Deep Learning Evaluation of Glaucoma Detection Using Fundus Photographs in Highly Myopic Populations.

OBJECTIVES: This study aimed to use deep learning to identify glaucoma and normal eyes in groups with high myopia using fundus photographs. METHODS: Patients who visited Tri-Services General Hospital from 1 November 2018 to 31 October 2022 were retrospectively reviewed. Patients with high myopia (spherical equivalent refraction of ≤-6.0 D) were included in the current analysis. Meanwhile, patients with pathological myopia were excluded. The participants were then divided into the high myopia group and high myopia glaucoma group. We used two classification models with the convolutional block attention module (CBAM), an attention mechanism module that enhances the performance of convolutional neural networks (CNNs), to investigate glaucoma cases. The learning data of this experiment were evaluated through fivefold cross-validation. The images were categorized into training, validation, and test sets in a ratio of 6:2:2. Grad-CAM visual visualization improved the interpretability of the CNN results. The performance indicators for evaluating the model include the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 3088 fundus photographs were used for the deep-learning model, including 1540 and 1548 fundus photographs for the high myopia glaucoma and high myopia groups, respectively. The average refractive power of the high myopia glaucoma group and the high myopia group were -8.83 ± 2.9 D and -8.73 ± 2.6 D, respectively (p = 0.30). Based on a fivefold cross-validation assessment, the ConvNeXt_Base+CBAM architecture had the best performance, with an AUC of 0.894, accuracy of 82.16%, sensitivity of 81.04%, specificity of 83.27%, and F1 score of 81.92%. CONCLUSIONS: Glaucoma in individuals with high myopia was identified from their fundus photographs.

Evolution of white matter hyperintensity segmentation methods and implementation over the past two decades; an incomplete shift towards deep learning.

This systematic review examines the prevalence, underlying mechanisms, cohort characteristics, evaluation criteria, and cohort types in white matter hyperintensity (WMH) pipeline and implementation literature spanning the last two decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we categorized WMH segmentation tools based on their methodologies from January 1, 2000, to November 18, 2022. Inclusion criteria involved articles using openly available techniques with detailed descriptions, focusing on WMH as a primary outcome. Our analysis identified 1007 visual rating scales, 118 pipeline development articles, and 509 implementation articles. These studies predominantly explored aging, dementia, psychiatric disorders, and small vessel disease, with aging and dementia being the most prevalent cohorts. Deep learning emerged as the most frequently developed segmentation technique, indicative of a heightened scrutiny in new technique development over the past two decades. We illustrate observed patterns and discrepancies between published and implemented WMH techniques. Despite increasingly sophisticated quantitative segmentation options, visual rating scales persist, with the SPM technique being the most utilized among quantitative methods and potentially serving as a reference standard for newer techniques. Our findings highlight the need for future standards in WMH segmentation, and we provide recommendations based on these observations.

Evaluating Digital Photography for Lip Print Recording: Compatibility With Traditional Classification Systems.

BACKGROUND: Direct digital photography for lip print recording is a recent trend, and there is a dearth of systematic research on the analysis of the recorded prints with existing clip print classification systems. AIMS AND OBJECTIVES: This study aims to compare the accuracy of the digital photographic method in lip print recording, comparing it with traditional methods, and assessing the suitability of commonly used lip print classification for analyzing lip prints recorded by photographic method. METHODOLOGY: A total of 72 participants aged between 20 and 26 were included. The lip print recording process involved photographing the lips without and with lipstick, followed by recording the lip print with cellophane tape on bond paper. The prints collected using the different methods were analyzed and compared for agreement, and the data were analyzed statistically. RESULTS: Inter-observer reliability was high for all methods (>0.800). The distribution of lip print patterns differed across the methods, suggesting a potential influence of the recording technique. The agreement between the conventional method and both digital methods was moderate (kappa=0.449-0.517). The agreement between digital methods with and without enhancement was also moderate (kappa=0.718). Notably, digital photographs with enhancement tend to have a higher positive agreement for several lip print types. CONCLUSION: Digital photography is a potential method for lip print recording. However, this study highlights the need for the calibration of lip print classification systems for digitally recorded lip prints. Further research is needed to refine the use of digital photography in forensic lip print analysis and to explore its integration with artificial intelligence for biometric identification.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians.

