Cognitive Effect of Transcranial Direct Current Stimulation on Left Dorsolateral Prefrontal Cortex in Mild Alzheimer's Disease: A Randomized, Double-Blind, Cross-Over Small-Scale Exploratory Study.

Background: Transcranial direct current stimulation (tDCS) is considered a potential therapeutic instrument for Alzheimer's disease (AD) because it affects long-term synaptic plasticity through the processes of long-term potentiation and long-term depression, thereby improving cognitive ability. Nevertheless, the efficacy of tDCS in treating AD is still debated. Dorsal lateral prefrontal cortex is the main role in executive functions. Objective: We investigate the cognitive effects of tDCS on AD patients. Methods: Thirty mild AD patients aged 66-86 years (mean = 75.6) were included in a double-blind, randomized, sham-controlled crossover study. They were randomly assigned to receive 10 consecutive daily sessions of active tDCS (2 mA for 30 min) or a sham intervention and switched conditions 3 months later. The anodal and cathodal electrodes were placed on the left dorsal lateral prefrontal cortex and the right supraorbital area, respectively. Subjects underwent various neuropsychological assessments before and after the interventions. Results: The results showed that tDCS significantly improved Cognitive Abilities Screening Instrument scores, especially on the items of "concentration and calculation", "orientation", "language ability", and "categorical verbal fluency". Mini-Mental State Examination and Wisconsin Card Sorting Test scores in all domains of "concept formation", "abstract thinking", "cognitive flexibility", and "accuracy" also improved significantly after tDCS. For the sham condition, no difference was found between the baseline scores and the after-intervention scores on any of the neuropsychological tests. Conclusion: >: Using tDCS improves the cognition of AD patients. Further large size clinical trials are necessary to validate the data.

Exacerbated gastrointestinal symptoms and long COVID in IBD patients with SARS-CoV-2 infection: A multi-center study from taiwan.

BACKGROUND/PURPOSE: Limited studies have addressed the exacerbation of symptoms and long COVID in inflammatory bowel disease (IBD) patients following non-severe COVID-19 infection, particularly with post-COVID-19 vaccination. We aim to investigate factors associated with exacerbated gastrointestinal symptoms (EGS) and long COVID in IBD patients with non-severe COVID-19, which is most common situation in daily practice. METHODS: This is an observational study by multiple centers in Taiwan from May 2020 to March 2023. We collected clinical manifestation, data, and medication information from IBD patients with non-severe COVID-19. EGS was defined as increased frequency of diarrhea, bloody stool, and abdomen pain within 14 days after SARS-COV-2 infection. Long COVID was defined following the guidelines of the World Health Organization. RESULTS: Out of 90 patients, most of them (88.9%) received at least standard two doses of COVID-19 vaccination and the majority (87.8%) were mild diseases of COVID-19.30% of patients experienced EGS during COVID-19 with higher ESR levels serving as a predictive factor (Odds ratio: 3.6, 95% confidence interval: 1.2-10.5, P = 0.02). 38.1% of those patients developed long COVID. The patients who experienced EGS during COVID-19 and with a history of longer IBD duration showed a significant association with long COVID (p = 0.03 and p = 0.02). CONCLUSIONS: Our study revealed that EGS and long COVID occurred in one third of IBD patients with non-severe COVID-19, even though most of them had received the standard plus booster vaccination. We identified associated factors for EGS and long COVID, emphasizing the importance of post-COVID-19 follow-up in IBD patients.

Modification in the ascorbate-glutathione cycle leads to a better acclimation to high light in the rose Bengal resistant mutant of Nannochloropsis oceanica.

