Neonatal inhibition of androgen activity alters the programming of body weight and orexinergic peptides differentially in male and female rats.

The involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flutamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5-alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypothalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female rats.

Higher versus lower nut consumption and changes in cognitive performance over two years in a population at risk of cognitive decline: a cohort study.

BACKGROUND: Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods rich in neuroprotective components; thus, their consumption could benefit cognitive health. However, evidence to date is limited and inconsistent regarding the potential benefits of nuts for cognitive function. OBJECTIVE: To prospectively evaluate the association between nut consumption and 2-y changes in cognitive performance in older adults at cognitive decline risk. METHODS: A total of 6,630 participants aged 55 to 75 y (mean age 65.0±4.9 y, 48.4% women) with overweight/obesity and metabolic syndrome completed a validated semi-quantitative food frequency questionnaire and a comprehensive battery of neuropsychological tests at baseline and a 2-y follow-up. Composite cognitive scores were used to assess global, general, attention, and executive function domains. Nut consumption was categorized as <1, ≥1 to <3, ≥3 to <7, and ≥7 servings/wk (1 serving=30 g). Multivariable-adjusted linear regression models were fitted to assess associations between baseline nut consumption and 2-y cognitive changes. RESULTS: Nut consumption was positively associated with 2-y changes in general cognitive function (P-trend <0.001). Compared with participants consuming <1 serving/wk of nuts, those categorized as consuming ≥3 to <7 and ≥7 servings/wk showed more favorable changes in general cognitive performance (ß z-score [95% CI] = 0.06 [0.00,0.12] and 0.13 [0.06,0.20], respectively). No significant changes were observed in the multivariable-adjusted models for other cognitive domains assessed. CONCLUSION: Frequent nut consumption was associated with a smaller decline in general cognitive performance over 2 y in older adults at risk of cognitive decline. Randomized clinical trials to verify our findings are warranted.

Genistein early in life modifies the arcuate nucleus of the hypothalamus morphology differentially in male and female rats.

In the present work we analyzed the effects of postnatal exposure to two doses of genistein (10 µg/g or 50 µg/g) from postnatal (P) day 6 to P13, on the morphology of the arcuate nucleus (Arc). The analyses of Arc coronal brain sections at 90 days showed that the ArcMP had higher values in volume, Nissl-stained neurons and GPER-ir neurons in males than in females and the treatment with genistein abolished these sex differences in most of the parameters studied. Moreover, in males, but not in females, the GPER-ir neurons decreased in the ArcMP but increased in the ArcL with both doses of genistein. In the ArcLP, GPER-ir population increased with the lowest doses and decreased with the highest one in males. Our results confirm that the Arc subdivisions have differential vulnerability to the effects of genistein during development, depending on which neuromorphological parameters, dose and sex are analyzed.

Activity-based anorexia alters hypothalamic POMC and orexin populations in male rats.

The objective of this study was to investigate the orexin and POMC populations in the hypothalamic nuclei of male Wistar rats after the activity-based anorexia (ABA) procedure. Four groups were established based on food restriction and activity: activity (A), ABA, diet (D) and control (C). The ABA protocol consisted of free access to a running wheel for a period of 22 h and access to food for 1 h. When the animals in the ABA group reached the ABA criterion, were sacrificed, and their brains were collected and serially sectioned. The free-floating sections were processed for orexin and POMC immunostaining. The number of orexin A-ir cells in the perifornical-dorsomedial-hypothalamus continuum (PFD) and lateral hypothalamus (LH) and the number of POMC-ir cells in the arcuate nucleus (Arc) were estimated. Data on food intake, body weight and wheel turns were also analyzed. The ABA procedure caused a significant decrease in body weight along with a significant increase in activity. Moreover, at the end of the ABA procedure, the number of POMC-ir cells decreased in the Arc in the A group, and significantly more in the ABA group, and the number of orexin A-ir positive cells decreased in the LH in D and ABA groups. The differential decrease in POMC in the ABA group emphasizes the importance of the melanocortin system in the maintenance of ABA, but more research is needed to elucidate the involvement of this peptide in the mechanism that promotes and maintains anorexia nervosa and how increased activity may interact with all these processes.

Continuity of care in disease-related malnutrition and nutritional medical treatment.

Disease-related malnutrition (DRM) continues to be a very significant healthcare problem, both in our hospitals and in the community. It is often not properly diagnosed or treated, despite a growing body of evidence highlighting its clinical and economic consequences. The transition between clinical care in the hospital and community services (Primary Care (PC) and Nursing Homes) is a key element in the prevention, detection and treatment of DRM. In October 2020, the Spanish Society of Endocrinology and Nutrition (SEEN) and the main societies of PC physicians in our country (SEMERGEN, SEMFYC and SEMG) met for the first time within the virtual NutriSEEN forum. From that moment on, a joint working group was created for this issue. This document tries to establish joint lines of work between the Clinical Nutrition and Dietetic Units (UNCyD) and the Primary Care teams to improve the detection and treatment of DRM. The clinical consequences and costs associated with DRE, nutritional risk screening, assessment and medical nutritional treatment are considered in a coordinated way between the PC teams and the UNCyD, as well as future proposals to improve the management of DRM.

