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Obesity affects 600 million people globally and increases the risk of developing cardiovascular disease, stroke, diabetes, and cancer. Bariatric surgery is an increasingly popular therapeutic intervention for morbid obesity to induce rapid weight loss and reduce obesity-related comorbidities. However, some bariatric surgery patients, after what is considered a successful surgical procedure, continue to manifest obesity-related health issues, including weight gain, reduced physical function, persistent elevations in blood pressure, and reduced cardiorespiratory fitness. Cardiorespiratory fitness is a strong predictor of mortality and several health outcomes and could be improved by an appropriate exercise prescription after bariatric surgery. This review provides a broad overview of exercise training for patients after bariatric surgery and discusses cardiorespiratory fitness and other potential physiological adaptations in response to exercise training.

Artificial intelligence (AI), in particular deep learning, has proven to be efficient in medical diagnosis. This paper introduces a new hybrid deep learning model for pneumonia diagnosis based on chest CT scans. At the core of the model, a Gaussian mixture is combined with the expectation-maximization algorithm (EMGMM) to extract the regions of interest (ROI), while a convolutional denoising autoencoder (DAE) and deep restricted Boltzmann machine (DRBM) are combined for the classification. In order to prevent the model from learning trivial solutions, stochastic noises were added as an input to the unsupervised learning phase. The dataset used in this work is a publicly available dataset of chest X-rays for pneumonia on the Kaggle website; it contains 5856 images with 1583 normal cases and 4273 pneumonia cases, with an imbalance ratio (IR) of 0.46. Several operations including zooming, flipping, shifting and rotation were used in the augmentation phase to balance the data distribution across the different classes, which led to enhancing the IR value to 0.028. The computational analysis of the results show that the proposed model is promising as it provides an average accuracy value of 98.63%, sensitivity value of 96.5%, and specificity value of 94.8%.

CD147 is a glycoprotein that stimulates the production of matrix metalloproteinases (MMPs), known contributors to cardiovascular risk. The activity of CD147 protein depends on its glycosylation. However, it is unclear whether CD147 protein expression or glycosylation are influenced by the diabetic milieu characterized by hyperglycemia and abundant glycation-end-products (AGEs). We examined the circulating and visceral adipose tissue (VAT) levels of CD147 and their correlation with vascular function in obese, obese diabetic, and non-obese controls (n = 40, each). The circulating levels of CD147 and the glycosylated CD147 protein in VAT were considerably higher in obese, particularly obese diabetic subjects compared to controls. Obese diabetics had the lowest brachial and arteriolar vasoreactivity and the highest carotid pulse-wave velocity (PWV, a measure of arterial stiffness) among the three groups. CD147 correlated positively with body mass index (BMI), total and visceral fat mass, PWV, and plasma levels of glucose, insulin, MMPs, and AGEs and negatively with brachial artery and VAT-arteriolar vasoreactivity and nitric oxide production. Multivariate regression revealed that BMI, body fat mass, insulin, and glucose levels significantly predicted CD147. Our data suggest that higher levels of CD147 in obese subjects, particularly those with diabetes, are linked to vascular dysfunction and several cardiometabolic risk factors.

Accurate discrimination of images features is a main success factor towards efficient content-based image retrieval systems. These features can be extracted using local and/or global descriptors. Researchers efforts showed that, hybrid descriptors reported superior results compared to methods that use single descriptor, where hybridization certainly complements benefits from different perspectives. Genetic Algorithm (GA) is a heuristic computational intelligence approach that can be used to achieve the optimal satisfactory user image retrieval requests. In this paper, a new hybrid efficient and effective evolutionary retrieval approach (CBIR-GAF) based on late fusion of four global descriptors is proposed. Each descriptor produces a list of retrieved similar images to user query image and if these lists are merged correctly by late fusion, the results are improved. Thus, GA occurs to assign different weights to each retrieved image while merging, and then it optimizes these weights with a suitable fitness function to select optimum heterogeneous retrieved images. The proposed approach is evaluated on two benchmark datasets (Inria Holidays and Oxford5k), and reported a promising results where it enhanced the average accuracy in comparison of literature techniques.

