Microglial TNFα controls daily changes in synaptic GABAARs and sleep slow waves.

Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNFα. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves, and support memory consolidation.

Laboratory Diagnostics Accuracy for COVID-19 versus Post-COVID-19 Syndrome in Lung Disease Patients with Multimorbidity.

The laboratory tests and identification of risk factors such as comorbidities are essential in the management, treatment and prognosis of patients with chronic respiratory diseases. Performing rigorous monitoring among patients with post-COVID-19 syndrome and early identification of risk factors associated with poor prognosis are crucial in improving patient outcomes. In the present study, 182 patients diagnosed with COVID-19 and PCI during 2020-2022 were included. A clinical and epidemiological evaluation was performed for each patient. Laboratory tests at admission included complete blood count, Erythrocyte Sedimentation Rate (ESR) and biochemical tests. Receiver operating curve (ROC) and area under the curve (AUC) were calculated to compare the diagnostic performance of each parameter. Regarding comorbidities, arterial hypertension, diabetes mellitus and obesity were the most frequent ones. In the case of chronic lung diseases, asthma and Chronic Obstructive Pulmonary Disease (COPD) were the most frequent. Pleurisy was found especially in patients with PCI Variations in serum LDH values were observed, especially in severe forms of COVID-19 in 2020, with a mean value of 481.44 U/L, compared to patients with PCI, whose mean values (122 U/L) were within the biological range of reference. High neutrophil/lymphocyte ratio (NLR) values quantified in this study were especially associated with moderate and severe forms of COVID-19 and also PCI. The Spearman correlation coefficient was determined to measure the correlations between the clinical parameters of all investigated subjects. A value of p < 0.05 was considered statistically significant. The statistical results indicated that serum lactate dehydrogenase (LDH), glucose and C-reactive protein (CRP) are sensitive markers with a diagnostic role in COVID-19, and lymphocyte (Ly) count, CRP, ESR and glucose were evidenced to be target markers in PCI. LDH values were observed to be statistically significant (p < 0.005) in patients with COVID-19 and obesity evaluated in 2021, while Ly count was statistically significant (p = 0.05) in patients with PCI and arterial hypertension. Regarding comorbidities, it has been observed that obesity, arterial hypertension and cardiovascular diseases represent risk factors in COVID-19/PCI, associated especially with the severe forms of the disease.

Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review.

Long COVID is a recently described entity that is responsible for significant morbidity and that has consequences ranging from mild to life-threatening. The underlying mechanisms are not completely understood, and treatment options are currently limited, as existing data focus more on risk factors and predictors. Smoking has been reported as a risk factor for poor outcomes of acute SARS-CoV-2 infection and seems to also play a role in mediating post-COVID-19 symptoms. We aimed to review relevant work addressing the interaction between smoking and long COVID in order to characterize smoking's role as a risk factor and possibly identify new research directions. Methods: The PubMed/MEDLINE database was searched using the keywords 'smoking', 'long COVID', and 'post-acute COVID' to identify relevant English-language articles published up to October 2023. Results and conclusions: From the 374 initial hits, a total of 36 papers were deemed relevant to the aim of the review. There was significant variability concerning the ways in which tobacco usage was quantified and reported; still, there is compelling evidence linking smoking to an increased risk of developing manifestations of post-acute-COVID disease. Some clinical conditions, such as dyspnea, cardiovascular symptoms, and cognitive or mental-health impairment, seem to be relatively strongly associated with smoking, while the connection between smoking and upper-airway involvement seems less certain. The available data support recommending smoking cessation as a clinical tool for the prevention of long COVID.

Phytochemical Profiling and Biological Activities of Quercus sp. Galls (Oak Galls): A Systematic Review of Studies Published in the Last 5 Years.

