The Epidemiology, Management and Therapeutic Outcomes of Subdural Empyema in Neonates with Acute Bacterial Meningitis.

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels (p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

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.

Occurrence and risk assessment of glycidyl and 3-monochloropropanediol esters in infant formulas marketed in Taiwan.

Glycidyl esters (GEs) and 3-monochloropropanediol esters (3-MCPDEs) are process contaminants commonly found in refined edible oils which are often added to infant formulas. The Taiwan Food and Drug Administration (TFDA) launched regulations for GEs in infant formulas that went into effect on 1 July 2021. To investigate levels of GEs and 3-MCPDEs in infant formula powder, 45 products were sampled and analysed during 2020-2021. The contents of GEs and 3-MCPDEs in formulas of different brands significantly varied, but their concentrations in all of the formulas complied with European Union (EU) regulations. Infant formulas containing palm oil had significantly higher 3-MCPDE levels in both extracted oils and milk powder than those without palm oil. Concentrations of GEs and 3-MCPDEs in infant formula powder and extracted oils were significantly lower in products from Europe than those from Australia and New Zealand. Infants aged 0-1 years in Taiwan who consumed only infant formula showed a margin of exposure (MoE) exceeding 25,000. Mean consumer exposures to 3-MCPDEs stayed below the tolerable daily intake (TDI), while high exposures at the 95th percentile (P95) exceeded the TDI by 1.7-fold. Herein, we present the changing trends in the risk assessment results of infant formula across various countries in the decade. Implementation of regulations and mitigation strategy effectively reduced the risk of infants being exposed to GEs and 3-MCPDEs through infant formula.

Altered cerebellar and caudate gray-matter volumes and structural covariance networks preceding dual cognitive and mobility impairments in older people.

INTRODUCTION: The neuroanatomical changes driving both cognitive and mobility impairments, an emerging preclinical dementia syndrome, are not fully understood. We examined gray-matter volumes (GMVs) and structural covariance networks (SCNs) abnormalities in community-based older people preceding the conversion to physio-cognitive decline syndrome (PCDS). METHODS: Voxel-wise brain GMV and established SCNs were compared between PCDS and non-PCDS converters. RESULTS: The study included 343 individuals (60.2 ± 6.9 years, 49.6% men) with intact cognitive and mobility functions. Over an average 5.6-year follow-up, 116 transitioned to PCDS. Identified regions with abnormal GMVs in PCDS converters were over cerebellum and caudate, which served as seeds for SCNs establishment. Significant differences in cerebellum-based (to right frontal pole and left middle frontal gyrus) and caudate-based SCNs (to right caudate putamen, right planum temporale, left precentral gyrus, right postcentral gyrus, and left parietal operculum) between converters and nonconverters were observed. DISCUSSION: This study reveals early neuroanatomic changes, emphasizing the cerebellum's role, in dual cognitive and mobility impairments. HIGHLIGHTS: Neuroanatomic precursors of dual cognitive and mobility impairments are identified. Cerebellar GMV reductions and increased right caudate GMV precede the onset of PCDS. Altered cerebellum- and caudate-based SCNs drive PCDS transformation. This research establishes a foundation for understanding PCDS as a specific dementia syndrome.

Sex differences in the frailty phenotype and mortality in the I-Lan longitudinal aging study cohort.

BACKGROUND: Frailty is a common geriatric syndrome related to multiple adverse outcomes. Sex differences in its prevalence and impact on mortality remain incompletely understood. METHODS: This study was conducted with data from the I-Lan Longitudinal Aging Study, in which community-dwelling subjects aged > 50 years without coronary artery disease or diabetes were enrolled. Sex disparities in phenotypically defined frailty and sex-morality predictor interactions were evaluated. Sex- and frailty-stratified analyses of mortality were performed. RESULTS: The sample comprised 1371 subjects (51.4% women, median age 61 years). The median follow-up period was 6.3 (interquartile range, 5.8-7.0) years. The frailty prevalence did not differ between men (5.3%) and women (5.8%). Frail individuals were older and less educated and had poorer renal function than did non-frail individuals. Body composition trends differed between sexes, regardless of frailty. Relative to non-frail men, frail men had significantly lower body mass indices (BMIs; 24.5 vs. 23.4 kg/m2, p = 0.04) and relative appendicular skeletal muscle masses (7.87 vs. 7.05 kg/m2, p < 0.001). Frail women had significantly higher BMIs (25.2 vs. 23.9 kg/m2, p = 0.02) and waist circumferences (88 vs. 80 cm, p < 0.001) than did non-frail women. Frailty was an independent mortality predictor for men only [hazard ratio (95% confidence interval) = 3.395 (1.809-6.371), psex-frailty interaction = 0.03]. CONCLUSION: Frailty reflected poorer health in men than in women in the present cohort. This study revealed sex disparities in the impact of frailty on mortality among relatively healthy community-dwelling older adults.

