Mcclearygottlieb4816

Rabies is caused by infection of rabies virus (RABV) and remains a serious threat to the global public health. Except for the requirement for cold chain and high cost of human rabies immune globulin, no small molecule drugs are currently available for clinical treatment of rabies. So, it is of great importance to identify novel compounds that can effectively inhibit RABV infection. Artesunate (ART) and dihydroartemisinin (DHA), two derivatives of artemisinin, are widely used for treatment of malaria in adults and children, showing high safety. In this study, we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration (0.1 μmol/L). The antiviral effects of ART and DHA were independent of viral strains and cell lines. Pre-treatment with ART or DHA for 2 h in vitro did not affect the viral replication in host cells, implying that ART and DHA neither reduced the viability of RABV directly nor inhibited the binding and entrance of the virus to host cells. Further studies revealed that ART and DHA inhibited RABV genomic RNA synthesis and viral gene transcription. Treatment with ART or DHA (5 mg/kg) by intramuscular injection improved, to some extent, the survival rate of RABV-challenged mice. Combination treatment with derivatives of artemisinin and mannitol significantly improved the survival rate of RABV-challenged mice. The results suggest that ART and DHA have a great potential to be explored as new anti-rabies agents for treatment of rabies.Secukinumab (Cosentyx®) is a fully human monoclonal antibody that selectively targets interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriatic arthritis (PsA). Administered subcutaneously, the first-in-class anti-IL-17 agent is approved in numerous countries worldwide for the treatment of adults with active PsA. In the phase III FUTURE trials, secukinumab 150 or 300 mg improved the clinical signs and symptoms of PsA versus placebo in patients with active disease despite previous treatment with NSAIDs, biological disease-modifying anti-rheumatic drugs (bDMARDs) and/or tumour necrosis factor inhibitors (TNFi). The benefits of secukinumab were seen regardless of whether or not patients had received previous TNFi therapy, and were maintained during longer term (up to 5 years) treatment. In FUTURE 1 and 5, secukinumab inhibited structural joint damage and was associated with sustained low rates of radiographic progression through 1-3 years of treatment. Treatment with secukinumab improved physical function and health-related quality of life (HR-QOL) and was generally well tolerated, both in the short- and longer-term. In the head-to-head EXCEED trial, secukinumab did not quite attain statistical significance for superiority versus adalimumab in the joint domain. In conclusion, secukinumab is effective across all key PsA domains and is generally well tolerated, and thus represents a useful treatment alternative to TNFi and other bDMARDs in adult patients with active PsA.The small intestine plays roles in the absorption and metabolism of orally administered drugs and chemicals. Tight junctions between intestinal epithelial cells, which form a tight barrier preventing the invasion of pathogens and toxins, are essential components of the intestinal defense system. These intestinal functions have generally been evaluated using established cell lines or primary cells in two-dimensional culture. However, these culture systems have not shown the complexity of the three-dimensional structure and diversity of cell types comprising the intestinal epithelial tissue. Here, we report the generation of intestinal organoids using human induced pluripotent stem cells subjected to sequential treatment with different cytokines and compounds. We further describe the tool for evaluating intestinal barrier functions using organoids as a physiologically relevant human platform.The pathogenesis of primary paroxysmal kinesigenic dyskinesia (PKD) remains unclear, and channelopathy is a possibility. In a pilot study, we found that PKD patients had abnormal exercise test (ET) results. To investigate the ET performances in patients affected by PKD, and the role of the channelopathies in the pathogenesis of PKD, we compared the ET results of PKD patients, control subjects, and hypokalemic periodic paralysis (HoPP) patients, and we analyzed ET changes in 32 PKD patients before and after treatment. Forty-four PKD patients underwent genetic testing for the PRRT2, SCN4A, and CLCN1 genes. Sixteen of 59 (27%) patients had abnormal ET results in the PKD group, while 28 of 35 (80%) patients had abnormal ET results in the HoPP group. Compared with the control group, the PKD group showed a significant decrease in the compound muscle action potential (CMAP) amplitude and area after the long ET (LET), while the HoPP group showed not only greater decreases in the CMAP amplitude and area after the LET but also greater increases in the CMAP amplitude and area immediately after the LET. The ET parameters before and after treatment were not significantly different. Nine of 44 PKD patients carried PRRT2 mutations, but the gene abnormalities were unrelated to any ET parameter. The PKD group demonstrated an abnormal LET result by electromyography (EMG), and this abnormality did not seem to correlate with the PRRT2 variant or sodium channel blocker therapy.