Deep Learning approach dragged the full attention of researcher in medical images due to their superior literature reported success and promising directions. Concluding the most discriminative set of features greatly represents a valuable guide for achieving the satisfaction performance of a medical diagnosing system. Despite, many methods proposed for such objective, the restricted Boltzmann machines outperform as they learn features directly from data, however they lack the optimal classification performance due to data complexity. Additionally, the contractive au-toencoder offers regularized term that explicitly increases the robustness of features representation and enhancement in overall performance. This paper proposes a novel deep learning framework for diagnosing female brain disorder from fMRI scans. The configuration combines the contractive autoencoder and the discriminative restricted Boltz-mann machine (DRBM) as we seek an improvement for the classification of fMRI. The demonstrated effectiveness of the contractive autoencoder supports fitting the probability distribution model of the DRBM and transfer learning to a deeper level. Our experimental indicates that the proposed model is able to detect female brain disorder with an accuracy of 88.17% and improved literature reported results on common issues.

Background: Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147) is a transmembrane glycoprotein that stimulates the production of matrix metalloproteinases (MMPs). These MMPs mediate vascular remodeling and are considered biomarkers for cardiovascular risk. The activity of CD147 depends mainly on its glycosylation, which varies significantly among different conditions. However, it is unclear if CD147 glycosylation or its role in MMP upregulation is influenced by the diabetic milieu characterized by high glucose levels and abundant glycation end products (AGEs). In this study, we sought to investigate the differential expression and glycosylation levels of CD147 in obese, diabetic (OB-T2D) individuals compared to non-OB controls. Methods: Blood and adipose tissue (AT) samples were obtained from OB-T2D individuals and controls (n=40, each). DEXA scanning was used for body composition analyses. Flow-induced dilation (FID) was assessed in vivo in the brachial artery and ex vivo in AT-isolated arterioles. Other cardiometabolic risk factors related to glucose and lipid metabolism and systemic inflammation were measured. Results: Circulating CD147 was considerably greater in OB individuals, mirroring the glycosylated CD147 and the N-acetylglucosaminyltransferase, MGAT5 protein levels in the AT. Within the OB-T2D group, AT and circulating CD147 correlated with higher body mass index, total and visceral fat percentage, fasting plasma glucose and insulin, insulin resistance measurement (HOMA-IR), glycosylated hemoglobin, systolic BP, and plasma levels of MMP2/9, AGEs (Carboxymethyl lysine and methyl-glyoxal-lysine dimer), C-reactive protein, interleukin 6, and tumor necrosis factor-alpha. AT-arteriolar FID was significantly lower in the OB-T2D individuals across all pressure gradients, while carotid pulse wave velocity (PWV) was higher, indicating arterial stiffness. CD147 correlated negatively with brachial artery and AT-arteriolar FID and flow-induced nitric oxide production and positively with PWV. Conclusion: Our findings imply that vascular dysfunction in OB-T2D patients is linked to higher levels of CD147 and its glycosylated fraction, which in turn is associated with other cardiometabolic risk factors.

A large percentage of obese patients in the United States suffer a comorbid substance use disorder, mainly alcohol use. Alcohol consumption interferes with the absorption of dietary methyl donors such as folate required for the one-carbon metabolism pathway and subsequently for DNA methylation. In this study, we assessed the association between alcohol consumption and DNA methylation in obese subjects. We obtained visceral adipose tissue (VAT) biopsies from bariatric patients. DNA methylation of 94 genes implicated in inflammation and immunity were analyzed in VAT in relation to alcohol consumption data obtained via questionnaires. Vasoreactivity was measured in the brachial artery and the VAT-isolated arterioles. Pro-inflammatory genes were significantly hypomethylated in the heavy drinking category correlating with higher levels of circulating inflammatory cytokines. Alcohol consumption correlated positively with body mass index (BMI), fat percentage, insulin resistance, impaired lipid profile, and systemic inflammation and negatively with plasma folate and vitamin B12, inflammatory gene DNA methylation, and vasoreactivity. In conclusion, these data suggest that alcohol intake is associated with lower DNA methylation and higher inflammation and cardiometabolic risk in obese individuals.