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016-2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40-70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Pharmacokinetic analysis of antiviral drug ritonavir across the blood-brain barrier and its interaction with Scutellaria baicalensis using multisite microdialysis in rats.

Ritonavir, an excellent inhibitor of CYP3A4, has recently been combined with nirmatrelvir to form Paxlovid for the treatment of severe acute respiratory syndrome coronavirus 2 infections. The root of Scutellaria baicalensis Georgi (S. baicalensis), a traditional Chinese medicinal (TCM) herb commonly used to treat heat/inflammation in the lung and digestive tracts, which are major organs targeted by viral infections, contains flavones that can influence the CYP3A metabolism pathway. To investigate the ability of ritonavir to cross the bloodbrain barrier (BBB) and its potential herb-drug interactions with an equivalent TCM clinical dose of S. baicalensis, multisite microdialysis coupled with an LCMS/MS system was developed using rat model. Pretreatment with S. baicalensis extract for 5 days, which contains less flavones than those used in previous studies, had a significant influence on ritonavir, resulting in a 2-fold increase in the total concentration of flavones in the blood and brain. Treatment also boosted the maximum blood concentration of flavones by 1.5-fold and the maximum brain concentration of flavones by 2-fold, all the while exerting no noticeable influence on the transfer ratio across the bloodbrain barrier. These experimental results demonstrated that the use of a typical traditional Chinese medicinal dose of S. baicalensis is sufficient to influence the metabolic pathway and synergistically increase the concentration of ritonavir in rats.

Associations between multidomain modifiable dementia risk factors with AD biomarkers and cognition in middle-aged and older adults.

This study aimed to determine associations between modifiable dementia risk factors (MDRF), across domains mood symptomatology, lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology, with cognition, beta-amyloid (Aß) and tau, and brain volume. Middle-aged/older adults (n=82) enrolled in a sub-study of the Healthy Brain Project completed self-report questionnaires and a neuropsychological battery. Cerebrospinal fluid levels of Aß 1-42, total tau (t-tau), and phosphorylated tau (p-tau181) (Roche Elecsys), and MRI markers of hippocampal volume and total brain volume were obtained. Participants were classified as no/single domain risk (≤1 domains) or multidomain risk (≥2 domains). Compared to the no/single domain risk group, the multidomain risk group performed worse on the Preclinical Alzheimer's Cognitive Composite (d=0.63, p=.005), and Executive Function (d=0.50, p=.016), and had increased p-tau181 (d=0.47, p=.042) and t-tau (d=0.54, p=.021). In middle-aged/older adults, multidomain MDRFs were related to increases in tau and worse cognition, but not Aß or brain volume. Findings suggest that increases in AD biomarkers are apparent in midlife, particularly for individuals with greater burden, or variety of MDRFs.

BDNF Val66Met moderates episodic memory decline and tau biomarker increases in early sporadic Alzheimer's disease.

OBJECTIVE: Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been shown to moderate rates of cognitive decline in preclinical sporadic Alzheimer's disease (AD; i.e., Aß + older adults), and pre-symptomatic autosomal dominant Alzheimer's disease (ADAD). In ADAD, Met66 was also associated with greater increases in CSF levels of total-tau (t-tau) and phosphorylated tau (p-tau181). This study sought to determine the extent to which BDNF Val66Met is associated with changes in episodic memory and CSF t-tau and p-tau181 in Aß + older adults in early-stage sporadic AD. METHOD: Aß + Met66 carriers (n = 94) and Val66 homozygotes (n = 192) enrolled in the Alzheimer's Disease Neuroimaging Initiative who did not meet criteria for AD dementia, and with at least one follow-up neuropsychological and CSF assessment, were included. A series of linear mixed models were conducted to investigate changes in each outcome over an average of 2.8 years, covarying for CSF Aß42, APOE ε4 status, sex, age, baseline diagnosis, and years of education. RESULTS: Aß + Met66 carriers demonstrated significantly faster memory decline (d = 0.33) and significantly greater increases in CSF t-tau (d = 0.30) and p-tau181 (d = 0.29) compared to Val66 homozygotes, despite showing equivalent changes in CSF Aß42. CONCLUSIONS: These findings suggest that reduced neurotrophic support, which is associated with Met66 carriage, may increase vulnerability to Aß-related tau hyperphosphorylation, neuronal dysfunction, and cognitive decline even prior to the emergence of dementia. Additionally, these findings highlight the need for neuropsychological and clinicopathological models of AD to account for neurotrophic factors and the genes which moderate their expression.

