Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions. Using a prostate cancer tissue microarray, it was previously established that the reduction of SELENOF in the cancers from African American men was significantly greater than in cancers from Caucasian men. When SELENOF levels in human prostate immortalized epithelial cells were reduced with an shRNA construct, those cells acquired the ability to grow in soft agar, increased the ability to migrate in a scratch assay and acquired features of energy metabolism associated with prostate cancer. These results support a role of SELENOF loss in prostate cancer progression and further indicate that SELENOF loss and genotype may contribute to the disparity in prostate cancer mortality experienced by African American men.

Abstract 1122‐000026: Factors Associated with Gender Differences in Patients with Lewy Body Dementia

Introduction : Several studies have investigated gender differences in patients with Lewy Body Dementia (LBD), however, whether the observed differences are associated with demographic and pharmacological factors is not fully understood. The current study tested the hypothesis that specific demographic or pharmacological factors may contribute to the observed gender difference. Methods : A 5‐year data collected from a regional registry from 608 LBD patients including 332 men and 276 women were analyzed. Factors associated with men and women patients with LBD were determined using the logistic regression model. Multicollinearity was evaluated using variance inflation factors (VIFs), with values greater than five suggestive of multicollinearity Results : The results indicate that Caucasian men (94.3% vs 83.3%) were more likely to present with LBD. In the adjusted analysis, increasing age (OR = 1.042, 95% CI, 1.025‐ 1.058, P ˂ 0.001) was more likely to be associated with women with LBD, while olanzapine (OR = 2.871, 95% CI, 1.902‐4.334, P˂ 0.001), buspirone (OR = 2.388, 95% CI, 1.527‐3.735, P˂ 0.001), escitalopram (OR = 1.444, 95% CI, 1.079‐1.932, P = 0.014) and tobacco use (OR = 1.424, 95% CI, 1.075‐1.887, P = 0.014) were associated with men with LBD Conclusions : More men presented with LBD compared to women. Our findings reveal specific demographic and pharmacological factors that contribute to gender differences among LBD patients.

Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men

The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients. Top-ranked sEV-associated miRs were then validated in 150 plasma samples (75 AA and 75 CA) collected from two independent cohorts; NIH (n = 90) and Washington University (n = 60) cohorts. Receiver operating characteristic (ROC) curve, Kaplan–Meier and Cox proportional hazards regression were used to assess these miRs as clinical biomarkers. Among nine top-ranked sEV-associated miRs, miR-6068 and miR-1915-3p were enriched in sEVs collected from PCa patients compared to healthy volunteers. Moreover, miR-6716-5p and miR-3692-3p segregated AA from CA men and low from high Gleason score (GS), respectively. Upregulation of sEV-associated miR-1915-3p, miR-3692-3p and miR-5001-5p was associated with improved survival time, and only miR-1915-3p was associated with longer recurrence-free survival (RFS) as an independent prognostic marker. Taken together, we identified novel sEV-associated miRs that can differentiate PCa patients from normal, AA from CA and high from low GS and predicts RFS.

Lymphoepithelial carcinoma of the larynx: an extremely rare tumour in a patient of Chinese descent

Lymphoepithelial carcinoma (LEC) of the larynx is an extremely rare tumour which, unlike its nasopharyngeal counterpart, has shown a propensity to affect elderly Caucasian men and is not commonly associated with Epstein-Barr virus. We present a 70-year-old Chinese man who complained of hoarseness and dysphagia. Nasoendoscopy revealed a left supraglottic tumour. Preoperative MRI (in particular Diffusion Weighted Imaging) showed the possibility of two distinct components within a tumour. The patient underwent total pharyngolaryngectomy and bilateral selective neck dissection. The final histology report confirmed the presence of a tumour with two distinct components: predominant LEC with a smaller conventional (keratinising) squamous cell carcinoma component. The patient recovered well after surgery and subsequently underwent adjuvant radiotherapy. Final staging was pT3 N2c M0 (AJCC stage IVA). Follow-up over 2 years revealed no tumour recurrence.

