Development of a smartphone screening test for preclinical Alzheimer's disease and validation across the dementia continuum.

BACKGROUND: Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer's disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10-20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. METHODS: Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50-92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30-40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50-100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. DISCUSSION: This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

Hugin+ neurons provide a link between sleep homeostat and circadian clock neurons.

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that hugin+ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of hugin+ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that hugin+ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide-dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.

Experimental laboratory models as tools for understanding modifiable dementia risk.

Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early-life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies. HIGHLIGHTS: Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention.

Temporal changes in the microglial proteome of male and female mice after a diffuse brain injury using label-free quantitative proteomics.

Traumatic brain injury (TBI) triggers neuroinflammatory cascades mediated by microglia, which promotes tissue repair in the short-term. These cascades may exacerbate TBI-induced tissue damage and symptoms in the months to years post-injury. However, the progression of the microglial function across time post-injury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome at 3-, 7-, or 28-days after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. Data are available via ProteomeXchange with identifier PXD033628. We identified a reduction in microglial proteins involved with clearance of neuronal debris via phagocytosis at 3- and 7-days post-injury. At 28 days post-injury, pro-inflammatory proteins were decreased and anti-inflammatory proteins were increased in microglia. These results indicate a reduction in microglial clearance of neuronal debris in the days post-injury with a shift to anti-inflammatory function by 28 days following TBI. The changes in the microglial proteome that occurred across time post-injury did not differ between biological sexes. However, we did identify an increase in microglial proteins related to pro-inflammation and phagocytosis as well as insulin and estrogen signaling in males compared with female mice that occurred with or without a brain injury. Although the microglial response was similar between males and females up to 28 days following TBI, biological sex differences in the microglial proteome, regardless of TBI, has implications for the efficacy of treatment strategies targeting the microglial response post-injury.

Microglia directly associate with pericytes in the central nervous system.

Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role in the regulation of CBF or the blood-brain-barrier (BBB). We explored the relationship between microglia and pericytes, a vessel-resident cell type that has a major role in the control of CBF and maintenance of the BBB, discovering a spatially distinct subset of microglia that closely associate with pericytes. We termed these pericyte-associated microglia (PEM). PEM are present throughout the brain and spinal cord in NG2DsRed × CX3 CR1+/GFP mice, and in the human frontal cortex. Using in vivo two-photon microscopy, we found microglia residing adjacent to pericytes at all levels of the capillary tree and found they can maintain their position for at least 28 days. PEM can associate with pericytes lacking astroglial endfeet coverage and capillary vessel width is increased beneath pericytes with or without an associated PEM, but capillary width decreases if a pericyte loses a PEM. Deletion of the microglia fractalkine receptor (CX3 CR1) did not disrupt the association between pericytes and PEM. Finally, we found the proportion of microglia that are PEM declines in the superior frontal gyrus in AD. In summary, we identify microglia that specifically associate with pericytes and find these are reduced in number in AD, which may be a novel mechanism contributing to vascular dysfunction in neurodegenerative diseases.

Association between chronic pain and risk of incident dementia: findings from a prospective cohort.

BACKGROUND: Chronic musculoskeletal pain has been linked to dementia; however, chronic pain typically occurs in multiple sites; therefore, this study was to investigate whether greater number of chronic pain sites is associated with a higher risk of dementia and its subtypes. METHODS: Participants (N = 356,383) in the UK Biobank who were dementia-free at baseline were included. Pain in the hip, knee, back, and neck/shoulder or 'all over the body' and its duration were assessed. Participants were categorised into six groups: no chronic pain; chronic pain in 1, 2, 3, and 4 sites, and 'all over the body'. All-cause dementia and its subtypes were ascertained using hospital inpatient and death registry records. Cox regression was used to investigate the associations between the number of chronic pain sites and the incidence of all-cause dementia and its subtypes. RESULTS: Over a median follow-up of 13 years, 4959 participants developed dementia. After adjustment for sociodemographic, lifestyle, comorbidities, pain medications, psychological problems, and sleep factors, greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia (hazard ratio [HR] = 1.08 per 1 site increase, 95% CI 1.05-1.11) and Alzheimer's disease (AD) (HR = 1.09 per 1-site increase, 95% CI 1.04-1.13) in a dose-response manner but not vascular and frontotemporal dementia. No significant association was found between the number of chronic pain sites and the risk of incident all-cause dementia among a subsample that underwent a fluid intelligence test. CONCLUSIONS: Greater number of chronic pain sites was associated with an increased risk of incident all-cause dementia and AD, suggesting that chronic pain in multiple sites may contribute to individuals' dementia risk and is an underestimated risk factor for dementia.