Unveiling the age-related dynamics in Sjögren's syndrome: Insights from heart rate variability and autonomic function.

BACKGROUND: Sjögren's Syndrome (SS), mainly affecting women in their midlife, is characterized by persistent inflammation in glands producing tears and saliva, often leading to significant complications. This study investigates the differences in autonomic system functioning between individuals with SS and healthy controls. METHODS: From April 2019 to December 2022, 329 diagnosed primary SS (pSS) patients and 30 healthy controls were enrolled at Taipei Veterans General Hospital, Taipei, Taiwan. The study assessed autonomic nervous system functioning using various HRV metrics. Participants were divided based on age and AECG criteria, including salivary gland biopsy and autoantibody status. RESULTS: Significant differences in Heart Rate Variability (HRV) were observed between pSS patients and healthy controls. The total power index was notably lower in pSS patients (4.98 ± 1.29) than in controls (5.54 ± 1.21, p = .022). Additionally, Vagal (VAG) activity was significantly reduced in the pSS group (4.95 ± 1.33) compared to the healthy control group (5.47 ± 1.19, p = .041). Age-stratified analysis highlighted that the ≤50 years pSS group had a higher heart rate (77.74 ± 10.42) compared to the >50 years group (73.86 ± 10.35, p = .005). This group also showed a higher total power index (5.78 ± 1.30) versus the >50 years group (4.68 ± 1.19, p < .001), and significantly lower VAG activity (4.70 ± 1.26, p = .007) compared to healthy controls. Furthermore, the Standard Deviation of Normal-to-Normal Intervals (SDNN) was greater in the ≤50 years SS group (44.45 ± 37.12) than in the >50 years group (33.51 ± 26.18, p = .007). In pSS patients, those positive for both salivary gland biopsy and autoantibodies demonstrated a lower Total Power (4.25 ± 1.32) and R-wave validity (93.50 ± 4.79, p < .05) than other groups, suggesting more severe autonomic imbalance. The R-R interval variation (RRIV) was also significantly higher in this dual-positive group (696.10 ± 975.41, p < .05). Additionally, the ESSPRI for dryness was markedly higher in the dual-positive group (8.10 ± 1.45, p < .05), indicating more severe symptoms. These findings reveal significant variations in autonomic function in SS patients, especially in those with dual-positive biopsy and autoantibody status. CONCLUSION: This study demonstrates significant autonomic dysfunction in pSS patients compared to healthy controls, particularly in those positive for both salivary gland biopsy and autoantibodies. The age-stratified analysis further emphasizes the impact of aging on autonomic system functioning in pSS, suggesting a need for age-specific management approaches in pSS patient care.

The cytokine genes of Oncorhynchus masou formosanus include a defective interleukin-4/13A gene.

Oncorhynchus masou formosanus (Formosa landlocked salmon) is a critically endangered salmonid fish endemic to Taiwan. To begin to understand how its drastic change in lifestyle from anadromous to exclusively river-dwelling is reflected in its immune genes, we characterized the genes encoding six cytokines (IL-2A, IL-2B, IL-4/13A, IL-4/13B1, IL-4/13B2, and IL-17A/F2a) important for T cell responses as no genomic data is available for this fish. Interestingly, all genes appeared homozygous indicative of a genetic bottleneck. The IL2 and IL17A/F2a genes and their products are highly similar to their characterized homologs in Oncorhynchus mykiss (rainbow trout) and other salmonid fish. Two notable differences were observed in IL4/13 family important for type 2 immune responses. First, O. m. formosanus carries not only one but two genes encoding IL-4/13B1 proteins and expansions of these genes are present in other salmonid fish. Second, the OmfoIL4/13A gene carries a 228 bp deletion that results in a premature stop codon and hence a non-functional IL-4/13A cytokine. This suggests a reduced ability for T cell responses against parasitic infections in this species.

