Predictive Criterion Validity of the Parsley Symptom Index Against the Patient-Reported Outcomes Measurement Information System-10 in a Chronic Disease Cohort: Retrospective Cohort Study.

BACKGROUND: Approximately 60% of US adults live with chronic disease, imposing a significant burden on patients and the health care system. With the rise of telehealth, patient-reported outcomes measures (PROMs) have emerged as pivotal tools for managing chronic disease. While numerous PROMs exist, few have been designed explicitly for telehealth settings. The Parsley Symptom Index (PSI) is an electronic patient-reported outcome measure (ePROM) developed specifically for telehealth environments. OBJECTIVE: Our aim is to determine whether the PSI predicts changes in the established Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10) Global Health, a 10-question short form. METHODS: We conducted a retrospective cohort study using data from 367 unique patients, amassing 1170 observations between August 30, 2017, and January 30, 2023. Patients completed the PSI and the PROMIS-10 multiple times throughout the study period. Using univariate regression models, we assess the predictive criterion validity of the PSI against PROMIS-10 scores. RESULTS: This study revealed significant relationships between the PSI and PROMIS-10 physical and mental health scores through comprehensive univariate analyses, thus establishing support for the criterion validity of the PSI. These analyses highlighted the PSI's potential as an insightful tool for understanding and predicting both mental and physical health dimensions. CONCLUSIONS: Our findings emphasize the importance of the PSI in capturing the nuanced interactions between symptomatology and health outcomes. These insights reinforce the value of the PSI in clinical contexts and support its potential as a versatile tool in both research and practice.

Contextualizing the revised Patient Perception of Patient-Centeredness (PPPC-R) scale in primary healthcare settings: a validity and reliability evaluation study.

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. SETTING/PARTICIPANTS: In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. RESULTS: The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: [Formula: see text], P < 0.001, RMSEA = 0.044, CFI = 0.981; factor loadings: 0.553 to 0.888). Cronbach's α also indicated good internal consistency reliability: The overall Cronbach's α was 0.922, and the Cronbach's α for each factor was 0.851, 0.872, and 0.717, respectively. CONCLUSIONS: The Chinese version of the PPPC scale provides a valuable tool for evaluating patient-centered medical service quality.

The use of cardiac magnetic resonance in hypertrophic cardiomyopathy over the past 10 years [2013-2023]: a CiteSpace-based bibliometric analysis.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder characterized by the hypertrophy of a segment of the myocardium. Cardiac magnetic resonance (CMR) has been widely used in the assessment of HCM. However, no bibliometric assessment has been conducted on the progress of research in this field. This study thus aimed to examine the current state of research into the application of CMR in HCM and the hotspots and trends that have emerged in this field over the past decade. Methods: A systematic search was conducted on the Web of Science regarding CMR in the assessment of HCM. The databases were searched from 2013 to June 2023. CiteSpace is an application that can be used to characterize the underlying knowledge of the scientific literature in a given field. We used it to analyze the relationship between publication year and country, institution, journal, author, bibliography, and keywords in the field of CMR for the assessment of HCM. Results: A total of 1,427 articles were included in the analysis. In the assessment of HCM, the findings from the past decade have consistently demonstrated a progressive rise in the quantity of articles pertaining to CMR. The country with the largest number of publications was the United States [310], and the institution with the greatest number of publications was the University College London [45]. The analysis of keywords revealed the diagnosis and management of HCM with CMR to be the current research focus and emerging trend within this academic field. Conclusions: This study used a novel approach to visually analyze the use of CMR in HCM assessment. The current research trajectory in CMR consists of the diagnosis and management of patients with HCM. Although most studies confirmed the indispensability of CMR in the assessment of HCM, larger-scale cohorts are still needed to more comprehensively evaluate the role of CMR in the differential diagnosis, pre- and post-treatment assessment, and long-term management of patients with HCM.

The predictive value of coronary microvascular dysfunction for left ventricular reverse remodelling in dilated cardiomyopathy.