Cyclic processes in the uterine tubes, endometrium, myometrium, and cervix: pathways and perturbations.

This review leads the 2023 Call for Papers in MHR: 'Cyclical function of the female reproductive tract' and will outline the complex and fascinating changes that take place in the reproductive tract during the menstrual cycle. We will also explore associated reproductive tract abnormalities that impact or are impacted by the menstrual cycle. Between menarche and menopause, women and people who menstruate living in high-income countries can expect to experience ∼450 menstrual cycles. The primary function of the menstrual cycle is to prepare the reproductive system for pregnancy in the event of fertilization. In the absence of pregnancy, ovarian hormone levels fall, triggering the end of the menstrual cycle and onset of menstruation. We have chosen to exclude the ovaries and focus on the other structures that make up the reproductive tract: uterine tubes, endometrium, myometrium, and cervix, which also functionally change in response to fluctuations in ovarian hormone production across the menstrual cycle. This inaugural paper for the 2023 MHR special collection will discuss our current understanding of the normal physiological processes involved in uterine cyclicity (limited specifically to the uterine tubes, endometrium, myometrium, and cervix) in humans, and other mammals where relevant. We will emphasize where knowledge gaps exist and highlight the impact that reproductive tract and uterine cycle perturbations have on health and fertility.

Isolated rapid eye movement sleep behaviour disorder (iRBD) in the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study: protocol and baseline characteristics.

Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder that is characterised by dream enactment episodes during REM sleep. It is the strongest known predictor of α-synuclein-related neurodegenerative disease (αNDD), such that >80% of people with iRBD will eventually develop Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy in later life. More research is needed to understand the trajectory of phenoconversion to each αNDD. Only five 'gold standard' prevalence studies of iRBD in older adults have been undertaken previously, with estimates ranging from 0.74% to 2.01%. The diagnostic recommendations for video-polysomnography (vPSG) to confirm iRBD makes prevalence studies challenging, as vPSG is often unavailable to large cohorts. In Australia, there have been no iRBD prevalence studies, and little is known about the cognitive and motor profiles of Australian people with iRBD. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study will investigate the prevalence of iRBD in Tasmania, an island state of Australia, using validated questionnaires and home-based vPSG. It will also explore several cognitive, motor, olfactory, autonomic, visual, tactile, and sleep profiles in people with iRBD to better understand which characteristics influence the progression of iRBD to αNDD. This paper details the ISLAND Sleep Study protocol and presents preliminary baseline results.

An online, public health framework supporting behaviour change to reduce dementia risk: interim results from the ISLAND study linking ageing and neurodegenerative disease.

