1,2-BF2 Shift and Photoisomerization Induced Multichromatic Response.

Adaptive materials that exhibit a multichromatic response as a function of applied stimulus are highly desirable, as they can result in applications ranging from smart surfaces to anticounterfeit devices. Here we report on such a system based on an intriguing thermal 1,2-BF2 shift that transforms a visible-light-activated azo-BF2 photoswitch into a BF2-hydrazone fluorophore (BODIHY) in both solution and the solid-state. Structure-property analysis, in conjunction with DFT calculations, reveals that the shift is catalyzed by the spatial proximity of an oxygen atom next to the BF2 group and that the activation originates from an electronic and not steric effect. Theoretical calculations also show that while the energy barrier for the trans → BODIHY transformation is accessible at room temperature (thermal half-life of 30 h), the cis → BODIHY transformation has a much higher barrier, which is why the 1,2-BF2 shift is not observed for the cis form. The photoswitching of the azo-BF2, in conjunction with the 1,2-BF2 shift, was then used in the multicolor modulation of a switch-containing cross-linked polydimethylsiloxane film using light and/or heat stimuli, elaborating the usefulness of the sophisticated reaction cascade that can be accessed from this simple system.

Gut microbiota disturbances in hospitalized older adults with malnutrition and clinical outcomes.

OBJECTIVE: Malnutrition is one of the most threatening conditions in geriatric populations. The gut microbiota has an important role in the host's metabolic and muscular health: however, its interplay with disease-related malnutrition is not well understood. We aimed to identify the association of malnutrition with the gut microbiota and predict clinical outcomes in hospitalized acutely ill older adults. METHODS: We performed a secondary longitudinal analysis in 108 geriatric patients from a prospective cohort evaluated at admission and 72 h of hospitalization. We collected clinical, demographic, nutritional, and 16S rRNA gene-sequenced gut microbiota data. Microbiota diversity, overall composition, and differential abundance were calculated and compared between patients with and without malnutrition. Microbiota features associated with malnutrition were used to predict clinical outcomes. RESULTS: Patients with malnutrition (51%) had a different microbiota composition compared to those who were well-nourished during hospitalization (ANOSIM R = 0.079, P = 0.003). Patients with severe malnutrition showed poorer α-diversity at admission (Shannon P = 0.012, Simpson P = 0.018) and follow-up (Shannon P = 0.023, Chao1 P = 0.008). Differential abundance of Lachnospiraceae NK4A136 group, Subdoligranulum, and Faecalibacterium prausnitzii were significantly lower and inversely associated with malnutrition, while Corynebacterium, Ruminococcaceae Incertae Sedis, and Fusobacterium were significantly increased and positively associated with malnutrition. Corynebacterium, Ruminococcaceae Incertae Sedis, and the overall composition were important predictors of critical care in patients with malnutrition during hospitalization. CONCLUSION: Older adults with malnutrition, especially in a severe stage, may be subject to substantial gut microbial disturbances during hospitalization. The gut microbiota profile of patients with malnutrition might help us to predict worse clinical outcomes.

Relationship between chronic pain, depressive symptoms, and functional disability in community-dwelling older adults: mediating role of frailty.

BACKGROUND: Borim et al. showed that older adults with chronic pain exhibited more depressive symptoms and frailty components. Depressive symptoms were associated with more frailty components, and those with more depressive symptoms and frailty faced greater limitations in IADL performance. Frailty appears to mediate the pathway from chronic pain to functional impairment Chronic pain is directly associated with depressive symptoms and frailty. Chronic pain is not directly associated with functional disability. Depression and frailty are both directly associated with functional disabilities. Frailty mediates the association between chronic pain and functional disability. Depression; Disability evaluation; Frailty; Frail elderly. OBJECTIVE: To evaluate the direct and indirect effects of chronic pain, depressive symptoms, frailty components, and functional disability through a pathway analysis approach in a sample of community-dwelling older adults. METHODS: Data of 419 participants were cross-sectionally evaluated for the presence of depressive symptoms (Geriatric Depression Scale [15 items]), physical frailty components (phenotype criteria), chronic pain, and limitations in performing instrumental activities of daily living (functional disability scale by Lawton and Brody). Structural equation modeling via path analysis was used to explore the direct and indirect effects among these four variables. Statistical significance was set at p<0.05. RESULTS: Of the total participants, 69.8% were women and 59.3% had low education (1-4 years); the mean age was 80.3±4.6 years. Chronic pain and depressive symptoms were directly related and were associated to frailty. The number of frailty components and depressive symptoms were directly associated with functional disability. Frailty had an indirect effect on the association between chronic pain, depressive symptoms, and functional disabilities. CONCLUSION: The pathway from chronic pain and depressive symptoms to functional disability is potentially mediated by the number of frailty components.

