Longitudinal Relationship Between Baseline Social Frailty and Cognitive Impairment in Older Adults: 14-Year Follow-Up Results From the Korean Longitudinal Study of Ageing.

OBJECTIVES: This study aimed to investigate the longitudinal relationship between social frailty and cognitive impairment among community-dwelling older adults. DESIGN: This retrospective cohort study is based on the first to eighth waves of the Korean Longitudinal Study of Ageing (2006-2020). SETTING AND PARTICIPANTS: The participants were 2106 community-dwelling older adults aged 65 years or older and without cognitive impairment in 2006. METHODS: Social frailty was assessed with 5 items including social support, social activity, social network, loneliness, and living alone (0 = social nonfrailty, 1 = social prefrailty, 2 or more = social frailty). Cognitive function was assessed using the Korean Mini-Mental State Examination, and scores below 24 indicated cognitive impairment. We used the generalized estimating equation to assess the longitudinal relationship between social frailty and cognitive impairment. RESULTS: Of the 2106 participants, 515 (24.4%) had social frailty, 669 (31.8%) had social prefrailty, and 922 (43.8%) were social nonfrailty based on the baseline assessments. Relative to the social nonfrailty group, the odds ratios of the social prefrailty and social frailty groups for cognitive impairment were 1.30 (95% CI 1.10-1.54) and 1.41 (95% CI 1.16-1.71), respectively, during the follow-up. Subgroup analysis showed that social inactivity and loneliness were significantly associated with cognitive impairment. CONCLUSIONS AND IMPLICATIONS: These findings highlight the need for health care providers to introduce and use available social resources for older adults with social frailty to increase the relationships between individual and social context. Social inactivity and loneliness were the major domains associated with cognitive impairment, and loneliness can be resolved by participating in social activities. Therefore, health care providers especially provide opportunities for social activities, such as group-based programs in the community, to reduce social frailty and cognitive impairment.

The Root Extract of Rosa multiflora Ameliorates Nonalcoholic Steatohepatitis Development via Blockade of De Novo Lipogenesis and Inflammation.

Nonalcoholic steatohepatitis (NASH) is characterized by severe inflammation and fibrosis due to an excessive accumulation of triglycerides (TGs) in the liver with a dysregulated de novo lipogenesis (DNL) pathway. In this study, we aimed to evaluate the effectiveness of YC-1102, an extract obtained from the roots of Rosa multiflora, as a nutritional supplement in a diet-induced NASH mouse model. C57BL/6 wild-type mice were fed a fructose, palmitate, and cholesterol (FPC)-containing diet for 16 weeks to induce experimental NASH. A daily oral gavage of YC-1102 and obetichoic acid (OCA) was conducted for 9 weeks. After sacrifice, disease parameters related to hepatic lipids, inflammation, and fibrosis were evaluated. The treatment with YC-1102 significantly decreased the liver/body weight ratio, epididymal fat weight, and plasma ALT and AST levels, which are indicators of NASH injuries. YC-1102 attenuated hepatic lipid accumulation by inhibiting the transcription of DNL genes in the livers exhibiting NASH. Additionally, we found that YC-1102 blocked the development of hepatic inflammation and fibrosis by directly disturbing macrophage activation, resulting in an amelioration of hepatic fibrosis. Our findings suggest that YC-1102 could ameliorate NASH progression by inhibiting uncontrolled DNL and inflammation.

Longer time horizons are associated with reduced risk of mortality and disability in older adults.

OBJECTIVES: Longer time horizons are associated with positive health behaviors, but the associations of time horizons with disability and mortality are less understood. This study aims to test the hypothesis that longer time horizons are associated with decreased disability and mortality in older adults. METHOD: Participants were 1052 older adults (mean age = 81 ± 7 years) without dementia. Proportional hazard models adjusted for age, sex, and education were used to examine the associations of time horizons with risk of mortality and disability. RESULTS: During up to 11 years of follow up (mean = 5.7), 317 participants died. In fully adjusted models, longer time horizons were associated with reduced mortality risk (hazard rate [HR] = 0.78, 95% confidence interval [CI] = 0.68-0.89). About 36.7% of participants developed disability in instrumental activities of daily living (ADLs) and 49.3% developed disability in basic ADLs during follow up. Longer time horizons were associated with a reduced risk of disability in basic ADLs (HR = 0.89, 95% CI = 0.79-0.99) but not instrumental ADLs (HR = 0.90, 95% CI = 0.80-1.03). CONCLUSION: Longer time horizons are associated with a reduced risk of all-cause mortality and disability in basic ADLs among community-dwelling older adults, thus highlighting a potentially modifiable psychological risk factor for negative health outcomes in aging.

