Analyzing sex-specific differences in sleep quality, resilience, and biomarkers among older adults in the Gan-Dau Healthy Longevity Plan.

BACKGROUND: Limited knowledge exists regarding the interrelations between sleep quality and resilience within the demographic of healthy, community-residing middle-aged and older adults, with a particular dearth of information regarding sex-specific associations. This study aimed to examine the sex-specific associations between sleep quality, resilience, and biomarkers in community-dwelling middle-aged and older adults. METHODS: This cross-sectional study was conducted using data from the 2022 Gan-Dau Healthy Longevity Plan survey initiated by the locality-based community hospital, Taipei Municipal Gan-Dau Hospital (TMGDH). A total of 770 participants (240 men, 530 women) who met the inclusion criteria were included in the study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), while resilience was measured using the Brief Resilience Scale (BRS). Patient demographic data, including age, education, marital status, and depression level, were also collected. The sex-specific associations between sleep quality and resilience were first examined using multivariate generalized linear models (GLMs). In addition, the associations between sleep quality, resilience, and selected biomarkers were examined using multivariate GLMs. RESULTS: Approximately 55% of men and 60% of women reported poor sleep quality. Individuals with good sleep quality had significantly lower levels of depressive symptoms (p=0.028 for men, p<0.001 for women) and fewer chronic conditions (p=0.0015 for men, p<0.001 for women). Notably, women in the "poor sleep quality" group exhibited higher proportions of low habitual sleep efficiency (35.9%) and frequent use of sleeping medications (23.2%), whereas the proportions were lower in men in the "poor sleep quality" group (29.8% and 9.9%, respectively). Good sleep quality was associated with better resilience in both men (mean BRS score: good sleep quality=25.1 [standard deviation (SD) 4.3] vs. poor sleep quality=23.4 [SD 4.7], p=0.044) and women (mean BRS score: good sleep quality=24.3 [SD 5.1] vs. poor sleep quality=22.3 [SD 5.4], p<0.001). After adjusting for depressive symptoms and chronic conditions, this association remained significant for men (p=0.022) and women (p=0.001). In addition, greater depressive symptoms were associated with poorer resilience in both sexes (p<0.001). No significant associations were noted between sleep quality or resilience and the selected biomarkers. CONCLUSION: This study highlights the association between sleep quality and resilience in older adults. Good sleep quality is related to better resilience, but greater depressive symptoms are also linked to poorer resilience in both sexes. Nevertheless, the low habitual sleep efficiency and frequent use of sleeping medications in women but not men with poor sleep quality highlight the need to explore sex-specific approaches to address the interplay of sleep quality, resilience and other demographic factors (such as depressive symptoms) in healthy aging.

A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.

Can assessment of human assumed central sensitisation improve the predictive accuracy of the STarT Back screening tool in acute low back pain?

BACKGROUND: The STarT Back Screening Tool (SBT) is recommended to provide risk-stratified care in low back pain (LBP), yet its predictive value is moderate for disability and low for pain severity. Assessment of human assumed central sensitisation (HACS) in conjunction with the SBT may improve its predictive accuracy. OBJECTIVES: To examine whether assessment of HACS in acute LBP improves the predictive accuracy of the SBT for LBP recovery at six months in people with acute non-specific LBP. DESIGN: A prospective longitudinal study. METHOD: Data were drawn from the UPWaRD study. One hundred and twenty people with acute non-specific LBP were recruited from the community. Baseline measures included SBT risk status, nociceptive flexor withdrawal reflex, pressure and heat pain thresholds and conditioned pain modulation. Primary outcome was the presence of LBP (pain numeric rating scale ≥1 and Roland Morris Disability Questionnaire score ≥3) at six-month follow-up. Regression coefficients were penalised using the least absolute shrinkage and selection operator technique to select predictor variables. Internal validation was performed using ten-fold cross-validation. RESULTS/FINDINGS: SBT risk status alone did not predict the presence of LBP at six months (area under receiver operating characteristic curve [AUC] = 0.58). Adding measures of HACS to the SBT did not improve discrimination for whether LBP was present at six months (AUC = 0.59). CONCLUSIONS: This study confirmed the suboptimal predictive accuracy of the SBT, administered during acute LBP, for LBP recovery at six months. Assessment of HACS in acute LBP does not improve the predictive accuracy of the SBT.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study.

BACKGROUND: There have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200-250 mm CSF. METHODS: This retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed. RESULTS: A total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200-250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar. CONCLUSIONS: It was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200-250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed.

The reliability and validity of rapid transcranial magnetic stimulation mapping for muscles under active contraction.

Rapid mapping is a transcranial magnetic stimulation (TMS) mapping method which can significantly reduce data collection time compared to traditional approaches. However, its validity and reliability has only been established for upper-limb muscles during resting-state activity. Here, we determined the validity and reliability of rapid mapping for non-upper limb muscles that require active contraction during TMS: the masseter and quadriceps muscles. Eleven healthy participants attended two sessions, spaced two hours apart, each involving rapid and 'traditional' mapping of the masseter muscle and three quadriceps muscles (rectus femoris, vastus medialis, vastus lateralis). Map parameters included map volume, map area and centre of gravity (CoG) in the medial-lateral and anterior-posterior directions. Low to moderate measurement errors (%SEMeas = 10-32) were observed across muscles. Relative reliability varied from good-to-excellent (ICC = 0.63-0.99) for map volume, poor-to-excellent (ICC = 0.11-0.86) for map area, and fair-to-excellent for CoG (ICC = 0.25-0.8) across muscles. There was Bayesian evidence of equivalence (BF's > 3) in most map outcomes between rapid and traditional maps across all muscles, supporting the validity of the rapid mapping method. Overall, rapid TMS mapping produced similar estimates of map parameters to the traditional method, however the reliability results were mixed. As mapping of non-upper limb muscles is relatively challenging, rapid mapping is a promising substitute for traditional mapping, however further work is required to refine this method.

The distinct impacts of sarcopenic and dynapenic obesity on mortality in middle-aged and older adults based on different adiposity metrics: Results from I-Lan Longitudinal Aging Study.

BACKGROUND & AIMS: Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender. METHODS: The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality. RESULTS: This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1-3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1-1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1-2.4, p = 0.019), while defined by other measurements showed no associations in both sexes. CONCLUSIONS: The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults.

The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm.

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

The Influence of Pain Hypersensitivity and Psychological Factors on Pain and Disability in the Transition From Acute to Chronic Low Back Pain: A Longitudinal Exploratory Investigation and Cluster Analysis.

Pain hypersensitivity is present in some people with acute low back pain (LBP) and thought to be involved in the development of chronic LBP. Early evidence suggests that pain hypersensitivity in acute LBP precedes poor long-term outcome. We aimed to examine whether the presence of pain hypersensitivity in acute LBP influenced recovery status at 6 months and differentiated how pain and disability changed over time. Participants with acute nonspecific LBP (<6 weeks after pain onset, N = 118) were included in this longitudinal study. Quantitative sensory testing, including pressure and heat pain thresholds, and conditioned pain modulation and questionnaires were compared at baseline and longitudinally (at 3 and 6 months) between recovered and unrecovered participants. Using k-means clustering, we identified subgroups based on baseline sensory measures alone, and in combination with psychological factors, and compared pain and disability outcomes between subgroups. Sensory measures did not differ at baseline or longitudinally between recovered (N = 50) and unrecovered (N = 68) participants. Subgrouping based on baseline sensory measures alone did not differentiate pain or disability outcomes at any timepoint. Participants with high psychological distress at baseline (N = 19) had greater disability, but not pain, at all timepoints than those with low psychological distress, regardless of the degrees of pain sensitivity. Our findings suggest that pain hypersensitivity in acute LBP does not precede poor recovery at 6 months or differentiate how pain and disability change over time. High psychological distress during acute LBP is associated with unremitting and pronounced disability, while pain severity is unaffected. PERSPECTIVE: Pain hypersensitivity is thought to be involved in the transition to chronic LBP. Contradictory to prevailing hypothesis, our findings suggest pain hypersensitivity alone in acute LBP does not precede poor recovery. High psychological distress in acute LBP has a stronger influence than pain hypersensitivity on long-term disability, but not pain outcomes.

Nailfold capillary measurements correlated to NOTCH3 R544C mutation in preclinical CADASIL patients.

BACKGROUND: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by NOTCH3 mutation. Nailfold capillaroscopy is a non-invasive technique typically used for rheumatic diseases. It has potential in other conditions linked to vascular pathology. However, capillaroscopy in CADASIL has not been explored. This study aims to investigate whether capillaroscopy measurements can correlate with brain vascular changes in preclinical CADASIL patients, specifically those with NOTCH3 mutation. METHODS: This study included 69 participants from the Taiwan Precision Medicine Initiative (TPMI) dataset who visited Taichung Veterans General Hospital from January to December 2022. All individuals underwent genetic studies, brain imaging and nailfold capillaroscopy. The Mann-Whitney U test was used to compare results of brain imaging between carriers and controls. It was also used to compare measurements in nailfold capillaroscopy within each group. Spearman Rank Correlation Analysis was used to explore the relationship between capillary measurements and brain MRI results. RESULTS: White matter hyperintensities (WMH) expression was positively correlated with capillary dimension and negatively correlated with density. Our results presented that R544C carriers exhibited a diffuse increase in WMH (p < 0.001) and a global reduction in gray matter volume but preserved in specific areas. The white matter lesion scores in all brain regions were higher in the mutation carriers than the controls. (p < 0.001). CONCLUSION: This research highlights the association of nailfold capillaroscopy findings with white matter lesions in preclinical CADASIL patients. Capillaroscopy guides an effective screening strategy in individuals with NOTCH3 mutations.

Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.

Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell subpopulation resists temozolomide, undergoes proneural-to-mesenchymal transition (PMT) to evade therapy, and drives recurrence. Through inference of transcriptional regulatory networks (TRNs) of patient-derived GSCs (PD-GSCs) at single-cell resolution, we demonstrate how the topology of transcription factor interaction networks drives distinct trajectories of cell-state transitions in PD-GSCs resistant or susceptible to cytotoxic drug treatment. By experimentally testing predictions based on TRN simulations, we show that drug treatment drives surviving PD-GSCs along a trajectory of intermediate states, exposing vulnerability to potentiated killing by siRNA or a second drug targeting treatment-induced transcriptional programs governing nongenetic cell plasticity. Our findings demonstrate an approach to uncover TRN topology and use it to rationally predict combinatorial treatments that disrupt acquired resistance in GBM.

Follistatin-respiratory connection predicting all-cause mortality among community-dwelling middle-to-old age individuals: Results from the I-Lan Longitudinal Study.

OBJECTIVES: The link between aging and pulmonary function decline is well-established, but the underlying mechanisms have yet to be fully revealed. Serum follistatin, a myokine implicated in muscle degeneration, may play a role in age-related pulmonary changes. This study aims to investigate the relationship between serum follistatin levels and pulmonary function decline in community-dwelling older adults, and evaluate their combined association with all-cause mortality. RESEARCH DESIGN AND METHODS: This longitudinal cohort study utilized data from 751 participants aged ≥50 years in the I-Lan Longitudinal Aging Study between 2018-2019. Serum follistatin levels, spirometry results, demographic and clinical data were retrieved. Participants were stratified based on their follistatin levels. Survival curves and group comparisons based on follistatin levels and decline in peak expiratory flow (PEF) using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards models were further used to identify independent predictors of all-cause mortality during the 52-month follow-up. RESULTS: Elevated follistatin levels significantly correlated with worse pulmonary function, particularly decreased PEF (p = 0.030). Kaplan-Meier analysis revealed the combination of elevated follistatin levels and decreased PEF was associated with increased risk of all-cause mortality (Log-rank p = 0.023). Cox proportional hazards models further identified that concurrent presence of higher follistatin levels and decreased PEF predicted higher risk of all-cause mortality (adjusted HR 3.58, 95% CI: 1.22-10.53, p = 0.020). CONCLUSION: Higher serum follistatin levels correlate with decreased pulmonary function, specifically PEF decline, in community-dwelling older adults. Furthermore, the coexistence of elevated follistatin levels and decreased PEF was associated with risk of all-cause mortality. Follistatin may serve as a biomarker for pulmonary aging and related adverse outcomes.

