Two chromosome-level genome assemblies of Rhodiola shed new light on genome evolution in rapid radiation and evolution of the biosynthetic pathway of salidroside.

Rhodiola L. is a genus that has undergone rapid radiation in the mid-Miocene and may represent a typic case of adaptive radiation. Many species of Rhodiola have also been widely used as an important adaptogen in traditional medicines for centuries. However, a lack of high-quality chromosome-level genomes hinders in-depth study of its evolution and biosynthetic pathway of secondary metabolites. Here, we assembled two chromosome-level genomes for two Rhodiola species with different chromosome number and sexual system. The assembled genome size of R. chrysanthemifolia (2n = 14; hermaphrodite) and R. kirilowii (2n = 22; dioecious) were of 402.67 and 653.62 Mb, respectively, with approximately 57.60% and 69.22% of transposable elements (TEs). The size difference between the two genomes was mostly due to proliferation of long terminal repeat-retrotransposons (LTR-RTs) in the R. kirilowii genome. Comparative genomic analysis revealed possible gene families responsible for high-altitude adaptation of Rhodiola, including a homolog of plant cysteine oxidase 2 gene of Arabidopsis thaliana (AtPCO2), which is part of the core molecular reaction to hypoxia and contributes to the stability of Group VII ethylene response factors (ERF-VII). We found extensive chromosome fusion/fission events and structural variations between the two genomes, which might have facilitated the initial rapid radiation of Rhodiola. We also identified candidate genes in the biosynthetic pathway of salidroside. Overall, our results provide important insights into genome evolution in plant rapid radiations, and possible roles of chromosome fusion/fission and structure variation played in rapid speciation.

Improve the dupilumab therapy evaluation with dermoscopy and high-frequency ultrasound in moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease. Monoclonal antibody dupilumab was approved to treat moderate-to-severe AD in recent years. An objective assessment of treatment response by skin imaging modality is adjuvant for clinical evaluations. This study aimed to explore the value of dermoscopy and high-frequency ultrasound (HFUS) imaging characteristics in treatment evaluation for moderate-to-severe AD patients treated with dupilumab. METHODS: Moderate-to-severe AD patients refractory to conventional therapy were enrolled in the study. All patients went through at least a 16-week standardized treatment of dupilumab. Clinical scores (eczema area scoring index [EASI], SCOARD, numerical rating scale of pruritus, dermatology life quality index), dermoscopy, and HFUS examinations were conducted at 0, 2, 4, 8, 12, and 16 weeks of treatment. Erythema, scales, erosion, and pigmentation under dermoscopy were scored, and subepidermal low-echogenic band (SLEB) thickness under HFUS was measured as quantitative indexes. Descriptive analysis and mixed effect linear regression models were used for statistical analysis. RESULTS: Sixteen patients were enrolled in the study and their average age was 45.63 ± 18.18 years. All clinical scores decreased with significant difference after 16-week treatment compared with baseline. All patients achieved EASI 50 (EASI score decreased by 50% or more), and 9/16 patients reached EASI 75 after 16-week treatment. Dermoscopy evaluation of erythema, scales and erosion scores were decreased, and the sign of pigmentation score was increased after treatment. For HFUS, the mean SLEB value was 0.51 ± 0.29 mm and decreased to 0.27 ± 0.15 mm after 16-week treatment (p < 0.01). SLEB value decreased linearly with treatment time and correlated with clinical scores. However, SLEB values of two patients were 0.57 and 0.68 mm at week 16, respectively, which were higher than the average, and one of the patients showed EASI 75. CONCLUSION: Dermoscopy and HFUS were able to reveal deeper inflammation response than clinical scores in AD and can be an effective method to evaluate and monitor clinical improvement during dupilumab treatment for AD patients. The preliminary value of imaging methods for predicting the treatment endpoint of dupilumab remains to be verified.

