of dermoscopy images. From the overall evaluation results, it is found that the segmentation of skin lesion is more efficient using Regularized Extreme Learning Machine if the multi-level pre-processing steps are used in proper sequence.

Electroretinographic findings in retinal vasculitis.

AIM: To describe and correlate electroretinographic responses with clinical and angiographic findings in retinal vasculitis (RV). METHODS: Medical records of patients with diagnosis of RV at a tertiary eye centre from December 2017 to May 2021 were reviewed. Cases in which fluorescein angiography (FFA) and full field electroretinography (ffERG) were done within 1 month were included. FFAs were graded according to the Angiography Scoring for Uveitis Working Group from 0 to 40, where 0 is normal. A novel ffERG grading system was implemented where individual waves were graded for timing and amplitude and general ffERG score was determined with 6 being a perfect score. RESULTS: 20 patients (34 eyes) were included. Mean age was 43.9±19.8 years; 70% were female. Median best-corrected visual acuity was 0.8 (0.08-1). Mean FFA score was 12.6±6.5. Median general ffERG score was 5 (0-6). 68% and 91% of eyes had responses with general ffERG scores ≥5 and 4, respectively. Flicker timing was most commonly affected.FFA scores weakly correlated with delayed photopic cone b-wave and flicker timing (p=0.03 and 0.016, respectively). Vitreous haze moderately correlated with delayed cone b-wave timing (p<0.001), delayed flicker timing (p=0.002) and weakly correlated with lower flicker amplitude (p=0.03). Underlying systemic disease was associated with poor ffERG responses. CONCLUSION: In this study, RV was not frequently associated with severe global retinal dysfunction Higher FFA scores, and vitreous haze grading were weakly, but significantly, correlated with cone-generated ffERG responses.

RNA interference-mediated silencing of Stat5 induces apoptosis and growth suppression of hepatocellular carcinoma cells.

It has been reported that Stat5 is overexpressed in a variety of human cancer cell lines and primary tumors. Inhibition of Stat5 in tumor cell lines has been associated with growth suppression and induction of apoptosis. However, no one of published studies have investigated the expression and role of Stat5 in hepatocellular carcinoma. In this study, we used human hepatocellular carcinoma cell line SMMC7721 as a model to demonstrate that Stat5 was highly expressed in these cells. Next we showed that RNAi mediated Stat5 knockdown could inhibit the proliferation and induce the apoptosis of SMMC7721 cells in vitro. Furthermore, we demonstrated that Stat5 knockdown inhibited the growth and induced the apoptosis of SMMC7721 cells in xenografts in nude mice. Taken together, our in vitro and in vivo data suggest that Stat5 plays an important role in human hepatocellular carcinoma. Inhibition of Stat5 by RNAi holds promise to be a novel gene therapy vector for hepatocellular carcinoma.

Hybrid multi-kernel SVM algorithm for detection of microaneurysm in color fundus images.

Diabetic retinopathy (DR) is a chronic disease that may cause vision loss in diabetic patients. Microaneurysms which are characterized by small red spots on the retina due to fluid or blood leakage from the weak capillary wall often occur during the early stage of DR, making screening at this stage is essential. In this paper, an automatic screening system for early detection of DR in retinal images is developed using a combined shape and texture features. Due to minimum number of hand-crafted features, the computational burden is much reduced. The proposed hybrid multi-kernel support vector machine classifier is constructed by learning a kernel model formed as a combination of the base kernels. This approach outperforms the recent deep learning techniques in terms of the evaluation metrics. The efficiency of the proposed scheme is experimentally validated on three public datasets - Retinopathy Online Challenge, DIARETdB1, MESSIDOR, and AGAR300 (developed for this study). Studies reveal that the proposed model produced the best results of 0.503 in ROC dataset, 0.481 in DIARETdB1, and 0.464 in the MESSIDOR dataset in terms of FROC score. The AGAR300 database outperforms the existing MA detection algorithm in terms of FROC, AUC, F1 score, precision, sensitivity, and specificity which guarantees the robustness of this system.

Polymorphisms of transforming growth factor-ß1 associated with increased risk of gastric cardia adenocarcinoma in north China.

Transforming growth factor beta 1 (TGF-ß1) is a multifunctional cytokine that has been implicated in the oncogenesis and tumour progression. However, the association of TGF-ß1 polymorphism with gastric cardia adenocarcinoma (GCA) remains unclear. The aim of the study was to investigate the possible association of the polymorphisms of TGF-ß1 with susceptibility to GCA in a population of north China. A case-control analysis was performed to assess the association of six single nucleotide polymorphisms (SNPs) of TGF-ß1 and GCA risk. The genotype and allele distributions of TGF-ß1 G-800A, C-988A, G915C and C788T in GCA patients were not significantly different from that in healthy controls (P>0.05). The -509T and 869C allele significantly elevated the risk of developing GCA (adjusted OR=1.45 and 1.41; 95% CI=1.04-2.10 and 1.07-2.08, respectively). The CT and TT genotype of C-509T and the TC and CC genotype of T869C significantly elevated the risk of developing GCA. When stratified by tumour stage, the -509T and 869C allele carriers had an increased risk of TNM stage III+IV GCA as compared with noncarriers. The C-509T and T869C SNP are in a strong linkage disequilibrium (D'=0.94). Compared with C/T haplotype, T/C haplotype significantly increased the risk of developing GCA. The TGF-ß1 level and expression were higher in GCA patients with -509T or 869C allele than in those without T or C allele (P<0.05). GCA patients with -509TT and 869CC genotype had higher apoptotic tumour-infiltrating lymphocytes in their cancer tissues than those with -509CC and 869TT genotype. In all, TGF-ß1 C-509T and T869C polymorphisms may be associated with an increased risk of GCA in north China.