A roadmap to human hippocampal neurogenesis in adulthood, aging and AD.

In the rodent, hippocampal neurogenesis plays critical roles in learning and memory1,2, is tightly regulated by inhibitory neurons3-7 and contributes to memory dysfunction in Alzheimer's disease (AD) mouse models8-10. In contrast, the mechanisms regulating neurogenesis in the adult human hippocampus, the dynamic shifts in the transcriptomic and epigenomic profiles in aging and AD and putative niche interactions within the cellular environment, remain largely unknown. Using single nuclei multi-omics of postmortem human hippocampi we map the molecular mechanisms of hippocampal neurogenesis across aging, cognitive decline, and AD neuropathology. Transcriptomic and epigenetic profiling of neural stem cells (NSCs), neuroblasts and immature neurons suggests that the earliest shift in the characteristics of neurogenesis takes place in NSCs in aging. Cognitive impairment was associated with changes in neuroblast profile. In AD, there was a widespread cessation of the transcription machinery in immature neurons, with robust downregulation of genes regulating ribosomal and mitochondrial function. Further, there was substantial loss of parvalbumin+ inhibitory neurons in the hippocampus in aging. The number of the rest of inhibitory neurons were reduced as a function of age and diagnosis. Notably, a similar system-level effect was observed between immature and inhibitory neurons in the transition from aging to AD, manifested by common molecular pathways that were ultimately lost in AD. The numbers of neuroblasts, immature and GABAergic neurons inversely correlated with extent of neuropathology. Using CellChat and NeuronChat, we inferred the ligands and receptors by which neurogenic cells communicate with their cellular environment. Loss of synaptic adhesion molecules and neurotransmitters, either sent or received by neurogenic cells, was observed in AD. Together, this study delineates the molecular mechanisms and dynamics of human neurogenesis, functional association with inhibitory neurons and a mechanism of hippocampal hyperexcitability in AD.

Current Status of Molecular Diagnosis of Hereditary Hemolytic Anemia in Korea.

Hereditary hemolytic anemia (HHA) is considered a group of rare hematological diseases in Korea, primarily because of its unique ethnic characteristics and diagnostic challenges. Recently, the prevalence of HHA has increased in Korea, reflecting the increasing number of international marriages and increased awareness of the disease. In particular, the diagnosis of red blood cell (RBC) enzymopathy experienced a resurgence, given the advances in diagnostic techniques. In 2007, the RBC Disorder Working Party of the Korean Society of Hematology developed the Korean Standard Operating Procedure for the Diagnosis of Hereditary Hemolytic Anemia, which has been continuously updated since then. The latest Korean clinical practice guidelines for diagnosing HHA recommends performing next-generation sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly next-generation sequencing, are proving critical in identifying and providing insight into cases of HHA with previously unknown diagnoses. These innovative molecular genetic testing methods have now become important tools for the management and care planning of patients with HHA. This review aims to provide a comprehensive overview of recent advances in molecular genetic testing for the diagnosis of HHA, with particular emphasis on the Korean context.

p62/sequestosome-1 as a severity-reflecting plasma biomarker in Charcot-Marie-Tooth disease type 1A.

Autophagy is a self-degradation system for recycling to maintain homeostasis. p62/sequestosome-1 (p62) is an autophagy receptor that accumulates in neuroglia in neurodegenerative diseases. The objective of this study was to determine the elevation of plasma p62 protein levels in patients with Charcot-Marie-Tooth disease 1A (CMT1A) for its clinical usefulness to assess disease severity. We collected blood samples from 69 CMT1A patients and 59 healthy controls. Plasma concentrations of p62 were analyzed by ELISA, and we compared them with Charcot-Marie-Tooth neuropathy score version 2 (CMTNSv2). A mouse CMT1A model (C22) was employed to determine the source and mechanism of plasma p62 elevation. Plasma p62 was detected in healthy controls with median value of 1978 pg/ml, and the levels were significantly higher in CMT1A (2465 pg/ml, p < 0.001). The elevated plasma p62 levels were correlated with CMTNSv2 (r = 0.621, p < 0.0001), motor nerve conduction velocity (r = - 0.490, p < 0.0001) and disease duration (r = 0.364, p < 0.01). In C22 model, increased p62 expression was observed not only in pathologic Schwann cells but also in plasma. Our findings indicate that plasma p62 measurement could be a valuable tool for evaluating CMT1A severity and Schwann cell pathology.