Understanding how to adapt outdoor cultures of Nannochloropsis oceanica to high light (HL) is vital for boosting productivity. The N. oceanica RB2 mutant, obtained via ethyl methanesulfonate mutagenesis, was chosen for its tolerance to Rose Bengal (RB), a singlet oxygen (1O2) generator. Compared to the wild type (WT), the RB2 mutant showed higher resilience to excess light conditions. Analyzing the ascorbate-glutathione cycle (AGC), involving ascorbate peroxidases (APX, EC 1.11.1.11), dehydroascorbate reductase (DHAR, EC 1.8.5.1), and glutathione reductase (GR, EC 1.8.1.7), in the RB2 mutant under HL stress provided valuable insights. At 250 µmol photon m-2 s-1 (HL), the WT strain displayed superoxide anion radicals (O2▪-) and hydrogen peroxide (H2O2) accumulation, increased lipid peroxidation, and cell death compared to normal light (NL) conditions (50 µmol photon m-2 s-1). The RB2 mutant didn't accumulate O2▪- and H2O2 after HL exposure, and exhibited increased APX, DHAR, and GR activities and transcript levels compared to WT and remained consistent after HL treatment. Although the RB2 mutant had a smaller ascorbate (AsA) pool than the WT, its ability to regenerate dehydroascorbate (DHA) increased post HL exposure, indicated by a higher AsA/DHA ratio. Additionally, under HL conditions, the RB2 mutant displayed an improved glutathione (GSH) regeneration rate (GSH/GSSG ratio) without changing the GSH pool size. Remarkably, H2O2 or menadione (a O2▪- donor) treatment induced cell death in the WT strain but not in the RB2 mutant. These findings emphasize the essential role of AGC in the RB2 mutant of Nannochloropsis in handling photo-oxidative stress.

The Association between Default-mode Network Functional Connectivity and Childhood Trauma on the Symptom Load in Male Adults with Methamphetamine Use Disorder.

Objective: : The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse. We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis. Methods: : Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging. Results: : There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences. Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC. Conclusion: : Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.

Multitask deep learning on mammography to predict extensive intraductal component in invasive breast cancer.

OBJECTIVES: To develop a multitask deep learning (DL) algorithm to automatically classify mammography imaging findings and predict the existence of extensive intraductal component (EIC) in invasive breast cancer. METHODS: Mammograms with invasive breast cancers from 2010 to 2019 were downloaded for two radiologists performing image segmentation and imaging findings annotation. Images were randomly split into training, validation, and test datasets. A multitask approach was performed on the EfficientNet-B0 neural network mainly to predict EIC and classify imaging findings. Three more models were trained for comparison, including a single-task model (predicting EIC), a two-task model (predicting EIC and cell receptor status), and a three-task model (combining the abovementioned tasks). Additionally, these models were trained in a subgroup of invasive ductal carcinoma. The DeLong test was used to examine the difference in model performance. RESULTS: This study enrolled 1459 breast cancers on 3076 images. The EIC-positive rate was 29.0%. The three-task model was the best DL model with an area under the curve (AUC) of EIC prediction of 0.758 and 0.775 at the image and breast (patient) levels, respectively. Mass was the most accurately classified imaging finding (AUC = 0.915), followed by calcifications and mass with calcifications (AUC = 0.878 and 0.824, respectively). Cell receptor status prediction was less accurate (AUC = 0.625-0.653). The multitask approach improves the model training compared to the single-task model, but without significant effects. CONCLUSIONS: A mammography-based multitask DL model can perform simultaneous imaging finding classification and EIC prediction. CLINICAL RELEVANCE STATEMENT: The study results demonstrated the potential of deep learning to extract more information from mammography for clinical decision-making. KEY POINTS: • Extensive intraductal component (EIC) is an independent risk factor of local tumor recurrence after breast-conserving surgery. • A mammography-based deep learning model was trained to predict extensive intraductal component close to radiologists' reading. • The developed multitask deep learning model could perform simultaneous imaging finding classification and extensive intraductal component prediction.

Nontuberculous mycobacterial infection mimicking gynecologic malignancy in a woman living with HIV.

The weakened immune system in people living with HIV (PLWH) can lead to infectious diseases occurring more aggressively and mimicking the clinical manifestations of malignancies. Mycobacterium sherrisii, a slow-growing nontuberculous mycobacterium, may cause opportunistic infections among PLWH. We present a case of a 41-year-old woman who initially presented with fever, vaginal spotting, and a bulky pelvic mass, raising suspicion of uterine malignancy. Following a surgical resection, she was pathologically diagnosed with leiomyoma and endometriosis. However, during an event of needlestick injury, she was unexpectedly found to be HIV-infected and the CD4 count was 157 cells/µL at diagnosis, which prompted a diagnostic work-up for opportunistic infections. The diagnosis of disseminated M. sherrisii infection was confirmed through cultures and special staining of specimens obtained from the pelvic tumor and blood. Subsequently, she was treated with a combination of ethambutol, azithromycin, and levofloxacin. Two months after treatment, abdominal and pelvic computed tomography revealed no evidence of recurrent tumor or abscess formation. Given the frequent association of pelvic masses with gynecologic malignancies in women living with HIV, it can be challenging to differentiate between a cancerous lesion and an infectious process, emphasizing the need for meticulous investigations to minimize the potential for misdiagnosis.