Intrinsic capacity and multimorbidity predicting incident disability-Insights from the I-Lan Longitudinal Aging Study.

OBJECTIVES: This longitudinal cohort study aimed to examine the effect of intrinsic capacity (IC) and multimorbidity on the development of new disabilities. METHODS: The study utilized data from 1,009 participants without disabilities from the I-Lan Longitudinal Aging Study. Multivariable logistic regressions were employed to assess the predictive capability of IC (ranging from 0 to 100) and multimorbidity for incident disability over a 7-year follow-up period. RESULTS: Both low IC (OR 4.9, 95 % CI 2.1-11.1, p < 0.001) and multimorbidity (OR 4.5, 95 % CI 2.2-9.2, p < 0.001) significantly predicted incident disability over the 7-year period. A one-point increase in IC reduced the risk of incident disability by 10 % (OR 0.9, 95 % CI 0.8-0.9, p < 0.001). Among IC subdomains, both better locomotion (OR 0.96, 95 % CI 0.94-0.99, p = 0.014) and psychology (OR 0.97, 95 %CI 0.94-1.00, p = 0.049) significantly reduced the risk of incident disability. Rapid declines in IC significantly predicted incident disability (OR 4.1, 95 % CI 1.8-9.3, p = 0.001), whereas the onset of new multimorbidity or changes in the number of chronic conditions did not demonstrate a significant association with incident disability. The interaction terms between IC and multimorbidity, both categorically (low IC * multimorbidity, p = 0.959) and numerically (IC (per point) * multimorbidity, p = 0.660) were all statistically insignificant. CONCLUSIONS: IC exhibited better predictive capacity for 7-year incident disability compared to multimorbidity, so health care services targeting older adults should adopt an integrated care approach that combines both function- and disease-centric strategies.

Probabilistic risk assessment for determining nonessential metals in commercial infant formula products in Taiwan.

During the early months of life, infant formula plays a crucial role as a primary source of both food and essential nutrients for infants, serving as a replacement for or supplement to breast milk. However, nonessential metals in infant formulas are a concern because infants are highly vulnerable to chemical exposure. The aim of this study was to investigate infant exposure to nonessential metals in infant formula products in Taiwan and assess the associated health risks. In this study, concentrations of arsenic (As), barium (Ba), cadmium (Cd), manganese (Mn), lead (Pb), and vanadium (V) in 45 formula products for 0-1-year-old infants were determined by inductively coupled plasma mass spectrometry. The mean As, Ba, Cd, Mn, Pb, and V concentrations were 6.42, 280, 3.72, 1425, 20.4, and 21.9 µg/kg, respectively. According to our probabilistic simulation of the estimated daily intake of metals, the proportion of hazard quotients exceeding one was 7.69% for As and 3.29% for Mn, and that of hazard index (HI) values exceeding 1 was >17% for metals. Arsenic had the largest HI contribution (46.9%), followed by Mn (22.3%) and Pb (12.7%). The nonessential metals content in infant formula raises potential noncarcinogenic health concerns for infants in Taiwan. Therefore, regulations for nonessential metals must be imposed on related food products in Taiwan, with a particular focus on As and Mn.

Enhancing Intrinsic Capacity and Related Biomarkers in Community-Dwelling Multimorbid Older Adults Through Integrated Multidomain Interventions: Ancillary Findings From the Taiwan Integrated Geriatric (TIGER) Trial.

