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ObjectivesDetection of dementia is essential for improving the lives of patients but the extent of underdetection worldwide and its causes are not known. This study aimed to quantify the prevalence of undetected dementia and to examine its correlates.Methods/setting/participantsA systematic search was conducted until October 2016 for studies reporting the proportion of undetected dementia and/or its determinants in either the community or in residential care settings worldwide. Random-effects models calculated the pooled rate of undetected dementia and subgroup analyses were conducted to identify determinants of the variation.Primary and secondary outcome measuresThe outcome measures of interest were the prevalence and determinants of undetected dementia.Results23 studies were eligible for inclusion in this review. The pooled rate of undetected dementia was 61.7% (95% CI 55.0% to 68.0%). The rate of underdetection was higher in China and India (vs Europe and North America), in the community setting (vs residential/nursing care), age of <70 years, male gender and diagnosis by general practitioner. However, it was lower in the studies using Mini-Mental State Examination (MMSE) diagnosis criteria.ConclusionsThe prevalence of undetected dementia is high globally. Wide variations in detecting dementia need to be urgently examined, particularly in populations with low socioeconomic status. Efforts are required to reduce diagnostic inequality and to improve early diagnosis in the community.

Periodontal disease (PD) is common and increases cardiovascular diseases. However, it is unclear whether PD is associated with increased risk of dementia. We carried out a systematic review and meta-analysis to investigate the influence of PD on dementia. We projected the number of dementia cases to be saved by reducing PD prevalence in the world. We searched cohort and case–control studies reporting the association of PD with all dementia (or any specific type of dementia) through PubMed, MEDLINE, PsycINFO, SocINDEX, CINHAL, and CNKI until 7th November 2018. Five cohorts and seven case–control studies were identified for review. We pooled eligible data to calculate relative risk (RR) of dementia in relation to PD and computed the number of dementia cases saved through reducing PD prevalence. Of 12 studies, six were undertaken in Asia, four in Europe and two in America. Eleven studies showed a positive association between PD and the risk of dementia, of which 10 were significant, and one reported a non-significant inverse association. Overall their quality was good. Pooled RR of dementia in relation to PD from all high quality studies was 1.38 (95%CI 1.01–1.90); in the five cohorts was 1.18 (1.06–1.31) and in the two case–control studies 2.25 (1.48–3.42). A 50% reduction in the current prevalence of 20% of PD in the population could save 850,000 (630,000–1,420,000) patients with dementia in the world. PD could increase the risk of incident dementia. Preventing and treating PD could contribute to controlling the global epidemic of dementia.

Purpose Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life. Methods Data from 11 population studies on depression in persons aged 65 and above were pooled, yielding a total of 15,890 respondents. Level of functional disability was trichotomised (no, intermediate, high). A person was considered to have death wishes if the death wish/suicidal ideation item of the EURO-D scale was endorsed. Odds ratios for death wishes associated with functional disability were calculated in a multilevel logistic regression model. Results In total, 5 % of the men and 7 % of the women reported death wishes. Both intermediate (OR 1.89, 95 % CI 1.42; 2.52) and high functional disability (OR 3.22, 95 % CI 2.34; 4.42) were associated with death wishes. No sex differences could be shown. Results remained after adding depressive symptoms to the model. Conclusions Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.

Cytoplasmic microtubules exist as distinct dynamic and stable populations within the cell. Stable microtubules direct and maintain cell polarity and it is thought that their stabilization is dependent on coordinative organization between the microtubule network and the actin cytoskeleton. A growing body of work suggests that some members of the formin family of actin remodeling proteins also regulate microtubule organization and stability. For example, we showed previously that expression of the novel formin INF1 is sufficient to induce microtubule stabilization and tubulin acetylation, but not tubulin detyrosination. An important issue with respect to the relationship between formins and microtubules is the determination of which formin domains mediate microtubule stabilization. INF1 has a distinct microtubule-binding domain at its C-terminus and the endogenous INF1 protein is associated with the microtubule network. Surprisingly, the INF1 microtubule-binding domain is not essential for INF1-induced microtubule acetylation. We show here that expression of the isolated FH1 + FH2 functional unit of INF1 is sufficient to induce microtubule acetylation independent of the INF1 microtubule-binding domain. It is not yet clear whether or not microtubule stabilization is a general property of all mammalian formins; therefore we expressed constitutively active derivatives of thirteen of the fifteen mammalian formin proteins in HeLa and NIH3T3 cells and measured their effects on stress fiber formation, MT organization and MT acetylation. We found that expression of the FH1 + FH2 unit of the majority of mammalian formins is sufficient to induce microtubule acetylation. Our results suggest that the regulation of microtubule acetylation is likely a general formin activity and that the FH2 should be thought of as a dual-function domain capable of regulating both actin and microtubule networks.

