Sexual Dysfunction as a Marker of Cardiovascular Disease in Males With 50 or More Years of Type 1 Diabetes

OBJECTIVE Vascular dysfunction is a major contributor to diabetes complications. It is also the primary physiologic cause of erectile dysfunction and considered an independent predictor of cardiovascular disease (CVD) in males over age 40 years. A cohort of individuals with 50 or more years of type 1 diabetes, Joslin Medalists, have low rates of small but not large vessel complications. This study aims to identify the prevalence and longitudinal association of sexual dysfunction (SD) with CVD in Joslin Medalists. RESEARCH DESIGN AND METHODS Description and association of self-assessment of SD in males of the Medalist cohort by self-reported sexual problems with CVD. SD is validated through the use of the abbreviated International Index of Erectile Dysfunction (IIEF). RESULTS Of 301 males in the Medalist Study, 69.8% reported a history of SD. Unadjusted risk factors included elevated glycated hemoglobin (HbA1c) (P = 0.02), elevated BMI (P = 0.03), higher total cholesterol (P = 0.02), lower HDL (P 0.05) with SD. Current report of SD (IIEF score ≤17) in a subset of Medalists was significantly correlated with self-reported longitudinal SD. CONCLUSIONS SD in those with extreme-duration type 1 diabetes is independently associated with CVD, representing a large-vessel pattern. The findings suggest that SD may predict CVD in those with type 1 diabetes of long duration. These individuals have also been found to be relatively free of microvascular complications

Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction

Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (≥ 50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated. Mechanistically, we showed that hyperglycemia and diabetes decreased PKM2 tetramer formation and activity by sulfenylation in mouse glomeruli and cultured podocytes. Pkm-knockdown immortalized mouse podocytes had higher levels of toxic glucose metabolites, mitochondrial dysfunction and apoptosis. Podocyte-specific Pkm2-knockout (KO) mice with diabetes developed worse albuminuria and glomerular pathology. Conversely, we found that pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, reversed hyperglycemia-induced elevation in toxic glucose metabolites and mitochondrial dysfunction, partially by increasing glycolytic flux and PGC-1α mRNA in cultured podocytes. In intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes, TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and kidney pathology. Thus, PKM2 activation may protect against DN by increasing glucose metabolic flux, inhibiting the production of toxic glucose metabolites and inducing mitochondrial biogenesis to restore mitochondrial function

Young Offenders’ Emotion Recognition Dysfunction Across Emotion Intensities: Explaining Variation Using Psychopathic Traits, Conduct Disorder and Offense Severity

Antisocial individuals have problems recognizing negative emotions (e.g. Marsh & Blair in Neuroscience and Biobehavioral Reviews 32:454–465, 2009); however, due to issues with sampling and different methods used, previous findings have been varied. Sixty-three male young offenders and 37 age-, IQ- and socio-economic status-matched male controls completed a facial emotion recognition task, which measures recognition of happiness, sadness, fear, anger, disgust, and surprise and neutral expressions across 4 emotional intensities. Conduct disorder (YSR), and psychopathic and callous/unemotional traits (YPI) were measured, and offenders’ offense data were taken from the Youth Offending Service’s case files. Relative to controls, offenders were significantly worse at identifying sadness, low intensity disgust and high intensity fear. A significant interaction for anger was also observed, with offenders showing reduced low- but increased high-intensity anger recognition in comparison with controls. Within the young offenders levels of conduct disorder and psychopathic traits explained variation in sadness and disgust recognition, whereas offense severity explained variation in anger recognition. These results suggest that antisocial youths show specific problems in recognizing negative emotions and support the use of targeted emotion recognition interventions for problematic behavior

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio