Lindbergweinreich9888
After continuous exposure to ketamine, targeting NLRP3 and caspase-1 with MCC950 or VX765 improved pyroptosis, reduced neuropathological damages, and alleviated cognitive dysfunction.
NLRP3/Caspase-1 axis-dependent pyroptosis is involved in ketamine-induced neuroinflammation and cognitive dysfunction, and it provides a promising strategy to treat ketamine-related neurotoxicity.
NLRP3/Caspase-1 axis-dependent pyroptosis is involved in ketamine-induced neuroinflammation and cognitive dysfunction, and it provides a promising strategy to treat ketamine-related neurotoxicity.With the introduction of endovascular thrombectomy (EVT), a new era for treatment of acute ischemic stroke (AIS) has arrived. However, despite the much larger recanalization rate as compared to thrombolysis alone, final outcome remains far from ideal. This raises the question if some of the previously tested neuroprotective drugs warrant re-evaluation, since these compounds were all tested in studies where large-vessel recanalization was rarely achieved in the acute phase. This review provides an overview of compounds tested in clinical AIS trials and gives insight into which of these drugs warrant a re-evaluation as an add-on therapy for AIS in the era of EVT. A literature search was performed using the search terms "ischemic stroke brain" in title/abstract, and additional filters. After exclusion of papers using pre-defined selection criteria, a total of 89 trials were eligible for review which reported on 56 unique compounds. Trial compounds were divided into 6 categories based on their perceived mode of action systemic haemodynamics, excitotoxicity, neuro-inflammation, blood-brain barrier and vasogenic edema, oxidative and nitrosative stress, neurogenesis/-regeneration and -recovery. Main trial outcomes and safety issues are summarized and promising compounds for re-evaluation are highlighted. Looking at group effect, drugs intervening with oxidative and nitrosative stress and neurogenesis/-regeneration and -recovery appear to have a favourable safety profile and show the most promising results regarding efficacy. Finally, possible theories behind individual and group effects are discussed and recommendation for promising treatment strategies are described.
Lysophosphatidic acid receptors (LPARs) are G-protein-coupled receptors involved in many physiological functions in the central nervous system. However, the role of the LPARs in multiple sclerosis (MS) has not been clearly defined yet.
Here, we investigated the roles of LPARs in myelin oligodendrocyte glycoprotein peptides-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
Pre-inhibition with LPAR1-3 antagonist Ki16425 deteriorated motor disability of EAE
. Specifically, LPAR1-3 antagonist (intraperitoneal) deteriorated symptoms of EAE
associated with increased demyelination, chemokine expression, cellular infiltration, and immune cell activation (microglia and macrophage) in spinal cords of mice compared to the sham group. This LPAR1-3 antagonist also increased the infiltration of CD4
/IFN-γ
(Th1) and CD4
/IL-17
(Th17) cells into spinal cords of EAE
mice along with upregulated mRNA expression of IFN-γ and IL-17 and impaired blood-brain barrier (BBB) in the spinal cord. The underlying mechanism for negative effects of LPAR1-3 antagonist was associated with the overproduction of reactive oxygen species (ROS)-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) 2 and NOX3. Interestingly, LPAR1/2 agonist 1-oleoyl-LPA (LPA 181) (intraperitoneal) ameliorated symptoms of EAE
and improved representative pathological features of spinal cords of EAE
mice.
Our findings strongly suggest that some agents that can stimulate LPARs might have potential therapeutic implications for autoimmune demyelinating diseases such as MS.
Our findings strongly suggest that some agents that can stimulate LPARs might have potential therapeutic implications for autoimmune demyelinating diseases such as MS.
We prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide.
Our original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies.
During a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65-4.50). Each 1mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28-1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10-1.21) for SUA each 1mg/dL increment, 1.22 (1.14-1.30) for the highest versus lowest SUA group, and 1.17 (1.12-1.23) for hyperuricemia versus no hyperuricemia.
Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.
Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.
Physical activity is a modifiable risk factor for health and wellbeing, all-cause mortality and healthy aging. However, for middle- to older-age females less is known about the benefits of sports participation on these outcomes. Further, the acceptability and feasibility of setting-up, implementing and maintaining sports-based programmes for an aging population is an understudied area of inquiry. The current study used the RE-AIM framework to investigate a nationwide Walking Netball (WN) programme.