Organizational Effects of Estrogens and Androgens on Estrogen and Androgen Receptor Expression in Pituitary and Adrenal Glands in Adult Male and Female Rats.

Sex steroid hormones, such as androgens and estrogens, are known to exert organizational action at perinatal periods and activational effects during adulthood on the brain and peripheral tissues. These organizational effects are essential for the establishment of biological axes responsible for regulating behaviors, such as reproduction, stress, and emotional responses. Estradiol (E2), testosterone, and their metabolites exert their biological action through genomic and non-genomic mechanisms, bounding to canonical receptors, such as estrogen receptor (ER)α, ERß, and androgen receptor (AR) or membrane receptors, such as the G protein-coupled estrogen receptor (GPER), respectively. Expression of ERs and AR was found to be different between males and females both in the brain and peripheral tissues, suggesting a sex-dependent regulation of their expression and function. Therefore, studying the ERs and AR distribution and expression levels is key to understand the central and peripheral role of sex steroids in the establishment of sex-specific behaviors in males and females. We investigated the organizational effects of estrogens and androgens in the pituitary and adrenal glands of adult male and female rats. For this, selective blockade of AR with flutamide or 5α-reductase with finasteride or aromatase with letrozole during the first 5 days of life has been performed in male and female pups and then quantification of ERs and AR expression in both glands has been carried out in adulthood. Data show that inhibition of dihydrotestosterone (DHT) and E2 production during the first five postnatal days mainly decreases the ER expression in male to female values and AR expression in female to male levels in the pituitary gland and increases AR expression in female to male levels in the adrenal gland. In contrast, blocking the action of androgens differentially modulates the ERs in males and females and decreases AR in both males and females in both glands. Altogether, the results suggest that neonatal modifications of the androgen and estrogen pathways can potentially lead to permanent modifications of the neuroendocrine functions of the pituitary and adrenal glands in the adulthood of both sexes.

Prenatal Low-Protein and Low-Calorie Diets Differentially Alter Arcuate Nucleus Morphology in Newborn Male Rats.

Background: Malnutrition during the early stages of development produces alterations that can compromise the functioning of the hypothalamic circuits that regulate food intake. The purpose of this study is to analyze the effects that a low-protein and low-calorie diet has on the morphology of the arcuate nucleus (ARC) of the hypothalamus in newborn male and female rats. Methods: On gestational day 6 (G6), six pregnant rats were divided into two groups. One group was made up of three pregnant rats, which were fed ad libitum with a control diet (20% casein), and the other one was made up of three pregnant rats, which were fed ad libitum with a low-protein diet (8% casein) and 30% of a calorie-restricted diet. On the day of birth, pups were sacrificed, resulting in four experimental groups: control male, control female, low-protein and low-calorie diet male, and low-protein and low-calorie diet female (n = 5 in each group). The volume and number of neurons, together with the neuronal density and number of apoptotic cells, were measured. Results: Males on a low-protein and low-calorie diet showed a significant increase in the number of neurons and in the neuronal density of the ARC with regard to the rest of the groups studied. These increases were also reflected in the posterior part of the nucleus. Although the existence of sexual dimorphism was not detected in any of the parameters studied in the control groups, the number of neurons and neuronal density showed differences between males and females fed with a low-protein and low-calorie diets due to the increase in the number of neurons shown by the male. No significant differences were found in the number of apoptotic cells. Conclusion: Our results show that a low-protein and low-calorie diet during the prenatal stage produces alterations in the ARC of the hypothalamus in newborn animals and, more importantly, that the effects of malnutrition are evident in males but not in females. Therefore, it is essential to follow a balanced diet during the early stages of life to ensure optimal development of the neural circuits that regulate eating.

Genistein during Development Alters Differentially the Expression of POMC in Male and Female Rats.

Phytoestrogens are considered beneficial for health, but some studies have shown that they may cause adverse effects. This study investigated the effects of genistein administration during the second week of life on energy metabolism and on the circuits regulating food intake. Two different genistein doses, 10 or 50 µg/g, were administered to male and female rats from postnatal day (P) 6 to P13. Physiological parameters, such as body weight and caloric intake, were then analyzed at P90. Moreover, proopiomelanocortin (POMC) expression in the arcuate nucleus (Arc) and orexin expression in the dorsomedial hypothalamus (DMH), perifornical area (PF) and lateral hypothalamus (LH) were studied. Our results showed a delay in the emergence of sex differences in the body weight in the groups with higher genistein doses. Furthermore, a significant decrease in the number of POMC-immunoreactive (POMC-ir) cells in the Arc in the two groups of females treated with genistein was observed. In contrast, no alteration in orexin expression was detected in any of the structures analyzed in either males or females. In conclusion, genistein can modulate estradiol's programming actions on the hypothalamic feeding circuits differentially in male and female rats during development.