Sex-specific implications of inflammation in covert cerebral small vessel disease.

BACKGROUND: The relationship between inflammation and covert cerebral small vessel disease (SVD) with regards to sex difference has received limited attention in research. We aim to unravel the intricate associations between inflammation and covert SVD, while also scrutinizing potential sex-based differences in these connections. METHODS: Non-stroke/dementia-free study population was from the I-Lan longitudinal Aging Study. Severity and etiology of SVD were assessed by 3T-MRI in each participant. Systemic and vascular inflammatory-status was determined by the circulatory levels of high-sensitivity C-reactive protein (hsCRP) and homocysteine, respectively. Sex-specific multivariate logistic regression to calculate odds ratios (ORs) and interaction models to scrutinize women-to-men ratios of ORs (RORs) were used to evaluate the potential impact of sex on the associations between inflammatory factors and SVD. RESULTS: Overall, 708 participants (62.19 ± 8.51 years; 392 women) were included. Only women had significant associations between homocysteine levels and covert SVD, particularly in arteriosclerosis/lipohyalinosis SVD (ORs[95%CI]: 1.14[1.03-1.27] and 1.15[1.05-1.27] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively). Furthermore, higher circulatory levels of homocysteine were associated with a greater risk of covert SVD in women compared to men, as evidenced by the RORs [95%CI]: 1.14[1.01-1.29] and 1.14[1.02-1.28] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively. No significant associations were found between circulatory hsCRP levels and SVD in either sex. CONCLUSION: Circulatory homocysteine is associated with covert SVD of arteriosclerosis/lipohyalinosis solely in women. The intricacies underlying the sex-specific effects of homocysteine on SVD at the preclinical stage warrant further investigations, potentially leading to personalized/tailored managements. TRIAL REGISTRATION: Not applicable.

A 5-day course of rTMS before pain onset ameliorates future pain and increases sensorimotor peak alpha frequency.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise as an intervention for pain. An unexplored research question is whether the delivery of rTMS prior to pain onset might protect against a future episode of prolonged pain. The present study aimed to determine i) whether 5 consecutive days of rTMS delivered prior to experimentally-induced prolonged jaw pain could reduce future pain intensity and ii) whether any effects of rTMS on pain were mediated by changes in corticomotor excitability (CME) and/or sensorimotor peak alpha frequency (PAF). On each day from Day 0-4, forty healthy individuals received a single session of active (n = 21) or sham (n = 19) rTMS over the left primary motor cortex. PAF and CME were assessed on Day 0 (before rTMS) and Day 4 (after rTMS). Prolonged pain was induced via intramuscular injection of nerve growth factor (NGF) in the right masseter muscle after the final rTMS session. From Days 5-25, participants completed twice-daily electronic dairies including pain on chewing and yawning (primary outcomes), as well as pain during other activities (e.g. talking), functional limitation in jaw function and muscle soreness (secondary outcomes). Compared to sham, individuals who received active rTMS subsequently experienced lower pain on chewing and yawning. Although active rTMS increased PAF, the effects of rTMS on pain were not mediated by changes in PAF or CME. This study is the first to show that rTMS delivered prior to pain onset can protect against future pain and associated functional impairment. Thus, rTMS may hold promise as a prophylactic intervention for persistent pain.