The evaluation used a mixed-methods approach incorporating a multiple-baseline study, quasi-experimental study, programme monitoring data and qualitative studies to evaluate the programme inthe Women's Institutes (WI) in England. Data were analysed using multilevel growth modelling, mixed-design ANOVAs, multilevel regression, t-testing, and thematic analysis. Data were triangulated to address each dimension of the RE-AIM framework.
The programme reached 1.4% (n = 3148) of the WI population across 82.0% of WI lth in middle- to older- aged women. Future programmes may consider adapted styles of set-up and delivery. These include adapting to people, places and spaces through personalised support and providing a range of resources. Future designs may seek to understand how participation can contribute to healthy aging through longitudinal research beyond 12-months.
The evaluation protocol was published in Open Science Framework in December 2018 prior to follow-up data collection being collected ( https//www.osf.io/dcekz ). Date of registration 17 December 2018.
The evaluation protocol was published in Open Science Framework in December 2018 prior to follow-up data collection being collected ( https//www.osf.io/dcekz ). Date of registration 17 December 2018.
Numerous reports have demonstrated the disproportionate impact that COVID-19 has had on vulnerable populations. Our purpose is to describe our health care system's response to this impact.
We convened a Workgroup with the goal to mitigate the impact of COVID-19 on the most medically vulnerable people in Springfield, Massachusetts, USA, particularly those with significant social needs. We did this through (1) identifying vulnerable patients in high-need geographic areas, (2) developing and implementing a needs assessment/outreach tool tailored to meet cultural, linguistic and religious backgrounds, (3) surveying pharmacies for access to medication delivery, (4) gathering information about sources of food delivery, groceries and/or prepared food, (5) gathering information about means of travel, and (6) assessing need for testing. We then combined these six elements into a patient-oriented branch and a community outreach/engagement branch.
Our highly intentional and methodical approach to patient and communships and created new partnerships that continue to inform us-healthcare entities, healthcare employees, and clinical teams-so that we can grow and learn in order to authentically build trust and engagement.Cumulative studies have shown that metabolic reprogramming is a hallmark of malignant tumors. The emergence of technological advances, such as omics studies, has strongly contributed to the knowledge of cancer metabolism. Cervical cancer is among the most common cancers in women worldwide. Because cervical cancer is a virus-associated cancer and can exist in a precancerous state for years, investigations targeting the metabolic phenotypes of cervical cancer will enhance our understanding of the interference of viruses on host cells and the progression of cervical carcinogenesis. The purpose of this review was to illustrate metabolic perturbations in cervical cancer, the role that human papillomavirus (HPV) plays in remodeling cervical cell metabolism and recent approaches toward application of metabolomics in cervical disease research. Cervical cancer displays typical cancer metabolic profiles, including glycolytic switching, high lactate levels, lipid accumulation and abnormal kynurenine/tryptophan levels. HPV, at least in part, contributes to these alterations. Furthermore, emerging metabolomics data provide global information on the metabolic traits of cervical diseases and may aid in the discovery of biomarkers for diagnosis and therapy.
The C580Y mutation in the Plasmodium falciparum kelch13 gene is the most commonly observed variant in artemisinin-resistant isolates in the Greater Mekong Subregion (GMS). Until 2017, it had not been identified outside the GMS, except for Guyana/Amazonia. In 2017, three parasites carrying the C580Y mutation were identified in Papua New Guinea (PNG). As the C580Y allele rapidly spread in the GMS, there is concern that this mutant is now spreading in PNG.
In 2020, a cross-sectional survey was conducted at two clinics in Wewak, PNG. Symptomatic patients infected with P. falciparum were treated with artemether plus lumefantrine following a national treatment policy. Blood samples were obtained before treatment, and polymorphisms in kelch13, pfcrt, and pfmdr1 were determined. Parasite positivity was examined on day 3. The results were compared with those of previous studies conducted in 2002, 2003, and 2016-2018.
A total of 94 patients were included in this analysis. The proportion of C580Y was significantlyine treatment regimen of artemether plus lumefantrine. Therefore, nationwide surveillance of molecular markers for drug resistance and assessment of its therapeutic effects are important.