Associations of adverse childhood experiences with common psychiatric disorder in later life: results from the China mental health survey.

BACKGROUND: Associations between adverse childhood experiences (ACEs) and common psychiatric disorders among older Chinese individuals have not been well reported. The objectives of this study are to examine the prevalence of ACEs and the associations of ACEs with common psychiatric disorders among older adults in China. METHODS: The study used data from the China Mental Health Survey (CMHS), a nationally representative epidemiological survey, which used computer-assisted personal interviewing (CAPI), logistic regression models were used to examine community-based adult psychiatric disorders and associated risk factors. Finally, 2,317 individuals aged 60 years or over were included in the CMHS. The national prevalence of ACEs in older adults were estimated and logistic regression were used to analyse the association between ACEs and past-year psychiatric disorders. RESULTS: Prevalence of ACEs among older adults in China was 18.1%. The three most common types of ACEs were neglect (11.6%), domestic violence (9.2%), and parental loss (9.1%). This study proved the association between ACEs and common past-year psychiatric disorders in older adults. ACEs increased the risk of past-year psychiatric disorders in older adults. After adjustment for age, sex, marital status, employment status, education, rural or urban residence, region, and physical diseases, the association between ACEs and past-year psychiatric disorders were still significant. CONCLUSIONS: ACEs are linked to an increased risk for past-year psychiatric disorders in older adults. ACEs may have long-term effects on older adults' mental well-being. Preventing ACEs may help reduce possible adverse health outcomes in later life.

Group V Chitin Deacetylases Influence the Structure and Composition of the Midgut of Beet Armyworm, Spodoptera exigua.

Chitin deacetylase (CDA) can accelerate the conversion of chitin to chitosan, influencing the mechanical properties and permeability of the cuticle structures and the peritrophic membrane (PM) in insects. Putative Group V CDAs SeCDA6/7/8/9 (SeCDAs) were identified and characterized from beet armyworm Spodoptera exigua larvae. The cDNAs of SeCDAs contained open reading frames of 1164 bp, 1137 bp, 1158 bp and 1152 bp, respectively. The deduced protein sequences showed that SeCDAs are synthesized as preproteins of 387, 378, 385 and 383 amino acid residues, respectively. It was revealed via spatiotemporal expression analysis that SeCDAs were more abundant in the anterior region of the midgut. The SeCDAs were down-regulated after treatment with 20-hydroxyecdysone (20E). After treatment with a juvenile hormone analog (JHA), the expression of SeCDA6 and SeCDA8 was down-regulated; in contrast, the expression of SeCDA7 and SeCDA9 was up-regulated. After silencing SeCDAV (the conserved sequences of Group V CDAs) via RNA interference (RNAi), the layer of intestinal wall cells in the midgut became more compact and more evenly distributed. The vesicles in the midgut were small and more fragmented or disappeared after SeCDAs were silenced. Additionally, the PM structure was scarce, and the chitin microfilament structure was loose and chaotic. It was indicated in all of the above results that Group V CDAs are essential for the growth and structuring of the intestinal wall cell layer in the midgut of S. exigua. Additionally, the midgut tissue and the PM structure and composition were affected by Group V CDAs.

The association between community-level socioeconomic status and depressive symptoms among middle-aged and older adults in China.

