Interference with the Cannabinoid Receptor CB1R Results in Miswiring of GnRH3 and AgRP1 Axons in Zebrafish Embryos

The G protein-coupled cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), and their endocannabinoid (eCBs) ligands, have been implicated in several aspects of brain wiring during development. Here we aim to assess whether interfering with CB1R affects development, neuritogenesis and pathfinding of GnRH and AgRP neurons, forebrain neurons that control respectively reproduction and appetite. We pharmacologically and genetically interfered with CB1R in zebrafish strains with fluorescently labeled GnRH3 and the AgRP1 neurons. By applying CB1R antagonists we observed a reduced number of GnRH3 neurons, fiber misrouting and altered fasciculation. Similar phenotypes were observed by CB1R knockdown. Interfering with CB1R also resulted in a reduced number, misrouting and poor fasciculation of the AgRP1 neuron’s axonal projections. Using a bioinformatic approach followed by qPCR validation, we have attempted to link CB1R functions with known guidance and fasciculation proteins. The search identified stathmin-2, a protein controlling microtubule dynamics, previously demonstrated to be coexpressed with CB1R and now shown to be downregulated upon interference with CB1R in zebrafish. Together, these results raise the likely possibility that embryonic exposure to low doses of CB1R-interfering compounds could impact on the development of the neuroendocrine systems controlling sexual maturation, reproduction and food intake

Low-frequency internal friction in silica glass

Precise low-frequency internal friction measurements on vitreous silica, taken over a wide temperature (4 K160 K the loss angle develops a distinct step-like structure followed by a plateau, both independent of ν, thus signalling the onset of a competing relaxation mechanism with much higher an activation energy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58117/2/epl_80_5_50008.pd

Post-acute COVID-19 neurological syndrome: A new medical challenge

In December 2019, in Wuhan (China), a highly pathogenic coronavirus, named SARS-CoV-2, dramatically emerged. This new virus, which causes severe pneumonia, is rapidly spreading around the world, hence it provoked the COVID-19 pandemic. This emergency launched by SARS-CoV-2 also had, and still has, devastating socio-economic aspects. Assessing the impact of COVID-19 on vulnerable groups of people is crucial for the adaptation of governments’ responses. Growing scientific evidence suggests that it is essential to keep the attention on people after acute SARS-CoV-2 infection; indeed, some clinical manifestations are frequently present even after recovery. There is consensus on the need to define which symptoms persist after the infection and which disabilities may arise after COVID-19. Recent reviews, case reports, and original contributions suggest that various organs may be affected, and neurological symptoms are present in about one third of patients with COVID-19. Neurological complications after severe COVID-19 infection might include delirium, brain inflammation, stroke, and nerve damage. In the recent pandemic, neurologists and neurobiologists have a chance to study key features of infection neurology. Furthermore, the psychological impact of the pandemic should not be underestimated, although there is currently no definition for this condition

5.16 Left Ventricular Geometry In Chronic Kidney Disease

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Comparison of the intestinal microbiome of italian patients with multiple sclerosis and their household relatives

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, caused by a combination of genetic and environmental factors. In recent years, a role in MS pathogenesis was assigned to the gut microbiota. However, different signatures of gut dysbiosis have been shown to depend on environmental factors, like diet and lifestyle. In this study, we compared the gut microbiome in MS patients and their household healthy relatives sharing lifestyle and environmental factors. Faecal metagenomic DNA was extracted and the V3-V4 regions of the conserved bacterial 16S ribosomal RNA gene were amplified and sequenced. While overall bacterial communities were similar, specific families differed between healthy and MS subjects. We observed an increase in Ruminococcaceae, Christensenellaceae, Desulfovibrionaceae, Clostridiales, and Family XIII in MS patients, while Bacteroidaceae, Tannerellaceae, Veillonellaceae, and Burkholderiaceae were more abundant in healthy controls. In addition, principle coordinate analysis showed that the gut microbiome of all MS patients formed a cluster being less diverse than the household relatives and that gut microbiota of MS patients with EDSS 4.5-7 formed a distinct cluster in respect to their controls. Overall, our study is consistent with the hypothesis that MS patients have gut microbial dysbiosis and evidenced the importance of environmental factors in shaping the gut microbiome

Influence of metabolic syndrome on hypertension-related target organ damage

OBJECTIVES: The aim of our study was to analyse, in a wide group of essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS) (defined according to the criteria laid down in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) on markers of preclinical cardiac, renal and retinal damage. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS AND METHODS: A total of 353 young and middle-aged hypertensives, free from cardiovascular and renal diseases (and 37% of whom had MS), underwent echocardiographic examination, microalbuminuria determination and non-mydriatic retinography. RESULTS: When compared with subjects without MS, hypertensive patients with MS exhibited more elevated left ventricular (LV) mass (either normalized by body surface area or by height elevated by a power of 2.7), higher myocardial relative wall thickness, albumin excretion rate (AER) and a greater prevalence of LV hypertrophy (57.7% vs. 25.1%; P < 0.00001), of microalbuminuria (36.2% vs. 19.3%; P = 0.002) and of hypertensive retinopathy (87.7% vs. 48.4%; P < 0.00001). These results held even after correction for age, 24-h blood pressures, duration of hypertension, previous antihypertensive therapy, and gender distribution. The independent relationships between LV mass and MS, and between AER and MS, were confirmed in multivariate regression models including MS together with its individual components. CONCLUSIONS: MS may amplify hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. As these markers of target organ damage are well-known predictors of cardiovascular events, our results may partly explain the enhanced cardiovascular risk associated with MS