Quercus species have been widely used in traditional medicine, and recently, researchers' attention has focused on galls of the genus Quercus as a source of health-promoting phytochemicals. This review presents a summary of the most recent findings on the phytochemistry and bioactivity of oak galls, following the screening of scientific papers published in two relevant databases, PubMed and Embase, between January 2018 and June 2023. The oak galls are rich in active compounds, mostly gallotannins and phenolic acids. Due to these secondary metabolites, the reviewed studies have demonstrated a wide range of biological activities, including antioxidant and anti-inflammatory actions, antimicrobial properties, tissue-protective effects, and antitumor, anti-aging, and hypoglycemic potential. Thus, oak galls are a promising natural matrix, to be considered in obtaining pharmaceutical and cosmetic preparations used in anti-aging strategies and, together with medications, in the management of age-related diseases. In further evaluations, the valuable functional properties of oak galls, reported mostly in preclinical studies, should be confirmed with clinical studies that would also take into account the potential health risks of their use.

Prognostic Role of Clinical Features of Moderate Forms of COVID-19 Requiring Hospitalization.

INTRODUCTION: We aimed to characterize the clinical features of moderate forms of COVID-19 requiring hospitalization and potentially identify predictors for unfavorable outcomes. METHODS: Pooled anonymized clinical data from 452 COVID-19 patients hospitalized in two regional Romanian respiratory disease centers during the Alpha and Delta variant outbreaks were included in the analysis. RESULTS: Cough and shortness of breath were the most common clinical features; older patients exhibited more fatigue and dyspnea and fewer upper airway-related symptoms such as smell loss or sore throat. The presence of confusion, shortness of breath and age over 60 years were significantly associated with worse outcomes (odds ratios 5.73, 2.08 and 3.29, respectively). CONCLUSION: The clinical picture on admission may have a prognostic role for moderate forms of COVID-19. Clear clinical definitions and developing adequate informational infrastructure allowing complex data sharing and analysis might be useful for fast research response should a similar outbreak occur in the future.

Plant-Derived Nutraceuticals Involved in Body Weight Control by Modulating Gene Expression.

Obesity is the most prevalent health problem in the Western world, with pathological body weight gain associated with numerous co-morbidities that can be the main cause of death. There are several factors that can contribute to the development of obesity, such as diet, sedentary lifestyle, and genetic make-up. Genetic predispositions play an important role in obesity, but genetic variations alone cannot fully explain the explosion of obesity, which is why studies have turned to epigenetics. The latest scientific evidence suggests that both genetics and environmental factors contribute to the rise in obesity. Certain variables, such as diet and exercise, have the ability to alter gene expression without affecting the DNA sequence, a phenomenon known as epigenetics. Epigenetic changes are reversible, and reversibility makes these changes attractive targets for therapeutic interventions. While anti-obesity drugs have been proposed to this end in recent decades, their numerous side effects make them not very attractive. On the other hand, the use of nutraceuticals for weight loss is increasing, and studies have shown that some of these products, such as resveratrol, curcumin, epigallocatechin-3-gallate, ginger, capsaicin, and caffeine, can alter gene expression, restoring the normal epigenetic profile and aiding weight loss.

Cerebellar control of fear learning via the cerebellar nuclei-Multiple pathways, multiple mechanisms?

Fear learning is mediated by a large network of brain structures and the understanding of their roles and interactions is constantly progressing. There is a multitude of anatomical and behavioral evidence on the interconnection of the cerebellar nuclei to other structures in the fear network. Regarding the cerebellar nuclei, we focus on the coupling of the cerebellar fastigial nucleus to the fear network and the relation of the cerebellar dentate nucleus to the ventral tegmental area. Many of the fear network structures that receive direct projections from the cerebellar nuclei are playing a role in fear expression or in fear learning and fear extinction learning. We propose that the cerebellum, via its projections to the limbic system, acts as a modulator of fear learning and extinction learning, using prediction-error signaling and regulation of fear related thalamo-cortical oscillations.

The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice.

Fear extinction is a form of inhibitory learning that suppresses the expression of aversive memories and plays a key role in the recovery of anxiety and trauma-related disorders. Here, using male mice, we identify a cerebello-thalamo-cortical pathway regulating fear extinction. The cerebellar fastigial nucleus (FN) projects to the lateral subregion of the mediodorsal thalamic nucleus (MD), which is reciprocally connected with the dorsomedial prefrontal cortex (dmPFC). The inhibition of FN inputs to MD in male mice impairs fear extinction in animals with high fear responses and increases the bursting of MD neurons, a firing pattern known to prevent extinction learning. Indeed, this MD bursting is followed by high levels of the dmPFC 4 Hz oscillations causally associated with fear responses during fear extinction, and the inhibition of FN-MD neurons increases the coherence of MD bursts and oscillations with dmPFC 4 Hz oscillations. Overall, these findings reveal a regulation of fear-related thalamo-cortical dynamics by the cerebellum and its contribution to fear extinction.