BACKGROUND: There was little evidence concerning the association of community socioeconomic status (SES) and the cross-level interaction between community- and individual-level SES with depressive symptoms in China. This study aimed to investigate the association of community-level SES with depressive symptoms among Chinese middle-aged and older people and to examine whether individual-level SES moderates this relationship. METHODS: Using data from the China Health and Retirement Longitudinal 2011-2018 Study, the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10) short form was used to measure depressive symptoms in 35,546 Chinese individuals aged 45 years and older. Community SES was calculated as a sum of z scores of the average years of schooling and household income per capita, which were derived by aggregating the individual measures to the community level. Two-level hierarchical linear regression was used. RESULTS: Community SES was negatively related to CES-D-10 scores (coef=-0.438). A 1-SD increase in individual SES was associated with lower CES-D-10 scores (coef=-0.490). The cross-level interaction on individual- and community-level SES was significantly associated with depressive symptoms, indicating that with the increase of individual-level SES, the effect of community-level SES on depression decreases. Stratified analyses observed robust associations of community SES with CES-D scores between urban and rural residents. CONCLUSIONS: This study showed that individuals who live in lower-SES communities had more severe depressive symptoms, particularly individuals with low SES. Additional attention should be given to the community socioeconomic context of middle-aged and older adults with lower SES, which may be helpful to reduce SES inequalities in depressive symptoms in China.

Long-term disability in common mental disorders in Chinese community: evidence from a five-year follow-up study.

BACKGROUND: Common mental disorders are general term for mental disorders with high disability rates and significant social burden. The purpose of this study was to determine the degree of long-term disability associated with common mental disorders and to interpret the relationship between common mental disorders and long-term disability. METHODS: Participants in the 2013 China Mental Health Survey were followed up by telephone between April and June 2018. This study evaluated long-term disability over a five-year period using the World Health Organization's Disability Assessment Schedule 2.0. Poisson regression was used to analyze the relationship between common mental disorders and long-term disability. RESULTS: A total of 6269 patients were followed up by telephone. In patients with common mental disorders, the prevalence of disability ranged from 7.62% to 43.94%. The long-term disabilities were significantly associated with dysthymic disorder (DD, RR:2.40; 95% CI:1.87-3.03), major depressive disorder (MDD, RR:1.63; 95% CI:1.34-1.98), generalized anxiety disorder (GAD, RR:1.95; 95% CI:1.15-3.09), obsessive-compulsive disorder (OCD, RR:1.68; 95% CI:1.24-2.22) and alcohol use disorder (AUD, RR: 1.42; 95% CI:0.99-1.96). CONCLUSIONS: In China, common mental disorders raise the risk of long-term disability, and there is a critical need for monitoring patients with DD, MDD, GAD, OCD, and AUD. For improved quality of life and reduced disability levels, more resources need to be dedicated to mental health in the future.

Value of high-frequency ultrasound in the treatment of moderate and severe acne vulgaris.

BACKGROUND: Acne treatment may fail or cause undesirable side effects due to inaccurate evaluation. High-frequency ultrasound (HFUS) can monitor systemic treatment in patients with moderate-to-severe acne vulgaris. MATERIALS AND METHODS: In this prospective study, consecutive patients with moderate-to-severe acne vulgaris were recruited. Patients were graded by a comprehensive clinical assessment before and after therapy. Simultaneous HFUS grading was independently evaluated according to the sonographic scoring system for acne (SSSA). Clinical and HFUS grades were compared through kappa analysis. RESULTS: A total of 70 patients were enrolled. At baseline, 36 (51.4%) and 34 (48.6%) patients were graded as moderate and severe, respectively, through clinical assessment. However, 27 patients (38.6%) scored SSSA-Grade II and 43 (61.4%) scored SSSA-Grade III in the HFUS grading. Sixty-one patients (87.1%) were in the consistent category as per clinical assessment and HFUS grades, with Kappa1  = 0.745, whereas higher HFUS grades were observed in nine patients. By the end of the observation, 65 of all patients (92.9%) showed significant improvement and 5 (7.1%) showed no apparent improvement after the treatment. According to the clinical assessment, 14, 52, and 4 patients were graded as mild, moderate, and severe, respectively. On the other hand, 11, 51, and 8 patients had SSSA-Grade I, II, and III, respectively. Of all patients, 63 (90.0%) had consistent evaluation results, with Kappa2  = 0.762, whereas the remaining seven patients had an HFUS grade higher than the clinical. CONCLUSION: HFUS is a useful tool for dermatologists to monitor the treatment of moderate and severe acne vulgaris.