OBJECTIVE: This study aimed to evaluate the efficacy of integrated multidomain interventions and primary health care on intrinsic capacity (IC) and related biomarkers. DESIGN: An ancillary analysis from the Taiwan Integrated Geriatric Care (TIGER) study: a randomized controlled trial. SETTING AND PARTICIPANTS: A total of 398 community-dwelling older adults aged ≥65 years with ≥3 chronic conditions. METHODS: Participants were randomized into the 12-month pragmatic multidomain intervention or usual care groups. The primary outcome was the change in IC and its subdomains (locomotion, cognition, vitality, psychological, and sensory) at baseline and 3-, 6-, 9-, and 12-month follow-ups. Generalized linear mixed models were used to evaluate the multidomain intervention effects on these changes. RESULTS: The intervention arm had greater improvement in IC than the usual care arm (overall difference 1.5; 95% CI 0.5-2.5; P = .005), mainly from subdomains of locomotion (overall difference 1.4; 95% CI 0.5-2.4; P = .004) and cognition (2.9; 95% CI 2.1-3.7; P < .001). Changes in neutrophil-to-lymphocyte ratio (NLR -2.4; 95% CI -3.9 to -0.8, P = .003), serum levels of albumin (35.1; 95% CI 23.1-47.2; P < .001), dehydroepiandrosterone sulfate (DHEA-S 2.8; 95% CI 1.9-3.8; P < .001), free androgen index (FAI 1.5; 95% CI 1.1-1.9; P < .001), and vitamin D (4.0; 95% CI 2.0-6.1; P < .001) were associated with changes in IC over time. CONCLUSIONS AND IMPLICATIONS: The incorporation of multidomain interventions into primary health care significantly enhanced IC over the 12-month program. Changes in NLR, FAI, and serum levels of albumin, DHEA-S, vitamin D were associated with changes in IC over time. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03528005.

Multi-Trajectories of Intrinsic Capacity Decline and Their Impact on Age-Related Outcomes: A 20-Year National Longitudinal Cohort Study.

The existence of intrinsic capacity (IC) subtypes and their distinct impacts on age-related outcomes remain unexplored. This study sought to investigate IC impairment trajectories across domains and their associations with the risk of age-related outcomes, including falls, functional limitations, reduced quality of life (QoL) and mortality at 4- and 8-year follow-ups. The study sample comprised 1,782 older adults residing in the community from the Taiwan Longitudinal Study on Ageing (TLSA). Utilizing group-based multitrajectory modeling, distinct subtypes of IC decline trajectories across various domains were identified. Cox proportional hazard models and multivariable logistic regression analyses were employed to assess the associations between the identified subtypes and age-related outcomes. We identified four subtypes of IC decline: robust with mild decline (n=902), hearing loss with cognitive decline (n=197), physio-cognitive decline (PCD) with depression (n=373), and severe IC decline (n=310). Over the 4-year study period, compared to the robust with mild decline group, hearing loss with cognitive decline group exhibited a significantly higher risk of diminished QoL (OR=2.53 [1.66-3.86], p>0.01), whereas those in the PCD with depression group experienced an elevated risk of falls (OR=1.62 [1.18-2.23], p>0.01), as well as functional limitation (OR=2.61 [1.81-3.75], p>.01). Individuals in the severe IC decline group faced a substantially increased risk of all outcomes of interest. Distinct subtypes of IC decline across different domains have varying impacts on age-related outcomes, highlighting the need for a personalized approach to promote healthy ageing at the population level, while further investigation into specific pathophysiological mechanisms is warranted as well.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

The Clinical and Genetic Characteristics of Streptococcus agalactiae Meningitis in Neonates.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an important pathogen of bacterial meningitis in neonates. We aimed to investigate the clinical and genetic characteristics of neonatal GBS meningitis. All neonates with GBS meningitis at a tertiary level medical center in Taiwan between 2003 and 2020 were analyzed. Capsule serotyping, multilocus sequence typing, antimicrobial resistance, and whole-genome sequencing (WGS) were performed on the GBS isolates. We identified 48 neonates with GBS meningitis and 140 neonates with GBS sepsis. Neonates with GBS meningitis had significantly more severe clinical symptoms; thirty-seven neonates (77.8%) had neurological complications; seven (14.6%) neonates died; and 17 (41.5%) survivors had neurological sequelae at discharge. The most common serotypes that caused meningitis in neonates were type III (68.8%), Ia (20.8%), and Ib (8.3%). Sequence type (ST) is highly correlated with serotypes, and ST17/III GBS accounted for more than half of GBS meningitis cases (56.3%, n = 27), followed by ST19/Ia, ST23/Ia, and ST12/Ib. All GBS isolates were sensitive to ampicillin, but a high resistance rates of 72.3% and 70.7% to erythromycin and clindamycin, respectively, were noted in the cohort. The virulence and pilus genes varied greatly between different GBS serotypes. WGS analyses showed that the presence of PezT; BspC; and ICESag37 was likely associated with the occurrence of meningitis and was documented in 60.4%, 77.1%, and 52.1% of the GBS isolates that caused neonatal meningitis. We concluded that GBS meningitis can cause serious morbidity in neonates. Further experimental models are warranted to investigate the clinical and genetic relevance of GBS meningitis. Specific GBS strains that likely cause meningitis requires further investigation and clinical attention.