Development of Respiratory Infection Prevention and Control Self-Efficacy Scale for Adults.

Purpose: This study aimed to develop a scale for respiratory infection prevention and control self-efficacy (R-PACS) to measure self-efficacy in the prevention and control of the spread of respiratory infections among adults and to confirm the applicability of the developed scale by testing its validity and reliability. Methods: This methodological study was conducted in two phases. During the first phase, the R-PACS scale was developed after conducting a thorough literature review, content validity, and a pilot test. In the second phase, its validity and reliability were verified against 210 university students in Korea. The criterion validity of the developed R-PACS scale was tested using the correlation with resilience scale. Item analysis, explanatory factor analysis, and convergent and discriminant validity analyses were conducted in order to verify construct validity. Furthermore, Cronbach's α was used to verify internal consistency reliability. Results: The final version of the R-PACS scale comprises 4 factors and 16 items rated on a 5-point Likert scale. Higher scores are interpreted as higher levels of self-efficacy in the prevention and control of respiratory infection. The R-PACS scale exhibited good content validity, construct validity, criterion validity, and reliability. The correlation coefficient of the four factors was ≥.4, confirming the validity of item convergence; meanwhile, the Cronbach's α coefficient for the final 16 items of the developed scale was 0.923, verifying reliability. This scale consists of four factors: "environmental management", "contact restrictions", "general infection prevention and control", and "early detection". Conclusion: The applicability of the R-PACS scale exhibited acceptable validity and reliability. This scale can be utilized to assess and evaluate the degree of self-efficacy in the prevention and control of respiratory infections among adults. Data obtained using this scale can be utilized for preparing health behavior change and health promotion programs, and practical policies for preventing respiratory infections.

Decoding the principle of cell-fate determination for its reverse control.

Understanding and manipulating cell fate determination is pivotal in biology. Cell fate is determined by intricate and nonlinear interactions among molecules, making mathematical model-based quantitative analysis indispensable for its elucidation. Nevertheless, obtaining the essential dynamic experimental data for model development has been a significant obstacle. However, recent advancements in large-scale omics data technology are providing the necessary foundation for developing such models. Based on accumulated experimental evidence, we can postulate that cell fate is governed by a limited number of core regulatory circuits. Following this concept, we present a conceptual control framework that leverages single-cell RNA-seq data for dynamic molecular regulatory network modeling, aiming to identify and manipulate core regulatory circuits and their master regulators to drive desired cellular state transitions. We illustrate the proposed framework by applying it to the reversion of lung cancer cell states, although it is more broadly applicable to understanding and controlling a wide range of cell-fate determination processes.

Digital quantification of the MMSE interlocking pentagon areas: a three-stage algorithm.

The Mini-Mental State Examination (MMSE) is a widely employed screening tool for the severity of cognitive impairment. Among the MMSE items, the pentagon copying test (PCT) requires participants to accurately replicate a sample of two interlocking pentagons. While the PCT is traditionally scored on a binary scale, there have been limited developments of granular scoring scale to assess task performance. In this paper, we present a novel three-stage algorithm, called Quantification of Interlocking Pentagons (QIP) which quantifies PCT performance by computing the areas of individual pentagons and their intersection areas, and a balance ratio between the areas of the two individual pentagons. The three stages of the QIP algorithm include: (1) detection of line segments, (2) unraveling of the interlocking pentagons, and (3) quantification of areas. A set of 497 PCTs from 84 participants including their baseline and follow-up PCTs from the Rush Memory and Aging Project was selected blinded about their cognitive and clinical status. Analysis of the quantified data revealed a significant inverse relationship between age and balance ratio (beta = - 0.49, p = 0.0033), indicating that older age was associated with a smaller balance ratio. In addition, balance ratio was associated with perceptual speed (r = 0.71, p = 0.0135), vascular risk factors (beta = - 3.96, p = 0.0269), and medical conditions (beta = - 2.78, p = 0.0389). The QIP algorithm can serve as a useful tool for enhancing the scoring of performance in the PCT.

The Effects of Fermented Rice Drink With Lactiplantibacillus plantarum JSA22 in Overweight Irritable Bowel Syndrome Patients: A Randomized, Double-blind, Placebo-controlled Study.