The Potential Benefits of Quercetin for Brain Health: A Review of Anti-Inflammatory and Neuroprotective Mechanisms.

Neuroinflammation is a critical factor in developing and progressing numerous brain diseases, including neurodegenerative diseases. Chronic or excessive neuroinflammation can lead to neurotoxicity, causing brain damage and contributing to the onset and progression of various brain diseases. Therefore, understanding neuroinflammation mechanisms and developing strategies to control them is crucial for treating brain diseases. Studies have shown that neuroinflammation plays a vital role in the progression of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD), and stroke. Additionally, the effects of PM2.5 pollution on the brain, including neuroinflammation and neurotoxicity, are well-documented. Quercetin is a flavonoid, a plant pigment in many fruits, vegetables, and grains. Quercetin has been studied for its potential health benefits, including its anti-inflammatory, antioxidant, and anti-cancer properties. Quercetin may also have a positive impact on immune function and allergy symptoms. In addition, quercetin has been shown to have anti-inflammatory and neuroprotective properties and can activate AMP-activated protein kinase (AMPK), a cellular energy sensor that modulates inflammation and oxidative stress. By reducing inflammation and protecting against neuroinflammatory toxicity, quercetin holds promise as a safe and effective adjunctive therapy for treating neurodegenerative diseases and other brain disorders. Understanding and controlling the mechanisms of NF-κB and NLRP3 inflammasome pathways are crucial for preventing and treating conditions, and quercetin may be a promising tool in this effort. This review article aims to discuss the role of neuroinflammation in the development and progression of various brain disorders, including neurodegenerative diseases and stroke, and the impact of PM2.5 pollution on the brain. The paper also highlights quercetin's potential health benefits and anti-inflammatory and neuroprotective properties.

Combined CRAFITY score and α-fetoprotein response predicts treatment outcomes in patients with unresectable hepatocellular carcinoma receiving anti-programmed death-1 blockade-based immunotherapy.

Biomarkers for predicting the treatment efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with unresectable hepatocellular carcinoma (uHCC) are crucial. Previous studies demonstrated that C-reactive protein and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score at baseline predicted treatment outcomes and that patients with uHCC with AFP response, defined as > 15% decline in AFP level within the initial 3 months of ICI-based therapy, had favorable outcomes when receiving ICI-based therapy. However, whether the combination of CRAFITY score and AFP response could be used to predict treatment efficacy of programmed death-1 (PD-1) blockade-based therapy in uHCC patients remains unclear. We retrospectively enrolled 110 consecutive uHCC patients from May 2017 to March 2022. The median ICI treatment duration was 2.85 (1.67-6.63) months, and 87 patients received combination therapies. The objective response and disease control rates were 21.8% and 46.4%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 2.87 (2.16-3.58) months and 8.20 (4.23-12.17) months, respectively. We categorized patients into three groups based on CRAFITY score (2 vs 0/1) and AFP response: patients with a CRAFITY score of 0/1 and AFP response (Group 1), those with a CRAFITY score of 2 and no AFP response (group 3), and those who did not belong to Group 1 and 3 (i.e., Group 2). The combination of CRAFITY score and AFP response could predict disease control and could predict PFS compared with CRAFITY score or AFP response alone. The combination of CRAFITY score and AFP response was an independent predictor of OS (Group 2 vs Group 1, HR: 4.513, 95% CI 1.990-10.234; Group 3 vs Group 1, HR: 3.551, 95% CI 1.544-8.168). Our findings indicated that the combination of CRAFITY score and AFP response could predict disease control, PFS, and OS in uHCC patients receiving PD-1 blockade-based immunotherapy.

Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. METHOD: We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-ß1 (TGF-ß1), and brain-derived neurotrophic factor (BDNF)] were assessed. RESULTS: BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). CONCLUSION: Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Bevacizumab-Induced Thrombotic Microangiopathy (TMA) in Metastatic Lung Adenocarcinoma Patients Receiving Nivolumab Combined with Bevacizumab, Carboplatin and Paclitaxel: Two Case Reports.

Anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs), combined with bevacizumab and platinum-based chemotherapy, have shown promising efficacy in treating metastatic non-squamous cell lung cancer in phase 3 clinical trials. However, drug-induced nephrotoxicity is an uncommon but threatening adverse effect when using this combination therapy, and should be evaluated and managed carefully. Here, we present two patients experiencing late-onset asymptomatic heavy proteinuria during the clinical trial. Kidney biopsies performed finally identified bevacizumab-induced thrombotic microangiopathy (TMA), and the proteinuria was decreased after discontinuing bevacizumab permanently. Our report suggests that a kidney biopsy is needed for those receiving ICIs in combination with bevacizumab and chemotherapy and experiencing nephrotoxicity such as heavy proteinuria.

Characteristics of and Outcomes After Dialysis-Treated Acute Kidney Injury, 2009-2018: A Taiwanese Multicenter Study.

RATIONALE & OBJECTIVE: Dialysis-treated acute kidney injury (AKI) is increasingly common in intensive care units (ICUs) and is associated with poor outcomes. Few studies have explored the temporal trends in severity of acute illness at dialysis initiation, indications for dialysis, and their association with patient outcomes. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 9,535 adult patients admitted to the ICU who received their first dialysis treatment from Chang Gung Memorial Hospital system in Taiwan from 2009 through 2018. EXPOSURE: Calendar year. OUTCOMES: ICU mortality and dialysis treatment at discharge among hospital survivors. ANALYTICAL APPROACH: The temporal trends during the study period were investigated using test statistics suited for continuous or categorical data. The association between the study year and the risk of mortality was analyzed using multivariable Cox regression with adjustment for relevant clinical variables, including the severity of acute illness, defined by Sequential Organ Failure Assessment (SOFA) score. RESULTS: The mean SOFA score at dialysis initiation decreased slightly from 14.0 in 2009 to 13.6 in 2018. There was no significant trend in the number of indications for dialysis initiation that were fulfilled over time. Observed ICU mortality decreased over time, and the curve appeared to be reverse J-shaped, with a substantial decrease from 56.1% in 2009 to 46.3% in 2015 and a slight increase afterward. The risk of mortality was significantly reduced from 2013 to 2018 compared with 2009 in adjusted models. The decreasing trend in ICU mortality over time remained significant. There was an increase in dialysis treatment at discharge among survivors, mainly in patients with estimated glomerular filtration rate<60mL/min/1.73m2, from 36.8% in 2009 to 43.9% in 2018. LIMITATIONS: Residual confounding from unmeasured factors over time such as severity of comorbidities, detailed medication interventions, and delivered dialysis dose. CONCLUSIONS: We observed reductions in mortality among ICU patients with dialysis-treated acute kidney injury between 2009 and 2018, even after adjusting for dialysis indication and severity of illness at dialysis initiation. However, dialysis treatment at discharge among survivors has increased over time, mainly in patients with preexisting kidney disease. PLAIN-LANGUAGE SUMMARY: The current medical management of severe acute kidney injury (AKI) is primarily limited to supportive care and kidney replacement therapy if indicated, leading to perceptions that outcomes among intensive care unit (ICU) patients with dialysis-treated AKI have not improved. In this multicenter retrospective study of ICU patients with dialysis-treated AKI between 2009 and 2018 in Taiwan, patient mortality decreased over time despite increasing comorbidities. Moreover, the decreasing linear trends remained significant even when considering severity of acute illness at dialysis initiation, which was based on physiologic and laboratory measurements seldom evaluated in previous studies. Further research should explore the basis for these improvements.

Association Between Inflammatory Cytokines, Executive Function, and Substance Use in Patients With Opioid Use Disorder and Amphetamine-Type Stimulants Use Disorder.