Breaking the photoswitch speed limit.

The forthcoming generation of materials, including artificial muscles, recyclable and healable systems, photochromic heterogeneous catalysts, or tailorable supercapacitors, relies on the fundamental concept of rapid switching between two or more discrete forms in the solid state. Herein, we report a breakthrough in the "speed limit" of photochromic molecules on the example of sterically-demanding spiropyran derivatives through their integration within solvent-free confined space, allowing for engineering of the photoresponsive moiety environment and tailoring their photoisomerization rates. The presented conceptual approach realized through construction of the spiropyran environment results in ~1000 times switching enhancement even in the solid state compared to its behavior in solution, setting a record in the field of photochromic compounds. Moreover, integration of two distinct photochromic moieties in the same framework provided access to a dynamic range of rates as well as complementary switching in the material's optical profile, uncovering a previously inaccessible pathway for interstate rapid photoisomerization.

Anorexia of aging: An international assessment of healthcare providers' knowledge and practice gaps.

BACKGROUND: Anorexia of aging is a common geriatric syndrome that includes loss of appetite and/or reduced food intake, with associated undernutrition, unintended weight loss, sarcopenia, functional decline, loss of independence and other adverse health outcomes. Anorexia of aging can have multiple and severe consequences and is often overlooked by healthcare professionals (HCPs). Even more concerningly, clinicians commonly accept anorexia of aging as an inevitable part of 'normal' aging. The aim of this assessment was to identify current gaps in professional knowledge and practice in identifying and managing older persons with anorexia. Results may guide educational programmes to fill the gaps identified and therefore improve patient outcomes. METHODS: This international assessment was conducted using a mixed-methods approach, including focus group interviews with subject matter experts and an electronic survey of practicing HCPs. The assessment was led by the Society on Sarcopenia, Cachexia and Wasting Disorders (SCWD) and was supported by in-country collaborating organizations. RESULTS: A quantitative survey of 26 multiple-choice questions was completed by physicians, dietitians and other HCPs (n = 1545). Most HCPs (56.8%) recognize a consistent definition of anorexia of aging as a loss of appetite and/or low food intake. Cognitive changes/dementia (91%) and dysphagia (87%) are seen as the biggest risk factors. Most respondents were confident to give nutritional (62%) and physical activity (59.4%) recommendations and engaged caregivers such as family members in supporting older adults with anorexia (80.6%). Most clinicians assessed appetite at each visit (66.7%), although weight is not measured at every visit (41.5%). Apart from the Mini-Nutritional Assessment Short Form (39%), other tools to screen for appetite loss are not frequently used or no tools are used at all (29.4%). A high number of respondents (38.7%) believe that anorexia is a normal part of aging. Results show that treatment is focused on swallowing disorders (78%), dentition issues (76%) and increasing oral intake (fortified foods [75%] and oral nutritional supplements [74%]). Nevertheless, the lack of high-quality evidence is perceived as a barrier to optimal treatment (49.2%). CONCLUSIONS: Findings from this international assessment highlight the challenges in the care of older adults with or at risk for anorexia of aging. Identifying professional practice gaps between individual HCPs and team-based gaps can provide a basis for healthcare education that is addressed at root causes, targeted to specific audiences and developed to improve individual and team practices that contribute to improving patient outcomes.

Visible light activated energy storage in solid-state Azo-BF2 switches.

