Concept Typicality Responses in the Semantic Memory Network

For decades concept typicality has been recognized as critical to structuring conceptual knowledge, but only recently has typicality been applied in better understanding the processes engaged by the neurological network underlying semantic memory. This previous work has focused on one region within the network – the Anterior Temporal Lobe (ATL). The ATL responds negatively to concept typicality (i.e., the more atypical the item, the greater the activation in the ATL). To better understand the role of typicality in the entire network, we ran an fMRI study using a category verification task in which concept typicality was manipulated parametrically. We argue that typicality is relevant to both amodal feature integration centers as well as category-specific regions. Both the Inferior Frontal Gyrus (IFG) and ATL demonstrated a negative correlation with typicality, whereas inferior parietal regions showed positive effects. We interpret this in light of functional theories of these regions. Interactions between category and typicality were not observed in regions classically recognized as category-specific, thus, providing an argument against category specific regions, at least with fMRI

A switch from high-fat to normal diet does not restore sperm quality but prevents metabolic syndrome

In recent decades, the prevalence of metabolic diseases has concomitantly increased with a decline on fertility rates and sperm quality. High-fat diets (HFD) are seldom considered part of the problem, but the molecular mechanisms underlying its effects on male fertility remain poorly understood. Herein we postulated that HFD alter sperm quality. We evaluated the effects of switching from a HFD to a normal diet in early adulthood on metabolic disease onset, testicular metabolism and sperm quality. Thirty-six male C57BL6/J mice were divided in: a control group fed with standard chow; a group fed with HFD for 200 days; and a group fed with HFD for 60 days and then with standard chow (HFDt). Biometric data and whole-body metabolism were assessed. Epididymal sperm was studied for concentration, motility, viability and morphology. 1H-NMR metabolomics approach was performed on testicular extracts to trace the metabolic changes. Diet switch reduced body weight and fat mass, preventing metabolic syndrome onset. However, sperm viability, motility and morphology were deteriorated by HFD consumption and not restored by diet switch. HFD induced irreversible changes in pyruvate and glutamate metabolism, ethanol degradation and ammonia recycling in testis. Furthermore, HFDt changed purine and cysteine metabolism, urea cycle, and glutathione content. Overall, HFD caused irreversible changes in testicular metabolism even after switching to normal diet. HFD feeding until early adulthood decreases sperm quality, which cannot be restored by diet switch or weight loss, even when development of metabolic syndrome is avoided

First Incidence and Progression Study for Diabetic Retinopathy in Portugal, the RETINODIAB Study: Evaluation of the Screening Program for Lisbon Region

PURPOSE: To estimate the 5-year incidence and progression of diabetic retinopathy (DR) among persons with type 2 diabetes mellitus (DM). DESIGN: Population-based, prospective, cohort study. PARTICIPANTS: The RETINODIAB (Study Group for Diabetic Retinopathy Screening) program was implemented in the Lisbon and Tagus Valley area between July 2009 and December 2014. A total of 109 543 readable screening examinations were performed and corresponded to 56 903 patients who attended the screening program at entry. A total of 30 641 patients (53.85%) had at least 1 further screening event within the study period and were included in the analysis. METHODS: Participants underwent two 45° nonstereoscopic retinal digital photographs per eye according to RETINODIAB protocol. All images were graded according to the International Clinical Diabetic Retinopathy Scale. Referable diabetic retinopathy (RDR) was defined for all patients graded as moderate nonproliferative DR (NPDR), severe NPDR, or proliferative DR (PDR), with or without maculopathy or mild NPDR with maculopathy. Nonparametric estimates of the annual and cumulative incidences were obtained by Turnbull's estimator. Associations between the potential risk factors and the time to onset/progression of retinopathy were assessed through a parametric survival analysis for interval-censored data. MAIN OUTCOME MEASURES: The authors estimated the onset and progression incidence rates of DR. RESULTS: Yearly incidence of any DR in patients without retinopathy at baseline was 4.60% (95% confidence interval [CI], 3.96-4.76) in the first year, decreasing to 3.87% (95% CI, 2.57-5.78) in the fifth year. In participants with mild NPDR at baseline, the progression rate to RDR in year 1 was 1.18% (95% CI, 0.96-1.33). Incidence of any DR and RDR and DR progression rate were associated with known duration of diabetes, age at diagnosis, and use of insulin treatment. CONCLUSIONS: This longitudinal epidemiologic study provides the first Portuguese incidence DR data in a large-scale population-based cohort of type 2 diabetes after a 5-year follow-up. Duration of diabetes, age at diagnosis, and insulin treatment were associated with increasing risk of incidence and progression of DR. A personalized schedule distribution of screening intervals according to the individual patient's profile should be implemented, with resulting benefits in terms of health costs.info:eu-repo/semantics/publishedVersio