Mental, neurological, and substance use (MNS) disorders are leading causes of the global burden of disease and profoundly impact the social and economic well-being of individuals and communities. The majority of people affected by MNS disorders globally do not have access to evidence-based interventions and many experience discrimination and abuses of their human rights. A United Nations General Assembly Special Session (UNGASS) is needed to focus global attention on MNS disorders as a core development issue requiring commitments to improve access to care, promote human rights, and strengthen the evidence on effective prevention and treatment.

Current knowledge about incident dementia is mainly derived from studies undertaken in the West, showing that dementia is related to older age, low socio-economic status, lack of social network, depression and cardiovascular disease risk factors. We know little about incidence and predictors of dementia in China, where the prevalence is increasing and the patterns of risk factors are different. Using a standard interview method, we examined 1526 non-demented people aged ≥65 years who had at least minimal educational level in China in a 7.5-year follow up. Incident dementia was diagnosed by GMS-AGECAT algorithms and psychiatrists. Age-standardised incidence of dementia was 14.7 per 1000 person-years (95%CI 11.3-18.2 per 1000 person-years). The increased risk was significantly associated with age, female gender (adjusted odds ratio 2.48, 95%CI 1.20-5.13), low educational levels, smoking, angina (2.58, 1.01-6.59) and living with fewer family members. Among participants with low educational level, the increased risk was associated with higher income, and with the highest and lowest occupational classes; adjusted odds ratio 2.74 (95%CI 1.12-6.70) for officers/teachers, 3.11 (1.61-6.01) for manual labourers/peasants. Our findings of high incidence of dementia and increased risk among people having low education levels but high income suggest a more potential epidemic and burden of dementia populations in China. Maintaining social network and activities and reducing cardiovascular factors in late life could be integrated into current multi-faceted preventive strategies for curbing the epidemic of dementia.

Formin Homology Proteins (Formins) are a highly conserved family of cytoskeletal regulatory proteins that participate in a diverse range of cellular processes. FMNL2 is a member of the Diaphanous-Related Formin sub-group, and previous reports suggest FMNL2’s role in filopodia assembly, force generation at lamellipodia, subcellular trafficking, cell–cell junction assembly, and focal adhesion formation. How FMNL2 is recruited to these sites of action is not well understood. To shed light on how FMNL2 activity is partitioned between subcellular locations, we used biotin proximity labeling and proteomic analysis to identify an FMNL2 interactome. The interactome identified known and new FMNL2 interacting proteins with functions related to previously described FMNL2 activities. In addition, our interactome predicts a novel connection between FMNL2 and extracellular vesicle assembly. We show directly that FMNL2 protein is present in exosomes.