The association between community-level socioeconomic status and cognitive function among Chinese middle-aged and older adults: a study based on the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Although numerous studies focused on the relationship between area socioeconomic status (SES) and health, only a few of them investigated how community-level SES was linked to late-life cognitive function as well as the potential pathways underlying this association, and very few of them focused on the context of China. This study examined how community-level SES was linked to cognitive function and the potential pathways underlying this association among middle-aged and older adults in China. METHODS: Data was drawn from the waves 1-4 of China Health and Retirement Longitudinal Study. We measured cognitive function with the components of the Telephone Interview of Cognitive Status battery. Community-level SES was derived from a sum of z scores of the percentage of the illiterate and the per-capita net income status within communities. We adopted two-level hierarchical linear regression models to explore the associations between community-level SES and cognitive function. A multilevel mediation analysis with structural equation modeling was undertaken to disaggregate the direct and indirect pathways of the associations. RESULTS: Higher community-level SES was associated with better cognitive function (ß = 0.562, 95% CI = 0.390, 0.734), and this significant association was only present in rural participants, not in urban participants. Furthermore, we discovered the mediating effects of outdoor exercise facilities within communities (ß = 0.023, 95% CI = 0.000, 0.056) and individual-level SES (ß = 0.108, 95% CI = 0.057, 0.156) to explain the relationship between community SES and cognitive function. CONCLUSIONS: These findings highlight the importance of community environmental interventions in maintaining individuals' cognitive health in China, especially for older adults. Our results provided solid empirical evidence for reducing mental health inequalities in China, and suggested that developing an aging-friendly environment and properly distributing community resources are important to improve cognitive function of older adults.

Identification and functional analysis of two potential RNAi targets for chitin degradation in Holotrichia parallela Motschulsky (Insecta Coleoptera).

Chitin metabolism enzymes are safe and desirable targets for pest management. ß-N-acetylglucosaminidase (NAG) and N-acetylglucosamine kinase (NAGK) are involved in chitin degradation. NAG is the main glycosidase that works synergistically with chitinases. NAGK is a key enzyme for the generation of UDP-Nacetylglucosamine (UDP-GlcNAc) and for the conversion of GlcNAc into GlcNAc 6-phosphate (GlcNAc-6-P). In this study, NAG and NAGK genes were identified from Holotrichia parallela, a polyphagous soil pest that causes serious damage to crops. The spatiotemporal expression investigated by RT-qPCR indicated that the two genes are expressed in all larval developmental stages. HpNAG is highly expressed in the integument and HpNAGK overexpressed in the midgut. After injection of dsHpNAG and dsHpNAGK, a significant RNAi effect was found after 72 h and larvae stopped growing. The survival rates of larvae were 13.3% and 16.7%, respectively. RNAi of HpNAG and HpNAGK regulated the expression levels of chitin metabolism-related genes, indicating that these two genes could be critical in the chitin metabolism. Furthermore, silencing HpNAG and HpNAGK reduced the thickness of the cuticle, and decreased its content of chitin. The study will lay a foundation for further clarifying the mechanism of chitin metabolism and provide potential targets for the biological control of H. parallela larvae.

Intrinsic capacity and its associations with incident dependence and mortality in 10/66 Dementia Research Group studies in Latin America, India, and China: A population-based cohort study.

BACKGROUND: The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach-testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death. METHODS AND FINDINGS: We conducted population-based cohort studies (baseline, 2003-2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008-2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3-76.3 years; 62.4% were female, range 53.4%-67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69-2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49-1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias. CONCLUSIONS: In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes.

Correlates of transitions from alcohol use to disorder diagnosed by DSM-5 in China.