Serum brain-derived neurotrophic factor levels as a predictor for Alzheimer disease progression.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of Alzheimer's disease (AD), and decreased peripheral levels of this protein are associated with an increased risk of developing the disease. This study focuses on whether serum BDNF levels could be used as a predictor of AD progression. METHODS: In this longitudinal observational study, we recruited cognition normal participants (N = 98) and AD (N = 442) from the Clinic at the Taipei Veterans General Hospital. We conducted a mini-mental status exam, a 12-item memory test, a categorical verbal fluency test, and a modified 15-item Boston naming test. A Serum BDNF level and apolipoprotein E ( APOE ) allele status were measured. The AD patients were followed prospectively. Based on the difference of MMSE scores, these patients were divided into fast decliners (decline ≥ 3/y) and slow decliners (MMSE decline < 3/y). Logistic regression was conducted to examine the impact of serum BDNF levels and other factor on the likelihood of AD patients being slow decliners. Pearson's correlation was used to estimate the relationship between serum BDNF levels and the score of neuropsychological tests. RESULTS: In a logistic regression model containing serum BDNF levels, age, sex, APOE4 carrier status, education levels, and baseline MMSE score, higher serum BDNF levels were associated with a slower rate of cognitive decline in the AD group. Serum BDNF levels positively correlated with the results of multiple neuropsychological tests. CONCLUSION: BDNF is a protective factor against AD progression and likely plays a role in establishing a link between AD pathology and clinical manifestations.

Diagnosis and outcomes of cachexia in Asia: Working Consensus Report from the Asian Working Group for Cachexia.

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Evaluation of convolutional neural network for non-destructive detection of imidacloprid and acetamiprid residues in chili pepper (Capsicum frutescens L.) based on visible near-infrared spectroscopy.

Consumption of agricultural products with pesticide residue is risky and can negatively affect health. This study proposed a nondestructive method of detecting pesticide residues in chili pepper based on the combination of visible and near-infrared (VIS/NIR) spectroscopy (400-2498 nm) and deep learning modeling. The obtained spectra of chili peppers with two types of pesticide residues (acetamiprid and imidacloprid) were analyzed using a one-dimensional convolutional neural network (1D-CNN). Compared with the commonly used partial least squares regression model, the 1D-CNN approach yielded higher prediction accuracy, with a root mean square error of calibration of 0.23 and 0.28 mg/kg and a root mean square error of prediction of 0.55 and 0.49 mg/kg for the acetamiprid and imidacloprid data sets, respectively. Overall, the results indicate that the combination of the 1D-CNN model and VIS/NIR spectroscopy is a promising nondestructive method of identifying pesticide residues in chili pepper.

Clinical practice for sarcopenia in Asia: Online survey by the Asian Working Group for Sarcopenia.

OBJECTIVE: This study aimed to (1) investigate the clinical practice for the management of sarcopenia among healthcare professionals in Asia, (2) determine the characteristics of clinical care provided by geriatricians versus by other healthcare professionals, and (3) clarify the awareness of sarcopenia. METHODS: From December 1 to 31, 2022, an online survey was completed by 1990 healthcare professionals in Asia. The survey comprises demographics and institutional characteristics, basic sarcopenia-related details, and sarcopenia-related assessment and treatment details. RESULTS: The mean respondent age was 44.2 ± 10.7 years, 36.4% of the respondents were women, and the mean years of experience in clinical practice were 19.0 ± 10.6 years. The percentages of respondents who were aware of the term "sarcopenia", its definition and the importance of its management were high, at 99.3%, 91.9%, and 97.2%, respectively. The percentages of respondents who had screened patients for, diagnosed patients with, and treated patients for sarcopenia were 42.4%, 42.9%, and 58.8%, respectively. Medical doctors had higher performance rates compared to allied health professionals (45.5% vs. 40.5% for screening, 56.8% vs. 34.5% for diagnosis, and 65.0% vs. 55.0% for treatment) (P < 0.001). Especially, among medical doctors, geriatricians had significantly higher rates compared to non-geriatricians (64.3% vs. 34.1% for screening; 76.7% vs. 44.8% for diagnosis; 82.7% vs. 54.4% for treatment, respectively) (P < 0.001). CONCLUSION: Although the importance of the concept and management of sarcopenia is well recognized, there is a gap in its detection and management in clinical practice between medical doctors and allied health professionals, and also between geriatricians and non-geriatricians. Many geriatricians collaborate with other healthcare professionals to appropriately manage sarcopenia. In the future, educating all medical staff on the proper management of sarcopenia is necessary.