Enhanced Melanoma Classifier with VGG16-CNN

Melanoma is the most severe kind of skin cancer that is becoming more common in the Western world. This is still thought to be caused primarily by exposure to the sun. Patients with malignant melanoma have a wide range of prognoses; however public awareness initiatives encouraging early detection have resulted in considerable reductions in mortality rates. This disease primarily affects Caucasian men and women and has a terrible prognosis once it has spread to other parts of the body. As a result, early detection of this malignancy is critical for patient treatment success. In this paper, we present an experimental result of a Melanoma Image Classifier using the VGG16 model for preprocessing the images dataset. Thedataset comprises 4596 image samples with 2239 images for training, 2239 images formodel validationand 118 images for testing the model. The resultant images were trained with a Convolutional Neural Network(CNN) Sequential model of a learning rate of 0.0001,adam optimizer with binary cross-entropy as loss and accuracy as a metric. The model yields an accuracy of 93%, thereby outperforming other Deep learning models. The approach is viable and effective, and it achieves the preliminary goal of classifying melanoma lesion images.

Eales’ Disease: When the Rare Sounds Frequent

Eales’ disease is a peripheral occlusive retinal phlebitis, with an unclear pathogenesis. The classic association with hypersensitivity to Mycobacterium tuberculosis protein infers that immunologic disturbance may be involved. Here, we described three cases of Eales’ disease. All patients are Caucasian men aged 27-58 years and presented with vitreous hemorrhage and/or peripheral venous vasculitis. Tuberculin skin sensitive test (Mantoux screening test) and interferon-gamma release assay (IGRA) were positive in all patients. Therapeutic approach included antituberculosis therapy and systemic steroids, associated or not to immunosuppressive therapy, and retinal scatter photocoagulation in all cases. Antivascular endothelial grow factor (VEGF) intravitreal injections were also required in two cases. Since various retinal diseases can resemble this presentation, Eales’ disease is considered a diagnosis of exclusion. Early diagnosis and appropriate therapeutic approach are both essential to accomplish disease control and reduce ophthalmologic complications.

Metabolic syndrome is not associated to an increased risk of low bone mineral density in men at risk for osteoporosis

Purpose We have recently demonstrated a significant association between osteoporosis (Op) and metabolic syndrome (MetS) in Caucasian women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op. This cross-sectional study was performed to evaluate the association between MetS and Op in Caucasian men enrolled in the same geographical area, with identical criteria and in the same time range. Methods Among subjects enrolled in the SIMON study, we selected the medical records of all free-living men who performed a contextual evaluation of both bone mineral density (BMD) by DXA and MetS constitutive elements (arterial blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose). All enrolled subjects refer to “COMEGEN” general practitioners’ cooperative operating in Naples, Southern Italy. Results Overall, the medical records of 880 men were examined. No significant association between MetS and Op was observed. Among MetS constitutive elements, waist circumference was inversely related to Op risk. Conclusion In Caucasian men examined by DXA for suspected Op, no significant association was observed between Op and MetS. The study results contrast to those observed in women enrolled in the same geographical area, with identical criteria and in the same time range and may be related to sexual dimorphism occurring in clinical expressiveness of both MetS and Op.

Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men

Background Testicular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. In this study we aimed to investigate whether serum concentrations of AMH and the AMH to total testosterone ratio (AMH/T) might be predictive factors for sperm retrieval outcomes during TESE in a cohort of 155 adult Caucasian men with azoospermia. Results AMH serum levels were significantly lower in nonobstructive azoospermia (NOA) that was unexplained, cryptorchidism-related, cytotoxic and genetic (medians [pmol/l] = 30.1; 21.8; 26.7; 7.3; and p = 0.02; 0.001; 0.04; <0.0001, respectively]) compared with obstructive azoospermia (OA) (median = 44.8 pmol/l). Lowest values were observed in cases of genetic NOA (p < 0.0001, compared with unexplained NOA) and especially in individuals with non-mosaic Klinefelter syndrome (median = 2.3 pmol/l, p <0.0001). Medians of AMH/T values were significantly lower in genetic NOA compared to unexplained, cryptorchidism-related NOA as well as OA. Only serum concentrations of AMH differed significantly between positive and negative groups in men with non-mosaic Klinefelter syndrome. The optimal cut-off of serum AMH was set at 2.5 pmol/l. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off to predict negative outcomes of SR were 100 %, 76.9 %, 66.6 %, 100 and 84.2 %, respectively. Conclusions Serum AMH levels, but not AMH/T values, are a good marker for Sertoli and germ cell population dysfunction in adult Caucasian men with non-mosaic Klinefelter syndrome and could help us to predict negative outcomes of SR at TESE with 100 % sensitivity when serum levels of AMH are below 2.5 pmol/l.

Case Report: TNFα Antagonists Are an Effective Therapy in Cardiac Sarcoidosis

Introduction: Cardiac sarcoidosis (CS) is a life-threatening disease in which clear recommendations are lacking. We report a case series of CS successfully treated by tumor necrosis factor (TNF)α antagonists.Methods: We conducted a single-center retrospective study of our patients with CS treated by TNFα antagonists.Results: Four cases (4/84, 4.7%) were found in our database. Mean age was 40 years (range 34–53 years), and all were Caucasian men. Mean follow-up was 54.75 months (range 25–115 months). All patients received corticosteroid therapy (CT) and immunosuppressive therapy (IT). TNFα antagonists (infliximab or adalimumab) were started after the first or second CS relapse under CT and IT. One patient experienced relapse under TNFα antagonists (isolated decreased left ventricular ejection) and responded to a shorter interval of TNFα antagonist infusion. CT was discontinued in three patients treated with TNFα antagonists without relapse or major cardiac events during follow-up. No serious adverse event occurred in our case series, possibly due to dose sparing and frequent arrest of CT.Conclusion: TNFα antagonists were effective in refractory and/or relapsing CS treated by corticosteroids and/or immunosuppressive agents, without serious adverse events, and should be considered earlier in CS treatment scheme.

A Stronger Effect of Body Mass Index and Waist Circumference on the Prevalence of Uncontrolled Hypertension among Caucasian Men than Women

<b><i>Background:</i></b> Gender-related differences in fat distribution may affect blood pressure (BP) control in hypertensive subjects. The aim of the study was to assess how body mass (BM), BMI, and waist circumference (WC) influence the effectiveness of antihypertension therapy in hypertensive men and women in daily clinical practice. <b><i>Patients and Methods:</i></b> The observational study involved 12,289 adult hypertensive Caucasians (6,163 women) declaring regular use of antihypertensive drugs. BP control was scored based on the mean values of 2 attended office BP measurements. WC thresholds for visceral obesity were adopted from definitions of the International Diabetes Federation (≥94/80 cm for men/women) and National Cholesterol Education Program Adult Treatment Panel III (≥102/88 cm for men/women). Stepwise backward multivariable logistic regression was used to analyse correlates of the effectiveness of hypertension therapy. <b><i>Results:</i></b> The predictive value of BMI ≥30 (for uncontrolled hypertension) was stronger than that of visceral obesity, regardless of the criteria used. In men, BP control rapidly deteriorated with BMI (odds ratio [OR] up to 8.58 [95% CI: 5.74–12.83]) and WC (OR up to 5.09 [3.84–6.74]), while in women, the association was more flattened (OR up to 3.63 [2.78–4.74] and 1.93 [1.59–2.35], respectively). However, the highest risk of uncontrolled BP occurred in women with BM ≥110 kg (OR = 10.47 [5.05–21.71]) and men with BM ≥125 kg (OR = 9.66 [5.86–15.94]). <b><i>Conclusions:</i></b> (1) Obesity and visceral obesity limit the effectiveness of antihypertension therapy more in men than in women. (2) This phenomenon should be taken into account in the prescription of adequate doses of antihypertensive drugs.