Aims: To evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR). Methods: In this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Timemax), maximum signal intensity (SImax), baseline signal intensity (SIbaseline), and the difference between maximum and baseline signal intensity (SImax-baseline) were measured. Additionally, left ventricular (LV) structure, function parameters, and late gadolinium enhancement (LGE) were also recorded. The parameters were compared between healthy controls and DCM patients. Univariable and multivariable logistic regression analyses were used to determine the predictors of LVRR. Results: With a median follow-up period of 12 months [interquartile range (IQR), 8-13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SIbaseline, and increased Timemax (all p < 0.01). Timemax, SImax, and SImax-baseline were further decreased in LVRR than non-LVRR group (Timemax: 60.35 [IQR, 51.46-74.71] vs. 72.41 [IQR, 59.68-97.70], p = 0.017; SImax: 723.52 [IQR, 209.76-909.27] vs. 810.92 [IQR, 581.30-996.89], p = 0.049; SImax-baseline: 462.99 [IQR, 152.25-580.43] vs. 551.13 [IQR, 402.57-675.36], p = 0.038). In the analysis of multivariate logistic regression, Timemax [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.95-1.00; p = 0.032)], heart rate (OR 1.04; 95% CI 1.01-1.08; p = 0.029), LV remodelling index (OR 1.73; 95% CI 1.06-3.00; p = 0.038) and LGE extent (OR 0.85; 95% CI 0.73-0.96; p = 0.021) were independent predictors of LVRR. Conclusions: CMD could be found in DCM patients and was more impaired in patients with non-LVRR than LVRR patients. Timemax at baseline was an independent predictor of LVRR in DCM.

Ochrobactrum chromiisoli sp. nov., Isolated from Chromium-Contaminated Soil.

A Gram-stain-negative, non-spore-forming, flagellated, motile, aerobic, rod-shaped bacteria strain, designated YY2XT, was isolated from chromium-contaminated soil. Phylogenetic analysis based on 16S rRNA gene, recA gene, and whole genome indicated that the strain represented a new member of the genus Ochrobactrum, family Brucellaceae, class Alphaproteobacteria. The phylogenetic trees based on 16 s rRNA gene, revealed that Falsochrobactrum ovis DSM26720T (96.7%), Ochrobactrum gallinifaecis DSM15295T (96.2%), and Pseudochrobactrum asaccharolyticum DSM25619T (96.2%) are the most closely related phylogenetic neighbors of strain YY2XT. The draft genome of YY2XT was approximately 4,650,646 bp in size with a G + C content of 53.0 mol%. Average nucleotide identity and digital DNA-DNA hybridization values among strain YY2XT and the selected Brucellaceae species were 71.4-83.1% and 13.5-42.7%, which are below the recommended cut-off values for species delineation. Growth of strain YY2XT occurred within pH 5-10 (optimum, pH 7-8), 4 â„ƒ-42 °C (optimum, 30 °C), and NaCl concentrations of 0.0-6.0% (optimum, 1.0%). Major quinone system was ubiquinone 10, the major fatty acids were C16:0, C18:1ω7c, and C16:1ω7c and the major polyamines were spermidine and putrescine. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, and four undefined lipids. On the basis of the phenotypic, genotypic and chemotaxonomic traits, strain YY2XT was considered to represent a novel species of the genus Ochrobactrum, for which the name Ochrobactrum chromiisoli sp. nov. is proposed. The type strain is YY2XT (= CCTCC AB 2023035T = JCM 36000T).

The potential predictive value of cardiac mechanics for left ventricular reverse remodelling in dilated cardiomyopathy.