Diet during early life defines testicular lipid content and sperm quality in adulthood

Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health but few studies addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism leading to permanent damage to sperm parameters. After weaning (day 21 after birth), 36 male mice were randomly divided into 3 groups and fed with different diet regimen for 200 days: CTRL-standard chow; HFD-high-fat diet (Carbohydrate: 35.7%, Protein: 20.5%, Fat: 36.0%); HFDt-high-fat diet for 60 days then replaced by standard chow. Biometric and metabolic data were monitored. Animals were then sacrificed, and tissues collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Our results show that mice fed with high-fat diet, even if only until early adulthood, had lower sperm viability and motility, and higher incidence of head and tail defects. Although diet reversion with weight loss during adulthood prevents the progression of metabolic syndrome, testicular content in fatty acids is irreversibly affected. Excessive fat intake promoted an over-accumulation of pro-inflammatory n-6 polyunsaturated fatty acids in testis, which are strongly correlated with negative effects upon sperm quality. Therefore, the adoption of high-fat diets during early life correlates to irreversible changes in testicular lipid content and metabolism, which are related to permanent damage to sperm quality later in life

Lifestyle, metabolic disorders and male hypogonadism - A one-way ticket?

Hypogonadism is more frequent among men with common metabolic diseases, notably obesity and type 2 diabetes. Indeed, endocrine disruption caused by metabolic diseases can trigger the onset of hypogonadism, although the underlying molecular mechanisms are not entirely understood. Metabolic diseases are closely related to unhealthy lifestyle choices, such as dietary habits and sedentarism. Therefore, hypogonadism is part of a pathological triad gathering unhealthy lifestyle, metabolic disease and genetic background. Additionally, hypogonadism harbors the potential to aggravate underlying metabolic disorders, further sustaining the mechanisms leading to disease. To what extent does lifestyle intervention in men suffering from these metabolic disorders can prevent, improve or reverse hypogonadism, is still controversial. Moreover, recent evidence suggests that the metabolic status of the father is related to the risk of inter and transgenerational inheritance of hypogonadism. In this review, we will address the proposed mechanisms of disease, as well as currently available interventions for hypogonadism

Pediatric diabetes training for healthcare professionals in Europe: Time for change.

BACKGROUND: Training for healthcare professionals (HCPs) in Europe who care for children and young people (CYP) with type 1 diabetes and their families is variable depending on the country. Building on the work of SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) and using the German Certified Diabetes Educators (CDEs) curriculum, a European collaboration of pediatric diabetes experts aimed to (1) establish current core elements that should be included in a pediatric diabetes education training course and (2) create a template for a European CDE's training curriculum. METHODS: A qualitative methodology incorporating a survey questionnaire, focus group discussions, individual semi-structured interviews and workshops was employed to explore participants' experiences and opinions. HCPs-pediatric consultants, diabetes nurses, dietitians and psychologists, national and local diabetes leads, academic and education leads and children, and young people with diabetes and families took part in the study. The total number of participants equaled 186. RESULTS: A template for a European Certified Diabetes Educator Curriculum (EU-CDEC) was developed based on the themes that emerged from the participants' expertise and experiences. This provides a model for HCPs' pediatric diabetes training provision. CONCLUSIONS: There is a severe shortage of high quality, standardized training for HCPs across the majority of European countries. Lack of trained HCPs for CYP with diabetes will result in the delivery of suboptimal care and impact on health, wellbeing and clinical and psychological outcomes. The EU-CDEC template can be used to increase access to high quality training provision for all HCPs across Europe and worldwide