BACKGROUND: Unmanaged cardiometabolic health, low physical and cognitive activity, poor diet, obesity, smoking and excessive alcohol consumption are modifiable health risk factors for dementia and public health approaches to dementia prevention have been called for. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) is a dementia prevention public health study examining whether improving knowledge about modifiable dementia risk factors supports behaviour changes that reduce future dementia risk. METHODS: Residents of Tasmania, Australia, aged 50 + years who joined the 10-year ISLAND study were asked to complete annual online surveys about their knowledge, motivations and behaviours related to modifiable dementia risk. ISLAND included two knowledge-based interventions: a personalised Dementia Risk Profile (DRP) report based on survey responses, and the option to do a 4-week Preventing Dementia Massive Open Online Course (PDMOOC). Longitudinal regression models assessed changes in the number and type of risk factors, with effects moderated by exposures to the DRP report and engagement with the PDMOOC. Knowledge and motivational factors related to dementia risk were examined as mediators of risk behaviour change. RESULTS: Data collected between October 2019 and October 2022 (n = 3038, av. 63.7 years, 71.6% female) showed the mean number of modifiable dementia risk factors per participant (range 0 to 9) reduced from 2.17 (SD 1.24) to 1.66 (SD 1.11). This change was associated with the number of exposures to the DRP report (p = .042) and was stronger for PDMOOC participants (p = .001). The interaction between DRP and PDMOOC exposures yielded a significant improvement in risk scores (p = .004). The effect of PDMOOC engagement on behaviour change was partly mediated by increased knowledge (12%, p = .013). Self-efficacy enhanced the effect of knowledge on behaviour change, while perceived susceptibility to dementia mitigated this relationship. CONCLUSIONS: The ISLAND framework and interventions, a personalised DRP report and the four-week PDMOOC, work independently and synergistically to increase dementia risk knowledge and stimulate health behaviour change for dementia risk reduction. ISLAND offers a feasible and scalable public health approach for redressing the rising prevalence of dementia.

Seeing Neurodegeneration in a New Light Using Genetically Encoded Fluorescent Biosensors and iPSCs.

Neurodegenerative diseases present a progressive loss of neuronal structure and function, leading to cell death and irrecoverable brain atrophy. Most have disease-modifying therapies, in part because the mechanisms of neurodegeneration are yet to be defined, preventing the development of targeted therapies. To overcome this, there is a need for tools that enable a quantitative assessment of how cellular mechanisms and diverse environmental conditions contribute to disease. One such tool is genetically encodable fluorescent biosensors (GEFBs), engineered constructs encoding proteins with novel functions capable of sensing spatiotemporal changes in specific pathways, enzyme functions, or metabolite levels. GEFB technology therefore presents a plethora of unique sensing capabilities that, when coupled with induced pluripotent stem cells (iPSCs), present a powerful tool for exploring disease mechanisms and identifying novel therapeutics. In this review, we discuss different GEFBs relevant to neurodegenerative disease and how they can be used with iPSCs to illuminate unresolved questions about causes and risks for neurodegenerative disease.

Digital Dependence in Organizations: Impacts on the Physical and Mental Health of Employees.

Digital Dependence is a person's persistent inability to regulate digital devices on which they have become highly dependent. Internet dependence has been described since the mid-1990s, and studies on this topic have intensified since 2010. This type of individual dependence has received considerable published literature, but it is new in the collective setting of organizations, offering the hypothesis that it can also be collective, given the impacts it can provide. Research has evolved geographically from three countries to 17 since the beginning of the last decade, with 7 new scales for digital dependence. There were 13 new revalidations of the Nomophobia Questionnaire (NMP-Q), with an increase from 1,000 to 13,000 volunteers. Geographical evolution and an increase in the number of scales and volunteers and their different profiles were described. New approaches reinforce evolution and its impacts on human behavior. This study provides historical insight into Digital Dependence and opens new prospects for research on the differences between nations and people, sexes, professionals, and the need for further research in organizations.

Sarm1 knockout modifies biomarkers of neurodegeneration and spinal cord circuitry but not disease progression in the mSOD1G93A mouse model of ALS.