Background/Aims: This study aims to investigate the effect of a fermented rice drink with Lactiplantibacillus plantarum JSA22 on symptoms, blood tests, microbiomes, and fecal metabolites in patients with irritable bowel syndrome (IBS) who were overweight. Methods: Sixty overweight (body mass index ≥ 23 kg/m2) patients aged between 20 and 65 with IBS were enrolled. Patients were divided into 2 groups and administered either a fermented rice drink or an nonfermented rice drink for a month. The symptom questionnaire, blood samples, and stool samples for microbiome and metabolite were collected before and after the month of rice drink administration. The primary efficacy variable was the subject's global assessment of IBS symptoms. Results: In both groups, global IBS symptoms, including abdominal pain, bowel habit, urgency, and abdominal distension, improved significantly (P < 0.01). The abdominal bloating was more significantly improved in the fermented rice drink group than in the nonfermented rice drink group (P < 0.05). Significant changes were not observed in metabolic syndrome-related blood tests or fecal metabolites in either group. However, microbiome analysis showed significant differences in genus levels before and after consuming fermented rice drink, such as in Blautia in stool (P = 0.020) and Prevotella (P = 0.017) and Oribacterium (P = 0.018) in saliva. Conclusions: The fermented rice drink with L. plantarum JSA22 showed a beneficial effect in reducing abdominal distension in IBS patients. Bacteria that reduce visceral fat accumulation increased in the stool and saliva of patients who consumed fermented rice drinks.

Understanding South Korean women workers' career transition experiences: using the career decision tree model.

Introduction: Relatively little research has explored non-Western women workers and their career transitions within their unique cultural contexts. Thus, more context-sensitive approaches to women's career trajectories are needed. Methods: Based on Bian and Wang's Career Decision Tree Model (2019) as a conceptual framework, the reasons for South Korean women workers' career transitions and influencing factors were explored using a qualitative approach with in-depth interviews with 35 South Korean women workers at various career stages. Results and Discussion: Their main motive of career transitions was difficulty maintaining their physical and mental health, which stemmed from their demanding work life. A typical issue, the burden of child rearing and family responsibilities, was also reported, but it was not the primary reason for their career transitions. Instead, the women workers often mentioned these responsibilities along with other reasons. Other reasons were unresolved career interests and expectations associated with their lack of career goals and preparation prior to joining the labor market. These factors led to significant changes in women's values and priorities along their career path, which finally triggered a decision to make a career transition. South Korean socio-cultural characteristics embedded in the South Korean women's personal and organizational lives provide insights on how to interpret the findings. Although on the surface some of our findings appeared to confirm previous studies on women's career transitions in Western-based literature, noteworthy differences were discovered when delving deeper into women's career transitions in the South Korean context.

Network visualization to interpret which healthcare services are central to people living with HIV.

AIM: To employ network analysis to identify the central healthcare service needs of people living with HIV (PLWH) for integrated care. DESIGN: Cross-sectional survey. METHODS: A list of healthcare services was identified through literature reviews, expert workshops and validity evaluations by PLWH. A total of 243 PLWH participated at five hospitals and self-reported their need for healthcare services on a four-point Likert scale. Centrality of healthcare service needs was analysed using network analysis. RESULTS: The mean score for 20 healthcare service needs was 3.53 out of 4. The highest scoring need, "Precaution for interaction between antiretroviral therapy and other drugs," received a rating of 3.73 but had a centrality of only 0.31. The most central node in the network of healthcare service needs, "Information and coping with opportunistic infections," had a strength centrality of 1.63 and showed significant relationships with "non-HIV-related medical services (e.g., health check-ups)" and "Regular dental services." The correlation stability coefficient, which quantifies the stability of centrality, was 0.44 with an acceptable value. CONCLUSIONS: The most central need was information on opportunistic infections that had connections with many nodes in network analysis. By interpreting the relationships between needs, healthcare providers can design interventions with an integrative perspective. IMPLICATIONS FOR PATIENT CARE: Network visualization provides dynamic relationships between needs that are unknown from the score scale by presenting them graphically and qualitatively. IMPACT: Using network analysis to interpret need assessment offers an integrated nursing perspective. Coping with opportunistic infection is central to connecting the chain of healthcare. This study highlights the multifaceted understanding of patients' needs that nurses gain when they conduct network analysis. REPORTING METHOD: We adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Case report: Tolosa-Hunt syndrome-expanding the neuromyelitis optica spectrum disorder phenotype?