Mutations in or near the Transmembrane Domain Alter PMEL Amyloid Formation from Functional to Pathogenic

PMEL is a pigment cell-specific protein that forms physiological amyloid fibrils upon which melanins ultimately deposit in the lumen of the pigment organelle, the melanosome. Whereas hypomorphic PMEL mutations in several species result in a mild pigment dilution that is inherited in a recessive manner, PMEL alleles found in the Dominant white (DW) chicken and Silver horse (HoSi)—which bear mutations that alter the PMEL transmembrane domain (TMD) and that are thus outside the amyloid core—are associated with a striking loss of pigmentation that is inherited in a dominant fashion. Here we show that the DW and HoSi mutations alter PMEL TMD oligomerization and/or association with membranes, with consequent formation of aberrantly packed fibrils. The aberrant fibrils are associated with a loss of pigmentation in cultured melanocytes, suggesting that they inhibit melanin production and/or melanosome integrity. A secondary mutation in the Smoky chicken, which reverts the dominant DW phenotype, prevents the accumulation of PMEL in fibrillogenic compartments and thus averts DW–associated pigment loss; a secondary mutation found in the Dun chicken likely dampens a HoSi–like dominant mutation in a similar manner. We propose that the DW and HoSi mutations alter the normally benign amyloid to a pathogenic form that antagonizes melanosome function, and that the secondary mutations found in the Smoky and Dun chickens revert or dampen pathogenicity by functioning as null alleles, thus preventing the formation of aberrant fibrils. We speculate that PMEL mutations can model the conversion between physiological and pathological amyloid

Inherited Metabolic Memory of High-Fat Diet Impairs Testicular Fatty Acid Content and Sperm Parameters

Scope Exposure to a high-fat diet (HFD) from early-life is associated with a testicular metabolic signature link to abnormal sperm parameters up to two generations after exposure in mice. Hereby, this study describes a testicular lipid signature associate with "inherited metabolic memory" of exposure to HFD, persisting up to two generations in mice. Methods and Results Diet-challenged mice (n = 36) are randomly fed after weaning with standard chow (CTRL); HFD for 200 days or transient HFD (HFDt) (60 days of HFD + 140 days of standard chow). Subsequent generations (36 mice per generation) are fed with chow diet. Mice are euthanized 200 days post-weaning. Glucose homeostasis, serum hormones, testicular bioenergetics, and antioxidant enzyme activity are evaluated. Testicular lipid-related metabolites and fatty acids are characterized by H-1-NMR and GC-MS. Sons of HFD display impaired choline metabolism, mitochondrial activity, and antioxidant defenses, while grandsons show a shift in testicular omega 3/omega 6 ratio towards a pro-inflammatory environment. Grandsons of HFDt raise 3-hydroxybutyrate levels with possible implications to testicular insulin resistance. Sperm counts decrease in grandsons of HFD-exposed mice, regardless of the duration of exposure. Conclusion HFD-induced "inherited metabolic memory" alters testicular fatty acid metabolism with consequences to sperm parameters up to two generations

Diet during early life defines testicular lipid content and sperm quality in adulthood

Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health, but few studies have addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism, leading to permanent damage to sperm parameters. After weaning (day 21 after birth), 36 male mice were randomly divided into three groups and fed with a different diet regimen for 200 days: a standard chow diet (CTRL), a high-fat diet (HFD) (carbohydrate: 35.7%, protein: 20.5%, and fat: 36.0%), and a high-fat diet for 60 days, then replaced by standard chow (HFDt). Biometric and metabolic data were monitored. Animals were then euthanized, and tissues were collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Our results show that mice fed with a high-fat diet, even if only until early adulthood, had lower sperm viability and motility, and higher incidence of head and tail defects. Although diet reversion with weight loss during adulthood prevents the progression of metabolic syndrome, testicular content in fatty acids is irreversibly affected. Excessive fat intake promoted an overaccumulation of proinflammatory n-6 polyunsaturated fatty acids in the testis, which is strongly correlated with negative effects upon sperm quality. Therefore, the adoption of high-fat diets during early life correlates with irreversible changes in testicular lipid content and metabolism, which are related to permanent damage to sperm quality later in life