Phytochemicals and Biological Activities of Walnut Septum: A Systematic Review.

In the last few decades, scientific evidence has stressed the importance of plants in the prevention and/or supportive treatment of a plethora of diseases, many of them chronic, age-associated disorders. Juglans regia L. is a traditional plant that has been integrated into traditional medicine since ancient times. Due to the presence of biologically active compounds, walnut was used in the treatment of various maladies. Recently, investigations have focused on the walnut by-products and waste products, with research on their valuable constituents and active properties. Among these secondary products, walnut septum was analyzed in several studies, its phytochemical profile described, and some of the biological activities examined. However, compared to other walnut by-products, no comprehensive review to gather all the pertinent scientific knowledge was found in the literature. Therefore, the aim of this study was to critically assess the information furnished by peer-reviewed articles regarding the walnut septum chemical composition and the related biological activities, including antioxidant activities, anti-inflammatory effects, antimicrobial properties, antidiabetic activities, anti-tumor properties, and anti-aging potential. In conclusion, as these preclinical studies showed that walnut septum metabolites were responsible for a wide range of preventive and therapeutic uses, further research should confirm the beneficial outcomes in clinical trials.

The Impact of Ellagitannins and Their Metabolites through Gut Microbiome on the Gut Health and Brain Wellness within the Gut-Brain Axis.

Ellagitannins (ETs) are a large group of bioactive compounds found in plant-source foods, such as pomegranates, berries, and nuts. The consumption of ETs has often been associated with positive effects on many pathologies, including cardiovascular diseases, neurodegenerative syndromes, and cancer. Although multiple biological activities (antioxidant, anti-inflammatory, chemopreventive) have been discussed for ETs, their limited bioavailability prevents reaching significant concentrations in systemic circulation. Instead, urolithins, ET gut microbiota-derived metabolites, are better absorbed and could be the bioactive molecules responsible for the antioxidant and anti-inflammatory activities or anti-tumor cell progression. In this review, we examined the dietary sources, metabolism, and bioavailability of ETs, and analyzed the last recent findings on ETs, ellagic acid, and urolithins, their intestinal and brain activities, the potential mechanisms of action, and the connection between the ET microbiota metabolism and the consequences detected on the gut-brain axis. The current in vitro, in vivo, and clinical studies indicate that ET-rich foods, individual gut microbiomes, or urolithin types could modulate signaling pathways and promote beneficial health effects. A better understanding of the role of these metabolites in disease pathogenesis may assist in the prevention or treatment of pathologies targeting the gut-brain axis.

Assessment of Some Risk Factors and Biological Predictors in the Post COVID-19 Syndrome in Asthmatic Patients.

Long COVID-19 or post-COVID infection (PCI) refers to the prolongation of symptoms in people who have been infected with the SARS-CoV-2 virus. Some meta-analysis studies have shown that patients with comorbidities, such as diabetes, obesity or hypertension, have severe complications after infection with the SARS-CoV-2 virus. The presence of chronic respiratory diseases such as bronchial asthma, COPD, pulmonary hypertension or cystic fibrosis increases the risk of developing severe forms of the COVID-19 disease. The risk of developing the severe form of COVID-19 was observed in patients with bronchial asthma being treated with corticosteroids, but also in those hospitalized with severe asthma. The biological variables determined in patients with PCI infection showed changes, especially in the hematological parameters, but also in some inflammatory markers. The aim of this study was to investigate some biological predictors in post-COVID-19 infection in patients with asthma and various comorbidities. In the case of patients diagnosed with moderate and severe forms of COVID-19, the variation in biological tests has shown high concentrations for serum glucose, lactate dehydrogenase and C-reactive protein. Additionally, the calculation of the relative risk (RR) based on the associated comorbidities in patients with PCI points to higher values for patients with asthma, hypertension, diabetes and obesity (RR moderate/severe form = 0.98/1.52), compared to patients with PCI and asthma (RR moderate/severe form = 0.36/0.63). Based on the statistical results, it can be concluded that the alanine aminotransferase (ALT) activity (p = 0.006) and the age of patients (p = 0.001) are the variables that contribute the most to the separation of the four classes of comorbidities considered.

