Publications by authors named "Ivan Aprahamian"

140 Publications

Shaping the next steps of research on frailty: challenges and opportunities.

BMC Geriatr 2021 Jul 19;21(1):432. Epub 2021 Jul 19.

Department of Medicine Division of Geriatric Medicine and Gerontology, School of Medicine, and the Center on Aging and Health, Johns Hopkins University, Baltimore, MD, USA.

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http://dx.doi.org/10.1186/s12877-021-02370-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290538PMC
July 2021

Three definitions of probable sarcopenia and associations with falls and functional disability among community-dwelling older adults.

Osteoporos Sarcopenia 2021 Jun 25;7(2):69-74. Epub 2021 May 25.

Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil.

Objectives: To assess the prevalence of probable sarcopenia according to 3 different definitions ("strength, assistance with walking, rise from a chair, climb stairs, falls"- SARC-F score, low grip strength, and the guidelines indicated by the European Working Group on Sarcopenia in Older People 2 - EWGSOP2) and assess the association of probable sarcopenia with functional disability and falls among community-dwelling older adults.

Methods: Cross-sectional study with 419 older adults. Probable sarcopenia was assessed by 3 definitions: a SARC-F ≥ 4, low grip strength (< 27 kg for men and < 16 kg for women), and the EWGSOP2 criteria. Associations were investigated using Pearson's chi-square test and prevalence ratios were estimated by Poisson regression (P < 0.05).

Results: Of the total, probable sarcopenia was identified in 23.0% of participants (SARC-F ≥ 4 score), 33.7% (low grip strength), and 10.4% (EWGSOP2) according to each different definition. In adjusted regression models, having at least 1 instrumental activities of daily living (IADL) disability and having fallen in the last 12 months were significantly associated with a SARC-F ≥ 4 (prevalence ratio, PR = 1.60; and PR = 2.50, respectively) and EWGSOP2 (PR = 1.78; and PR = 2.19, respectively).

Conclusions: IADL disability and falls were associated with a SARC-F ≥ 4 and the EWGSOP2 criteria (SARC-F ≥ 4 and low grip strength). Probable sarcopenia may be used in clinical practice in order to facilitate the diagnosis of definite sarcopenia and to implement early interventions that could prevent functional decline and falls in older people.
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http://dx.doi.org/10.1016/j.afos.2021.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261724PMC
June 2021

A multidimensional program including standing exercises, health education, and telephone support to reduce sedentary behavior in frail older adults: Randomized clinical trial.

Exp Gerontol 2021 Jul 13;153:111472. Epub 2021 Jul 13.

Laboratory of Studies in Technology, Functionality and Aging of the Department of Physical Therapy, Speech and Occupational Therapy, School of Medicine, University of São Paulo, São Paulo, SP, Brazil.

Objectives: The primary aim of this study was to evaluate the effect of a multidimensional program including home-based standing exercises, health education, and telephone support for the reduction of sedentary behavior in community-dwelling frail older adults. The secondary aim of this study was to evaluate the safety and adherence of the program.

Study Design: A single-blind, randomized controlled trial.

Methods: A total of 43 frail older adults were randomly assigned to the intervention and control groups. The intervention consisted of combined strategies including home-based standing exercises, health education, and telephone support for 16 weeks for frail older adults. The control group received orientation regarding the harmful effects of a sedentary lifestyle. Sedentary behavior was evaluated by total sedentary time, accumulated sedentary time in bouts of at least 10 min, and by the break in sedentary time, measured by an accelerometer used for at least 600 min/day for 4 days. Safety was assessed by self-reporting of possible adverse events. Adherence was assessed based on the number of days in which standing exercises were performed by the participants. Repeated measures ANOVA and Tukeys post hoc test were used to analyze the collected data.

Results: The intervention group reduced the sedentary time by 30 min/day (p= 0.048), but without significant maintenance after 30 days of the program. Of the total number of participants, 82% (n = 14) of the intervention group participants showed more than 70% adherence to the program. The main adverse effects faced by the intervention group participants were tiredness (53%; n = 9) and lower limb pain (47%; n = 8).

