Mcgeeyilmaz6425
The synaptonemal complex (SC) is a proteinaceous structure that is transiently formed during meiosis to promote homologous recombination between maternal and paternal chromosomes. As this structure is required only for meiotic recombination, the proteins constituting the complex are almost undetectable in normal somatic cells, but they can be expressed under the conditions in which the transcriptional machinery is deregulated. Accumulating evidence indicates that they are epigenetically expressed in cancers of various origin. Not surprisingly, in contrast to their meiotic roles, the somatic roles of the SC proteins remain to be investigated. However, it has recently been reported that SYCP3 and SYCE2 control DNA double-strand break repair negatively and positively, respectively, suggesting that the ectopic expression of the SC proteins in somatic cells could be associated with the maintenance of genomic instability. Thus, it is highly likely that the investigation of the somatic roles of the SC proteins would improve our understanding of the mechanisms underlying tumor development.
NLRP3 inflammasome is a critical part of the innate immune system and plays an important role in a variety of inflammatory diseases. However, the effects of NLRP3 inflammasome on periodontitis have not been fully studied.
We used ligature-induced periodontitis models of NLRP3 knockout mice (NLRP3
) and their wildtype (WT) littermates to compare their alveolar bone phenotypes. We further used Lysm-Cre/Rosa
mouse to trace the changes of Lysm-Cre
osteoclast precursors in ligature-induced periodontitis with or without MCC950 treatment. At last, we explored MCC950 as a potential drug for the treatment of periodontitis in vivo and in vitro.
Here, we showed that the number of osteoclast precursors, osteoclast differentiation and alveolar bone loss were reduced in NLRP3
mice compared with WT littermates, by using ligature-induced periodontitis model. Next, MCC950, a specific inhibitor of the NLRP3 inflammasome, was used to inhibit osteoclast precursors differentiation into osteoclast. Further, we used Lysm-Cre/Rosa
mice to demonstrate that MCC950 decreases the number of Lysm-Cre
osteoclast precursors in ligature-induced periodontitis. At last, treatment with MCC950 significantly suppressed alveolar bone loss with reduced IL-1β activation and osteoclast differentiation in ligature-induced periodontitis.
Our findings reveal that NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation.
Our findings reveal that NLRP3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation.
Oral anticoagulation (OAC) based on estimated stroke risk is recommended following catheter ablation (CA) of atrial fibrillation (AF), regardless of the extent of arrhythmia control. However, discontinuing OAC in selected patients may be safe. We sought to evaluate a strategy of OAC discontinuation following AF ablation guided by continuous rhythm monitoring.
We prospectively studied AF ablations performed at our institution from June 2015 to December 2019. Patients that had pre-existing cardiac implantable electronic devices (CIEDs) or underwent insertable cardiac monitor (ICM) implantation immediately following AF ablation were included. OAC was continued for 6 weeks following CA in all patients, following which OAC management was guided by CHA
DS
-VASc score and continuous rhythm monitoring results, according to a prespecified protocol. AF recurrence was defined as ≥30 s (CIEDs) or ≥2 min (ICM). We studied 196 patients (mean age 64.7 ± 11.3 years, 66.8% male, 85.7% ICM, 14.3% CIEDs). Mean CHA
DS
VASc score was 2.2 ± 1.5. One-year AF-free survival following CA was 83% for paroxysmal AF and 63% for persistent AF patients. Diphenhydramine molecular weight Over 3 year follow-up, OAC was discontinued in 57 (33.7%) patients, mean 7.4 ± 7.1 months following ablation. Following discontinuation, OAC was restarted for AF recurrence in 9 (15.8%) patients, mean 11.7 ± 6.8 months after stopping. This discontinuation protocol led to a 21.9% reduction in overall time exposed to OAC. There were no thromboembolic or major bleeding events.
OAC can be discontinued in a significant percentage of patients following CA of AF. When guided by continuous rhythm monitoring, this practice does not unacceptably increase the risk of thromboembolic events.
OAC can be discontinued in a significant percentage of patients following CA of AF. When guided by continuous rhythm monitoring, this practice does not unacceptably increase the risk of thromboembolic events.
To investigate (1) all-payer inpatient volume changes at rural hospitals and (2) whether trends in inpatient volume differ by organizational and geographic characteristics of the hospital and characteristics of the patient population.
We used a retrospective, longitudinal study design. Our study sample consisted of rural hospitals between 2011 and 2017. Inpatient volume was measured as inpatient average daily census (ADC). Additional measured hospital characteristics included census region, Medicare payment type, ownership type, number of beds, local competition, total margin, and whether the hospital was located in a Medicaid expansion state. Measured characteristics of the local patient population included total population size, percent of population aged 65 years or older, and percent of population in poverty. To identify predictors of inpatient volume trends, we fit a linear multiple regression model using generalized estimating equations.
Rural hospitals experienced an average change in ADC of -13% between 2011 and 2017. We found that hospital characteristics (eg, census region, Medicare payment type, ownership type, total margin, whether the hospital was located in a Medicaid expansion state) and patient population characteristics (eg, percent of population in poverty) were significant predictors of inpatient volume trends.
Trends in inpatient volume differ by organizational and geographic characteristics of the hospital and characteristics of the patient population. Researchers and policy makers should continue to explore the causal mechanisms of inpatient volume decline and its role in the financial viability of rural hospitals.
Trends in inpatient volume differ by organizational and geographic characteristics of the hospital and characteristics of the patient population. Researchers and policy makers should continue to explore the causal mechanisms of inpatient volume decline and its role in the financial viability of rural hospitals.