SEEDO-SEMERGEN consensus document on continuous care of obesity between Primary Care and Specialist Hospital Units 2019. / Documento de consenso de la Sociedad Española de Obesidad (SEEDO) y de la Sociedad Española de Médicos de Atención Primaria (SEMERGEN) sobre la continuidad asistencial en obesidad entre Atención Primaria y Unidades Especializadas Hospitalarias 2019.

The high prevalence of obesity in our environment, a chronic disease of complex management and responsible for multiple comorbidities, requires the implementation of coordination strategies in clinical care between primary care and specialist hospital units. In a cross-sectional care model, primary care physicians guide all therapeutic management related to obesity. Together with them, specialists in endocrinology and nutrition and other health staff help to form a functional unit that focuses on obesity. The main goal of this document is to improve the coordination between care levels, to optimize resources, avoid patients' unrealistic expectations and improve patient follow-up after discharge from hospital.

Exploring Genetic Factors Involved in Huntington Disease Age of Onset: E2F2 as a New Potential Modifier Gene.

Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor.

[Influence of weather in the incidence of acute myocardial infarction in Galicia (Spain)]. / Influencia del clima en el infarto de miocardio en Galicia.

OBJECTIVE: To assess the interactions between weather and the impact of each individual meteorological parameters in the incidence of acute myocardial infarctions (AMI) in Galicia. METHODS: Retrospective study analyzing the number of AMI diagnosed and transferred to the hospital by the Emergencies Sanitary System of Galicia between 2002 and 2009. We included patients with clinical and ECG findings of AMI. The correlation between 10-minute meteorological variables (temperature, humidity, pressure, accumulated rainfall and wind speed) recorded by MeteoGalicia and the incidence of AMI was assessed. RESULTS: A total of 4,717 AMI were registered (72.8% men, 27.2% women). No seasonal variations were found. No significant correlations were detected with regard to average daily temperature (P=.683) or wind speed (P=.895). Correlation between atmospheric pressure and incidence of AMI was significant (P<.005), as well as with the daily relative humidity average (P=.005). CONCLUSIONS: Our study showed a statistical significant association with atmospheric pressure and with the daily relative humidity average. Since the local conditions of weather are widely variable, future studies should establish the relationship between weather patterns (including combinations of meteorological parameters), rather than seasonal variations, and the incidence of AMI.

[Levodopa in the treatment of Parkinson's disease: myths and realties]. / Levodopa en el tratamiento de la enfermedad de Parkinson: mitos y realidades.

In recent years we have witnessed a growing tendency to opt for the use of dopamine agonists (DA) as treatment for Parkinson's disease (PD), with the aim of delaying as far as possible the development of fluctuations and dyskinesias. Yet, levodopa continues to be the most effective antiparkinson drug and is probably the one that improves the greatest number of symptoms of the disease. This article reports on the results of a comprehensive review of the literature dealing with the benefits and risks of levodopa treatment in patients with PD which was conducted by a group of expert neurologists and members of the Spanish Neurology Society's Movement Disorder Group. The main conclusion reached in this article is that levodopa continues to be the most effective treatment for PD. Although the risk and incidence of developing dyskinesias remains at a lower level in the group initially treated with DA, the number of patients who develop disabling dyskinesias is very low in all the studies and is similar for DA and for levodopa. Scores on the quality of life scales are also similar in the two groups, which casts some doubt on the impact that these motor complications have on the quality of life of patients with PD. In view of these findings, we should consider whether there is any real justification for depriving patients of the good control of their symptoms offered by levodopa owing to the fear of developing dyskinesias or mild motor fluctuations that are not really going to have any negative effect on their quality of life. There is also the possibility of their developing severe side effects, which are more frequent with the use of DA.

Caregiver burden in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder that imposes an important burden upon the patient's caregiver. This study aims at assessing caregiver burden (CB) and analyzing its relationship with sociodemographic, emotional, and functional factors, as well as health-related quality of life (HRQoL). The following measures were applied to 80 patients with PD: the Hospital Anxiety and Depression Scale (HADS); the EuroQoL (for HRQoL); and PD-specific measures (Hoehn and Yahr staging and SCOPA-Motor ADL subscale). Patients' main caregivers completed the HADS, SF-36, EuroQoL, and Zarit CB Inventory (ZCBI). The ZCBI was found to be a valid and reliable measure in the context of PD. There was a significant association between CB and caregivers' HRQoL (r = -0.29 to -0.64). Mental aspects of caregivers' HRQoL and burden were affected by disability and disease severity. The presence of caregivers' depression had a significant negative effect on both CB and HRQoL. The main predictors of CB were caregivers' psychological well-being, patients' mood and clinical aspects of PD (disability and severity), and HRQoL of patients and caregivers. This study underscores the need to consider the impact of PD on caregivers' well-being.