The aim of this study was to determine the type, etiology and the rates of epilepsy and to identify accompanying cognitive and behavioral problems in patients with epileptiform abnormalities in the posterior cerebral localization.

In this study, 3500 patients with at least one EEG record at the EEG Laboratory of Clinical Child Neurology Department of Cerrahpaşa Medical Faculty of Istanbul University were evaluated in 2014-2015. Three hundred forty-six patients were included in the study.

Of the 346 patients included in the study, 42.4% were female and 57.5% were male. The age range of the cases was 1-21 (mean 8.7) years. Epileptiform activities were observed in post TPO region isolatedly in 58,95% (n = 204), post-TPO epileptiform focus with focal epileptiform focus in different localizations in 31.21% (n = 108), generalized epileptiform activity with more than one epileptiform focus in 9.8% (n= 34). In the period of EEG examinations 250 (72.25%) patients had a history of epileptic seizures and / or epilepsy, while 96 (27.74%) had non-epileptic clinical conditions such as behavioral disorder and autism.

In the EEG recordings we examined, sharp and spike wave activities were frequently observed in the post TPO region isolatedly. We believe that this study, which investigated the relationship between focal epilptiform activity in post TPO region and different clinical conditions, will serve as an example for other studies.

In the EEG recordings we examined, sharp and spike wave activities were frequently observed in the post TPO region isolatedly. We believe that this study, which investigated the relationship between focal epilptiform activity in post TPO region and different clinical conditions, will serve as an example for other studies.

Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke.

We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies.

In tgency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Parkinson's disease (PD) is a neurodegenerative pathology characterized by motor and non-motor symptoms that often lead to several impairments. Many studies show the efficacy of different rehabilitation protocols aimed to improve balance and gait functions in PD patients. However, multiple factors may influence rehabilitation outcome. Recently, it has been observed as the cognitive reserve (CR) may influence the rehabilitation outcome, helping to address the patient toward technological or conventional rehabilitation. Our study investigated how CR may affect motor rehabilitation outcomes in PD patients who undergo virtual reality (VR) rehabilitation, aimed at improving walking and balance.

Thirty patients affected by idiopathic PD were enrolled. Patients underwent 12 sessions VR training, over 6 weeks (45 min). Six-Minute Walk Test (6MWT) and Berg Balance Scale (BBS) were used to assess walking and balance, respectively. CR was assessed by Cognitive Reserve Index questionnaire (CRIq).

Significant correlations between CR and change from baseline in walking and balance measures were found, with a significant positive correlation between CRIq and 6MWT (r=0.50, p=0.01) and between CRIq and BBS (r=0.41, p=0.04).

Our results showed that PD patients with higher CR treated with VR improved significantly more in their balance and walking distance than those with lower CR. The current study suggests that VR when aimed to improve balance and walking in PD patients is more effective in patients with higher CR.

Our results showed that PD patients with higher CR treated with VR improved significantly more in their balance and walking distance than those with lower CR. find more The current study suggests that VR when aimed to improve balance and walking in PD patients is more effective in patients with higher CR.

The association between visual impairment and mild cognitive impairment (MCI) has not been investigated to date. Thus, we assessed this association among older adults from six low- and middle-income countries (LMICs) (China, India, Ghana, Mexico, Russia, and South Africa) using nationally representative datasets.

Cross-sectional, community-based data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. Visual acuity was measured using the tumbling ElogMAR chart, and vision impairment (at distance and near) was defined as visual acuity worse than 6/18 (0.48 logMAR) in the better-seeing eye. The definition of MCI was based on the National Institute on Aging-Alzheimer's Association criteria. Multivariable logistic regression was conducted.

Data on 32,715 individuals aged ≥ 50years [mean (SD) age 62.1 (15.6) years; 51.2% females] were analyzed. Compared to those without far or near vision impairment, those with near vision impairment but not far vision impairment (OR = 1.33; 95% CI = 1.