BACKGROUND: Long-term opioid and amphetamine-type stimulants (ATS) abuse may affect immunological function and impair executive function. We aimed to determine whether biomarkers of inflammation and executive function were associated with substance use in individuals with opioid use disorder (OUD) and ATS use disorder (ATSUD). The interactions between these biomarkers were also explored. METHODS: We assessed plasma cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, transforming growth factor (TGF)-ß1, brain-derived neurotrophic factor (BDNF), and executive function in terms of the Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) in OUD and ATSUD patients and healthy controls (HC). OUD and ATSUD patients were followed for 12 weeks, and their urine morphine and amphetamine tests, cytokine levels, and executive function were repeatedly measured. RESULTS: We enrolled 483 patients and 145 HC. Plasma TNF-α, CRP, IL-8, IL-6, and BDNF levels and most subscale scores on the WCST and CPT significantly differed between OUD and ATSUD patients and HC. Increased TNF-α levels and more perseveration error on the WCST were significantly associated with more urine drug-positive results and less abstinence. Plasma IL-6 and CRP levels were significantly negatively correlated with WCST and CPT performance. CONCLUSION: OUD and ATSUD patients had more inflammation and worse executive function than HC. Inflammatory markers and WCST performance were associated with their urinary drug results, and higher inflammation was associated with poor executive function. Studies on regulating the inflammatory process and enhancing executive function in OUD and ATSUD are warranted.

Integration of Clinical and CT-Based Radiomic Features for Pretreatment Prediction of Pathologic Complete Response to Neoadjuvant Systemic Therapy in Breast Cancer.

The purpose of the present study was to examine the potential of a machine learning model with integrated clinical and CT-based radiomics features in predicting pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) in breast cancer. Contrast-enhanced CT was performed in 329 patients with breast tumors (n = 331) before NST. Pyradiomics was used for feature extraction, and 107 features of seven classes were extracted. Feature selection was performed on the basis of the intraclass correlation coefficient (ICC), and six ICC thresholds (0.7−0.95) were examined to identify the feature set resulting in optimal model performance. Clinical factors, such as age, clinical stage, cancer cell type, and cell surface receptors, were used for prediction. We tried six machine learning algorithms, and clinical, radiomics, and clinical−radiomics models were trained for each algorithm. Radiomics and clinical−radiomics models with gray level co-occurrence matrix (GLCM) features only were also built for comparison. The linear support vector machine (SVM) regression model trained with radiomics features of ICC ≥0.85 in combination with clinical factors performed the best (AUC = 0.87). The performance of the clinical and radiomics linear SVM models showed statistically significant difference after correction for multiple comparisons (AUC = 0.69 vs. 0.78; p < 0.001). The AUC of the radiomics model trained with GLCM features was significantly lower than that of the radiomics model trained with all seven classes of radiomics features (AUC = 0.85 vs. 0.87; p = 0.011). Integration of clinical and CT-based radiomics features was helpful in the pretreatment prediction of pCR to NST in breast cancer.

Correlation between loneliness, personality traits, and treatment outcomes in patients with methamphetamine use disorder.

The aim of this study was to investigate whether loneliness and personality traits correlate with the treatment outcome of methamphetamine use disorder. In this 1-year longitudinal study, a total 106 participants (98 males, 8 females), with a mean age 36.3 ± 9.6 years were enrolled. We measured UCLA Loneliness Scale and Tridimensional Personality Questionnaire at baseline, while craving level at baseline, week 12, 24, 36, and 48. Urinary methamphetamine tests were given 17 times. For the evaluation of the data, multiple linear regression and generalized linear mixed models were used. The baseline results showed lower levels of the harm avoidance trait and higher levels of loneliness were significantly associated with higher craving levels (p=0.04 and 0.04). Moreover, loneliness was not only positively associated with craving levels (B=0.05, p<0.01) but with urinary methamphetamine positive results (B= 0.08, p=0.03) during one-year treatment. The findings suggested that loneliness was associated with poor methamphetamine treatment outcome (greater craving levels and higher proportion of positive methamphetamine urine tests) and lower harm avoidance traits are associated with higher craving levels.

Loneliness and isolated living status in middle-aged and older adults in Taiwan: exploration on stress-related biomarkers, depressive symptoms, and disability.