Cardiovascular Risk Prediction using JBS3 Tool: A Kerala based Study.

BACKGROUND: Accuracy of Joint British Society calculator3 (JBS3) cardiovascular (CV) risk assessment tool may vary across the Indian states, which is not verified in south Indian, Kerala based population. OBJECTIVES: To evaluate the traditional risk factors (TRFs) based CV risk estimation done in Kerala based population. METHODS: This cross-sectional study uses details of 977 subjects aged between 30 and 80 years, recorded from the medical archives of clinical locations at Ernakulum district, in Kerala. The risk categories used are Low (<7.5%), Intermediate (≥7.5% and <20%), and High (≥20%) 10-year risk classifications. The lifetime classifications are Low lifetime (≤39%) and High lifetime (≥40%) are used. The study evaluated using statistical analysis; the Chi-square test was used for dependent and categorical CV risk variable comparisons. A multivariate ordinal logistic regression analysis for the 10-year risk and odds logistic regression analysis for the lifetime risk model identified the significant risk variables. RESULTS: The mean age of the study population is 52.56±11.43 years. With 39.1% in low, 25.0% in intermediate, and 35.9% has high 10-year risk. Low lifetime risk with 41.1%, the high lifetime risk has 58.9% subjects. The intermediate 10-year risk category shows the highest reclassifications to High lifetime risk. The Hosmer-Lemeshow goodness-of-fit statistics indicates a good model fit. CONCLUSION: Timely interventions using risk predictions can aid in appropriate therapeutic and lifestyle modifications useful for primary prevention. Precaution to avoid short-term incidences and reclassifications to a high lifetime risk can reduce the CVD related mortality rates.

Relative Estimate of Revised Cardiovascular Risk Combining Traditional and Non-traditional Image-based CV Markers: A Kerala Based Study.

BACKGROUND: Non-traditional image markers can improve the traditional cardiovascular risk estimation, is untested in Kerala based participants. OBJECTIVE: To identify the relationship between the 'Modified CV risk' categories with traditional and non-traditional image-based risk markers. The correlation and improvement in reclassification, achieved by pooling atherosclerotic non-traditional markers with Intermediate (≥7.5% and <20%) and High (≥20%) 10-year participants is evaluated. METHODS: The cross-sectional study with 594 participants has the ultrasound measurements recorded from the medical archives of clinical locations at Ernakulum district, Kerala. With carotid Intima-Media Thickness (cIMT) measurement, the Plaque (cP) complexity was computed using selected plaque characteristics to compute the carotid Total Plaque Risk Score (cTPRS) for superior risk tagging. Statistical analysis was done using RStudio, the classification accuracy was verified using the decision tree algorithm. RESULTS: The mean age of the participants was (58.14±10.05) years. The mean cIMT was (0.956±0.302) mm, with 65.6% plaque incidence. With 94.90% variability around its mean, the Multinomial Logistic Regression model identifies cIMT and cTPRS, age, diabetics, Familial Hypercholesterolemia (FH), Hypertension treatment, the presence of Rheumatoid Arthritis (RA), Chronic Kidney Disease (CKD) as significant (p<0.05). cIMT and cP were found significant for 'Intermediate High', 'High' and 'Very High' 'Modified CV risk' categories. However, age, diabetes, gender and use of hypertension treatment are significant for the 'Intermediate' 'Modified CV risk' category. The overall performance of the MLR model was 80.5%. The classification accuracy verified using the decision tree algorithm has 78.7% accuracy. CONCLUSION: The use of atherosclerotic markers shows a significant correlation suitable for a nextlevel reclassification of the traditional CV risk.

Identification of a nuclear receptor for bile acids.

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.

Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers.

Several nuclear hormone receptors involved in lipid metabolism form obligate heterodimers with retinoid X receptors (RXRs) and are activated by RXR agonists such as rexinoids. Animals treated with rexinoids exhibited marked changes in cholesterol balance, including inhibition of cholesterol absorption and repressed bile acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR heterodimeric partners that mediate these effects by regulating expression of the reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid synthesis, CYP7A1, respectively. Thus, these RXR heterodimers serve as key regulators of cholesterol homeostasis by governing reverse cholesterol transport from peripheral tissues, bile acid synthesis in liver, and cholesterol absorption in intestine.