The mechanisms underlying the loss of motor neuron axon integrity in amyotrophic lateral sclerosis (ALS) are unclear. SARM1 has been identified as a genetic risk variant in sporadic ALS, and the SARM1 protein is a key mediator of axon degeneration. To investigate the role of SARM1 in ALS-associated axon degeneration, we knocked out Sarm1 (Sarm1KO) in mSOD1G93ATg (mSOD1) mice. Animals were monitored for ALS disease onset and severity, with motor function assessed at pre-symptomatic and late-stage disease and lumbar spinal cord and sciatic nerve harvested for immunohistochemistry at endpoint (20 weeks). Serum was collected monthly to assess protein concentrations of biomarkers linked to axon degeneration (neurofilament light (NFL) and tau), and astrogliosis (glial fibrillary acidic protein (GFAP)), using single molecule array (Simoa®) technology. Overall, loss of Sarm1 in mSOD1 mice did not slow or delay symptom onset, failed to improve functional declines, and failed to protect motor neurons. Serum NFL levels in mSOD1 mice increased between 8 -12 and 16-20 weeks of age, with the later increase significantly reduced by loss of SARM1. Similarly, loss of SARM1 significantly reduced an increase in serum GFAP between 16 and 20 weeks of age in mSOD1 mice, indicating protection of both global axon degeneration and astrogliosis. In the spinal cord, Sarm1 deletion protected against loss of excitatory VGluT2-positive puncta and attenuated astrogliosis in mSOD1 mice. In the sciatic nerve, absence of SARM1 in mSOD1 mice restored the average area of phosphorylated neurofilament reactivity towards WT levels. Together these data suggest that Sarm1KO in mSOD1 mice is not sufficient to ameliorate functional decline or motor neuron loss but does alter serum biomarker levels and provide protection to axons and glutamatergic synapses. This indicates that treatments targeting SARM1 could warrant further investigation in ALS, potentially as part of a combination therapy.

The TAS Test project: a prospective longitudinal validation of new online motor-cognitive tests to detect preclinical Alzheimer's disease and estimate 5-year risks of cognitive decline and dementia.

BACKGROUND: The worldwide prevalence of dementia is rapidly rising. Alzheimer's disease (AD), accounts for 70% of cases and has a 10-20-year preclinical period, when brain pathology covertly progresses before cognitive symptoms appear. The 2020 Lancet Commission estimates that 40% of dementia cases could be prevented by modifying lifestyle/medical risk factors. To optimise dementia prevention effectiveness, there is urgent need to identify individuals with preclinical AD for targeted risk reduction. Current preclinical AD tests are too invasive, specialist or costly for population-level assessments. We have developed a new online test, TAS Test, that assesses a range of motor-cognitive functions and has capacity to be delivered at significant scale. TAS Test combines two innovations: using hand movement analysis to detect preclinical AD, and computer-human interface technologies to enable robust 'self-testing' data collection. The aims are to validate TAS Test to [1] identify preclinical AD, and [2] predict risk of cognitive decline and AD dementia. METHODS: Aim 1 will be addressed through a cross-sectional study of 500 cognitively healthy older adults, who will complete TAS Test items comprising measures of motor control, processing speed, attention, visuospatial ability, memory and language. TAS Test measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 (p-tau181). Aim 2 will be addressed through a 5-year prospective cohort study of 10,000 older adults. Participants will complete TAS Test annually and subtests of the Cambridge Neuropsychological Test Battery (CANTAB) biennially. 300 participants will undergo in-person clinical assessments. We will use machine learning of motor-cognitive performance on TAS Test to develop an algorithm that classifies preclinical AD risk (p-tau181-defined) and determine the precision to prospectively estimate 5-year risks of cognitive decline and AD. DISCUSSION: This study will establish the precision of TAS Test to identify preclinical AD and estimate risk of cognitive decline and AD. If accurate, TAS Test will provide a low-cost, accessible enrichment strategy to pre-screen individuals for their likelihood of AD pathology prior to more expensive tests such as blood or imaging biomarkers. This would have wide applications in public health initiatives and clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05194787 , 18 January 2022. Retrospectively registered.

Effects of TDP-43 overexpression on neuron proteome and morphology in vitro.