Conclusions: The multidimensional program reduced sedentary behavior, was safe, and showed satisfactory adherence in frail older adults.
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http://dx.doi.org/10.1016/j.exger.2021.111472DOI Listing
July 2021

The association between cardiovascular risk factors and major cardiovascular diseases decreases with increasing frailty levels in geriatric outpatients.

Exp Gerontol 2021 Jul 12;153:111475. Epub 2021 Jul 12.

Department of Psychiatry, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.

Background: Frailty marks a process of increasing dysregulation of physiological systems which increases the risk of adverse health outcomes. This study examines the hypothesis that the association between multiple cardiovascular risk factors (CVRF) and cardiovascular diseases (CVD) becomes stronger with increasing frailty severity.

Methods: Cross-sectional analysis of 339 older adults (55.2% women; aged 75.2 ± 9.1 years) from an outpatient geriatric clinic from a middle-income country. The frailty index (FI) was calculated as the proportion of 30 possible health deficits. We assessed hypertension, diabetes, obesity, dyslipidemia, sedentarism and smoking as CVRF (determinants) and myocardial infarction, stroke, heart failure as CVD. Poisson regression models adjusted for age, sex, and education was applied to estimate the association between frailty as well as CVRF (independent variables) with CVD (dependent variable).

Results: Of the 339 patients, 18,3% were frail (FI ≥ 0.25) and 32.7% had at least one CVD. Both frailty and CVRF were significantly associated with CVD (PR = 1.03, 95% CI 1.01 to 1.05; p = 0.001, and PR = 1.46, 95% 1.24 to 1.71; p < 0.001, respectively) adjusted for covariates. The strength of the association between CVRF and CVD decreased with increasing frailty levels, as indicated by a significant interaction term of frailty and CVRF (p < 0.001).

Conclusion: Frailty and CVRF are both associated with CVD, but the impact of CVRF decreases in the presence of frailty. When confirmed in longitudinal studies, randomized controlled trials or causal inference methods like Mendelian randomization should be applied to assess whether a shift from traditional CVRF to frailty would improve cardiovascular outcome in the oldest old.
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http://dx.doi.org/10.1016/j.exger.2021.111475DOI Listing
July 2021

Decision-making executive function profile and performance in older adults with major depression: a case-control study.

Aging Ment Health 2021 Jul 15:1-7. Epub 2021 Jul 15.

Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Objectives: Decision making (DM) is a component of executive functioning, essential for choosing appropriate decisions. Executive dysfunctioning is particularly common in late-life depression, however the literature is scarce on DM. This case-control study aimed to evaluate the DM profile and performance in participants with and without unipolar major depression.

Method: The DM profile and performance were assessed by the Melbourne Decision Making Questionnaire and the Iowa Gambling Task (IGT), respectively, in three groups of older adults from a university-based geriatric psychiatry clinic, i.e. current depression ( = 30), remitted depression ( = 43) and healthy controls ( = 59). The Hamilton Depression scale (HAM-D) 21 items, the Hamilton Anxiety scale, and the Mini-Mental State Examination were used to access depressive symptoms, anxiety symptoms, and cognitive impairment, respectively. Multinomial, nominal and binary logistic regression was used to evaluate the associations between depression, depressive symptomatology and DM.

Results: In comparison to the control group, patients with current depression presented higher scores in buck-passing and proscratination DM profiles. In the hypervigilance profile, there was a significant difference between current and remitted depression groups. A higher value ​in the HAM-D scale increased the probability of disadvantageous DM profiles. Depressive patients showed a tendency of a higher mean score in both disadvantageous decks (A and B) of IGT. Patients with current depression showed a worse performance compared to the remitted depression group in the IGT netscore.

Conclusion: Older adults with current depression showed DM profiles considered maladaptive or disadvantageous compared to both remitted depression and healthy controls groups.
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http://dx.doi.org/10.1080/13607863.2021.1950617DOI Listing
July 2021

Probable sarcopenia is associated with cognitive impairment among community-dwelling older adults: results from the FIBRA study.