BACKGROUND: This study aimed to describe the prevalence and lifetime criteria profiles of DSM-5 alcohol use disorder (AUD) and the transitions from alcohol use to disorder in Chifeng, China. METHODS: Face-to-face interviews were conducted using Composite International Diagnostic Interview-3.0 (CIDI-3.0) among 4528 respondents in Chifeng. RESULTS: The weighted lifetime and 12-month prevalence of DSM-5 AUD were 3.03 and 1.05%, respectively. Mild lifetime AUD was the most prevalent severity level (69.53%). The two most common criteria were "failure to quit/cutdown" and "drinking more or for longer than intended." Lifetime prevalence was 65.59% for alcohol use, and 22.97% for regular drinking. Male and domestic violence were risk factors for the transition from alcohol use to regular drinking or AUD and from regular drinking to AUD. Younger age was risk factor for the transition to AUD from alcohol use or regular drinking. Poverty (OR = 2.49) was risk factor for the transition from alcohol use to regular drinking. The earlier drinkers were more likely to develop to regular drinking (OR = 2.11). CONCLUSION: AUD prevalence in Chifeng was not as high as that in Western countries. The study revealed that multiple risk factors might contribute to the transition across different stages of alcohol use. Further research should explore the underlying mechanisms.

RNA interference-mediated functional characterization of Group I chitin deacetylases in Holotrichia parallela Motschulsky.

Chitin deacetylases (CDAs, EC 3.5.1.41) catalyze the N-deacetylation of chitin to produce chitosan, which is essential for insect survival. Hence, CDAs are promising targets for the development of novel insecticidal drugs. In this study, the putative Group I chitin deacetylase genes HpCDA1, HpCDA2-1 and HpCDA2-2 were identified from Holotrichia parallela. Conserved domain database search identified a chitin-binding peritrophin-A domain (ChBD), a low-density lipoprotein receptor class A domain (LDLa), and a putative CDA-like catalytic domain. RT-qPCR analysis showed that the Group I HpCDAs were expressed in various tissues and predominant in the integument. The developmental expression patterns from the first-instar to third-instar larvae showed that HpCDAs were highly expressed on the first day and gradually declined after molting. The functional characteristics of the Group I CDAs in cuticle organization were examined using RNA interference (RNAi) and transmission electron microscopy (TEM) methods. Administration of double-stranded HpCDA (dsHpCDA) through larval injection could suppress the expression levels of HpCDA1 and HpCDA2, thus resulting in abnormal or lethal phenotypes. TEM analysis revealed that RNAi of either HpCDA1 or HpCDA2 remarkably affected the cuticle integrity, as evidenced by cuticle disorganization and chitin laminae disruption, suggesting the crucial role of CDAs in chitin modification. These experimental results demonstrate the important contribution of putative key genes involved in chitin metabolism, and provide a foundation for developing new strategies to control H. parallela.

Schizophrenia, Bipolar Disorder, and Alzheimer's Disease are not Causal Factors of Bone Mineral Density: A Mendelian Randomization Analysis.

Until recently, it remains unclear whether schizophrenia, bipolar disorder (BD), and Alzheimer's disease (AD) is associated with bone mineral density (BMD). We aimed to investigate the causal effects of schizophrenia, BD and AD on BMD with Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) strongly associated with these three neuropsychiatric diseases as instrumental variables were selected from genome-wide association studies in the MR Base database. We analyzed the effects of these SNPs on the femoral neck BMD (FN-BMD), lumbar spine BMD (LS-BMD) and forearm BMD (FA-BMD), and evaluated the heterogeneities and pleiotropy of these genetic variants. We also evaluated the potential confounding factors in the association between these three neuropsychiatric diseases and the BMD level. It was found that none of these genetic variants were significantly associated with BMD or confounding factors. Using these genetic variants, we did not find statistically significant causal effects of per unit increase in the log-odds of having schizophrenia, BD or AD with FN-BMD, LS-BMD and FA-BMD changes (e.g. schizophrenia and FN-BMD, MR-Egger OR 0.9673, 95% CI 0.8382 to 1.1163, p = 0.6519). The MR results also revealed that directional pleiotropy was unlikely to bias the causality (e.g., schizophrenia and FN-BMD, intercept = 0.0023, p = 0.6887), and no evidence of heterogeneity was found between the genetic variants (e.g., schizophrenia and FN-BMD, MR-Egger Q = 46.1502, I2 = 0.0899, p = 0.3047). Our MR study did not support causal effects of increased risk of schizophrenia, BD and AD status with BMD level.