TDP-43 is pathologically and genetically with associated amyotrophic lateral sclerosis and frontotemporal lobar degeneration. These diseases are characterized by significant neurite defects, including cytoskeletal pathology. The involvement of TDP-43 in the degeneration of neurons in these diseases are not yet well understood, however accumulating evidence shows involvement in neurite outgrowth, remodelling and in regulation of many components of the neuronal cytoskeleton. In order to investigate how alterations to TDP-43 expression levels may exert effects on the neuronal cytoskeleton, primary cortical neurons from transgenic mice overexpressing one or two copies of human wildtype TDP-43 under the prion promoter were examined. Label-free quantitative proteomic analysis, followed by functional annotation clustering to identify protein families that clustered together within up- or down-regulated protein groups, revealed that actin-binding proteins were significantly more abundant in neurons overexpressing TDP-43 compared to wildtype neurons. Morphological analysis demonstrated that during early development neurons expressing one copy of human TDP-43 had an increased number of neurite branches and alterations to growth cone morphology, while no changes were observed in neurons expressing two copies of TDP-43. These developmental processes require specific expression and organization of the cytoskeleton. The results from these studies provide further insight into the normal function of TDP-43 and how alterations in TDP-43 expression may impact the cytoskeleton.

Use of Digital Technologies in Home Office Work during the COVID-19 Pandemic.

Background: Social distancing as a preventive measure to contain the spread of the COVID-19 pandemic has resulted in many people working from home, using online digital resources. Staying at home has led to the adaptation of many work activities to allow continuity of people´s jobs. It can also affect home routines and ways of working, thereby leading to changes in behavior, as the main interest of this study. Objective: The study aimed to assess the impact on human behavior of working conditions in home office format due to social distancing. Methods: Data collection was done online, using a specific computational tool (Google Forms) for this type of research, using the Home Office Work Scale (HOWS) validated and published in Mental Health and Addiction Research in 2021, with a total sample of 1,056 valid questionnaires. After the data collection, a database was created for statistical analysis of the results. Results: More women than men volunteered to answer the questionnaire, although the results were similar between women and men. Home office work has impacts on human behavior and results in changes in routines and adaptations in people´s personal and professional lives. Conclusion: Proportionally, more women participated, and there was low participation by young and elderly people. In general, people accepted home office work and the possibility of continuing to work in this format. Changes to routines and restrictive adaptations were necessary. The limitations reported for applying the scale did not compromise the results.

Rod microglia and their role in neurological diseases.

The striking morphology of microglia is one of their most prominent characteristics, with many studies categorising microglial function based on morphology e.g. ramified, hyper-ramified, activated, or amoeboid. Communications regarding rod microglia in neurological disease are scant, and where reported, these cells are rarely the focus of discussion. These factors make it difficult to determine how widespread these cells are not only through the brain but also across diseases. Studies in experimental diffuse brain injury are the first reports of not only significant numbers of rod microglia, but distinct arrangements of these cells, reminiscent of carriages of a train. This review summarises the available reports of rod microglia in vivo and rod-like microglia in vitro and eludes to possible functions and signalling cascades that may evoke this distinct morphology. More investigations are required to fully elucidate the function that rod microglia play in neurological diseases.

Poor oral hygiene, oral microorganisms and aspiration pneumonia risk in older people in residential aged care: a systematic review.

BACKGROUND: aspiration pneumonia increases hospitalisation and mortality of older people in residential aged care. OBJECTIVES: determine potentially pathogenic microorganisms in oral specimens of older people with aspiration pneumonia and the effect of professional oral care in reducing aspiration pneumonia risk. DATA SOURCES: PUBMED/MEDLINE, CINAHL, EMBASE, COCHRANE, PROQUEST, Google Scholar, Web of Science. STUDY ELIGIBILITY CRITERIA: published between January 2001 and December 2019 addressing oral microorganisms, aspiration pneumonia, oral health and treatment. PARTICIPANTS: people 60 years and older in residential aged care. STUDY APPRAISAL AND SYNTHESIS METHODS: the Newcastle-Ottawa Scale and the Standard Protocol Items: Recommendations for Intervention Trials checklist. RESULTS: twelve studies (four cross-sectional, five cohort and three intervention) reported colonisation of the oral cavity of older people by microorganisms commonly associated with respiratory infections. Aspiration pneumonia occurred less in people who received professional oral care compared with no such care. Isolation of Candida albicans, Staphylococcus aureus, methicillin-resistant S. aureus and Pseudomonas aeruginosa was related to mortality due to aspiration pneumonia. An interesting finding was isolation of Escherichia coli, a gut bacterium. LIMITATIONS: more information may be present in publications about other co-morbidities that did not meet inclusion criteria. A high degree of heterogeneity prevented a meta-analysis. Issues included sampling size, no power and effect size calculations; different oral health assessments; how oral specimens were analysed and how aspiration pneumonia was diagnosed. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: pathogenic microorganisms colonising the oral microbiome are associated with aspiration pneumonia in older people in residential care; professional oral hygiene care is useful in reducing aspiration pneumonia risk.