Can non-invasive brain stimulation modulate peak alpha frequency in the human brain? A systematic review and meta-analysis.

Peak alpha frequency (PAF), the dominant oscillatory frequency within the alpha range (8-12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions, potentially providing new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non-invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre- and post-NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk-of-bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta-analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk-of-bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta-analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = -0.12, 95% CI = -0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. However, it is crucial to note that small sample sizes were used, there was substantial variation in stimulation protocols, and most studies did not specifically target PAF alteration. Further studies are needed to determine NIBS's potential for modulating PAF.

Safeguarding vitality and cognition: The role of sarcopenia in intrinsic capacity decline among octogenarians from multiple cohorts.

BACKGROUND: Sarcopenia and intrinsic capacity (IC) declines pose significant challenges to healthy aging, particularly in the rapidly growing octogenarian population. This study aimed to elucidate the relationship between sarcopenia and declines in IC across multiple cohorts of community-dwelling older adults. METHODS: Data from four Taiwanese cohorts were analyzed. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria (algorithm 1: categorized as either having possible sarcopenia or not (robust); algorithm 2: categorized as robust, possible sarcopenia or sarcopenia). IC was operationalized using the World Health Organization's Integrated Care for Older People (ICOPE) framework (step 1 and step 2), encompassing six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being. Multivariable logistic regression models were adopted to assess the association between sarcopenia and IC decline. RESULTS: Among 599 octogenarians (median age 82.2 years, 54.8% male), the prevalence of possible sarcopenia (algorithm 1) was 64.6%. When adopting algorithm 2, the prevalence of possible sarcopenia and sarcopenia was 46,2% and 32.1%, respectively. After adjusting for covariates, participants with possible sarcopenia or sarcopenia (algorithm 2) were more likely to exhibit declines in vitality (ICOPE Step 1: possible sarcopenia aOR 3.65, sarcopenia aOR 4.74; ICOPE Step 2: possible sarcopenia aOR 5.11, sarcopenia aOR 14.77) and cognition (ICOPE Step 1: possible sarcopenia aOR 2.40, sarcopenia aOR 2.12; ICOPE Step 2: possible sarcopenia aOR 2.02, sarcopenia aOR 2.51) compared to robust individuals. CONCLUSIONS: This study underscores the robust association between sarcopenia and declines in vitality and cognition among octogenarians, highlighting the importance of sarcopenia screening and management in promoting healthy longevity in this vulnerable population.

Survey of hepatitis B virus infection status after 35 years of universal vaccination implementation in Taiwan.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination. METHODS: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated. RESULTS: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed. CONCLUSION: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV.

Numb positively regulates Hedgehog signaling at the ciliary pocket.

Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.

Different Splice Isoforms of Peripheral Triggering Receptor Expressed on Myeloid Cells 2 mRNA Expressions are Associated With Cognitive Decline in Mild Dementia Due to Alzheimer's Disease and Reflect Central Neuroinflammation.

Triggering receptor expressed on myeloid cells 2 (TREM2) is upregulated in activated microglia and may be related to cognitive decline in patients with Alzheimer's disease (AD). There is conflicting evidence regarding the association of peripheral TREM2 mRNA expression/soluble TREM2 (the extracellular domain of TREM2) with cognitive function/neuroinflammation in patients with AD. Herein, we studied the TREM2 and TREM2alt mRNA expression and their association with the cognitive performance in subjects with mild dementia due to AD and healthy controls. In a subgroup of patients with AD, magnetic resonance spectroscopy was used to measure the myo-inositol level in the posterior cingulate cortex, a surrogate marker for neuroinflammation. The results showed that increased TREM2 and TREM2alt mRNA expression is associated with AD pathogenesis at the mild dementia stage, thereby serving as a potential biomarker for early symptomatic stage of AD. TREM2 may exert protective effects on both cognition and central neuroinflammation.