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Front fibrosing alopecia: a new retrospective clinical overview of Fifty eight Egyptian patients together with treatment method result and long-term follow-up.
We demonstrated the brain structure-related and NREM/REM state-related heterogeneity of the motor cortical and hippocampal local sleep in control rats. The distinctly altered local NREM/REM states, alongside their episode dynamics and electroencephalographic (EEG) microstructures, suggest the importance of both the local neuronal network substrate and the NREM/REM neurochemical substrate in the control mechanisms of sleep.Background Oesophagectomy for cancer is associated with long-term decreased health-related quality of life (HRQoL). The aim of this study was to evaluate the effect of co-morbidities on HRQoL among survivors of oesophageal or gastro-oesophageal junctional cancers after 10 years or more. Methods The study included a prospectively collected, population-based cohort, comprising all patients who had surgery for oesophageal or gastro-oesophageal junctional cancer in Sweden in 2001-2005 with follow-up until 31 December 2016. All data regarding patient and tumour characteristics, treatment details and HRQoL were collected using a prospectively created database. Multivariable ANCOVA regression models, adjusting for age, sex, tumour histology, stage and surgical technique, were used to calculate adjusted mean scores with 95 per cent confidence intervals for all HRQoL outcomes. Results A total of 92 survivors (88·5 per cent) responded to the questionnaires. Patients were stratified in two groups according to whether they reported a low or high impact of co-morbidities on general health. Patients in the high-impact group had clinically significantly decreased HRQoL and an increased level of symptoms, but differences between these two groups were not statistically significant. Conclusion Co-morbidities with high impact on general health still contribute to impaired HRQoL 10 years after oesophagectomy for cancer.A group of patients with pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported from China in December 2019. Although several antiviral drugs are widely tested, none of them has been approved as specific antiviral therapy for coronavirus disease 2019 (COVID-19). Accumulating evidence established a hyperinflammatory states or cytokine storm in COVID-19. Among these cytokines, IL-6 plays a key role in cytokine storm and can predict the adverse clinical outcomes and fatality in these patients. Based on the evidence of the significant role of IL-6 in cytokine storm, diabetes mellitus, and cardiovascular diseases as principal comorbidities, it seems that anti-cytokine therapy may be useful in patients with severe COVID-19 to reduce mortality. Recent studies demonstrated that herbal-derived natural products had immunosuppressive and anti-inflammatory properties and exhibited exceptional act on mediators of inflammation. Parthenolide is the principal sesquiterpene lactones and the main biologically active constituent Tanacetum parthenium (commonly known as feverfew) which has could significantly reduce IL-1, IL-2, IL-6, IL-8, and TNF-α production pathways established in several human cell line models in vitro and in vivo studies. Therefore, parthenolide may be one of the herbal candidates for clinical evaluation.RAB7 is a small GTPase that belongs to the Rab family, and as a vesicle trafficking factor it is shown to regulate the transport to late endocytic compartments, autophagosome maturation and organelle function. In present study, we showed the critical roles of RAB7 GTPase on actin dynamics and mitochondria function in oocyte meiosis. RAB7 mainly accumulated at cortex and spindle periphery during oocyte maturation. RAB7 depletion caused the failure of polar body extrusion and asymmetric division, and Rab7 exogenous mRNA supplement could rescue the defects caused by RAB7 RNAi. Based on mass spectrometry analysis, we found that RAB7 associated with several actin nucleation factors and mitochondria-related proteins in oocytes. The depletion of RAB7 caused the decrease of actin dynamics, which further affected meiotic spindle migration to the oocyte cortex. In addition, we found that RAB7 could maintain mitochondrial membrane potential and the mitochondrial distribution in mouse oocytes, and this might be due to its effects on the phosphorylation of DRP1 at Ser616 domain. Taken together, our data indicated that RAB7 transported actin nucleation factor for actin polarization, which further affected the phosphorylation of DRP1 for mitochondria dynamics and the meiotic spindle migration in mouse oocytes.Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2 /FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.Background More women are being diagnosed with alcohol use disorder (AUD), are increasing the amount of alcohol they are drinking, and are partaking in risky drinking behaviors. Compulsive drinking which persists despite negative consequences is a hallmark of AUD. Preclinical aversion-resistant models suggest that females may be more vulnerable to the rewarding effects of alcohol such that they show increased compulsivity when drinking is punished with quinine, a bitter tastant. Methods Male and female C57BL/6J mice were trained in an operant response task on a first-order fixed ratio schedule. Experiment 1 tested responding for escalating concentrations (10 to 25%) of ethanol (EtOH). Experiment 2 assessed the effects of increasing concentrations of quinine (100, 250, or 500 μM) on responding for 10% EtOH followed by a 48-hour 2-bottle choice quinine preference test. Experiment 3 investigated the effects of increasing concentrations of quinine (100, 250, or 500 μM) on responding for 2.5% sucrose. Results Experiment 1 revealed that females respond more than males for 15% EtOH. Experiment 2 showed that females tolerate higher concentrations of quinine in EtOH than males. Males reduced responding for 10% EtOH when adulterated with 250 or 500 µM of quinine, while females did not reduce responding at any concentration of quinine. Males and females also exhibited similar preference for quinine in a 2-bottle drinking task. Experiment 3 demonstrated that both males and females reduced responding for 2.5% sucrose when quinine (100, 250, or 500 μM) was added. Conclusions Females respond more for EtOH at higher concentrations and continue to respond for 10% EtOH at all concentrations of quinine, suggesting that female mice are more motivated to respond for EtOH in an operant self-administration paradigm than males. Understanding behavioral and mechanistic sex differences in responding for alcohol will allow for the advancement of treatments for women with AUD.Background Young adults typically drink in social settings and report high levels of episodic heavy drinking despite a range of adverse consequences. Behavioral economics posits that this may reflect a reinforcer pathology in which alcohol is overvalued relative to other reinforcers. Theoretically, the value of alcohol is related to both the direct pharmacological effects of alcohol (euphoria, sedation) and the associated social reinforcement, but to date no studies have differentiated the value of social vs. solitary drinking. The current study examines two modified hypothetical alcohol purchase tasks (APTs), one explicitly social and one explicitly solitary, in order to quantify the reward value of social vs. solitary drinking and to determine whether there are unique clinical correlates of solitary alcohol demand. Methods Participants were young adults (N = 274, Mage = 25.15, SD = 4.10) recruited from Mturk and from a university subject pool. Participants completed a solitary and social APT, in addition to measures of alcohol consumption and problems. Results Participants reported significantly greater demand in the social APT compared to the solitary APT across all demand indices. Elevated solitary and social demand were associated with elevated levels of alcohol use and problems. Using a residualized change approach, solitary demand amplitude (maximum consumption and expenditure) and persistence (price sensitivity) contributed additional variance above and beyond their social APT composite counterparts in predicting typical drinks per week and the self-care, academic/occupational, and physical dependence subscales of the YAACQ. Conclusions The presence of peers increases alcohol demand compared to a solitary scenario, and greater relative solitary drinking demand may be a risk factor for greater alcohol consumption and problems.Objectives Gli1+ cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1+ cells respond to force and contribute to bone remodelling. Materials and methods We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force. The transgenic mice were utilized to label and inhibit Gli1+ cells, respectively. Additionally, mice that conditional ablate Yes-associated protein (Yap) in Gli1+ cells were applied in the present study. The tooth movement and bone remodelling were analysed. PHA-767491 cost Results We first found Gli1+ cells expressed in periodontal ligament (PDL). They were proliferated and differentiated into osteoblastic cells under tensile force. Next, both pharmacological and genetic Gli1 inhibition models were utilized to confirm that inhibition of Gli1+ cells led to arrest of bone remodelling. Furthermore, immunofluorescence staining identified classical mechanotransduction factor Yap expressed in Gli1+ cells and decreased after suppression of Gli1+ cells. Additionally, conditional ablation of Yap gene in Gli1+ cells inhibited the bone remodelling as well, suggesting Gli1+ cells are force-responsive cells. Conclusions Our findings highlighted that Gli1+ cells in PDL directly respond to orthodontic force and further mediate bone remodelling, thus providing novel functional evidence in the mechanism of bone remodelling and first uncovering the mechanical responsive property of Gli1+ cells.
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