Autophagy is required for performance adaptive response to resistance training and exercise-induced adult neurogenesis

Endurance training promotes exercise-induced adaptations in brain, like hippocampal adult neurogenesis and autophagy induction. However, resistance training effect on the autophagy response in the brain has not been much explored. Questions such as whether partial systemic autophagy or the length of training intervention affect this response deserve further attention. Therefore, 8-week-old male wild-type (Wt; n = 36) and systemic autophagy-deficient (atg4b^−/−, KO; n = 36) mice were randomly distributed in three training groups, resistance (R), endurance (E), and control (non-trained), and in two training periods, 2 or 14 weeks. R and E maximal tests were evaluated before and after the training period. Forty-eight hours after the end of training program, cerebral cortex, striatum, hippocampus, and cerebellum were extracted for the analysis of autophagy proteins (LC3B-I, LC3B-II, and p62). Additionally, hippocampal adult neurogenesis was determined by doublecortin-positive cells count (DCX+) in brain sections. Our results show that, in contrast to Wt, KO were unable to improve R after both trainings. Autophagy levels in brain areas may be modified by E training only in cerebral cortex of Wt trained for 14 weeks, and in KO trained for 2 weeks. DCX + in Wt increased in R and E after both periods of training, with R for 14 weeks more effective than E. Interestingly, no changes in DCX + were observed in KO after 2 weeks, being even undetectable after 14 weeks of intervention. Thus, autophagy is crucial for R performance and for exercise-induced adult neurogenesis.     

Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) joint consensus statement for MR imaging of placenta accreta spectrum disorders

This study was conducted in order to establish the joint Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) guidelines on placenta accreta spectrum (PAS) disorders and propose strategies to standardize image acquisition, interpretation, and reporting for this condition with MRI. The published evidence-based data and the opinion of experts were combined using the RAND–UCLA Appropriateness Method and formed the basis for these consensus guidelines. The responses of the experts to questions regarding the details of patient preparation, MRI protocol, image interpretation, and reporting were collected, analyzed, and classified as “recommended” versus “not recommended” (if at least 80% consensus among experts) or uncertain (if less than 80% consensus among experts). Consensus regarding image acquisition, interpretation, and reporting was determined using the RAND–UCLA Appropriateness Method. The use of a tailored MRI protocol and standardized report was recommended. A standardized imaging protocol and reporting system ensures recognition of the salient features of PAS disorders. These consensus recommendations should be used as a guide for the evaluation of PAS disorders with MRI. • MRI is a powerful adjunct to ultrasound and provides valuable information on the topography and depth of placental invasion. • Consensus statement proposed a common lexicon to allow for uniformity in MRI acquisition, interpretation, and reporting of PAS disorders. • Seven MRI features, namely intraplacental dark T2 bands, uterine/placental bulge, loss of low T2 retroplacental line, myometrial thinning/disruption, bladder wall interruption, focal exophytic placental mass, and abnormal vasculature of the placental bed, reached consensus and are categorized as “recommended” for diagnosing PAS disorders.     

Assessing inter- and intra-individual cognitive variability in patients at risk for cognitive impairment: the case of minimal hepatic encephalopathy

Recent evidence reveals that inter- and intra-individual variability significantly affects cognitive performance in a number of neuropsychological pathologies. We applied a flexible family of statistical models to elucidate the contribution of inter- and intra-individual variables on cognitive functioning in healthy volunteers and patients at risk for hepatic encephalopathy (HE). Sixty-five volunteers (32 patients with cirrhosis and 33 healthy volunteers) were assessed by means of the Inhibitory Control Task (ICT). A Generalized Additive Model for Location, Scale and Shape (GAMLSS) was fitted for jointly modeling the mean and the intra-variability of Reaction Times (RTs) as a function of socio-demographic and task related covariates. Furthermore, a Generalized Linear Mixed Model (GLMM) was fitted for modeling accuracy. When controlling for the covariates, patients without minimal hepatic encephalopathy (MHE) did not differ from patients with MHE in the low-demanding condition, both in terms of RTs and accuracy. Moreover, they showed a significant decline in accuracy compared to the control group. Compared to patients with MHE, patients without MHE showed faster RTs and higher accuracy only in the high-demanding condition. The results revealed that the application of GAMLSS and GLMM models are able to capture subtle cognitive alterations, previously not detected, in patients’ subclinical pathologies.     

