Disturbed neuronal cholesterol homeostasis has been observed in Alzheimer disease (AD) and contributes to the pathogenesis of AD. As the master switch of cholesterol biosynthesis, the sterol regulatory element-binding protein 2 (SREBP-2) translocates to the nucleus after cleavage/activation, but its expression and activation have not been studied in AD which is the focus of the current study. We found both a significant decrease in the nuclear translocation of N-terminal SREBP-2 accompanied by a significant accumulation of C-terminal SREBP-2 in NFT-containing pyramidal neurons in AD. N-terminal-SREBP-2 is also found in dystrophic neurites around plaques in AD brain. Western blot confirmed a significantly reduced nuclear translocation of mature SREBP-2 (mSREBP-2) in AD brain. Interestingly, reduced nuclear mSREBP-2 was only found in animal models of tauopathies such as 3XTg AD mice and P301L Tau Tg mice but not in CRND8 APP transgenic mice, suggesting that tau alterations likely are involved in the changes of mSREBP-2 distribution and activation in AD. Altogether, our study demonstrated disturbed SREBP-2 signaling in AD and related models, and proved for the first time that tau alterations contribute to disturbed cholesterol homeostasis in AD likely through modulation of nuclear mSREBP-2 translocation.
The incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and lifestyle interventions to treat this disease by addressing the underlying metabolic syndrome are often limited. Many pharmacological interventions are being studied to slow or even reverse NAFLD progression. This review for hepatologists aims to provide an updated understanding of the pathogenesis of NAFLD, current recommended therapies, and the most promising treatment options that are currently under development.
Introduction: Telemedicine emerged during the COVID-19 pandemic as a means for assessing patients in the outpatient setting while reducing the transmission of viral disease. In gastroenterology, several studies exist showing both patient and provider satisfaction with virtual visits. However, several unanswered questions remain regarding the long-term sustainability of telemedicine in clinical practice. The purpose of our study was to assess post-virtual visit patient satisfaction survey ratings and correlation with follow up order completion. Methods: Patient responses to an electronic survey distributed via MyChart from April 2020 to May 2022 were gathered with responses to various questions graded using a 5-point Likert scale. Using natural language processing, we assessed the number of orders placed for patients during these encounters and determined compliance based off order completion. A generalized linear mixed effects model with fixed effects for visit type, and random intercepts for intra-patient correlation was used. A multivariable model was built controlling for age, socioeconomic status, BMI, dementia, stroke and congestive heart failure. Results: Among 241 patients who responded to the satisfaction survey, 69.3% of patients reported a score of 5, equivalent to 'very good', 22.0% reported a score of 4, equivalent to 'good', and 8.7% reported a score between 1-3 equivalent to a range from 'very poor to fair'. Multivariate analysis revealed that patients who reported a score of 4 were 91% less likely to complete orders compared to those who reported a score between 1-3 (P 5 0.049). No significant difference was found comparing a score of 5 to 1-3. Conclusion: While a majority of patients overall rated a positive experience with virtual visits, patients who were to rate their virtual experience as 'good' were significantly less likely to complete their follow up orders. These findings highlight that some dissonance may indeed exist between virtual visit patient satisfaction and the clinical effectiveness of virtual visits.
Introduction: Hepatorenal syndrome (HRS) is a life-threatening complication of advanced cirrhosis with an 85% three-month mortality. However, the prevalence and mortality of HRS in relation to different stages of chronic kidney disease (CKD) are not well studied. Hence, we used the data from the 2019 National Inpatient Sample (NIS) database to compare the mortality in hospitalized patients with HRS across different stages of CKD. Methods: We utilized the 2019 NIS database to identify all adult (.18 years) patients with CKD (N18) and HRS (K76.7) using appropriate ICD-10-CM codes. We categorized chronic kidney disease into CKD I (GFR .590 ml/min), CKD II (GFR560-89 ml/min), CKD III (GFR530-59 ml/min), CKD IV (GFR515-29 ml/min) and CKD V (GFR , 15 ml/min) using the ICD codes N18.1, N18.2, N18.3, N18.4 and N18.5 respectively. A univariate screen followed by multivariate logistic regression was performed to adjust for potential hospital and patient level confounders. Stata 17.0 software was used to perform all statistical analyses. Results: In 2019, there were a total of 46,555 cases of HRS. HRS was found to be more prevalent in males (61.3%) of the white race (67.67%). The total prevalence of patients with HRS was highest among the patients with CKD 3. However, on multivariate analysis, the odds of mortality was higher among patients with CKD stage 2 compared to the other CKD stages (OR 8.1, CI (4.9-13.2), P , 0.01). Conclusion:We would expect that the odds of mortality from HRS will increase as the CKD stage progresses. However, according to our study, patients with CKD stage 2 were found to have the highest odds of mortality with HRS compared to the other stages. This could be explained by patients with CKD stage 4 being on hemodialysis, which decreases pre-transplant mortality in HRS. The findings also suggest potential comorbidities confounding the higher mortality in patients with advanced-stage CKD. Some limitations of this study would include fewer patients in CKD stage 2, leading to a large confidence interval, thus requiring further evaluation with a possible prospective design.
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