We present here a group of Azo-BF2 photoswitches that store and release energy in response to visible light irradiation. Unmodified Azo-BF2 switches have a planar structure with a large π-conjugation system, which hinders E-Z isomerization when in a compacted state. To address this challenge, we modified the switches with one or two aliphatic groups, which altered the intermolecular interactions and arrangement of the photochromes in the solid state. The derivative with two substituents exhibited a non-planar configuration that provided particularly large conformational freedom, allowing for efficient isomerization in the solid phase. Our discovery highlights the potential of using double aliphatic functionalization as a promising approach to facilitate solid-state switching of large aromatic photoswitches. This finding opens up new possibilities for exploring various photoswitch candidates for molecular solar thermal energy storage applications.

Metal and Proton Relay-Controlled Hierarchical Multistep Switching Cascade.

Transition metals play an important role in many biological processes including cellular regulation and signal transduction. Emulating such processes on the molecular level, while challenging, can help us learn how to manipulate intermolecular communication, an important requirement for the development of solution-based molecular machines. In this work, we demonstrate a transition metal-based artificial multistep switching cascade that exhibits intrinsic hierarchical level control. The process starts with Zn(II), which initiates a transition metal relay by displacing a macrocycle-encapsulated Pd(II). The latter then binds to a hydrazone switch leading to coordination-coupled deprotonation (CCD). Finally, the proton generated through CCD activates the E/Z isomerization of a second noncoordinating pH-sensitive hydrazone switch. This whole multistep process can be reset to the original state by removing the Pd(II) from the system.

Efficacy of cognitive remediation in bipolar disorder: systematic review and meta-analysis of randomized controlled trials.

A significant percentage of people with bipolar disorder (BD) exhibit suboptimal functional adjustment, even when appropriately treated and after symptomatic recovery is achieved. Given that cognitive impairment is one of the strongest correlates of socio-occupational outcomes and quality of life in BD, cognitive remediation (CR) is currently acknowledged as a promising treatment that could help bridge the gap between symptomatic and full functional recovery. The aim of this review was to explore the efficacy of CR approaches in improving cognitive and functional outcomes in BD patients. PubMed, PsycINFO, and CENTRAL were searched from inception to November 2022. Randomized controlled trials exploring the effects of CR on cognition and/or functional adjustment in adult BD patients were eligible. Ten studies based on seven independent trials (n = 586) were included. Change-score effect sizes (Hedges' g) were obtained for efficacy outcome measures and combined by means of meta-analytic procedures. Small but significant overall effects were observed for working memory (g = 0.32, 95% CI 0.11-0.52), planning (g = 0.30, 95% CI 0.03-0.56), and verbal learning (g = 0.40, 95% CI 0.15-0.66). However, CR was not found to exert any significant effects on functional outcomes at treatment completion or at follow-up assessment. Although CR may modestly enhance the cognitive performance of BD patients, this effect does not translate into an improvement at the functional level. The current data do not support the inclusion of CR as a treatment recommendation in clinical practice guidelines for the management of BD.

Association of Motoric Cognitive Risk Syndrome with Sarcopenia and Systemic Inflammation in Pre-Frail Older Adults.

Motoric cognitive risk syndrome (MCR) is defined by the presence of slow gait and subjective cognitive decline. It is well recognized as a prodrome for dementia, but the biological mechanism and trajectory for MCR are still lacking. The objective of this study was to explore the association of MCR with body composition, including sarcopenia and systemic inflammation, in pre-frail older adults in a cross-sectional study of 397 pre-frail community-dwelling older adults. Data on demographics, physical function, frailty, cognition (Montreal Cognitive Assessment (MoCA)), perceived health and depression were collected. Body composition was measured using a bioelectrical impedance analyzer. Systemic inflammatory biomarkers, such as progranulin, growth differentiation factor-15 (GDF-15), interleukin-10 (IL-10), interleukin-6 and tumor necrosis factor-α (TNF-α), were collected. Univariate and multivariate logistic regression were used to analyze the association between MCR, body composition, sarcopenia and systemic inflammatory biomarkers. The prevalence of MCR was 14.9%. They were significantly older and there were more females, depression, functional impairment, lower education, physical activity and MoCA scores. Body fat percentage (BF%), fat mass index, fat to fat free mass ratio (FM/FFM) and sarcopenia prevalence were significantly higher in MCR. Serum GDF-15 and TNF-α levels were highest with progranulin/TNF-α and IL-10/TNF-α ratio lowest in MCR. Compared to healthy patients, MCR was significantly associated with sarcopenia (aOR 2.62; 95% CI 1.46-3.17), BF% (aOR 1.06; 95% CI 1.01-1.12), FMI (aOR 1.16; 95% CI 1.02-1.30) and FM/FFM (aOR 6.38; 95% CI 1.20-33.98). The association of IL-10 to TNF-α ratio (aOR 0.98, 95% CI 0.97-0.99) and IL-10 (aOR 2.22, 95% CI 0.05-0.98) with MCR were independent of sarcopenia and BF%. Longitudinal population studies are needed to understand the role of body fat indices and IL-10 in pre-frail older adults with MCR and trajectory to dementia.