Efficient methods that enable high and rapid image retrieval are continuously needed, especially with the large mass of images that are generated from different sectors and domains like business, communication media, and entertainment. Recently, deep neural networks are extensively proved higher-performing models compared to other traditional models. Besides, combining hashing methods with a deep learning architecture improves the image retrieval time and accuracy. In this paper, we propose a novel image retrieval method that employs locality-sensitive hashing with convolutional neural networks (CNN) to extract different types of features from different model layers. The aim of this hybrid framework is focusing on both the high-level information that provides semantic content and the low-level information that provides visual content of the images. Hash tables are constructed from the extracted features and trained to achieve fast image retrieval. To verify the effectiveness of the proposed framework, a variety of experiments and computational performance analysis are carried out on the CIFRA-10 and NUS-WIDE datasets. The experimental results show that the proposed method surpasses most existing hash-based image retrieval methods.

Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.

Obesity is a major risk factor for cardiovascular disease. We previously demonstrated impaired vascular function that correlated with global DNA hypomethylation in adipose tissue (AT) isolated from obese adults (OB). Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers and stand as an unexploited precision medicine reserve. Hypothesis: We hypothesized a contributing role of DNA methylation to systemic inflammation in OB subjects compared to lean controls (CON). We also explored the correlation between these methylation profiles and cardiometabolic measurements. Methods: We obtained blood and AT samples from bariatric patients (n=24; age: 36±7 yrs; BMI: 50.7±8.7 kg/m2) and CON adults (n=24; age: 36±2 yrs; BMI: 25.8±1 kg/m2). AT-isolated arterioles were tested for flow-induced dilation (FID), nitric oxide (NO) and reactive oxygen species (ROS) production. Brachial artery flow-mediated dilation (FMD) was measured via Doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity (EpiTect Methyl II PCR Arrays) were analyzed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. Results: 70% of genes had a higher methylated fraction in CON compare to only 28% in OB subjects. After correction for multiple testing, 28 genes were significantly hypermethylated in CON compared to OB; on top of these genes are CXCL1, CXCL12, CXCL6, EGR1, HDAC4, IGF2BP2, IL12A, IL12B, and IL17RA. Ten of these genes had significantly higher mRNA in OB compared to CON indicating the functional impact of such signals on gene transcription; on top of these genes are CXCL6, TLR5, IL6ST, IL15RA, and HDAC4. Methylation % of differentially methylated genes inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and CRP (C-reactive protein), arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Conclusions: Our results suggest that vascular dysfunction in OB adults may be attributed to aberrant DNA methylation. A downstream target for this pathway could reside in endothelial cells resulting in vascular dysfunction

Obesity is a major risk factor for cardiovascular disease. We previously demonstrated an impaired vascular function in obese adults (OB). We now hypothesize a role of obesity-associated hypoxia in disturbing the methylation of genes involved in inflammation and vascular dysfunction and propose a mediating role of the hypoxia-inducible factor, HIF1α and the DNA hydroxymethylase, TET1. Methods: We obtained subcutaneous and visceral adipose tissue (AT) biopsies from bariatric patients (n=60; age: 36±7 yrs; BMI: 50.7±8.7 kg/m2) and non-obese (NOB) adults having elective surgeries (n=36; age: 36±2 yrs; BMI: 25.8±1 kg/m2). AT-isolated arterioles were tested for vasoreactivity in response to increasing pressure gradients. Arteriolar nitric oxide (NO) and reactive oxygen species (ROS) were measured. Protein expression of HIF1α and TET1 and promoter methylation/gene expression of leptin, IL1β, IL6, IL8, IL17, CXCL5, TNF-α, and IFNɣ were measured in the AT biopsy. Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Results: Flow-induced dilation (FID) was 40-50% higher in NOB than OB adults across all pressure gradients (p Conclusion: Our results suggest that vascular dysfunction in OB adults may be attributed to aberrant DNA methylation and increased expression of adipocytokines in the hypoxic AT. A downstream target for this pathway could reside in endothelial cells of nearby arterioles and remote arteries resulting in vascular dysfunction. Disclosure M.M. Ali: None. C. Hassan: None. M. Masrur: None. F. Bianco: Consultant; Self; Intuitive, Medtronic. S.A. Phillips: None. A.M. Mahmoud: None. Funding National Institutes of Health (4R00HL140049, 031K99, HL14004901)