Advanced brain age in community-dwelling population with combined physical and cognitive impairments.

We investigated whether advanced brain biological age is associated with accelerated age-related physical and/or cognitive functional decline: mobility impairment no disability (MIND), cognitive impairment no dementia (CIND), and physio-cognitive decline syndrome (PCDS). We constructed a brain age prediction model using gray matter features from the magnetic resonance imaging of 1482 healthy individuals (aged 18-92 years). Predicted and chronological age differences were obtained (brain age gap [BAG]) and analyzed in another 1193 community-dwelling population aged ≥50 years. Among the 1193 participants, there were 501, 346, 148, and 198 in the robust, CIND, MIND, and PCDS groups, respectively. Participants with PCDS had significantly larger BAG (BAG = 2.99 ± 8.97) than the robust (BAG = -0.49 ± 9.27, p = 0.002; η2 = 0.014), CIND (BAG = 0.47 ± 9.16, p = 0.02; η2 = 0.01), and MIND (BAG = 0.36 ± 9.69, p = 0.036; η2 = 0.013) groups. Advanced brain aging is involved in the pathophysiology of the co-occurrence of physical and cognitive decline in the older people. The PCDS may be a clinical phenotype reflective of accelerated biological age in community-dwelling older individuals.

Invasive Candida parapsilosis Bloodstream Infections in Children: The Antifungal Susceptibility, Clinical Characteristics and Impacts on Outcomes.

Background: Candida parapsilosis is the most common non-albicans candida species that causes invasive candidiasis, but little is known about its impacts on the outcomes of pediatric patients. We aimed to characterize the clinical characteristics, risk factors and outcomes of C. parapsilosis bloodstream infections (BSIs) in children. Methods: All pediatric patients with Candida parapsilosis BSIs between 2005 and 2020 from a medical center in Taiwan were enrolled and analyzed. The antifungal susceptibility, clinical manifestations, management and outcomes were investigated. Cases of Candida parapsilosis BSIs were compared between patients with C. albicans BSIs and other Candida spp. BSIs. Results: During the study period, 95 episodes (26.0% of total cases) of Candida parapsilosis BSIs were identified and analyzed. No significant difference was found between pediatric patients with C. parapsilosis BSIs and those with C. albicans BSIs in terms of patients' demographics, most chronic comorbidities or risk factors. Pediatric patients with C. parapsilosis BSIs were significantly more likely to have previous azole exposure and be on total parenteral nutrition than those with C. albicans BSIs (17.9 vs. 7.6% and 76.8 vs. 63.7%, p = 0.015 and 0.029, respectively). The duration of C. parapsilosis candidemia was relatively longer, and therefore patients often required a longer duration of antifungal treatment when compared with those of C. albicans candidemia, although the candidemia-attributable mortality rates were comparable. Of the C. parapsilosis isolates, 93.7% were susceptible to all antifungal agents, and delayed appropriate antifungal treatment was an independent factor in treatment failure. Conclusions: Pediatric patients with C. parapsilosis BSIs were more likely to have previous azole exposure and be on total parenteral nutrition, and the clinical significances included a longer duration of candidemia and patients often required a longer duration of antifungal treatment.

Sebacic Acid as a Potential Age-Related Biomarker of Liver Aging: Evidence Linking Mice and Human.

The aging process is complicated and involves diverse organ dysfunction; furthermore, the biomarkers that are able to reflect biological aging are eagerly sought after to monitor the system-wide decline associated with the aging process. To address this, we performed a metabolomics analysis using a longitudinal cohort study from Taiwan (N = 710) and established plasma metabolomic age using a machine learning algorithm. The resulting estimation of age acceleration among the older adults was found to be correlated with HOMA-insulin resistance. In addition, a sliding window analysis was used to investigate the undulating decrease in hexanoic and heptanoic acids that occurs among the older adults at different ages. A comparison of the metabolomic alterations associated with aging between humans and mice implied that ω-oxidation of medium-chain fatty acids was commonly dysregulated in older subjects. Among these fatty acids, sebacic acid, an ω-oxidation product produced by the liver, was significantly decreased in the plasma of both older humans and aged mice. Notably, an increase in the production and consumption of sebacic acid within the liver tissue of aged mice was observed, along with an elevation of pyruvate-to-lactate conversion. Taken together, our study reveals that sebacic acid and metabolites of ω-oxidation are the common aging biomarkers in both humans and mice. The further analysis suggests that sebacic acid may play an energetic role in supporting the production of acetyl-CoA during liver aging, and thus its alteration in plasma concentration potentially reflects the aging process.