Non-equilibrium Steady States in Catalysis, Molecular Motors, and Supramolecular Materials: Why Networks and Language Matter.

All chemists are familiar with the idea that, at equilibrium steady state, the relative concentrations of species present in a system are predicted by the corresponding equilibrium constants, which are related to the free energy differences between the system components. There is also no net flux between species, no matter how complicated the reaction network. Achieving and harnessing non-equilibrium steady states, by coupling a reaction network to a second spontaneous chemical process, has been the subject of work in several disciplines, including the operation of molecular motors, the assembly of supramolecular materials, and strategies in enantioselective catalysis. We juxtapose these linked fields to highlight their common features and challenges as well as some common misconceptions that may be serving to stymie progress.

Cognitive Impairment Predicts Sarcopenia 9 Years Later among Older Adults.

OBJECTIVE: To assess the longitudinal association between cognitive impairment and sarcopenia in a sample of Brazilian community-dwelling older adults. DESIGN: Nine-year observational prospective study. SETTING AND PARTICIPANTS: A total of 521 community-dwelling older adults from 2 Brazilian sites of the Frailty in Brazilian Older Adults (FIBRA in Portuguese) study. METHODS: Sarcopenia was defined as low hand-grip strength and low muscle mass. Cognitive impairment was determined at baseline using the Mini-Mental State Examination, with education-adjusted cutoff scores. The logistic regression model was used to assess the association between cognitive impairment and incident sarcopenia after adjusting for gender, age, education, morbidities, physical activity, and body mass index. Inverse probability weighting was applied to correct for sample loss at follow-up. RESULTS: The mean age of the study population was 72.7 (±5.6) years, and 365 were women (70.1%). Being 80 years and older [odds ratio (OR), 4.62; 95% CI, 1.38-15.48; P = .013], being under- and overweight (OR, 0.29; 95% CI, 0.11-0.76; P = .012, and OR, 5.12; 95% CI, 2.18-12.01; P < .001, respectively) and having cognitive impairment (OR, 2.44; 95% CI, 1.18-5.04; P = .016) at baseline predicted sarcopenia after 9 years. CONCLUSION AND IMPLICATIONS: Cognitive impairment may predict sarcopenia in Brazilian older adults. More studies are necessary to identify the main mechanisms shared by sarcopenia and cognitive decline, which could support the development of prevention interventions.

Weight loss severity and functional decline among the oldest old in a middle-income country: The FIBRA study longitudinal findings.

BACKGROUND AND AIMS: Nutritional status is a key modifiable risk factor associated with disability, and further evidence suggests that weight change is also linked to this adverse outcome. Thus, this study aims to evaluate weight loss severity and functional decline in instrumental activities of daily living (IADL) in a seven-year period among a sample of Brazilian oldest-old adults. METHODS: Longitudinal prospective study using data from the FIBRA study (Frailty in Older Brazilians), a population-based investigation carried out in 2008/2009, with follow-up data collected in 2016/2017 from participants who were 80 years and older in the follow-up in Campinas, Brazil. Of the 167 participants with complete data in 2016-2017, 16 had improved their functional status and were excluded, so the final sample was restricted to 151 participants who maintained or declined functional status. We considered functional decline when a subject had greater IADL dependencies at follow-up than baseline. Logistic regression was performed to assess the effect of weight loss, according to severity (moderate weight loss: 5-10% of body weight; severe weight loss >10%) in increasing the number of disabilities than the group with stable weight, controlling for covariates (gender, age, education, and morbidity). An alpha level of <5% was adopted. RESULTS: During the follow-up period, 60.3% of the participants kept stable weight, 21.8% had moderate weight loss, and 17.9% had severe weight loss. During the follow-up, only severe weight loss was associated with a higher risk of functional decline (OR = 2.74; p = 0.032). CONCLUSIONS: Severe weight loss was associated with functional decline. This finding reinforces the importance of early identification of weight loss among older adults.