The association between, depression, anxiety, and mortality in older people across eight low- and middle-income countries: Results from the 10/66 cohort study.

OBJECTIVES: Depression and anxiety are common mental disorders in later life. Few population-based studies have investigated their potential impacts on mortality in low- and middle-income countries (LMICs). The aim of this study is to examine the associations between depression, anxiety, their comorbidity, and mortality in later life using a population-based cohort study across eight LMICs. METHODS: This analysis was based on the 10/66 cohort study including 15 991 people aged 65 years or above in Cuba, Dominican Republic, Venezuela, Mexico, Peru, Puerto Rico, China, and India, with an average follow-up time of 3.9 years. Subthreshold and clinical levels of depression were determined using EURO-D and ICD-10 criteria, and anxiety was based on Geriatric Mental State (GMS)-Automated Geriatric Examination for Computer Assisted Taxonomy (AGECAT). Cox proportional hazard modelling was used to estimate how having depression, anxiety, or both was associated with mortality adjusting for sociodemographic and health factors. RESULTS: Participants with clinical depression (hazard ratio [HR]: 1.45; 95% CI, 1.24-1.70) and subthreshold anxiety (HR: 1.26; 95% CI, 1.15-1.38) had higher risk of mortality than those without the conditions after adjusting for sociodemographic factors and health conditions. Comorbidity of depression and anxiety was associated with a 30% increased risk of mortality but the effect sizes varied across countries (Higgins I2  = 58.8%), with the strongest association in India (HR: 1.99; 95% CI, 1.21-3.27). CONCLUSIONS: Depression and anxiety appear to be associated with mortality in older people living in LMICs. Variation in effect sizes may indicate different barriers to health service access across countries. Future studies may investigate underlying mechanisms and identify potential interventions to reduce the impact of common mental disorders.

The association between frailty and incidence of dementia in Beijing: findings from 10/66 dementia research group population-based cohort study.

BACKGROUND: The relationship between frailty and dementia is unclear and there are very few population-based studies regarding this issue in China. The purpose of this study is to estimate the association between frailty and incident dementia in China, and to explore different effects of frailty established by three definitions of frailty on dementia incidence. METHODS: A five-year prospective cohort study was carried out in 2022 participants aged 65 years and over in urban and rural sites in Beijing, China. The participants were interviewed by trained community primary health care workers from 2004 to 2009. Frailty was defined using modified Fried frailty phenotype, physical frailty definition, and multidimensional frailty definition. Dementia was diagnosed using the 10/66 dementia criterion for calculating cumulative incidence. Both competing risk regression models and Cox proportional hazards models were applied to examine the associations between frailty at baseline and five-year cumulative incidence of dementia. RESULTS: At the end of follow-up the five-year cumulative incidence rates of dementia with frailty and without frailty defined by the modified Fried frailty were 21.0% and 9.6%, those defined by the physical frailty were 19.9% and 9.0%, and those defined by the multidimensional frailty were 22.8% and 8.9%, respectively. Compared with non-frail participants, frail people had a higher risk of incident dementia using multidimensional frailty definition after adjusting covariates based on competing risk regression model (HR = 1.47, 95% CI 1.01~2.17) and Cox proportional hazards model (HR = 1.56, 95% CI 1.07~2.26). The association between frailty and incident dementia was statistically significant in participants in the upper three quartiles of age (aged 68 years and over) using the multidimensional frailty definition based on the competing risk regression model (HR = 1.61, 95% CI 1.06~2.43) and Cox proportional hazard model (HR = 1.76, 95% CI 1.19~2.61). CONCLUSIONS: Multidimensional frailty may play an inherent role in incident dementia, especially in the people aged over 68, which is significant for distinguishing high risk people and determining secondary prevention strategies for dementia patients.