PURPOSE: Loneliness is a subjective feeling by which an individual perceives a lack of closeness in interpersonal relationships. An isolated living status is linked with higher odds of risky health behavior. The conflicting impacts of loneliness and isolated living status on stress-related biomarkers, depressive symptoms, and disability remain unexplained. METHODS: Six hundred twenty-nine participants aged 66.0 (SD=7.3) separated into four groups: "Lonely and Isolated," "Not Lonely, but Isolated," "Lonely, but Not Isolated," and "Neither Lonely, nor Isolated," were retrieved from the Social Environment and Biomarkers of Aging Study conducted in 2000. Follow-up health indicators in 2006 included three stress-related biomarkers, depressive symptoms, and two physical disability indicators. A hierarchical regression was performed for the analysis. RESULTS: Firstly, compared to the "Neither Lonely nor Isolated" group, only the "Lonely, but Not Isolated" participants at baseline retained positive associations with the stress-related biomarkers levels 6 years later (urine cortisol level (B=9.25, 95% CI=3.24-15.27), serum Interleukin-6 level (B=2.76, 95% CI=0.72-4.79) and the serum high sensitivity C-reactive protein (hsCRP) level (B=0.40, 95% CI=0.17-0.62)). However, such associations were not observed in the "Lonely and Isolated" participants. Secondly, only "Lonely and Isolated" participants at baseline were positively associated with depressive symptoms 6 years later (B=1.70, 95% CI=0.11-3.30). Finally, the associations between combinations of loneliness and isolated living status and physical disability were eliminated after adjusting the covariables. CONCLUSION: Four combinations of loneliness and isolated living status were associated with different impacts on stress-related biomarkers, depressive symptoms, and physical disability. Further dynamic investigations are warranted.

Liver and Spleen Stiffness Surveillance Through Elastography During and After Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C.

OBJECTIVES: Direct-acting antiviral agents achieve a high cure rate, resulting in early hepatic necroinflammatory resolution and sustained fibrosis regression. This study aimed to obtain longitudinal, concurrent within-subject measurements of liver stiffness (LS) and spleen stiffness (SS) and their correlates over time. METHODS: Participants with hepatitis C (n = 592) receiving direct-acting antiviral-based therapy were monitored through point shear-wave elastography from the treatment baseline (TW0) across follow-up visits in terms of LS and SS. RESULTS: Generalized linear mixed modeling indicated that all LS values (2301 visits) were negatively correlated with the follow-up times (all P < .05) from TW0 to 24 weeks (PW24) after the end of treatment (EOT) and positively correlated with baseline LS values (P < .001). The slopes of declines (preceding minus next) differed significantly (P < .001) between TW0-TW4 (treatment week 4) (0.060 [-0.050 to 0.225] meter/second/month [m/s/mo]) and TW4-EOT (0.010 [-0.030 to 0.075] m/s/mo). All SS values (1704 visits) were negatively correlated with time only at PW24 (P < .001) and positively correlated with baseline SS values (P < .001). The slopes of the SS values differed significantly (P < .001) only between EOT-PW12 (-0.010 [-0.110 to 0.083] m/s/mo) and PW12-PW24 (0.043 [-0.063 to 0.160] m/s/mo). CONCLUSIONS: The biphasic fast-to-slow decline in LS occurred early in the on-treatment phase, which is consistent with the resolution of hepatic necroinflammation. The slow-to-fast decline in SS occurred off treatment. Future studies should investigate the association with regressions in liver fibrosis and portal hypertension.

Hypotensive effect of captopril on deoxycorticosterone acetate-salt-induced hypertensive rat is associated with gut microbiota alteration.

The role of the gut microbiota in various metabolic diseases has been widely studied. This study aims to test the hypothesis that gut microbiota dysbiosis is associated with DOCA-salt-induced hypertension, while captopril, an antihypertensive drug, is able to rebalance the gut microbiota alterations caused by hypertension. Treatment with captopril resulted in an approximate 32 mmHg reduction in systolic blood pressure (162.57 vs. 194.61 mmHg) in DOCA-salt-induced hypertensive rats, although it was significantly higher than that in SHAM rats (136.10 mmHg). Moreover, the nitric oxide (NO) level was significantly increased (20.60 vs. 6.42 µM) while the angiotensin II (Ang II) content (42.40 vs. 59.47 pg/ml) was attenuated nonsignificantly by captopril treatment in comparison to those of DOCA-salt-induced hypertensive rats. The introduction of captopril significantly decreased the levels of tumor necrosis factor-α (TNF-ɑ) and interleukin-6 (IL-6). Hypertrophy and fibrosis in kidneys and hearts were also significantly attenuated by captopril. Furthermore, gut microbiota dysbiosis was observed in DOCA-salt-induced hypertensive rats. The abundances of several phyla and genera, including Proteobacteria, Cyanobacteria, Escherichia-Shigella, Eubacterium nodatum and Ruminococcus, were higher in DOCA-salt-induced hypertensive rats than in SHAM rats, while these changes were reversed by captopril treatment. Of particular interest, the genera Bifidobacterium and Akkermansia, reported as beneficial bacteria in the gut, were abundant in only hypertensive rats treated with captopril. These results provide evidence that captopril has the potential to rebalance the dysbiotic gut microbiota of DOCA-salt-induced hypertensive rats, suggesting that the alteration of the gut flora by captopril may contribute to the hypotensive effect of this drug.