Obesity impairs both macro- and microvascular endothelial function due to decreased bioavailability of nitric oxide. Current evidence on the effect of low-carbohydrate (LC) diet on endothelial function is conflicting and confounded by the provision of caloric restriction (CR). We tested the hypothesis that LC without CR diet, but not LC with CR diet, would improve macro- and microvascular endothelial function in women with obesity. Twenty-one healthy women with obesity (age: 33 &plusmn, 2 years, body mass index: 33.0 &plusmn, 0.6 kg/m2, mean &plusmn, SEM) were randomly assigned to receive either a LC diet (~10% carbohydrate calories) with CR (n = 12, 500 calorie/day deficit) or a LC diet without CR (n = 9) and completed the 6-week diet intervention. After the intervention, macrovascular endothelial function, measured as brachial artery flow-mediated dilation did not change (7.3 &plusmn, 0.9% to 8.0 &plusmn, 1.1%, p = 0.7). On the other hand, following the LC diet intervention, regardless of CR, blocking nitric oxide production decreased microvascular endothelial function, measured by arteriolar flow-induced dilation (p &le, 0.02 for both diets) and the magnitude was more than baseline (p &le, 0.04). These data suggest improved NO contributions following the intervention. In conclusion, a 6-week LC diet, regardless of CR, may improve microvascular, but not macrovascular endothelial function, via increasing bioavailability of nitric oxide in women with obesity.

There is a high prevalence of hyperhomocysteinemia that has been linked to high cardiovascular risk in obese individuals and could be attributed to poor nutritional status of folate and vitamin B12. We sought to examine the association between blood homocysteine (Hcy) folate, and vitamin B12 levels and vascular dysfunction in morbidly obese adults using novel ex vivo flow-induced dilation (FID) measurements of isolated adipose tissue arterioles. Brachial artery flow-mediated dilation (FMD) was also measured. Subcutaneous and visceral adipose tissue biopsies were obtained from morbidly obese individuals and non-obese controls. Resistance arterioles were isolated in which FID, acetylcholine-induced dilation (AChID), and nitric oxide (NO) production were measured in the absence or presence of the NO synthase inhibitor, L-NAME, Hcy, or the superoxide dismutase mimetic, TEMPOL. Our results demonstrated that plasma Hcy concentrations were significantly higher, while folate, vitamin B12, and NO were significantly lower in obese subjects compared to controls. Hcy concentrations correlated positively with BMI, fat %, and insulin levels but not with folate or vitamin B12. Brachial and arteriolar vasodilation were lower in obese subjects, positively correlated with folate and vitamin B12, and inversely correlated with Hcy. Arteriolar NO measurements and sensitivity to L-NAME were lower in obese subjects compared to controls. Finally, Hcy incubation reduced arteriolar FID and NO sensitivity, an effect that was abolished by TEMPOL. In conclusion, these data suggest that high concentrations of plasma Hcy and low concentrations of folate and vitamin B12 could be independent predictors of vascular dysfunction in morbidly obese individuals.

A successful intelligent control of patient food for treatment purpose must combines patient interesting food list and doctors efficient treatment food list. Actually, many rural communities in Sudan have extremely limited access to diabetic diet centers. People travel long distances to clinics or medical facilities, and there is a shortage of medical experts in most of these facilities. This results in slow service, and patients end up waiting long hours without receiving any attention. Hence diabetic diet expert systems can play a significant role in such cases where medical experts are not readily available. This paper presents the design and implementation of an intelligent medical expert system for diabetes diet that intended to be used in Sudan. The development of the proposed expert system went through a number of stages such problem and need identification, requirements analysis, knowledge acquisition, formalization, design and implementation. Visual prolog was used for designing the graphical user interface and the implementation of the system. The proposed expert system is a promising helpful tool that reduces the workload for physicians and provides diabetics with simple and valuable assistance.