Neighbourhood environment and dementia in older people from high-, middle- and low-income countries: results from two population-based cohort studies.

BACKGROUND: A growing number of studies have explored how features of the neighbourhood environment can be related to cognitive health in later life. Yet few have focused on low- and middle-income countries and compared the results across different settings. The aim of this study is to investigate the cross-sectional associations between neighbourhood amenities and dementia in older people from high-, middle- and low-income countries. METHODS: This study was based on two population-based cohort studies of people aged≥65: the Cognitive Function and Ageing Study II (CFAS II) in UK (N = 4955) and a subset of the 10/66 study in China, Dominican Republic and Mexico (N = 3386). In both cohorts, dementia was assessed using the Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) algorithm. The 10/66 dementia diagnostic algorithm was also used as an additional criterion in the 10/66 study. Publicly accessible databases, Google Maps and Open Street Map, were used to obtain geographic information system data on distance to neighbourhood amenities, including lifestyle (cafés, libraries, movie theatres, parks), daily life (post offices, convenience stores), healthcare (hospitals, pharmacies) and percentages of local green and blue spaces within 400 and 800 m of participants' residences. Multilevel logistic regression was used to investigate the associations between these environmental features and dementia adjusting for sociodemographic factors and self-rated health. RESULTS: Living far from daily life amenities was associated with higher odds of dementia in both CFAS II (1.47; 95% CI: 0.96, 2.24) and the 10/66 study (1.53; 95% CI: 1.15, 2.04), while living far from lifestyle (1.50; 95% CI: 1.13, 1.99) and healthcare amenities (1.32; 95% CI: 0.93, 1.87) was associated with higher odds of dementia only in the 10/66 study. A high availability of local green and blue spaces was not associated with dementia in either cohort yet living far from public parks was associated with lower odds of dementia in CFAS II (0.64; 95% CI: 0.41, 1.00). CONCLUSIONS: The different relationships across cohorts may indicate a varying role for local amenities in diverse settings. Future research may investigate mechanisms related to these differences and social, cultural and historical influences on the interaction between neighbourhood amenities and older people.

Value of High-Frequency Ultrasound in Accurate Staging of Mycosis Fungoides/Sézary Syndrome.

OBJECTIVES: This study was aimed to assess the ultrasound (US) characteristics of mycosis fungoides (MF)/Sézary syndrome (SS) and explore the value of high-frequency US in accuracy staging for classic mycosis fungoides (cMF). METHODS: A prospective study was designed. Twenty-six patients with histopathologically confirmed MF or SS were enrolled to undergo HF-US examinations. Both 50- and 20-MHz US images of the most prominent lesion of each patient were collected by a cutaneous diagnostic US system, and the US characteristics in different stages were analyzed by 2 physicians independently. The Fisher exact test was used for the statistical analysis. RESULTS: A total of 26 patients underwent this study, including 23 with cMF, 2 with folliculotropic mycosis fungoides (FMF), and 1 with SS. Among cMF, 16 patients with patches or plaques (the early-stage group) showed a subepidermal low-echogenic band, and only 3 lesions in the plaque stage partially extended to the superficial dermis. Seven patients with tumors (the advanced-stage group) showed lesions that infiltrated to the deep dermis or subcutaneous tissue. The infiltration depth (P < .001), clarity of the boundary (P = .002), and homogeneity of internal echoes (P = .001) were significantly different between the early and advanced stages. Additionally, the 2 FMF lesions and 1 SS lesion had characteristic manifestations, showing a well-defined subepidermal low-echogenic band with patchy hypoechoic regions around the hair follicles in the dermis. CONCLUSIONS: High-frequency US can be used to accurately detect the infiltration depth and morphologic features of MF/SS lesions and provide important information for tumor staging of cMF. Additionally, the characteristic US features in FMF and SS might be helpful for diagnosis.

Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer deaths, and an increased number of GC patients adopt to next-generation sequencing (NGS) to identify tumor genomic alterations for precision medicine. METHODS: In this study, we established a hybridization capture-based NGS panel including 612 cancer-associated genes, and collected sequencing data of tumors and matched bloods from 153 gastric cancer patients. We performed comprehensive analysis of these sequencing and clinical data. RESULTS: 35 significantly mutated genes were identified such as TP53, AKAP9, DRD2, PTEN, CDH1, LRP2 et al. Among them, 29 genes were novel significantly mutated genes compared with TCGA study. TP53 is the top frequently mutated gene, and tends to mutate in male (p = 0.025) patients and patients whose tumor located in cardia (p = 0.011). High tumor mutation burden (TMB) gathered in TP53 wild-type tumors (p = 0.045). TMB was also significantly associated with DNA damage repair (DDR) genes genotype (p = 0.047), Lauren classification (p = 1.5e-5), differentiation (1.9e-7), and HER2 status (p = 0.023). 38.31% of gastric cancer patients harbored at least one actionable alteration according to OncoKB database. CONCLUSIONS: We drew a comprehensive mutational landscape of 153 gastric tumors and demonstrated utility of target next-generation sequencing to guide clinical management.

Treatment gap for anxiety disorders is global: Results of the World Mental Health Surveys in 21 countries.

BACKGROUND: Anxiety disorders are a major cause of burden of disease. Treatment gaps have been described, but a worldwide evaluation is lacking. We estimated, among individuals with a 12-month DSM-IV (where DSM is Diagnostic Statistical Manual) anxiety disorder in 21 countries, the proportion who (i) perceived a need for treatment; (ii) received any treatment; and (iii) received possibly adequate treatment. METHODS: Data from 23 community surveys in 21 countries of the World Mental Health (WMH) surveys. DSM-IV mental disorders were assessed (WHO Composite International Diagnostic Interview, CIDI 3.0). DSM-IV included posttraumatic stress disorder among anxiety disorders, while it is not considered so in the DSM-5. We asked if, in the previous 12 months, respondents felt they needed professional treatment and if they obtained professional treatment (specialized/general medical, complementary alternative medical, or nonmedical professional) for "problems with emotions, nerves, mental health, or use of alcohol or drugs." Possibly adequate treatment was defined as receiving pharmacotherapy (1+ months of medication and 4+ visits to a medical doctor) or psychotherapy, complementary alternative medicine or nonmedical care (8+ visits). RESULTS: Of 51,547 respondents (response = 71.3%), 9.8% had a 12-month DSM-IV anxiety disorder, 27.6% of whom received any treatment, and only 9.8% received possibly adequate treatment. Of those with 12-month anxiety only 41.3% perceived a need for care. Lower treatment levels were found for lower income countries. CONCLUSIONS: Low levels of service use and a high proportion of those receiving services not meeting adequacy standards for anxiety disorders exist worldwide. Results suggest the need for improving recognition of anxiety disorders and the quality of treatment.

The worldwide costs of dementia 2015 and comparisons with 2010.

INTRODUCTION: In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates. METHODS: This is a societal, prevalence-based global COI study. RESULTS: The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries. Costs of informal care and the direct costs of social care still contribute similar proportions of total costs, whereas the costs in the medical sector are much lower. The threshold of US $1 trillion will be crossed by 2018. DISCUSSION: Worldwide costs of dementia are enormous and still inequitably distributed. The increase in costs arises from increases in numbers of people with dementia and in increases in per person costs.