Effects of Black Garlic Extract and Nanoemulsion on the Deoxy Corticosterone Acetate-Salt Induced Hypertension and Its Associated Mild Cognitive Impairment in Rats.

Organosulfur compounds, phenolic acids and flavonoids in raw and black garlic were determined, and followed by preparation of black garlic nanoemulsion for studying their effects on deoxycorticosterone acetate-salt-induced hypertension and associated mild cognitive impairment in rats. Three organosulfur compounds, including diallyl sulfide (87.8 µg/g), diallyl disulfide (203.9 µg/g) and diallyl trisulfide (282.6 µg/g) were detected in black garlic by GC-MS, while gallic acid (19.19 µg/g), p-coumaric acid (27.03 µg/g) and quercetin (22.77 µg/g) were detected by UPLC-MS/MS. High doses of both black garlic extract and nanoemulsion prepared using Tween-80, glycerol, grapeseed oil and water could decrease systolic blood pressure through the elevation of bradykinin and nitric oxide levels as well as diminish aldosterone and angiotensin II levels in rats. In Morris water maze test, they could significantly decrease escape latency and swimming distance and increase the time spent in the target quadrant, accompanied by a decline of acetylcholinesterase activity and malondialdehyde level in the hippocampus as well as a rise in glutathione level and activities of superoxide dismutase, catalase and glutathione peroxidase. In addition, the levels of tumor necrosis factor, interleukin-6 and interleukin-1ß were reduced. Effects of lowering blood pressure and improving learning/memory ability in rats followed the order: lisinopril > black garlic nanoemulsion > black garlic extract.

Lactobacillus plantarum TWK10 Improves Muscle Mass and Functional Performance in Frail Older Adults: A Randomized, Double-Blind Clinical Trial.

Sarcopenia is a condition in which there is a loss of muscle caused by aging and it is one of the most significant factors that affects physical fragility. In recent years, the role of the gut-muscle axis has garnered attention as, along with the gut microbiota, it potentially plays a significant role in muscle regeneration, in addition to nutritional supplements and exercise training. Past studies have found that supplementation with Lactobacillus plantarum TWK10 could effectively increase the muscle mass of animals or adult humans. Therefore, in this study, we investigated whether the supplementation of L. plantarum TWK10 produces increased muscle mass and improves the functional performance of elderly persons with mild fragility. A total of 68 elderly subjects were recruited, of which 13 subjects were excluded or withdrew from the study. We adopted a double-blind design, and the 55 subjects were randomly divided into three groups: the placebo group, the TWK10 low-dose group (2 × 1010 CFU/day) (TWK10-L), and the TWK10 high-dose group (6 × 1010 colony-forming unit (CFU)/day) (TWK10-H). For 18 weeks, all subjects were required to regularly take experimental samples, perform functional activity testing, and have their body composition analyzed before the study and every six weeks after the intervention. Finally, 17 subjects in the placebo group, 12 subjects in the TWK10-L group, and 13 subjects in the TWK10-H group finished the study. It was found that supplementation with TWK10 had a tendency to increase and improve muscle mass, left hand grip strength, lower limb muscle strength, and gait speed and balance after the sixth week, especially in the TWK10-H group, and, as the supplement time was longer up to the 18th week, it had an even greater effect (p < 0.05). In conclusion, consecutive supplementation of L. plantarum TWK10 for more than six weeks could effectively improve the muscle strength and endurance of the elderly, reducing sarcopenia and physical fragility. This trial was registered as NCT04893746.