AIMS: Left ventricular reverse remodelling (LVRR) is an important objective of optimal medical management for dilated cardiomyopathy (DCM) patients, as it is associated with favourable long-term outcomes. Cardiac magnetic resonance (CMR) can comprehensively assess cardiac structure and function. We aimed to assess the CMR parameters at baseline and investigate independent variables to predict LVRR in DCM patients. METHODS AND RESULTS: Nighty-eight initially diagnosed DCM patients who underwent CMR and echocardiography examinations at baseline were included. CMR parameters and feature tracking (FT) based left ventricular (LV) global strain (nStrain) and nStrain indexed to LV cardiac mass index (rStrain) were measured. The predictors of LVRR were determined by multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of CMR parameters and were compared by the DeLong test. At a median follow-up time of 9 [interquartile range, 7-12] months, 35 DCM patients (36%) achieved LVRR. The patients with LVRR had lower LV volume, mass, LGE extent and stroke volume index (LVSVi) and higher left ventricular remodelling index (LVRI), nStrains, rStrains, and peak systolic strain rate (PSSR) in the longitudinal direction and rStrains in the circumferential direction at baseline (all P < 0.05). In the multivariate logistic regression analyses, LVRI [per SD, odds ratio (OR) 1.79; 95% confidence interval (CI) 1.08-2.98; P = 0.024] and the ratio of global longitudinal peak strain (rGLPS) (per SD, OR 1.88; 95% CI 1.18-3.01; P = 0.008) were independent predictors of LVRR. The combination of LVSVi, LVRI, and rGLPS had a greater area under the curve (AUC) than the combination of LVSVi and LVRI (0.75 vs. 0.68), but not significantly (P = 0.09). CONCLUSIONS: Patients with LVRR had a lower LV volume index, lower LVSV index, lower LGE extent, higher LVRI, and preserved myocardial deformation in the longitudinal direction at baseline. LVRI and rGLPS at baseline were independent determinants of LVRR.

Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma.

Emerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed that NAT10 enhanced the metastasis ability and apoptosis resistance of HCC cells in ERS and ERS state. NAT10 could upregulate the modification level of HSP90AA1 mRNA ac4C, maintain the stability of HSP90AA1, and upregulate the expression of HSP90AA1, which further promotes the metastasis of ERS hepatoma cells and the resistance to apoptosis of Lenvatinib. This study proposes a novel mechanism by which NAT10-mediated mRNA ac4C modification regulates tumor metastasis. In addition, we demonstrated the regulatory effect of NAT10-HSP90AA1 on metastasis and drug resistance of ERS in HCC cells.

Population Prevalence of Vision Impairment in US Adults 71 Years and Older: The National Health and Aging Trends Study.

Importance: Existing estimates of the prevalence of vision impairment (VI) in the United States are based on self-reported survey data or measures of visual function that are at least 14 years old. Older adults are at high risk for VI and blindness. There is a need for up-to-date, objectively measured, national epidemiological estimates. Objective: To present updated national epidemiological estimates of VI and blindness in older US adults based on objective visual function testing. Design, Setting, and Participants: This survey study presents a secondary data analysis of the 2021 National Health and Aging Trends Study (NHATS), a population-based, nationally representative panel study of Medicare beneficiaries 65 years and older. NHATS includes community-dwelling older adults or their proxies who complete in-person interviews; annual follow-up interviews are conducted regardless of residential status. Round 11 NHATS data were collected from June to November 2021, and data were analyzed in August 2022. Interventions: In 2021, NHATS incorporated tablet-based tests of distance and near visual acuity and contrast sensitivity with habitual correction. Main Outcomes and Measures: National prevalence of impairment in presenting distance visual acuity (>0.30 logMAR, Snellen equivalent worse than 20/40), presenting near visual acuity (>0.30 logMAR, Snellen equivalent worse than 20/40), and contrast sensitivity (>1 SD below the sample mean). Prevalence estimates stratified by age and socioeconomic and demographic data were calculated. Results: In the 2021 round 11 NHATS sample, there were 3817 respondents. After excluding respondents who did not complete the sample person interview (n = 429) and those with missing vision data (n = 362), there were 3026 participants. Of these, 29.5% (95% CI, 27.3%-31.8%) were 71 to 74 years old, and 55.2% (95% CI, 52.8%-57.6%) were female respondents. The prevalence of VI in US adults 71 years and older was 27.8% (95% CI, 25.5%-30.1%). Distance and near visual acuity and contrast sensitivity impairments were prevalent in 10.3% (95% CI, 8.9%-11.7%), 22.3% (95% CI, 20.3%-24.3%), and 10.0% (95% CI, 8.5%-11.4%), respectively. Older age, less education, and lower income were associated with all types of VI. A higher prevalence of near visual acuity and contrast sensitivity impairments was associated with non-White race and Hispanic ethnicity. Conclusions and Relevance: More than 1 in 4 US adults 71 years and older had VI in 2021, higher than prior estimates. Differences in the prevalence of VI by socioeconomic and demographic factors were observed. These data could inform public health planning.