Sex, Digital Devices, Social Media, and Social Isolation: A Study on Sexual Behavioral During COVID -19 Pandemic.

INTRODUCTION: Coronavirus (COVID-19) pandemic has caused social and economic damages. People have adapted to a new reality of physical distance. OBJECTIVE: The study aimed to assess the use of digital devices and social media, focusing on psychosocial and demographic factors of people´s sexual behavior during the pandemic. METHODS: A total of 1,357 Brazilian adults participated in a cross-sectional online survey. They were recruited through social media to obtain information regarding sexual behavior and the use of digital devices and social media. RESULTS: Digital devices and social media were used by 38.8% of the participants. Among the group that used technological devices, most claimed to have changed their sexual behavior, with 76.9% consuming more sexual content through movies or series. CONCLUSION: In a smaller group, technological resources appeared as an alternative for safer sex, reducing the risks of COVID-19 transmission.

Microtubule-dependent processes precede pathological calcium influx in excitotoxin-induced axon degeneration.

Axon degeneration and axonal loss is a feature of neurodegenerative disease and injury and occurs via programmed pathways that are distinct from cell death pathways. While the pathways of axonal loss following axon severing are well described, less is known about axonal loss following other neurodegenerative insults. Here we use primary mouse cortical neuron cultures grown in compartmentalized chambers to investigate the role of calcium in the degeneration of axons that occurs following a somal insult by the excitotoxin kainic acid. Calcium influx has been implicated in both excitotoxicity and axon degeneration mechanisms, however the link between a somal insult and axonal calcium increase is unclear. Live imaging of axons demonstrated that pharmacologically preventing intracellular calcium increases through the endoplasmic reticulum or mitochondria significantly (p < 0.05) reduced axon degeneration. Live calcium-imaging with the Ca2+ indicator Fluo-4 demonstrated that kainic acid exposure to the soma resulted in a rapid, and transient, increase in calcium in the axon, which occured even at low kainic acid concentrations that do not cause axon degeneration within 24 h. However, this calcium transient was followed by a gradual increase in axonal calcium, which was associated with axonal loss. Furthermore, treatment with a range of doses of the microtubule stabilizing drug taxol, which protects against axon fragmentation in this model, prevented this gradual calcium increase, suggesting that the intra-axonal calcium changes are downstream of microtubule associated events. Biochemical analysis of taxol treated neurons demonstrated a shift in microtubule post-translational modifications, with a significant (p < 0.05) increase in acetylated tubulin and a significant (p < 0.05) decrease in tyrosinated tubulin, suggestive of a more stable microtubule pool. Together our results suggest that axonal degeneration following excitotoxicity is dependent on an increase in axonal calcium, which is downstream of a microtubule-dependent event.

Molecular and circuit mechanisms mediating circadian clock output in the Drosophila brain.

A central question in the circadian biology field concerns the mechanisms that translate ~24-hr oscillations of the molecular clock into overt rhythms. Drosophila melanogaster is a powerful system that provided the first understanding of how molecular clocks are generated and is now illuminating the neural basis of circadian behavior. The identity of ~150 clock neurons in the Drosophila brain and their roles in shaping circadian rhythms of locomotor activity have been described before. This review summarizes mechanisms that transmit time-of-day signals from the clock, within the clock network as well as downstream of it. We also discuss the identification of functional multisynaptic circuits between clock neurons and output neurons that regulate locomotor activity.