Effects of mind-body exercise on body constitution and circadian rhythm in people with suboptimal health status.

BACKGROUND: Suboptimal health status (SHS) is a dynamic state in which people have not been diagnosed with a disease but tend to develop diseases. People with SHS are more prone to conditions such as cardiovascular disease and metabolic syndrome. Suitable interventions in people with SHS can prevent disease development. SHS is correlated with traditional Chinese medicine (TCM)-based constitutions, including Yang-Xu (yang deficiency), Yin-Xu (yin deficiency), and stasis types. The circadian rhythm is a potential biomarker of health and metabolism. Baduanjin exercise, a kind of mind-body exercise, has been regarded to adjust body constitution and metabolism, but few studies have evaluated the effects of Baduanjin exercise on body constitution and circadian rhythms. Therefore, this randomized controlled trial investigated the effects of Baduanjin exercise on body constitution and circadian rhythms in people with SHS. METHODS: Seventy-six participants with SHS were divided into the Baduanjin exercise and control groups (watching a Baduanjin video), with the interventions lasting 12 weeks. The Body Constitution Questionnaire (BCQ), SHS Questionnaire-25 (SHSQ-25), and actigraphy for circadian rhythm measurement were conducted. RESULTS: The scores of SHSQ-25, Yang-Xu, Yin-Xu, and BCQ stasis decreased significantly after 12 weeks in the Baduanjin exercise group, but not in the control group. Interdaily stability of the circadian rhythm increased significantly in the Baduanjin exercise group but not in the control group. CONCLUSION: This is the first report of improved health status, modulated body constitution, and increased interdaily stability of the circadian rhythm in participants with SHS who practiced Baduanjin exercise.

Sensitivity of Individual and Composite Test Scores from the Cogstate Brief Battery to Mild Cognitive Impairment and Dementia Due to Alzheimer's Disease.

BACKGROUND: The Cogstate Brief Battery (CBB) is a computerized cognitive test battery used commonly to identify cognitive deficits related to Alzheimer's disease (AD). However, AD and normative samples used to understand the sensitivity of the CBB to AD in the clinic have been limited, as have the outcome measures studied. OBJECTIVE: This study investigated the sensitivity of CBB outcomes, including potential composite scores, to cognitive impairment in mild cognitive impairment (MCI) and dementia due to AD, in carefully selected samples. METHODS: Samples consisted of 4,871 cognitively unimpaired adults and 184 adults who met clinical criteria for MCI (Clinical Dementia Rating (CDR) = 0.5) or dementia (CDR > 0.5) due to AD and CBB naive. Speed and accuracy measures from each test were examined, and theoretically- and statistically-derived composites were created. Sensitivity and specificity of classification of cognitive impairment were compared between outcomes. RESULTS: Individual CBB measures of learning and working memory showed high discriminability for AD-related cognitive impairment for CDR 0.5 (AUCs ∼ 0.79-0.88), and CDR > 0.5 (AUCs ∼ 0.89-0.96) groups. Discrimination ability for theoretically derived CBB composite measures was high, particularly for the Learning and Working Memory (LWM) composite (CDR 0.5 AUC = 0.90, CDR > 0.5 AUC = 0.97). As expected, statistically optimized linear composite measures showed strong discrimination abilities albeit similar to the LWM composite. CONCLUSIONS: In older adults, the CBB is effective for discriminating cognitive impairment due to MCI or AD-dementia from unimpaired cognition with the LWM composite providing the strongest sensitivity.

Exploring the Potential Association Between Self-Reported Psychological Stress and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in Midlife: A Cross-Sectional Study.

Psychological stress is associated with dementia risk. However, the underlying mechanisms are unclear. This cross-sectional study examined the association between self-reported psychological stress and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease and neurodegeneration in 73 cognitively unimpaired middle-aged adults from the Healthy Brain Project (mean age = 58±7 years). Linear regression analyses did not reveal any significant associations of psychological stress with CSF amyloid-ß42, phosphorylated tau-181, total tau, or neurofilament light chain. Cohen's f2 effect sizes were small in magnitude (f2≤0.08). Further research is needed to replicate our findings, particularly given that the sample reported on average low levels of stress.