Arq Neuropsiquiatr 2021 05;79(5):376-383

Universidade de São Paulo, Escola de Artes, Ciências e Humanidades, São Paulo SP, Brazil.

Background: The link between sarcopenia and cognitive impairment has not yet been thoroughly evaluated, especially among older adults.

Objective: To evaluate the relationship between probable sarcopenia and cognitive impairment among community-dwelling older adults in two Brazilian cities.

Methods: Probable sarcopenia was assessed using the EWGSOP2 (2018) criteria. Thus, participants were classified as probably having sarcopenia if they had SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs and Falls) ≥4 points and low grip strength. Cognitive function was evaluated through the Mini-Mental State Examination (MMSE), verbal fluency (VF) and clock drawing test (CDT).

Results: In a sample of 529 older adults (mean age 80.8±4.9 years; mean education 4.2±3.67 years; 70.1% women), 27.3% of the participants had SARC-F≥4, 38.3% had low grip strength and 13.6% were classified as probable sarcopenia cases. After adjusting for possible confounders (age, sex, education, depression, diabetes, hypertension, leisure-time physical activity and obesity), probable sarcopenia was found to be associated with impairment in the MMSE (OR 2.52; 95%CI 1.42‒4.47; p=0.002) and in VF (OR 2.17; 95%CI 1.17‒4.01; p=0.014). Low grip strength was found to be associated with impairment in the MMSE (OR 1.83; 95%CI 1.18‒2.82; p=0.006) and in the CDT (OR 1.79; 95%CI 1.18‒2.73; p=0.006). SARC-F scores were found to be associated with impairment in the MMSE (OR 1.90; 95%CI 1.18‒3.06; p=0.008).

Conclusion: The results suggested that probable sarcopenia and its components present a significant association with cognitive deficits among community-dwelling older adults. Future longitudinal studies will further explore the causal relationship.
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http://dx.doi.org/10.1590/0004-282X-ANP-2020-0186DOI Listing
May 2021

A 6-year prospective clinical cohort study on the bidirectional association between frailty and depressive disorder.

Int J Geriatr Psychiatry 2021 Jun 15. Epub 2021 Jun 15.

Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Introduction: Depressive disorder has been conceptualised as a condition of accelerated biological ageing. We operationalised a frailty index (FI) as marker for biological ageing aimed to explore the bidirectional, longitudinal association between frailty and either depressive symptoms or depressive disorder.

Methods: A cohort study with 6-year follow-up including 377 older (≥60 years) outpatients with a DSM-IV-defined depressive disorder and 132 never-depressed controls. Site visits at baseline, 2 and 6-year follow-up were conducted and included the CIDI 2.0 to assess depressive disorder and relevant covariates. Depressive symptom severity and mortality were assessed every 6 months by mail and telephone. A 41-item FI was operationalised and validated against the 6-year morality rate by Cox regression (HR  = 1.04 [95% CI: 1.02-1.06]).

Results: Cox regression showed that a higher FI was associated with a lower chance of remission among depressed patients (HR  = 0.98 [95% CI: 0.97-0.99]). Nonetheless, this latter effect disappeared after adjustment for baseline depressive symptom severity. Linear mixed models showed that the FI increased over time in the whole sample (B[SE] = 0.94 (0.12), p < .001) with a differential impact of depressive symptom severity and depressive disorder. Higher baseline depressive symptom severity was associated with an attenuated and depressive disorder with an accelerated increase of the FI over time.

Conclusions: The sum score of depression rating scales is likely confounded by frailty. Depressive disorder, according to DSM-IV criteria, is associated with accelerated biological ageing. This argues for the development of multidisciplinary geriatric care models incorporating frailty to improve the overall outcome of late-life depression.
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http://dx.doi.org/10.1002/gps.5588DOI Listing
June 2021

Frailty as a Predictor of Mortality in Late-Life Depression: A Prospective Clinical Cohort Study.