Validation of a Measure of Role Overload and Gains for End-of-Life Dementia Caregivers.

OBJECTIVES: Caregiving stress process models suggest that heterogeneous contexts differentially contribute to caregivers' experiences of role overload and gains. End-of-life (EOL) caregivers, especially EOL dementia caregivers, facing unique challenges and care tasks, may experience role overload and gains in different ways than other caregivers. This study evaluates measurement invariance of role overload and gains between EOL caregivers and non-EOL caregivers and between EOL dementia and EOL non-dementia caregivers. METHODS: We utilized role gains and overload data from 1,859 family caregivers who participated in Round 7 of the National Study of Caregiving. We ran confirmatory factor analyses to investigate the factorial structure across all caregivers and then examined the structure's configural, metric, and scalar invariance between (a) EOL caregivers and non-EOL caregivers and (b) EOL dementia and EOL non-dementia caregivers. RESULTS: Across the entire sample, the two-factor overload and gains model had good fit (χ 2(19) = 121.37, p < .0001; RMSEA = .053, 90% CI = [.044, .062]; CFI = .954; TLI = .932). Tests of invariance comparing EOL caregivers to non-EOL caregivers and EOL dementia caregivers to EOL non-dementia caregivers maintained configural, metric, and partial scalar invariance. Latent mean comparisons revealed that EOL caregivers had higher role overload (p = .0002), but no different role gains (p = .45), than non-EOL caregivers. Likewise, EOL dementia caregivers had higher role overload (p = .05), but no different role gains (p = .42), than EOL non-dementia caregivers. DISCUSSION: Results offer both a deeper theoretical understanding of end-of-life dementia caregivers' experiences of role overload and gains, and a practical tool to measure those experiences.

Risk factors of vestibular migraine-related brain white matter lesions.

OBJECTIVE AND PURPOSE: Migraine is related to white matter lesions (WMLs), and attack frequency and duration in migraine patients are thought to increase WMLs. However, the relationship between vestibular migraine (VM) and WMLs remains unclear. This study explored the risk factors for WMLs in VM patients and provided a basis for the prevention of WMLs in VM patients. METHODS: A large single-center cross-sectional study of patients with VM was conducted. None of the patients had comorbidities, such as hypertension and diabetes, or adverse lifestyle habits (smoking and drinking). All patients were divided into WML + and WML- groups after assessment of WMLs using magnetic resonance imaging (MRI). After collecting the patient's detailed medical history, statistical analysis was performed. RESULTS: In univariate analysis, the frequency of vertigo was statistically significant between the WML + and WML- groups. However, there was no significant difference in other clinical features. Multivariate regression analysis found that the frequency of vertigo (OR 2.399; 95% CI 1.014-5.679; p = 0.046) was an independent risk factor for WMLs. High frequency of vertigo episodes showed more pronounced risk factors (OR 9.607; 95% CI 1.061-87.014; p = 0.044). CONCLUSION: These results substantiate that vertigo frequency is an independent risk factor for WMLs in VM. A high frequency of vertigo episodes is more likely to be associated with WMLs than a low frequency. These results suggest a possible approach to the prevention of WMLs in VM patients.

Shared Care Networks Assisting Older Adults: New Insights From the National Health and Aging Trends Study.

