NLRC3 alleviates hypoxia/reoxygenation induced inflammation in RAW264.7 cells by inhibiting K63-linked ubiquitination of TRAF6

BackgroundNOD-like receptor family CARD domain containing 3 (NLRC3) plays an important role in both innate and adaptive immunity. This study was to explore the function and related mechanisms of NLRC3 in a hypoxia/reoxygenation (H/R)-induced inflammatory response in RAW264.7 cells.MethodsLiver ischemia-reperfusion (I/R) model in mice and H/R model in RAW264.7 cells were constructed. Western blotting was used to determine the protein expression level of NLRC3 in liver tissue and NLRC3, TRAF6, p–p65, p65, IκB–α, and the K63-linked ubiquitination level of TRAF6 in cells. The immunofluorescence assay was performed to evaluate the nuclear level of the NF–κB (p65). ELISA was conducted to measure the content of IL–1β in serum and cell supernatant. The interaction between NLRC3 and TRAF6 in cells was analyzed by the Co-IP assay.ResultsThe NLRC3 protein level in liver tissue was decreased with the prolongation of reperfusion time (P < 0.05). The expression of NLRC3 and IκB–α protein in RAW264.7 was decreased gradually, while the expression of p–p65 and TRAF6 proteins and K63-linked ubiquitination of TRAF6 were increased gradually with the prolongation of reoxgenation time (P < 0.05). The Co-IP assay revealed that NLRC3 and TRAF6 can bind to each other directly. However, NLRC3 had no effect on the expression of TRAF6 protein. The ubiquitination test results showed that the K63-linked ubiquitination level of TRAF6 in H/R + Lv–NLRC3 group was significantly lower than that in the H/R + negative control (NC) group (P < 0.05). Moreover, the activation of NF–κB in H/R + Lv–NLRC3 group was inhibited compared with that in the H/R + NC group, and the level of the inflammatory factor IL–1β in the cell culture supernatant was also decreased accordingly (P < 0.05).ConclusionsNLRC3 might alleviate H/R-induced inflammation in RAW264.7 cells by inhibiting K63-linked ubiquitination of TRAF6.     

Yield of ASPECTS and Collateral CTA Selection for Mechanical Thrombectomy within 6–24 hours from Symptom Onset in a Hub and Spoke System

BackgroundRecent extended window trials support the benefit of mechanical thrombectomy in anterior circulation large vessel occlusions with clinical-radiographic dissociation. Using trial imaging criteria, 6% were found eligible for MT in the EW in a hub-and-spoke system. We examined the eligibility and outcomes in consecutive extended window-mechanical thrombectomy patients using more pragmatic selection criteria.MethodsWe retrospectively analyzed single-institution data of anterior circulation large vessel occlusions patients presenting between 6–24 h who underwent mechanical thrombectomy based on a priori determined criteria including non-contrast CT head ASPECTS ≥ 6 and/or CTA collateral scores ASITN/SIR 2-4. Primary outcomes consisted of post-mechanical thrombectomy TICI 2b-3 and 3-month modified Rankin scores; safety outcomes consisted of in-hospital mortality and symptomatic intracerebral hemorrhage.Results767 consecutive acute ischemic strokes patients presented within the 6-24 hour window, and of these 48 (6%) anterior circulation large vessel occlusions patients underwent mechanical thrombectomy. In this cohort the mean age was 63±17 years, 56% were male, the median NIHSS was 16 [IQR 10–19], the median ASPECTS was 9 (IQR 8-10), and 79% (n=38) had good CTA collaterals. Occlusions were primarily M1 MCA (46%), with 29% tandem occlusions. Successful recanalization (mTICI 2b or 3) was achieved in 73% (n=35), while 6% (n=3) of patients developed symptomatic intracerebral hemorrhage. In-hospital mortality was 25% (n=12) while 40% (n=19) achieved 3-month modified Rankin Scores 0–2.ConclusionsOur data suggest the use of pragmatic imaging approach of ASPECTS ≥6 with CTA collateral grade in extended time window which is already established in most hospitals.     

Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.     

Chronic obstructive pulmonary disease with tracheostomy: report of case involving endodontic treatment

Modern medicine has made many advances in the capability to sustain life. The dental profession needs to keep up to date with these changes and be creative in caring for these individuals who are medically compromised and who require special care.¹¹ This sometimes requires the purchase of new equipment; other times it means modifying that which exists. In all instances, the level of care for these individuals requires a team approach and mandates education of all team members. In the case presented, the medical problems necessitated such a team effort to achieve optimal care.