Confinement-Driven Photophysics in Hydrazone-Based Hierarchical Materials.

Confinement-imposed photophysics was probed for novel stimuli-responsive hydrazone-based compounds demonstrating a conceptual difference in their behavior within 2D versus 3D porous matrices for the first time. The challenges associated with photoswitch isomerization arising from host interactions with photochromic compounds in 2D scaffolds could be overcome in 3D materials. Solution-like photoisomerization rate constants were realized for sterically demanding hydrazone derivatives in the solid state through their coordinative immobilization in 3D scaffolds. According to steady-state and time-resolved photophysical measurements and theoretical modeling, this approach provides access to hydrazone-based materials with fast photoisomerization kinetics in the solid state. Fast isomerization of integrated hydrazone derivatives allows for probing and tailoring resonance energy transfer (ET) processes as a function of excitation wavelength, providing a novel pathway for ET modulation.

Relationship between chronic pain, depressive symptoms, and functional disability in community-dwelling older adults: mediating role of frailty

ABSTRACT Objective To evaluate the direct and indirect effects of chronic pain, depressive symptoms, frailty components, and functional disability through a pathway analysis approach in a sample of community-dwelling older adults. Methods Data of 419 participants were cross-sectionally evaluated for the presence of depressive symptoms (Geriatric Depression Scale [15 items]), physical frailty components (phenotype criteria), chronic pain, and limitations in performing instrumental activities of daily living (functional disability scale by Lawton and Brody). Structural equation modeling via path analysis was used to explore the direct and indirect effects among these four variables. Statistical significance was set at p<0.05. Results Of the total participants, 69.8% were women and 59.3% had low education (1-4 years); the mean age was 80.3±4.6 years. Chronic pain and depressive symptoms were directly related and were associated to frailty. The number of frailty components and depressive symptoms were directly associated with functional disability. Frailty had an indirect effect on the association between chronic pain, depressive symptoms, and functional disabilities. Conclusion The pathway from chronic pain and depressive symptoms to functional disability is potentially mediated by the number of frailty components.

Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology.

Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers.

A doença de Alzheimer (DA) e outras demências neurodegenerativas têm um curso progressivo com comprometimento da cognição, capacidade funcional e comportamento. A maioria dos estudos enfocou a DA. A demência grave está associada ao aumento da idade, maior morbimortalidade e aumento dos custos de cuidados. É fundamental reconhecer que a demência grave é o período mais longo de progressão, com o paciente vivendo muitos anos nesta fase. É a fase mais heterogênea do processo, com diferentes habilidades e expectativa de vida. Esta diretriz de prática concentra-se na demência grave para melhorar o manejo e o cuidado nessa fase da demência. Como um longo período no continuum da demência, as abordagens não farmacológicas e farmacológicas devem ser consideradas. Intervenções multidisciplinares (fisioterapia, fonoaudiologia, nutrição, enfermagem, entre outras) são essenciais, além de educacionais e de apoio aos cuidadores.

Patterns of participation restriction among older adults at risk of falls and relationship with intrinsic capacity: A latent cluster analysis.