Obesity is associated with the accumulation of dysfunctional adipose tissue that secretes several pro-inflammatory cytokines (adipocytokines). Recent studies have presented evidence that adipose tissues in obese individuals and animal models are hypoxic, which may result in upregulation and stabilization of the hypoxia inducible factor HIF1&alpha, Epigenetic mechanisms such as DNA methylation enable the body to respond to microenvironmental changes such as hypoxia and may represent a mechanistic link between obesity-associated hypoxia and upregulated inflammatory adipocytokines. The purpose of this study was to investigate the role of hypoxia in modifying adipocytokine DNA methylation and subsequently adipocytokine expression. We suggested that this mechanism is mediated via the DNA demethylase, ten-eleven translocation-1 (TET1), transcription of which has been shown to be induced by HIF1&alpha, To this end, we studied the effect of hypoxia (2% O2) in differentiated subcutaneous human adipocytes in the presence or absence of HIF1&alpha, stabilizer (Dimethyloxalylglycine (DMOG), 500 &mu, M), HIF1&alpha, inhibitor (methyl 3-[[2-[4-(2-adamantyl) phenoxy] acetyl] amino]-4-hydroxybenzoate, 30 &mu, M), or TET1-specific siRNA. Subjecting the adipocytes to hypoxia significantly induced HIF1&alpha, and TET1 protein levels. Moreover, hypoxia induced global hydroxymethylation, reduced adipocytokine DNA promoter methylation, and induced adipocytokine expression. These effects were abolished by either HIF1&alpha, inhibitor or TET1 gene silencing. The major hypoxia-responsive adipocytokines were leptin, interleukin-1 (IL6), IL1&beta, tumor necrosis factor &alpha, (TNF&alpha, ), and interferon &gamma, (IFN&gamma, ). Overall, these data demonstrate an activation of the hydroxymethylation pathway mediated by TET1. This pathway contributes to promoter hypomethylation and gene upregulation of the inflammatory adipocytokines in adipocytes in response to hypoxia.

Breast cancer cells frequently express tumor-associated antigens that can elicit immune responses to eradicate cancer. Cancer-testis antigens (CTAs) are a group of tumor-associated antigens that might serve as ideal targets for cancer immunotherapy because of their cancer-restricted expression and robust immunogenicity. Previous clinical studies reported that CTAs are associated with negative hormonal status, aggressive tumor behavior and poor survival. Furthermore, experimental studies have shown the ability of CTAs to induce both cellular and humoral immune responses. They also demonstrated the implication of CTAs in promoting cancer cell growth, inhibiting apoptosis and inducing cancer cell invasion and migration. In the current review, we attempt to address the immunogenic and oncogenic potential of CTAs and their current utilization in therapeutic interventions for breast cancer.

Endothelium-dependent vasodilation is reduced after acute exercise or after high intraluminal pressure in isolated arterioles from sedentary adults but not in arterioles from regular exercisers. The preserved vasodilation in arterioles from exercisers is hydrogen peroxide (H2O2) dependent, whereas resting dilation is nitric oxide (NO) dependent. We hypothesize chronic exercise elicits adaptations allowing for maintained vasodilation when NO bioavailability is reduced.

Medical images magnetic resonance imaging (MRI) analysis is a very challenging domain especially in the segmentation process for predicting tumefactions with high accuracy. Although deep learning techniques achieve remarkable success in classification and segmentation phases, it remains a rich area to investigate, due to the variance of tumefactions sizes, locations and shapes. Moreover, the high fusion between tumors and their anatomical appearance causes an imprecise detection for tumor boundaries. So, using hybrid segmentation technique will strengthen the reliability and generality of the diagnostic model. This paper presents an automated hybrid segmentation approach combined with convolution neural network (CNN) model for brain tumor detection and prediction, as one of many offered functions by the previously introduced IoMT medical service “DiaMe”. The developed model aims to improve extracting region of interest (ROI), especially with the variation sizes of tumor and its locations; and hence improve the overall performance of detecting the tumor. The MRI brain tumor dataset obtained from Kaggle, where all needed augmentation, edge detection, contouring and binarization are presented. The results showed 97.32% accuracy for detection, 96.5% Sensitivity, and 94.8% for specificity.