BACKGROUND AND OBJECTIVES: Caregiving research often assumes older adults receiving care have a primary caregiver who provides the bulk of care. Consequently, little is known about the extent to which care responsibilities are shared more evenly within a care network, the characteristics associated with sharing, or the consequences for meeting older adults' care needs. RESEARCH DESIGN AND METHODS: We analyze a sample of U.S. older adults receiving care from the 2011 National Health and Aging Trends Study (n = 2,398). Based on variables reflecting differences in care hours, activities, and care provided by the whole network, we create network typologies for those with two or more caregivers (n = 1,309) using K-means cluster analysis. We estimate multinomial and logistic regression models to identify factors associated with network type and the association between type and unmet needs. We conduct analyses overall and for older adults living with and without dementia. RESULTS: Analyses reveal four network types: Small, low-intensity shared care network (SCN); large, moderate-intensity SCN; small, low-intensity primary caregiver network (PCN); and moderate-sized, high-intensity PCN. Among all older adults receiving care, 51% have a sole caregiver, 20% have an SCN with no primary caregiver, and 29% have a PCN. Among older adults with dementia receiving intense care, unmet needs are lower among those with an SCN (vs. PCN). DISCUSSION AND IMPLICATIONS: Findings underscore that the primary caregiver construct, although common, does not apply to a substantial share of care networks. Moreover, having an SCN when needs are high may be beneficial to meeting older adult's needs.

Early Versus Late Tracheostomy in Stroke Patients: A Retrospective Analysis.

Objective: The timing of tracheostomy (TR) in severe stroke patients receiving mechanical ventilation has not been determined. In this study, we compared some prognostic indicators of early tracheostomy (ET) and late tracheostomy (LT). A meta-analysis was performed to obtain a higher level of evidence of the timing of TR in patients with severe stroke receiving mechanical ventilation. Methods: The study was a retrospective single-center study. We divided the severe stroke patients who received TR from June 2020 to June 2022 into the ET group and LT group. The demographic characteristics, clinical characteristics and prognostic indices were compared. For this meta-analysis, we systematically searched PubMed and other databases. The compared prognostic indicators included mechanical ventilation time, ICU length of stay (LOS), total LOS, ventilator-related pneumonia (VAP) incidence, and mortality. Results: A total of 61 patients were included in our study, including 32 patients in the ET group and 29 patients in the LT group. Univariate and multivariate analyses showed that the NIHSS score in the ET group was higher than that in the LT group (P < 0.05). In terms of outcome indicators, compared with the LT group, the median mechanical ventilation time in the ET group was shortened by 5.5 days (P = 0.034). The ICU LOS and total LOS in the ET group were significantly lower than those in the LT group (median 14.5 days vs 22 days, P = 0.004; 21 days vs 27 days, P = 0.019). The meta-analysis showed that ET could significantly shorten the ICU LOS (MD -3.89 [95% CI: -6.86, -0.92]) and the total LOS (MD -7.70 [95% CI: -8.57, -6.83]) and significantly reduce the occurrence of VAP (OR 0.75 [95% CI: 0.64, 0.87]). Conclusion: The results of our retrospective study and meta-analysis support that ET can shorten the ICU LOS and total LOS and reduce the occurrence of VAP. Therefore, it has a positive effect on the prognosis of patients with severe stroke who need mechanical ventilation support.

Decision Aid Interventions for Family Caregivers of Persons With Advanced Dementia in Decision-Making About Feeding Options: A Scoping Review.