J Clin Psychiatry 2021 Mar 30;82(3). Epub 2021 Mar 30.

University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Groningen, Netherlands.

Objective: Frailty is a clinical phenotype that predicts negative health outcomes, including mortality, and is increasingly used for risk stratification in geriatric medicine. Similar to frailty, late-life depression is also associated with increased mortality rates. Therefore, we examined whether frailty and frailty-related biomarkers predict mortality among depressed older patients.

Methods: In our study of 378 older patients aged ≥ 60 years with a depressive disorder (DSM-IV criteria), we examined whether frailty predicts time-to-death during a 6-year follow-up using Cox proportional hazard regression analyses adjusted for confounders. Baseline data were collected from 2007 to September 2010. Frailty was defined according to the Fried Frailty Phenotype criteria (muscle weakness, slowness, exhaustion, low activity level, unintended weight loss). Similarly, we examined the predictive value of 3 inflammatory markers, vitamin D level, and leukocyte telomere length and whether these effects were independent of the frailty phenotype.

Results: During follow-up, 27 (26.2%) of 103 frail depressed patients died compared with 35 (12.7%) of 275 non-frail depressed patients (P < .001). Adjusted for confounders, the number of frailty components was associated with an increased mortality rate (hazard ratio = 1.38 [95% CI, 1.06-1.78], P = .015). All biomarkers except for interleukin 6 were prospectively associated with mortality, but only higher levels of high-sensitivity C-reactive protein and lower levels of vitamin D were independent of frailty associated with mortality.

Conclusions: In late-life depression, frailty identifies older patients at increased risk of adverse negative health outcomes. Therefore, among frail depressed patients, treatment models that include frailty-specific interventions might reduce mortality rates.
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http://dx.doi.org/10.4088/JCP.20m13277DOI Listing
March 2021

Feasibility of reducing frailty components in older adults with Alzheimer's dementia: a randomized controlled home-based exercise trial (AD-HOMEX).

Exp Gerontol 2021 07 5;150:111390. Epub 2021 May 5.

Department of Physical Therapy, Federal University of São Carlos, São Carlos, Brazil.

Objectives: There is a need for interventions to reduce frailty in older people with Alzheimer's dementia (AD). The purpose of this study was to investigate the effect of a home-based multimodal exercise program for older adults with AD (AD-HOMEX) on frailty.

Design: A parallel single-blind randomized controlled trial comparing a home-based exercise program and usual care.

Setting And Participants: A home-based program in Brazil. Forty individuals aged 65years or older with mild to moderate AD.

Methods: The intervention group (IG) participated in a 16-week protocol involving three 60-minute sessions per week of progressive individualized physical exercises supervised by a physical therapist. The participants in the control group (CG) maintained their usual care. Frailty was assessed using the FRAIL questionnaire, the Edmonton Frail Scale (EFS) and a subjective assessment by the evaluator (SAE) at baseline and follow-up. Per-protocol analysis was performed.

Results: Thirty-five participants completed the program (IG = 16; CG = 19). Frailty improved in the IG based on the EFS (P = .004) and FRAIL (P ≤ .001). An interaction between group and time (P = .008) and a significant difference between times (P = .047) were found for the SAE responsiveness domain. An improvement in the classification of frailty (EFS and FRAIL) was found between times in the IG (P = .003) and between groups at follow-up (P = .027). A significant difference in the SAE classification was found between groups at follow-up (P = .034), with a worsening between times in the CG (P = .032). Interestingly, a more favorable frailty transition pattern was found in the IG based on both the EFS and FRAIL.

Conclusions And Implications: AD-HOMEX seems to reduce frailty and improve frailty transition patterns. Our findings provide a further theoretical basis for designing home-based physical interventions as routine practice for older frail adults with AD.
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http://dx.doi.org/10.1016/j.exger.2021.111390DOI Listing
July 2021

The concept of anorexia of aging in late life depression: A cross-sectional analysis of a cohort study.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104410. Epub 2021 Mar 31.