High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm2) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to H2O2. Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature. NEW & NOTEWORTHY We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/exercise-averts-high-pressure-induced-vascular-dysfunction/ .

There is a high prevalence of vitamin-D deficiency in obese individuals that could be attributed to vitamin-D sequestration in the adipose tissue. Associations between vitamin-D deficiency and unfavorable cardiometabolic outcomes were reported. However, the pathophysiological mechanisms behind these associations are yet to be established. In our previous studies, we demonstrated microvascular dysfunction in obese adults that was associated with reduced nitric oxide (NO) production. Herein, we examined the role of vitamin D in mitigating microvascular function in morbidly obese adults before and after weight loss surgery. We obtained subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies from bariatric patients at the time of surgery (n = 15) and gluteal SAT samples three months post-surgery (n = 8). Flow-induced dilation (FID) and acetylcholine-induced dilation (AChID) and NO production were measured in the AT-isolated arterioles &plusmn, NO synthase inhibitor N(&omega, )-nitro-L-arginine methyl ester (L-NAME), hydrogen peroxide (H2O2) inhibitor, polyethylene glycol-modified catalase (PEG-CAT), or 1,25-dihydroxyvitamin D. Vitamin D improved FID, AChID, and NO production in AT-isolated arterioles at time of surgery, these effects were abolished by L-NAME but not by PEG-CAT. Vitamin-D-mediated improvements were of a higher magnitude in VAT compared to SAT arterioles. After surgery, significant improvements in FID, AChID, NO production, and NO sensitivity were observed. Vitamin-D-induced changes were of a lower magnitude compared to those from the time of surgery. In conclusion, vitamin D improved NO-dependent arteriolar vasodilation in obese adults, this effect was more significant before surgery-induced weight loss.

Obesity is associated with microvascular dysfunction. While low-fat diet improves cardiovascular risk, its contributions on microvascular function, independent of weight loss, is unknown. We tested the hypothesis that nitric oxide (NO)-dependent vasodilation in microvessels is improved by low-fat diets designed for weight loss (LFWL) compared to low-fat weight maintenance (LFWM) diet. Obese adults were randomly assigned to either a LFWL diet (n = 11) or LFWM diet (n = 10) for six weeks. Microvessels were obtained from gluteal subcutaneous fat biopsies before and after the intervention for vascular reactivity measurements to acetylcholine (Ach) and flow, with and without L-NAME or indomethacin. Vascular and serum NO and C-reactive protein (CRP) were also measured. LFWL diet increased flow-induced (FID) and ACh-induced dilation (AChID), an effect that was inhibited by L-NAME. Conversely, LFWM diet did not affect FID or AChID. Indomethacin improved FID and AChID in the baseline and this effect was minimized in response to both diets. Serum NO or CRP did not change in response to either diet. In conclusion, LFWL diet improves microvascular reactivity compared to LFWM diet and increased vascular NO contribution to the improved microvascular dilation. These data suggest that weight reduction on low fat diet is critical for microvascular health.

Obesity affects 600 million people globally and over one third of the American population. Along with associated comorbidities, including cardiovascular disease, stroke, diabetes, and cancer; the direct and indirect costs of managing obesity are 21% of the total medical costs. These factors shed light on why developing effective and pragmatic strategies to reduce body weight in obese individuals is a major public health concern. An estimated 60–70% of obese Americans attempt to lose weight each year, with only a small minority able to achieve and maintain long term weight loss. To address this issue a precision medicine approach for weight loss has been considered, which places an emphasis on sustainability and real-world application to individualized therapy. In this article we review weight loss interventions in the context of precision medicine and discuss the role of genetic and epigenetic factors, pharmacological interventions, lifestyle interventions, and bariatric surgery on weight loss.