Antioxidants in Age-Related Diseases and Anti-Aging Strategies.

Aging is an intricate process and an important risk factor in the development and advancement of many disorders [...].

Protective Effects of Wine Polyphenols on Oxidative Stress and Hepatotoxicity Induced by Acrylamide in Rats.

In recent years, it has been increasingly suggested that the consumption of natural polyphenols, in moderate amounts, is beneficial for health. The aim of this study was to investigate the efficacy of a red wine (the administered dose of 7 mL/kg/day being equivalent to ~16.5 mg/kg/day total polyphenols) compared to a white wine (the administered dose of 7 mL/kg/day being equivalent to ~1.7 mg/kg/day total polyphenols), on the prevention of acrylamide-induced subacute hepatic injury and oxidative stress in Wistar rats. Hepatic damage due to acrylamide intoxication (the administered dose being 250 µg/kg body weight, for 28 days, by intragastric gavage) was assessed by employing biochemical parameters (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and by histopathological studies. Markers of oxidative damage were measured in terms of plasma malondialdehyde (MDA), hepatic Thiobarbituric Acid Reactive Substances (TBARS) and glutathione (GSH) levels, and liver antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) activities. Regarding hepatic enzyme activities, treatment with red wine significantly decreased the AST values (p < 0.05), while for the ALT values only a normalization tendency was observed. Treatment with red wine and white wine, respectively, significantly prevented the increase in MDA and TBARS levels (p < 0.05), as well as the depletion of GSH (p < 0.05). Red wine treatment normalized the activities of the antioxidant enzymes CAT and SOD in rats intoxicated with acrylamide, while supplementing the diet with white wine did not produce significant differences in the antioxidant enzyme activities. Histopathological findings revealed a moderate protective effect of red wine after four weeks of daily consumption. Our findings provide evidence that red wine, having a higher phenolic content than white wine, has a significant protective effect on oxidative stress and liver injury induced by acrylamide in rats, through its antioxidative activity.

Walnut Intake Interventions Targeting Biomarkers of Metabolic Syndrome and Inflammation in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Biomarkers of metabolic syndrome and inflammation are pathophysiological predictors and factors of senescence and age-related diseases. Recent evidence showed that particular diet components, such as walnuts rich in antioxidant bioactive compounds and with a balanced lipid profile, could have positive outcomes on human health. A systematic search in PubMed, EMBASE, Cochrane Library, Scopus, and ClinicalTrials.gov databases was performed to retrieve randomized controlled trials published from the beginning of each database through November 2021, reporting on the outcomes of walnut consumption over 22 metabolic syndrome and inflammatory markers in middle-aged and older adults. The search strategy rendered 17 studies in the final selection, including 11 crossover and 6 parallel trials. The study revealed that walnut-enriched diets had statistically significant decreasing effects for triglyceride, total cholesterol, and LDL cholesterol concentrations on some inflammatory markers and presented no consequences on anthropometric and glycemic parameters. Although further studies and better-designed ones are needed to strengthen these findings, the results emphasize the benefits of including walnuts in the dietary plans of this age group.

Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network.

Chronic Levodopa therapy, the gold-standard treatment for Parkinson's Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulation has been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulation induces LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving LID mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effects of cerebellar stimulation. Moreover, cerebellar stimulation reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide motor network, and may be valuable for LID treatment.

GluN3A excitatory glycine receptors control adult cortical and amygdalar circuits.