Introduction: The concept of participation restriction was first described by the World Health Organization in 2001 as a component of The International Classification of Functioning, Disability and Health Framework. Both falls and fear of falling (FOF) are associated with social isolation, depression, anxiety, poor quality of life and cognitive impairment resulting in participation restriction. Life-space mobility (LSM) is an important indicator for participation restriction which depends on multiple inter-related factors. We aimed to determine participation patterns using latent cluster analysis (LCA) in older adults at risk of falls, its relationship with intrinsic capacity (IC) and its risk prediction. Methods: Cross-sectional study of 154 community dwelling older adults ≥ 60 years with falls or risk of falls was conducted. Questionnaires were administered on demographics, hearing, LSM, frailty (FRAIL scale), anorexia of aging (SNAQ), cognition (Montreal Cognitive Assessment, MoCA), FOF (Falls Efficacy Scale-International), physical function, and assessment for handgrip strength (HGS), gait speed, 5-times sit to stand (STS), vision and times-up-and-go (TUG) were performed. Six IC domains (vision and hearing, cognition, nutrition, mobility and depression) were measured. Results: Three pattern of participation cluster were identified, high (n = 63, 40.9%), moderate (n = 83, 53.9%) and low (n = 8, 33 5.2%). Individuals in the high participation cluster were significantly younger, had higher LSM scores and lower FES-I scores, more robust, fewer ADL and IADL limitations, lower prevalence of low HGS, higher gait speed and shorter TUG. In the fully adjusted model compared to the high participation cluster, moderate participation was significantly associated with low MoCA scores (OR 4.2, 95% CI 1.7-10.4, p = 0.02), poor STS (OR 7.1, 95% CI 3.0-17.0, p < 0.001) whereas low participation was associated with anorexia of aging (OR 9.9, 95% CI 1.6-60.9, p = 0.014), poor STS (OR 19.1, 95% CI 2.0-187.5, p = 0.011) and hearing impairment (OR 9.8, 95% CI 1.4-70.8, p = 0.024). Participants with 3 out of 6 IC decline had a probability of greater than 80% to belong to the low/moderate participation class. Discussion: Physical function, cognition, hearing and nutrition were significantly associated with low and/or moderate participation class. Future studies are needed to evaluate improvement in participation of those with falls or at risk for falls through restoration of IC.

Cannabinoids in Late Life Parkinson's Disease and Dementia: Biological Pathways and Clinical Challenges.

The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of tremor, non-motor symptoms, anxiety, and sleep assistance in PD, and managing responsive behaviors of dementia such as agitation. However, strong evidence from clinical trials is scarce for most indications. Some clinicians consider cannabinoids an alternative for older adults bearing Parkinson's disease and Alzheimer's dementia with a poor response to first-line treatments. In our concept and experience, cannabinoids should never be considered a first-line treatment but could be regarded as an adjuvant therapy in specific situations commonly seen in clinical practice. To mitigate the risk of adverse events, the traditional dogma of geriatric medicine, starting with a low dose and proceeding with a slow titration regime, should also be employed with cannabinoids. In this review, we aimed to address preclinical evidence of cannabinoids in neurodegenerative disorders such as PD and AD and discuss potential off-label use of cannabinoids in clinical practice of these disorders.

Heparanase 1 Upregulation Promotes Tumor Progression and Is a Predictor of Low Survival for Oral Cancer.

Background: Oral cavity cancer is still an important public health problem throughout the world. Oral squamous cell carcinomas (OSCCs) can be quite aggressive and metastatic, with a low survival rate and poor prognosis. However, this is usually related to the clinical stage and histological grade, and molecular prognostic markers for clinical practice are yet to be defined. Heparanase (HPSE1) is an endoglycosidase associated with extracellular matrix remodeling, and although involved in several malignancies, the clinical implications of HPSE1 expression in OSCCs are still unknown. Methods: We sought to investigate HPSE1 expression in a series of primary OSCCs and further explore whether its overexpression plays a relevant role in OSCC tumorigenesis. mRNA and protein expression analyses were performed in OSCC tissue samples and cell lines. A loss-of-function strategy using shRNA and a gain-of-function strategy using an ORF vector targeting HPSE1 were employed to investigate the endogenous modulation of HPSE1 and its effects on proliferation, apoptosis, adhesion, epithelial-mesenchymal transition (EMT), angiogenesis, migration, and invasion of oral cancer in vitro. Results: We demonstrated that HPSE1 is frequently upregulated in OSCC samples and cell lines and is an unfavorable prognostic indicator of disease-specific survival when combined with advanced pT stages. Moreover, abrogation of HPSE1 in OSCC cells significantly promoted apoptosis and inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition by significantly decreasing the expression of N-cadherin and vimentin. Furthermore, a conditioned medium of HPSE1-downregulated cells resulted in reduced vascular endothelial growth. Conclusion: Our results confirm the overexpression of HPSE1 in OSCCs, suggest that HPSE1 expression correlates with disease progression as it is associated with several important biological processes for oral tumorigenesis, and can be managed as a prognostic marker for patients with OSCC.