Simple Summary Breast cancer, one of the leading causes of death among women, is a complex disease in which several factors, such as psychosocial stress, have been implicated in its initiation and progression. The glucocorticoid receptor (GCR) is one of the molecules that transfers the stress signal into the body. We measured the genetic variation and protein expression of GCR and the genes that regulate GCR function or response and examined whether these variations were associated with breast cancer. We found several genetic variants of functionally important SNPs associated with later disease stage, higher grade, and hormone receptor-negative status. The GCR protein expression was reduced in breast cancer tissue and correlated with the basal cell marker CK5/6. Abstract Background: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. Method: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. Results: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. Conclusion: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Recent advanced intelligent learning approaches that are based on using neural networks in medical diagnosing increased researcher expectations. In fact, the literature proved a straight-line relation of the exact needs and the achieved results. Accordingly, it encouraged promising directions of applying these approaches toward saving time and efforts. This paper proposes a novel hybrid deep learning framework that is based on the restricted boltzmann machines (RBM) and the contractive autoencoder (CA) to classify the brain disorder and healthy control cases in children less than 12 years. The RBM focuses on obtaining the discriminative set of high guided features in the classification process, while the CA provides the regularization and the robustness of features for optimal objectives. The proposed framework diagnosed children with autism recording accuracy of 91, 14% and proved enhancement compared to literature.

Background: BCL-2 is an antiapoptotic protein that regulates apoptosis and has been associated with poor prognosis for many cancer sites. Despite a function that encourages tumorigenesis, increased BCL-2 expression has been associated with improved clinical outcomes in ER+ breast cancers, with mixed results observed for ER/PR- cancers. BCL-2 has been hypothesized to be an indicator of intact and fully functioning hormone receptor pathways and has also been hypothesized to facilitate cell death after treatment through mitochondrial priming. BCL-2 expression correlates strongly with hormone receptor expression; therefore, its association with better prognosis may be due to the strong effect ER/PR status has on survival, or due to its own biologic mechanism. To date, no studies have been conducted on racial differences in BCL-2 expression. We characterized racial/ethnic differences in BCL-2 expression and the association of BCL-2 expression with breast cancer specific survival among participants in the Breast Cancer Care in Chicago Study (BCCC). Methods: The BCCC was a cross-sectional study of 989 recently diagnosed non-Latina (nL) White, nL Black and Latina breast cancer patients diagnosed with a first primary breast cancer aged 30-79 in Chicago from 2005-2008. Tumor tissue was available for BCL-2 immunohistochemical staining for 264 patients. BCL-2 staining scores of 0 were classified as negative and all positive scores (1D, 1H, 2D, 2H, and 3) were classified as positive. Cox proportional hazards models were conducted to estimate the association of BCL-2 expression with breast cancer-specific death. Results: Roughly three-fourths of tumors (77%) stained positive for BCL. The prevalence of positive BCL staining varied by race/ethnicity (p=0.007), being highest for nL Whites (87%) and lowest for nL Blacks (68%); variability in BCL staining appeared to be limited to ER/PR-negative tumors (N=53), for which prevalence of positive BCL staining appeared to be much higher for nL whites than for minority patients (44% vs. 16%, p=0.054). BCL-2 expression was associated with a strong protective effect on BC survival in age and race-adjusted models (HR=0.40, 95% CI: 0.19, 0.84) and BCL-2 expression remained strongly positively associated with protection from breast cancer death with additional adjustment for ER/PR status (HR=0.33, 95% CI: 0.12, 0.89). Within subgroups defined by ER/PR status, BCL2 expression was qualitatively associated with better survival for both ER/PR positive and ER/PR negative subtypes, although sample size was insufficient to conduct a formal stratified analysis. Conclusions: BCL-2 appears to be an independent predictor of improved prognosis for breast cancer even after controlling for ER/PR status. The apparently higher prevalence of BCL2 expression for nL White vs. nL Black patients may provide etiologic clues regarding disparities in BC survival. Citation Format: Jibril M. Alim, Kent Hoskins, Abeer M. Mahmoud, Virgilia Macias, Andre Kadjascy-Balla, Garth H. Rauscher. Racial disparity in the prevalence of BCL-2 expression and associations with breast cancer survival in the Breast Cancer Care in Chicago study [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C098.