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy caused by the autoantibody of aquaporin-4 (AQP4). Herein, we report a case of Tolosa-Hunt syndrome presenting with abducens palsy and AQP4 antibodies. This was a rare case of AQP4-immunoglobulin G seropositivity in a patient with Tolosa-Hunt syndrome. Our findings may expand the clinical phenotype of NMOSD and indicate that clinicians should consider testing for AQP4 antibodies in patients with Tolosa-Hunt syndrome.

Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes.

BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis. RESULTS: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION. CONCLUSION: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON.

Issues, challenges, and future perspectives of genetic counseling in Republic of Korea: Perspectives of laboratory physicians based on a 2022 survey.

The field of genetic counseling (GC) in the Republic of Korea has evolved from a single medical doctor's clinic to a multidisciplinary service with medical geneticists and non-medical professionals working as a team. Here, we assessed the current status of GC in the Republic of Korea based on professional surveys from the perspective of laboratory physicians. An electronic survey was designed and conducted, with the respondents being 50 certified laboratory physicians who were members of the Korean Society for Genetic Diagnostics. Among the 50 respondents, 12 (24%) operated GC clinics. The number of sessions and cases of GC have been on the rise over the last few years, and counseling for cancer genetics was the most common request. Most respondents considered a good understanding of the genetic test and the ability to interpret the test results as strengths of laboratory physicians as medical geneticists, while the lack of clinical experience was a weakness. Education programs regarding laboratory physicians' needs should be provided for high-quality counseling. Lastly, improving the efficiency of GC by strengthening the workforce through a multidisciplinary team is necessary.

Oral Administration of Alcohol-Tolerant Lactic Acid Bacteria Alleviates Blood Alcohol Concentration and Ethanol-Induced Liver Damage in Rodents.

Excessive alcohol consumption can have serious negative consequences on health, including addiction, liver damage, and other long-term effects. The causes of hangovers include dehydration, alcohol and alcohol metabolite toxicity, and nutrient deficiency due to absorption disorders. Additionally, alcohol consumption can slow reaction times, making it more difficult to rapidly respond to situations that require quick thinking. Exposure to a large amount of ethanol can also negatively affect a person's righting reflex and balance. In this study, we evaluated the potential of lactic acid bacteria (LAB) to alleviate alcohol-induced effects and behavioral responses. Two LAB strains isolated from kimchi, Levilactobacillus brevis WiKim0168 and Leuconostoc mesenteroides WiKim0172, were selected for their ethanol tolerance and potential to alleviate hangover symptoms. Enzyme activity assays for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were then conducted to evaluate the role of these bacteria in alcohol metabolism. Through in vitro and in vivo studies, these strains were assessed for their ability to reduce blood alcohol concentrations and protect against alcohol-induced liver damage. The results indicated that these LAB strains possess significant ethanol tolerance and elevate ADH and ALDH activities. LAB administration remarkably reduced blood alcohol levels in rats after excessive alcohol consumption. Moreover, the LAB strains showed hepatoprotective effects and enhanced behavioral outcomes, highlighting their potential as probiotics for counteracting the adverse effects of alcohol consumption. These findings support the development of functional foods incorporating LAB strains that can mediate behavioral improvements following alcohol intake.

Changes in an in-vivo classifier of ARTerioloSclerosis (ARTS) with simultaneous change in cognition for older African Americans.

At autopsy, African American decedents often have mixed Alzheimer's and cerebrovascular brain pathologies including arteriolosclerosis. We applied a novel in-vivo classifier of ARTerioloSclerosis (ARTS) in 167 older African Americans (∼75y of age) with > 2 biennial 3 T MRI scans and > 3 years of associated cognitive follow-up to determine if ARTS scores (higher score=higher likelihood of arteriolosclerosis) changed over time and if this change associated with changes in cognition in the same individuals. Mixed effects regression models tested whether ARTS scores increased over time, while simultaneous mixed effects regression models estimated the simultaneous rates of change in both ARTS and cognition and the correlation of these changes. ARTS scores increased over time (estimate=0.030, SE=0.002, p < 0.0001). Faster increases in ARTS were associated with faster rates of global cognitive decline (r = -0.447, p = 0.006) and domain-specific cognitive functions. Applying an in-vivo marker of arteriolosclerosis in an African American cohort revealed that the likelihood of arteriolosclerosis increases over time, and participants whose ARTS scores increased more rapidly tended to have faster than average rates of cognitive decline.