Outcomes in Hybrid Breast Reconstruction: A Systematic Review

Background and Objectives: Lipofilling is a commonly performed procedure worldwide for breast augmentation and correction of breast contour deformities. In breast reconstruction, fat grafting has been used as a single reconstructive technique, as well as in combination with other procedures. The aim of the present study is to systematically review available studies in the literature describing the combination of implant-based breast reconstruction and fat grafting, focusing on safety, complications rate, surgical sessions needed to reach a satisfying reconstruction, and patient-reported outcomes. Materials and Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) throughout the whole review protocol. A systematic review of the literature up to April 2022 was performed using Medline, Embase, and Cochrane Library databases. Only studies dealing with implant-based breast reconstruction combined with fat grafting were included. Results: We screened 292 articles by title and abstract. Only 48 articles were assessed for full-text eligibility, and among those, 12 studies were eventually selected. We included a total of 753 breast reconstructions in 585 patients undergoing mastectomy or demolitive breast surgeries other than mastectomy (quadrantectomy, segmentectomy, or lumpectomy) due to breast cancer or genetic predisposition to breast cancer. Overall, the number of complications was 60 (7.9%). The mean volume of fat grafting per breast per session ranged from 59 to 313 mL. The mean number of lipofilling sessions per breast ranged from 1.3 to 3.2. Conclusions: Hybrid breast reconstruction shows similar short-term complications to standard implant-based reconstruction but with the potential to significantly decrease the risk of long-term complications. Moreover, patient satisfaction was achieved with a reasonably low number of lipofilling sessions (1.7 on average)

The peritoneum: healing, immunity and diseases

The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation and activation of a variety of haematopoietic and stromal cells. In physiologic conditions, effective responses to injuries are organized, inflammatory triggers are eliminated, inflammation quickly abates, and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occur and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases

Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma

The expression of p16/CDKN2A, the second most commonly inactivated tumour suppressor gene in cancer, is lost in the majority of chordomas. However, the mechanism(s) leading to its inactivation and contribution to disease progression have only been partially addressed using small patient cohorts. We studied 384 chordoma samples from 320 patients by immunohistochemistry and found that p16 protein was lost in 53% of chordomas and was heterogeneously expressed in these tumours. To determine if CDKN2A copy number loss could explain the absence of p16 protein expression we performed fluorescence in situ hybridisation (FISH) for CDKN2A on consecutive tissue sections. CDKN2A copy number status was altered in 168 of 274 (61%) of samples and copy number loss was the most frequent alteration acquired during clinical disease progression. CDKN2A homozygous deletion was always associated with p16 protein loss but only accounted for 33% of the p16‐negative cases. The remaining immunonegative cases were associated with disomy (27%), monosomy (12%), heterozygous loss (20%) and copy number gain (7%) of CDKN2A, supporting the hypothesis that loss of protein expression might be achieved via epigenetic or post‐transcriptional regulatory mechanisms. We identified that mRNA levels were comparable in tumours with and without p16 protein expression, but other events including DNA promoter hypermethylation, copy number neutral loss of heterozygosity and expression of candidate microRNAs previously implicated in the regulation of CDKN2A expression were not identified to explain the protein loss. The data argue that p16 loss in chordoma is commonly caused by a post‐transcriptional regulatory mechanism that is yet to be defined

VALIDATION OF A MODIFIED MODEL OF TNBS-INDUCED COLITIS IN RATS. HOW TO INDUCE A CHEMICAL COLITIS IN RATS.

Background: there are no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of TNBS is preferred, because it will result in a local Th1 response that has the characteristics of Crohn's disease. material and Methods: A total of 30 rats were randomized into two groups, consisting of a saline control group of ten rats and a TNBS groups of 20 rats. After the animals were anesthesized, 0,5 ml of either 0,9 % saline 8controls) or TNBS 50 mg/Kg dissolved in 50% ethanol were instilled into the colon through a rubber catheter. The experiment was repeated weekly for four weeks, then, the rats were killed at day 40, and the distal colon removed. results: At day 40, the bowel wall basically normal in the control group. In the TNBS group, the bowel lumen became narrow with tickened wall, and the mucosal surface presented adherent membrane with brown black, linear ulcers, proliferous lymphocites tissue, inflammatory granulomas and submucosal neutrophil infiltration. The median score of the severity of the colonic damage was 0 in the control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the rats was 180+35 g in the TNBS group, while it was 215+25 in the control group. Conclusions: The presented experiment is a cost-effective and safe method to induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the risk of a massive loss of rats. This model is rather suitable for the assessment of the effects of potential therapeutic agent