Proposal to distinguish HER2-low from HER2-normal breast cancer by in situ hybridisation.

AIMS: 'HER2-low' breast cancer is an emerging issue as the clinical trials for anti-HER2 antibody-drug conjugates (trastuzumab deruxtecan) are making progress. A reliable method to identify HER2-low cancers is needed. This study aimed to evaluate immunohistochemistry (IHC) and in situ hybridisation (ISH) in detecting HER2-low status. METHODS: We evaluated the HER2 ISH data grouped by the IHC consensus in proficiency tests (PTs), and compared the HER2 ISH results between HER2 IHC scored 0 (IHC-0) and IHC scored 1+ (IHC-1+) tumours from in-house tissue microarrays (TMAs). Since benign/normal glands have HER2 expression and ideally should not be affected by targeted therapy, we evaluated HER2 ISH results in peritumoural benign glands of 52 breast cancers as reference values. RESULTS: None of the 565 tissue cores in PTs achieved an 80% participant agreement of IHC-1+. In PTs and in-house TMAs, HER2 signals of the IHC-1+cores (median: 2.6 and 2.0, respectively) were significantly higher than those of IHC-0 cores (median: 2.0 and 1.7, respectively). But the ranges of HER2 signals had a considerable overlap between IHC-1+and IHC-0 cores. The HER2 signals and HER2:CEP17 ratios of peritumoural benign glands exhibited normal distributions, and their upper bounds of the 95% reference intervals were 2.10 and 1.30, respectively. CONCLUSIONS: Current HER2 testing algorithms are unsatisfactory in detecting HER2-low cases. Using ISH to detect tumour with HER2 signals and HER2:CEP17 ratio higher than the upper bound of the benign glands can be an alternative method.

Associations of Perceived Stress and Psychological Resilience With Cognition and a Modifiable Dementia Risk Score in Middle-Aged Adults.

OBJECTIVES: Psychological stress has been proposed as a risk factor for cognitive impairment and dementia. However, it remains unclear how an individual's stress-coping ability (i.e., psychological resilience) is related to cognition. This cross-sectional study investigated whether perceived stress and psychological resilience were associated with cognition and a modifiable dementia risk score in a large community-based sample of cognitively normal adults. The moderating effect of psychological resilience was also examined. METHODS: Participants (mean age = 57 ± 7 years) enrolled in the web-based Healthy Brain Project completed the Perceived Stress Scale and the Connor-Davidson Resilience Scale. Domains of attention and working memory were assessed using the Cogstate Brief Battery (n = 1,709), and associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery (n = 1,522). Dementia risk was estimated for 1,913 participants using a modified version of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia dementia risk score, calculated using only readily modifiable dementia risk factors. RESULTS: In separate linear regression analyses adjusted for age, sex, education, and race, greater levels of perceived stress and lower levels of psychological resilience were associated with poorer performance across all cognitive domains, as well as a higher modifiable dementia risk score. Psychological resilience did not moderate the effect of perceived stress on cognition or the dementia risk score. DISCUSSION: Higher perceived stress and lower resilience were associated with poorer cognition and a greater burden of modifiable dementia risk factors. Intervention studies are required to determine if lowering stress and building resilience can mitigate cognitive deficits and reduce dementia risk.

Evaluation of different ensiling methods for Saccharina latissima preservation: influence on chemical composition and in vitro ruminal fermentation.