Frailty and affective disorders throughout adult life: A 5-year follow-up of the Lifelines Cohort Study.

BACKGROUND: Frailty is an important concept for risk stratification in clinical practice, but it is hardly acknowledged at all in mental healthcare settings. This paper aims to assess the impact of frailty on the course of depression and anxiety, and the impact of these affective disorders on the course of frailty. METHODS: Lifelines, a prospective population-based cohort study, evaluated 167,729 people living in the northern Netherlands. Frailty was based on the deficit accumulation model, which resulted in a 60-item frailty index (FI) at baseline and a 35-item FI at baseline and 5-year follow-up. Current depressive and anxiety disorders were assessed with the Mini International Neuropsychiatric Interview according to DSM-IV criteria. Bidirectional associations between frailty and affective disorders were investigated using separate multivariable regression analyses in younger (<60 years) and older adults (≥60 years). RESULTS: The FI was associated with the onset of a depressive disorder (younger adults: odds ratio [OR] = 1.12; 95% confidence interval [CI] 1.11-1.13; older adults: OR = 1.13; 95% CI 1.09-1.16) as well as any anxiety disorder (younger adults: OR = 1.10; 95% CI 1.09-1.10; older adults: OR = 1.07; 95% CI 1.04-1.09). The other way around, depressive disorder and anxiety disorders were associated with an accelerated increase of frailty over time (depressive disorder: younger adults: beta [ß] = 0.03, p < 0.001; older adults: ß = 0.04, p < 0.001; and any anxiety disorder: younger adults: ß = 0.02, p < 0.001; older adults: ß = 0.01, p < 0.142), although the effect of anxiety disorders was less equivocal among older adults. CONCLUSIONS: Affective disorders are reciprocally related to frailty. Results with respect to the impact of anxiety disorders on frailty suggest most impact at lower levels of frailty. Our results might imply that interventions to slow biological aging should be broadened towards younger and middle-aged people as well as non-frail older patients. To develop targeted treatment, future clinical and epidemiologic studies on the underlying pathways of this bidirectional association are needed.

Manejo das demências em fase avançada: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia / Management in severe dementia: recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology

RESUMO A doença de Alzheimer (DA) e outras demências neurodegenerativas têm um curso progressivo com comprometimento da cognição, capacidade funcional e comportamento. A maioria dos estudos enfocou a DA. A demência grave está associada ao aumento da idade, maior morbimortalidade e aumento dos custos de cuidados. É fundamental reconhecer que a demência grave é o período mais longo de progressão, com o paciente vivendo muitos anos nesta fase. É a fase mais heterogênea do processo, com diferentes habilidades e expectativa de vida. Esta diretriz de prática concentra-se na demência grave para melhorar o manejo e o cuidado nessa fase da demência. Como um longo período no continuum da demência, as abordagens não farmacológicas e farmacológicas devem ser consideradas. Intervenções multidisciplinares (fisioterapia, fonoaudiologia, nutrição, enfermagem, entre outras) são essenciais, além de educacionais e de apoio aos cuidadores.

ABSTRACT Alzheimer's disease (AD) and other neurodegenerative dementias have a progressive course, impairing cognition, functional capacity, and behavior. Most studies have focused on AD. Severe dementia is associated with increased age, higher morbidity-mortality, and rising costs of care. It is fundamental to recognize that severe dementia is the longest period of progression, with patients living for many years in this stage. It is the most heterogeneous phase in the process, with different abilities and life expectancies. This practice guideline focuses on severe dementia to improve management and care in this stage of dementia. As it is a long period in the continuum of dementia, clinical practice should consider non-pharmacological and pharmacological approaches. Multidisciplinary interventions (physical therapy, speech therapy, nutrition, nursing, and others) are essential, besides educational and support to caregivers.