Intrinsic capacity differs from functional ability in predicting 10-year mortality and biological features in healthy aging: results from the I-Lan longitudinal aging study.

This study aimed to explore the biological features and mortality risk of intrinsic capacity (IC) and functional ability (FA). Based on data from 1839 participants from the I-Lan Longitudinal Aging Study, multivariable Cox proportional hazard models were used to evaluate the predictive ability of IC (range 0-100) and FA (range 0-100) on 10-year mortality. Of 2038 repeated measurements for IC within a 7-year observational period, multivariable logistic regression was used to compare biological features of participants with maintained, improved and rapidly deteriorated IC. A 1-point increased IC value was associated with a 5% (HR 0.95, 95% CI 0.93-0.97, p < 0.001) decrease in mortality risk. Low IC (HR 1.94, 95% CI 1.39-2.70, p < 0.001) was associated with higher mortality risk. Hyperglycemia (OR 1.40, 95% CI 1.09-1.81, p = 0.010), low serum levels of DHEA-S (OR 3.33, 95% CI 1.32-8.41, p = 0.011), and high serum levels of C-reactive protein (OR 1.45, 95% CI 1.05-2.00, p = 0.023) were associated with low IC at baseline. Low serum levels of DHEA-S (middle tertile OR 1.84, 95% CI 1.15-2.95, p = 0.012; lowest tertile OR 2.25, 95% CI 1.34-3.77, p = 0.002) and vitamin D deficiency (OR 1.82, 95% CI 1.02-3.27, p = 0.044) were associated with rapid deterioration of IC. IC and FA predicted 10-year mortality, whereas chronic inflammation, hyperglycemia, and low DHEA-S were associated with low IC status. Low DHEA-S and vitamin D deficiency may be considered as potential biomarkers of rapid IC declines, which implies underlying biological mechanisms of healthy aging.

Anti-tumor necrosis factor-α is potentially better than tumor necrosis factor-α as the biomarker for sarcopenia: Results from the I-Lan longitudinal aging study.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine involved in the pathogenesis of sarcopenia, but its short half-life and inconsistent reproducibility limit the potential of TNF-α to be an ideal sarcopenia biomarker. Anti-TNF-α, a natural consequent autoantibody to TNF-α, is an indicator of relatively prolonged TNF-α exposure, has more stable concentrations than TNF-α and should be a better alternative as a biomarker of sarcopenia. Data from 484 participants from the I-Lan Longitudinal Aging Study were used for this study, and sarcopenia was defined by the Asian Working Group for Sarcopenia 2019 consensus. Plasma levels of anti-TNF-α were determined by a sandwich ELISA approach, and levels of TNF-α were determined by an immunoassay. Compared to nonsarcopenic participants, 43 sarcopenic participants had higher levels of anti-TNF-α (0.73 ± 0.19 vs. 0.79 ± 0.25 OD, p = 0.045). Plasma levels of anti-TNF-α were positively correlated with TNF-α (r = 0.24, p < 0.001), and plasma levels of anti-TNF-α were positively correlated with adiposity (r = 0.16, p < 0.001) and negatively correlated with lean body mass (r = -0.14, p = 0.003). Individuals with increasing levels of anti-TNF-α had higher odds of being sarcopenic (OR 5.4, 95 % CI: 1.1-25.8, p = 0.035), and these associations were stronger among women and younger adults. An association between TNF-α and sarcopenia was noted only in middle-aged adults (OR 6.2, 95 % CI: 1.8-21.7, p = 0.004). Plasma anti-TNF-α levels were positively correlated with TNF-α and were significantly associated with sarcopenia. Anti-TNF-α may be a more appropriate biomarker than TNF-α for sarcopenia, but further investigations are needed to confirm its roles in sarcopenia diagnosis and treatment response evaluation.