Saccharina latissima is a brown seaweed that could be used in ruminant feeding, but its fast deteriorating and seasonal growth nature limit their utilisation in the practice. Ensiling could be used as a preservation method, but information of its effects on the nutritional value of the seaweed is limited. This study evaluated the in vitro ruminal fermentation of different S. latissima silages using ruminal inoculum either from goats fed a mixed diet (60:40 oat hay:concentrate) or from sheep fed a high-forage diet (90:10 alfalfa hay:concentrate) to simulate different small ruminant production systems. S. latissima was ensiled in vacuum bags without additives (Control), with formic acid (4 g/kg seaweed; FA), with lactic acid bacteria (LAB) or with LAB after a pre-wilting treatment to reach a seaweed dry matter (DM) content of 30% (30LAB). Ensiling S. latissima decreased (p < 0.05) the content in DM, neutral detergent fibre and total extractable polyphenols, but nitrogen and fat content were unaffected. For both ruminal inoculums, ensiling decreased (p < 0.05) the asymptotic gas production after 120 h of fermentation (excepting for FA silage with goats' inoculum), but the total volatile fatty acid (VFA) production was unaffected. The VFA profile shifted towards greater (p < 0.05) acetate and lower (p < 0.05) propionate proportions in all silages compared with the pre-ensiling S. latissima. When goats inoculum was used, greater (p < 0.05) CH4 production compared with pre-ensiling S. latissima was observed in all silages, except Control one, which led to greater (p < 0.05) CH4/total VFA ratio. In contrast, no differences among samples (p > 0.05) in either CH4 production or CH4/total VFA ratio were observed when sheep' inoculum was used. Fermentation of all samples started earlier with goats' inoculum than with sheep' inoculum, which was attributed to the different diet fed to the animals. These results suggest that ensiling S. latissima with either formic acid or lactic acid bacteria could be a viable conservation method to preserve the nutritive value.

Bivalent Gadolinium Ions Forming Injectable Hydrogels for Simultaneous In Situ Vaccination Therapy and Imaging of Soft Tissue Sarcoma.

Doxorubicin (DOX) is the classic soft tissue sarcomas (STS) first-line treatment drug, while dose-dependent myelosuppression and cardiotoxicity limit its application in clinic. This research intends to apply DOX, which is also an inducer of immunogenic cell death as a part for "in situ vaccination" and conjointly uses PD-1 inhibitors to enhance antitumor efficacy. In order to achieve the sustained vaccination effect and real-time monitoring of distribution in vivo, the in situ forming and injectable hydrogel platform with the function of visualization is established for local delivery. The hydrogel platform is synthesized by hyaluronic acid-dopamine coordinated with gadolinium ions (Gd2+ ). Gd2+ provides the ability of magnetic resonance imaging, meanwhile further cross-linking the hydrogel network. Experiments show excellent ability of sustained release and imaging tracking for the hydrogel platform. In mouse STS models, the "in situ vaccination" hydrogels show the best effect of inhibiting tumor growth. Further analysis of tumor tissues show that "in situ vaccination" group can increase T cell infiltration, promote M1-type macrophage polarization and block elevated PD-1/PD-L1 pathway caused by DOX. These results are expected to prove the potential for synthesized hydrogels to achieve a universal platform for "in situ vaccination" strategies on STS treatments.

CSF Aß42 and tau biomarkers in cognitively unimpaired Aß- middle-aged and older APOE ε4 carriers.

This study aimed to determine the relationship between the apolipoprotein E (APOE) ε4 allele and cerebrospinal fluid (CSF) and neuroimaging biomarkers of Alzheimer's disease, and cognition in cognitively unimpaired (CU) middle-aged adults (n = 82; Mage = 58.2), and in Aß- CU older adults (n = 71; Mage = 71.8). Aß- CU middle-aged ε4 carriers showed lower CSF Aß42 levels, higher levels of CSF total tau (t-tau) and neurofilament light (NfL), and poorer cognitive performance compared to noncarriers (Cohen's d: 0.30-0.56). In Aß- CU older adults, ε4 carriers also had lower CSF Aß42 levels and higher levels of CSF t-tau and p-tau181, compared to noncarriers (Cohen's d: 0.65-0.74). In both Aß- middle-aged and older adults, hippocampal and total brain volume were equivalent between ε4 carriers and noncarriers. In Aß- CU middle-aged adults, APOE ε4 is associated with decreased levels of Aß, increased tau and NfL, and poorer cognition. Similar relationships were observed in Aß- CU older adults. These results have implications for understanding clinicopathological relationships between APOE ε4 and the emergence of cognitive and biomarker abnormalities in Aß- adults.

Effect of Acupoint Stimulation on Improving Gastrointestinal Motility in Patients After Gastrectomy: A Systematic Review and Meta-Analysis.