Grass carp Ctenopharyngodon idella have been widely introduced in aquatic ecosystems to combat outbreaks of problem aquatic plants. However, the extent to which introduced carp stray from intended habitats and ecosystems is frequently unevaluated. Grass carp were stocked into a temperate riverine and montane reservoir (Claytor Lake, VA USA) to control a rapidly spreading Hydrilla verticillata infestation. Fish introductions sparked concern that grass carp might exit the reservoir and impact adjacent river ecosystems and native plants. We conducted a 2-y telemetry study concurrent with annual grass carp stockings in Claytor Lake to investigate migration potential, habitat use, and annual survival of recently introduced grass carp. We radio-tagged 34 and 45 juvenile grass carp in 2011 and 2012, respectively. In both years, grass carp movements were highest during the first month post-stocking and declined dramatically thereafter, presumably due to carp settling in areas with high hydrilla biomass. Only 3% of radio-tagged grass carp exited the reservoir upriver over the study period. Statistical modeling indicated grass carp movements were driven largely by temperature, while other climatic (e.g., wind speed and barometric pressure) and habitat variables (depth, vegetation coverage) were occasionally also important. Year-1 survival of grass carp was 44% for the 2011 cohort, and 25% for the 2012 cohort. Even though young grass carp did not express an inclination for out-reservoir migrations during the study, these patterns may change as fish approach sexual maturity, hydrilla coverage declines, and divergent climate variations occur. We recommend managers continue monitoring grass carp movements alongside changes to the spatial and temporal dynamics of hydrilla in the reservoir over time.

Background Cells constantly sense and respond to changes in their local environment to adapt their behaviour and morphology. These external stimuli include chemical and mechanical signals, and much recent work has revealed the complexity of the cellular response to changes in substrate stiffness. We investigated the effects of substrate stiffness on the morphology and motility of A2058 human melanoma cells. FMNL2, a formin protein associated with actin cytoskeleton dynamics, regulates melanoma cell morphology and motility, but its role in stiffness sensing remains unclear. This study examines how A2058 cells respond to substrates of varying stiffness and evaluates the impact of FMNL2 depletion on these responses. Results We found that with increasing substrate stiffness the cells transitioned from a rounded cell morphology to progressively more elongated morphologies with a concomitant increase in actin stress fiber alignment. Depletion of FMNL2 expression amplified these morphological changes, with knockdown cells showing consistently greater elongation and more pronounced stress fiber alignment compared to controls. Notably, the orientational order parameter (S) revealed higher alignment of actin filaments along the cell’s long axis in knockdown cells. Substrate stiffness also affected cell motility, indicated by an apparent optimal stiffness that maximized motility followed by a notable decrease in distance travelled during migration on progressively stiffer substrates. This decrease was largely attributable to a decrease in the time the cells spent in motion as the substrate stiffness increased. FMNL2 depletion significantly exacerbated this effect, with knockdown cells traveling shorter net distances and spending less time moving across all substrates. Conclusions This study demonstrates that substrate stiffness profoundly influences A2058 melanoma cell morphology and motility, with FMNL2 playing a pivotal regulatory role. Our observations suggest that FMNL2 is critical for maintaining motility and morphological adaptability under increased stiffness. Loss of FMNL2 enhanced stress fiber alignment and cell elongation while impairing motility, particularly on stiff substrates, revealing FMNL2 as a mechanosensitive effector. This work highlights the need to study metastatic cell behaviour on substrates with biologically relevant properties and provides the foundation for future effort to determine the mechanism by which FMNL2 participates in the melanoma cell response to substrate stiffness.

Walleye Sander vitreus is a valued sportfish in eastern North America, including the upper New River of Virginia, where individuals can grow to a large size (>7 kg). After construction of dams, especially Claytor Dam in 1939, the population declined and non-native walleye were stocked. Stocking of non-native walleye was stopped in 1997, and molecular marker data showed that the presumptive native population had persisted. To restore the native stock, selection of broodstock candidates bearing native marker alleles and hatchery-based augmentation have been practiced over a 20-year period. We evaluated the success of the marker-assisted selection and hatchery-based augmentation program. Marker-assisted selection of native New River walleye began with mean frequencies of marker alleles at microsatellite loci Svi17 and Svi33 of ~30%, and continuing selection has driven marker allele frequencies to ~65–70%. Numbers of walleye collected in fall gillnet and spring electrofishing surveys were responsive to augmentations with hatchery fish 2–3 years earlier. Stocking was not practiced in 2012–2013, and a decrease in walleye catch rates was noted in 2016, suggesting that the native New River walleye population still depends upon hatchery-based augmentation. We recommend the development of a small panel of single nucleotide polymorphism markers for more rigorous selection of broodstock representative of the native walleye population.