OBJECTIVES: We provided an overview of the literature on decision aid interventions for family caregivers of older adults with advanced dementia regarding decision making about tube feeding. We synthesized (1) the use of theory during the development, implementation, and evaluation of decision aids; (2) the development, content, and delivery of decision aid interventions; (3) caregivers' experience with decision aid interventions; and (4) the effect of decision aid interventions on caregivers' quality of decision-making about feeding options. DESIGN: Scoping review. METHODS: We conducted a scoping review of peer-reviewed studies published January 1, 2000-June 30, 2022, in MEDLINE, EMBASE, The Cochrane Library, CINAHL, and Web of Science databases. The process was guided by Arksey and O'Malley's methodological framework, which includes identifying the research question, choosing related studies, charting the data, and summarizing results. Empirical articles concerning the decision aid interventions about feeding options were selected. RESULTS: Six publications reporting 4 unique decision aid interventions were included. All the interventions targeted caregivers of older adults with advanced dementia. Three decision aids were culturally adapted from existing decision aids. The Ottawa Decision Support Framework and the International Patient Decision Aid Standards Framework were used in these 6 publications. Interventions aimed to improve decision making regarding tube feeding for caregivers through static delivery methods. Caregivers rated these decision aids as helpful and acceptable. Decisional conflict and knowledge of feeding options were the most common outcomes evaluated. Reduction in decisional conflict and increase in knowledge were consistently found among dementia caregivers, but no intervention effects were found on preferences for the use of tube feeding. CONCLUSIONS AND IMPLICATIONS: Decision aid interventions effectively improve decision-making regarding tube feeding among the target population. Cultural adaptation of an existing decision aid intervention is the main strategy. However, the lack of guidance of a cultural adaptation framework in this process may lead to difficulties explaining caregivers' behavioral changes. Moreover, merely providing information is not enough to change caregivers' preferences or behavior of use of tube feeding. A systematic approach to cultural adaptation and interactive intervention is needed in future studies.

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway.

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target.

D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease.

This study investigated the protective properties and mechanisms of D-mannose against hepatic steatosis in experimental alcoholic liver disease (ALD). Drinking-water supplementation of D-mannose significantly attenuated hepatic steatosis in a standard mouse ALD model established by chronic-binge ethanol feeding, especially hepatocyte lipid deposition. This function of D-mannose on lipid accumulation in hepatocytes was also confirmed using ethanol-treated primary mouse hepatocytes (PMHs) with a D-mannose supplement. Meanwhile, D-mannose regulated lipid metabolism by rescuing ethanol-mediated reduction of fatty acid oxidation genes (PPARα, ACOX1, CPT1) and elevation of lipogenic genes (SREBP1c, ACC1, FASN). PI3K/Akt/mTOR signaling pathway was involved in this effect of D-mannose on lipid metabolism since PI3K/Akt/mTOR pathway inhibitors or agonists could abolish this effect in PMHs. Overall, our findings suggest that D-mannose exhibits its anti-steatosis effect in ALD by regulating hepatocyte lipid metabolism via PI3K/Akt/mTOR signaling pathway.

Mannan-Binding Lectin via Interaction With Cell Surface Calreticulin Promotes Senescence of Activated Hepatic Stellate Cells to Limit Liver Fibrosis Progression.

BACKGROUND & AIMS: Liver fibrosis represents a hallmark of most chronic liver diseases (CLD) triggered by recurrent liver injury and subsequent myofibroblast transdifferentiations of resident hepatic stellate cells (HSCs). Mannan-binding lectin (MBL) is potentially involved in hepatic fibrosis in CLD through unclear mechanisms. Therefore, we investigated the crosstalk between MBL and HSCs, and the consequent effects on fibrosis progression. METHODS: Samples from patients with liver cirrhosis were collected. MBL deficiency (MBL-/-) and wild-type (WT) C57BL/6J mice were used to construct a CCl4-induced liver fibrosis model. Administration of MBL-expressing, liver-specific, adeno-associated virus was performed to restore hepatic MBL expression in MBL-/- mice. The human HSC line LX-2 was used for in vitro experiments. RESULTS: MBL levels in patients with liver cirrhosis were correlated with disease severity. In the CCl4-induced liver fibrosis model, MBL-/- mice showed severer liver fibrosis accompanied by reduced senescent activated HSCs in liver tissue compared with WT mice, which could be inhibited by administering MBL-expressing, liver-specific, adeno-associated virus. Moreover, depleting senescent cells with senolytic treatment could abrogate these differences owing to MBL absence. Furthermore, MBL could interact directly with calreticulin associated with low-density lipoprotein receptor-related protein 1 on the cell surface of HSCs, which further promotes senescence in HSCs by up-regulating the mammalian target of rapamycin/p53/p21 signaling pathway. CONCLUSIONS: MBL as a newfound senescence-promoting modulator and its crosstalk with HSCs in the liver microenvironment is essential for the control of hepatic fibrosis progression, suggesting its potential therapeutic use in treating CLD associated with liver fibrosis.