Prevalence of anemia and its impact on the state of frailty in elderly people living in the community: SADEM study

Anemia represents a global health problem that negatively impacts quality of life in elderly population; however, its impact on the geriatric syndrome of frailty is unclear. We examined the prevalence of anemia among elderly and sought a relationship between hemoglobin and the phenotype of frailty. Baseline hemoglobin quintiles and anemia were assessed in relation to frailty status in a prospective study with 1,933 older community-dwelling adults enrolled in the Study on Aging and Dementia in Mexico (SADEM). Logistic regression was used to model the relationship between frailty and Hb, adjusting for risk factors of frailty, sociodemographic data, cognitive decline, chronic diseases, and some risky habits. Prevalence of frailty was 8.3 %. Frailty risk was highest at the lowest hemoglobin quintile (<14.3 g/dL for men; <13.3 g/dL for women), and 160 (8.3 %) were anemic (<13 g/dL for men; <12 g/dL for women). The relationship between frailty and Hb levels, adjusted for age and sex, observed in the first and fifth quintiles, compared with the fourth quintile, were 1.53 (95 % confidence interval (CI), 1.46–1.60) and 1.05 (95 % CI, 1.01–1.15). After multivariate adjustment, the odds ratios (ORs) were 1.23 (95 % CI, 1.17–1.13) and 1.06 (95 % CI, 1.01–1.11). The association was not diminished by risk factors for frailty (body mass index (BMI), comorbidity, cognitive decline, smoking, alcohol consumption, etc.). In community-dwelling older adults, low hemoglobin concentrations and anemia were independently associated with increased frailty risk. This suggests that mild anemia and low Hb levels are independent, modifiable risk factors for frailty.     

Embryology and variations of the recurrent artery of Heubner

The recurrent artery of Heubner (RAH) is a very fascinating artery for various reasons. The first one is its early development in the embryologic and phylogenic life. The second one is the discrepancy between its diameter and its functional importance and the last but not least reason is the many variations of origin and course of this artery. For more than a century, numerous studies furnished important information about variations in origin, course, and parenchymal territory of the RAH. The most important anomaly concerning the RAH is the accessory middle cerebral artery and well-illustrates the complexity of its embryologic development. For these reasons, authors provide a review of anatomical variations of this artery that could be encountered with a particular attention given to the history and embryological knowledge.     

The non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: A randomized clinical trial

Rationale

Moderate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients.

Objective

To compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors.

Methods

In this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30 g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30 g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored.

Results

The number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions.

Conclusions

The non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects.

Clinical trial registration

http://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245     

Lack of vitamin D receptor causes stress-induced premature senescence in vascular smooth muscle cells through enhanced local angiotensin-II signals

Objectives

The inhibition of the renal renin-angiotensin system by the active form of vitamin D contributes to the cardiovascular health benefits of a normal vitamin D status. Local production of angiotensin-II in the vascular wall is a potent mediator of oxidative stress, prompting premature senescence. Herein, our objective was to examine the impact of defective vitamin D signalling on local angiotensin-II levels and arterial health.

Methods

Primary cultures of aortic vascular smooth muscle cells (VSMC) from wild-type and vitamin D receptor-knockout (VDRKO) mice were used for the assessment of cell growth, angiotensin-II and superoxide anion production and expression levels of cathepsin D, angiotensin-II type 1 receptor and p57^Kip2. The in vitro findings were confirmed histologically in aortas from wild-type and VDRKO mice.

Results

VSMC from VDRKO mice produced more angiotensin-II in culture, and elicited higher levels of cathepsin D, an enzyme with renin-like activity, and angiotensin-II type 1 receptor, than wild-type mice. Accordingly, VDRKO VSMC showed higher intracellular superoxide anion production, which could be suppressed by cathepsin D, angiotensin-II type 1 receptor or NADPH oxidase antagonists. VDRKO cells presented higher levels of p57^Kip2, impaired proliferation and premature senescence, all of them blunted upon inhibition of angiotensin-II signalling. In vivo studies confirmed higher levels of cathepsin D, angiotensin-II type 1 receptor and p57^Kip2 in aortas from VDRKO mice.

Conclusion

The beneficial effects of active vitamin D in vascular health could be a result of the attenuation of local production of angiotensin-II and downstream free radicals, thus preventing the premature senescence of VSMC.