Missense Variant c.3301C>T (p.R1101W) in von Willebrand Factor A Sequence in a Patient with Recessive Dystrophic Epidermolysis Bullosa Pruriginosa with Compound Heterozygous COL7A1 Variants.

Dystrophic epidermolysis bullosa (DEB) pruriginosa is a rare subtype of DEB characterized by multiple, violaceous, and severe pruritic lichenified nodules along with blisters. Here, we report the case of a Korean male who, since the age of 3 years, had multiple pruritic nodules with blisters on both lower extremities. Genetic testing is required to diagnose DEB pruriginosa because its clinical and histologic features are inconclusive. We identified compound heterozygous COL7A1 variants of c.5797C>T (p.R1933*) and c.3301C>T (p.R1101W) in the patient, leading to a diagnosis of recessive DEB pruriginosa. Among the variants identified, c.3301C>T is a novel missense variant that has not been reported previously. This variant is in exon 26, which encodes von Willebrand factor A (vWFA) in collagen type VII. vWFA is known to preserve normal dermal structures by interacting with dermal collagens and basement membranes. Considering that this variant contradicts the general concept that autosomal dominant inheritance is more common and that variants typically occur in the triple helical collagenous domain of COL7A1 in DEB pruriginosa, we focus on the rarity of this case and the possible pathogenic role of the c.3301C>T (p.R1101W) variant.

Factors predicting different times for brushing teeth during the day: multilevel analyses.

BACKGROUND: The most effective and simple intervention for preventing oral disease is toothbrushing. However, there is substantial variation in the timing of brushing teeth during the day. We aimed to identify a comprehensive set of predictors of toothbrushing after lunch and after dinner and estimated contextual (i.e., geographic) variation in brushing behavior at different times of the day. METHODS: We constructed a conceptual framework for toothbrushing by reviewing health behavior models. The main data source was the 2017 Community Health Survey. We performed a four-level random intercept logistic regression to predict toothbrushing behavior. (individual, household, Gi/Gun/Gu, and Si/Do). RESULTS: Individuals under 30 years of age had higher likelihood of brushing after lunch, while brushing after dinner was higher among those aged 40-79 years. People engaged in service/sales, agriculture/fishing/labor/mechanics, as well as student/housewife/unemployed were 0.60, 0.41, and 0.49 times less likely to brush their teeth after lunch, respectively, compared to those working in the office, but the gap narrowed to 0.97, 0.96, 0.94 for brushing after dinner. We also found significant area-level variations in the timing of brushing. CONCLUSIONS: Different patterns in association with various factors at individual-, household- and Si/Gun/Gu-levels with toothbrushing after lunch versus toothbrushing after dinner suggests a need for tailored interventions to improve toothbrushing behavior depending on the time of day.

Alzheimer's Disease Pathology Outside of the Cerebrum Is Related to a Higher Odds of Dementia.

BACKGROUND: Assessments of Alzheimer's disease pathology do not routinely include lower brainstem, olfactory bulb, and spinal cord. OBJECTIVE: Test if amyloid-ß (Aß) and paired helical filament (PHF) tau-tangles outside the cerebrum are associated with the odds of dementia. METHODS: Autopsies were obtained in decedents with cognitive testing (n = 300). Aß plaques and PHF tau-tangles were assessed in 24 sites: cerebrum (n = 14), brainstem (n = 5), olfactory bulb, and four spinal cord levels. Since spinal Aß were absent in the first 165 cases, it was not assessed in the remaining cases. RESULTS: Age at death was 91 years old. About 90% had Aß in cerebrum and of these, half had Aß in the brainstem. Of the latter, 85% showed Aß in the olfactory bulb. All but one participant had tau-tangles in the cerebrum and 86% had brainstem tau-tangles. Of the latter, 80% had tau-tangles in olfactory bulb and 36% tau-tangles in one or more spinal cord levels. About 90% of adults with tau-tangles also had Aß in one or more regions. In a logistic model controlling for demographics, Aß and tau-tangles within the cerebrum, the presence of Aß in olfactory bulb [OR, 1.74(1.00, 3.05)]; tau-tangles in brainstem [OR, 4.00(1.1.57,10.21)]; and spinal cord [OR, 1.87 (1.21,3.11)] were independently associated with higher odds of dementia. CONCLUSION: Regional differences in Aß and tau-tangle accumulation extend beyond cerebrum to spinal cord and their presence outside the cerebrum are associated with a higher odds of dementia. Further studies are needed to clarify the extent, burden, and consequences of AD pathology outside of cerebrum.