Oral health conditions and COVID-19: A systematic review and meta-analysis of the current evidence.

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the importance of understanding the underlying conditions that lead to COVID-19. Oral health has systemic implications in the maintenance of a healthy state. This study aimed to summarize evidence on the prevalence of oral health conditions in participants with COVID-19 and assess the associations between oral health conditions and COVID-19 related outcomes. Methods: Article searches were conducted in five databases and the gray literature from December 1, 2019 to March 1, 2021. Studies that reported oral health conditions for participants with COVID-19 and/or examined associations between oral health and COVID-19 were included. Results: We identified 15 articles that encompassed 5,377 participants with COVID-19 from 10 countries. Dry mouth was the most common oral health condition reported (41.0%), followed by oral lesions (38.8%), orofacial pain (18.3%), and periodontal symptoms (11.7%). Based on the pooled odds ratios (ORs), periodontal symptoms were not associated with COVID-19 positivity (OR = 1.1; 95% confidence intervals [CI], 0.73-1.65) or mortality (OR = 2.71; 95% CI, 0.64-11.51), but were associated with COVID-19 severity (OR = 3.18; 95% CI, 1.81-5.58). Conclusions: Oral health conditions are common in participants with COVID-19 and should be considered in both the onset and progression of this disease. Knowledge in this area is still limited, and the quality of the data extracted was low. Further longitudinal studies are needed to ascertain whether oral health conditions are a consequence of infection with SARS-CoV-2 or whether they predate infection and are risk factors for COVID-19.

Development of a nomogram combining multiparametric magnetic resonance imaging and PSA-related parameters to enhance the detection of clinically significant cancer across different region.

OBJECTIVE: Prostate cancer (PCa) is the most prevalent cancer among males. This study attempted to develop a clinically significant prostate cancer (csPCa) risk nomogram including Prostate Imaging-Reporting and Data System (PI-RADS) score and other clinical indexes for initial prostate biopsy in light of the different prostate regions, and internal validation was further conducted. PATIENTS AND METHODS: A retrospective study was performed including 688 patients who underwent ultrasound-guided transperineal magnetic resonance imaging fusion prostate biopsy from December 2016 to July 2019. We constructed nomograms combining PI-RADS score and clinical variables (prostate-specific antigen [PSA], prostate volume (PV), age, free/total PSA, and PSA density) through univariate and multivariate logistic regression to identify patients eligible for biopsy. The performance of the predictive model was evaluated by bootstrap resampling. The area under the curve (AUC) of the receiver-operating characteristic (ROC) analysis was appointed to quantify the accuracy of the primary nomogram model for csPCa. Calibration curves were used to assess the agreement between the biopsy specimen and the predicted probability of the new nomogram. The χ2 test was also applied to evaluate the heterogeneity between fusion biopsy and systematic biopsy based on different PI-RADS scores and prostate regions. RESULTS: A total of 320 of 688 included patients were diagnosed with csPCa. csPCa was defined as Gleason score ≥7. The ROC and concordance-index both presented good performance. The nomogram reached an AUC of 0.867 for predicting csPCa at the peripheral zone; meanwhile, AUC for transitional and apex zones were 0.889 and 0.757, respectively. Statistical significance was detected between fusion biopsy and systematic biopsy for PI-RADS score >3 lesions and lesions at the peripheral and transitional zones. CONCLUSION: We produced a novel nomogram predicting csPCa in patients with suspected imaging according to different locations. Our results indicated that PI-RADS score combined with other clinical parameters showed a robust predictive capacity for csPCa before prostate biopsy. The new nomogram, which incorporates prebiopsy data including PSA, PV, age, and PI-RADS score, can be helpful for clinical decision-making to avoid unnecessary biopsy.