GluN3A is an atypical glycine-binding subunit of NMDA receptors (NMDARs) whose actions in the brain are mostly unknown. Here, we show that the expression of GluN3A subunits controls the excitability of mouse adult cortical and amygdalar circuits via an unusual signaling mechanism involving the formation of excitatory glycine GluN1/GluN3A receptors (eGlyRs) and their tonic activation by extracellular glycine. eGlyRs are mostly extrasynaptic and reside in specific neuronal populations, including the principal cells of the basolateral amygdala (BLA) and SST-positive interneurons (SST-INs) of the neocortex. In the BLA, tonic eGlyR currents are sensitive to fear-conditioning protocols, are subject to neuromodulation by the dopaminergic system, and control the stability of fear memories. In the neocortex, eGlyRs control the in vivo spiking of SST-INs and the behavior-dependent modulation of cortical activity. GluN3A-containing eGlyRs thus represent a novel and widespread signaling modality in the adult brain, with attributes that strikingly depart from those of conventional NMDARs.

Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia.

Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/-) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.

Comparative Assessment of the Functional Parameters for Metal-Ceramic and All-Ceramic Teeth Restorations in Prosthetic Dentistry-A Literature Review.

The metal-ceramic fixed partial prosthesis is the golden standard for posterior tooth restorations. Following the demands of patients and clinicians for metal-free restorations, all-ceramic materials were developed as they offer an adequate alternative with better optical qualities and good mechanical properties. This study aims to carry out a bibliographic review to assess the survival rate and the biological and technical complications of all-ceramic and metal-ceramic fixed partial dentures. An electronic search for articles in the English language literature was performed using PubMed (MEDLINE). This literature review focused on research studies between 2010 and 2020 that performed clinical studies on tooth-supported fixed partial dentures with a mean follow-up of at least 3 years. All the studies, which analyzed the survival and complications of tooth-supported fixed partial dentures, were included. Thus, 14 studies reporting on 756 all-ceramic and 160 metal-ceramic fixed partial dentures met the inclusion criteria. A comparative analysis was carried out based on all the data existing in the studies included in this review. The metal-ceramic fixed partial dentures showed survival rates of 95% to 100% at 3-, 5-, and 10-year follow-up periods. Zirconia fixed partial dentures were reported to have survival rates of 81% to 100% at 3-, 5-, 9-, 10-year follow-up evaluations. The reinforced glass-ceramic fixed partial dentures showed survival rates of 70% to 93.35% at 5 years, while the alumina FPDs showed a survival rate of 68% at 3 years follow-up. The incidence of caries and loss of vitality were reported as higher for all-ceramic prostheses as compared to the metal-ceramic ones. A significant framework fracture was reported for glass-infiltrated alumina fixed partial dentures in comparison to metal-ceramic fixed partial dentures. All-ceramic and metal-ceramic restorations showed similar survival rates after 3 years, although all-ceramic restorations have problems with technical complications such as chipping, which can lead to framework fractures over time.

The Epidemiology of Bruxism in Relation to Psychological Factors.

The aim of the present study was to establish the prevalence of sleep/awake bruxism among young students in Transylvania and to correlate the presence of this muscle activity with behavioral variations. This analytical, observational, cohort, cross-sectional, and prospective study involved 308 volunteers aged between 19 and 30 years of different nationalities, all students of the "Iuliu Hațieganu" University of Medicine and Pharmacy in Cluj-Napoca, Romania. Subjects were asked to complete an anonymous questionnaire which was structured in five sections. The results obtained from the questionnaires were analyzed separately for sleep bruxism and for awake bruxism. We did not find any statistically significant correlation between awake bruxism or sleep bruxism and age (p = 0.30 and p = 0.37, respectively), sex (p = 0.44 and p = 0.48, respectively), or nationality (p = 0.55 and p = 0.67, respectively). Only a high degree of stress and frustration (p = 0.035 and p = 0.020) was observed in European subjects except for the Romanians and the French, likely related to the difficulties of adapting to the language and lifestyle in Romania. Female sex was statistically significantly associated with an increased level of stress (p = 0.004), duty-related depression (p = 0.006), and duty-related anxiety (p = 0.003). Stress and anxiety can be favorable factors in the appearance of both types of bruxism; however, depression is associated only with awake bruxism.