Introduction: Gastrointestinal immobility is experienced by many patients who undergo gastric surgery. This complication delays enteral nutrition, prolongs hospitalization, and causes discomfort. Acupoint stimulation is a popular alternative nonpharmacological treatment for gastrointestinal immobility. This study aimed to explore the effects of acupoint stimulation on gastrointestinal immobility after gastrectomy. Design: Systematic review and meta-analysis. Methods: Databases (PubMed, Cochrane, Joanna Briggs Institute EBP Database, Medline, CINAHL Complete, and Airiti library) were searched from their inception to April 2022 for relevant articles. Articles in Chinese and English were included, without limitations on year, region, or country. The inclusion criteria were studies with participants >18 years of age, postgastric surgery, and hospitalization. In addition, randomized controlled trials (RCTs) were included. Data were analyzed using random effects models, and data heterogeneity was investigated using subgroup analysis. Meta-analysis was performed using Review Manager 5.4 software. Results: We included 785 participants from six studies. Invasive and noninvasive acupoint stimulation reduced the time of gastrointestinal mobility better than usual care. In the control group, the time of first flatus was 43.56 ± 9.57 h to 108 ± 19.2 h, and the time of first defecation was 77.27 ± 22.67 h to 139.2 ± 24 h. In the experimental group, the time of first flatus and defecation was 36.58 ± 10.75 h to 79.97 ± 37.31 h and 70.56 ± 15.36 h to 108.55 ± 10.75 h, respectively. Subgroup analysis showed that invasive acupoint stimulation with acupuncture reduced the time of first flatus and defecation to 15.03 h (95% confidence interval [CI] = -31.06 to 1.01) and 14.12 h (95% CI = -32.78 to 4.54), respectively. Noninvasive acupoint stimulation, including acupressure and transcutaneous electrical acupoint stimulation (TEAS), reduced the time of first flatus and defecation to 12.33 h and (95% CI = -20.59 to -4.06) and 12.20 h (95% CI = -24.92 to 0.52), respectively. Conclusions: Acupoint stimulation improved the gastrointestinal immobility of postgastrectomy. In the included RCT articles, invasive and noninvasive stimulations were effective. However, noninvasive acupoint stimulation, such as with TEAS and acupressure, was more efficient and convenient than invasive stimulation. Overall, health care professionals with adequate training or under the supervision of an acupuncturist can effectively perform acupoint stimulation to improve the quality of postgastrectomy care. They can select commonly used and effective acupoints to enhance gastrointestinal motility. Clinical relevance: Acupoint stimulation, such as acupressure, electrical acupoint stimulation, or acupuncture, can be included in postgastrectomy routine care to improve gastrointestinal motility and reduce abdominal discomfort.

Multidomain modifiable dementia risk factors are associated with poorer cognition in midlife.

OBJECTIVE: Studies of modifiable dementia risk factors (MDRFs) generally consider MDRFs individually, despite strong evidence that they co-occur in adult populations. In a large sample of middle-aged adults, this study aimed to determine the frequency and co-occurrence of MDRFs, spanning five domains (mood symptomatology, risky lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology). The relationship between number of domains in which MDRFs were reported with cognitive performance and subjective cognitive concerns was then determined. METHOD: Middle-aged adults (n = 1,610) enrolled in the Healthy Brain Project and completed self-report surveys about their health and lifestyle. Participants also completed the Cogstate Brief Battery and the Cognitive Function Instrument, a measure of subjective ratings of cognition. Participants were classified according to number of domains (mood symptomatology, risky lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology) in which they reported at least one MDRF (0-5). Age, sex, education, and ethnicity were adjusted for in analyses. RESULTS: Most individuals (66.5%) reported MDRFs in two or more domains. Compared with individuals displaying no MDRFs, individuals with MDRFs in 3-5 domains showed worse learning/working memory performance and greater subjective cognitive concerns, with the magnitude of these differences moderate-to-large (d = 0.30-0.93). Individuals displaying MDRFs in five domains also showed worse attention/psychomotor function (d = 0.58) compared to those displaying no MDRFs. CONCLUSIONS: These findings may suggest that multidomain MDRFs are highly frequent in middle-aged adults and are related to poorer cognition. This supports that modifiable dementia risk is multidimensional and raises the possibility that multidomain behavioral intervention trials in middle-aged adults may be useful to delay or prevent cognitive impairment or decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).