University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, the Netherlands.

Introduction: Anorexia of aging (AA) is classically associated with depression. However, robust evidence is lacking regarding general clinic populations. Our aim was to evaluate the association between AA and major depressive disorder (MDD) in geriatric outpatients from a middle-income country.

Methods: We conducted a cross-sectional analysis of a cohort study. MDD diagnosis was assessed with a psychiatric interview (SCID-5-CV) according to DSM-5 criteria. Depressive symptomatology was assessed by a 15-items Geriatric Depression Scale (GDS) and the PHQ-9 questionnaire. Appetite was measured with the Simple Nutrition Appetite Questionnaire (SNAQ), whereas AA was defined as a SNAQ score ≤13 points). Linear and logistic regression analysis adjusted for potential confounders were applied to assess the association between depressive symptomatology, MDD and AA.

Results: Of the total 339 participants, MDD was present in 65. AA was more frequent in patients with MDD compared to non-depressed patients (30.7 versus 7.7%; p<0.001). The SNAQ score was lower in depressed patients (14.5 vs. 16.6, p<0.001). Adjusted for confounding, linear and logistic regression showed a significant association between the GDS score, PHQ-9 score and MDD with the SNAQ score (p<0.001) and cut-off representing AA (p<0.001), respectively. Moreover, MDD and AA interacted significantly with their association with weight loss (p<0.001).

Conclusions: Depression scales (even without somatic complaints) and MDD were associated with AA in geriatric outpatients. AA is associated with weight loss in MDD. Prospective studies should expand these findings.
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http://dx.doi.org/10.1016/j.archger.2021.104410DOI Listing
June 2021

Fundamental studies to emerging applications of pyrrole-BF (BOPHY) fluorophores.

Chem Soc Rev 2021 May 15;50(9):5631-5649. Epub 2021 Mar 15.

Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA.

BF-based fluorophores, such as the well-known BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dye, are prevalently used in diverse research areas (e.g., bioimaging and chemosensing) as they exhibit promising features including high quantum yields, fine-tuned absorption and emission spectra as well as good photostability and biocompatibility. While BODIPY dyes are most commonly used in such applications, other BF-based fluorophores, such as BOPHY (bis(difluoroboron)-1,2-bis((1H-pyrrol-2-yl)methylene)hydrazine - which possess their own characteristic features - are rising in popularity and are being used in a range of applications spanning from molecular sensors to photosensitizers for solar cells. This review examines select examples of BOPHY dyes to highlight the progression of their development while detailing their syntheses and photophysical properties including structure-property relationships. Applications of a number of substituted BOPHYs made by the methods described in this review are also presented.
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http://dx.doi.org/10.1039/d1cs00122aDOI Listing
May 2021

Blood Brain-Derived Neurotrophic Factor (BDNF) and Major Depression: Do We Have a Translational Perspective?

Front Behav Neurosci 2021 12;15:626906. Epub 2021 Feb 12.

Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Major depressive disorder (MDD) affects millions of people worldwide and is a leading cause of disability. Several theories have been proposed to explain its pathological mechanisms, and the "neurotrophin hypothesis of depression" involves one of the most relevant pathways. Brain-derived neurotrophic factor (BDNF) is an important neurotrophin, and it has been extensively investigated in both experimental models and clinical studies of MDD. Robust empirical findings have indicated an association between increased BDNF gene expression and peripheral concentration with improved neuronal plasticity and neurogenesis. Additionally, several studies have indicated the blunt expression of BDNF in carriers of the Val66Met gene polymorphism and lower blood BDNF (serum or plasma) levels in depressed individuals. Clinical trials have yielded mixed results with different treatment options, peripheral blood BDNF measurement techniques, and time of observation. Previous meta-analyses of MDD treatment have indicated that antidepressants and electroconvulsive therapy showed higher levels of blood BDNF after treatment but not with physical exercise, psychotherapy, or direct current stimulation. Moreover, the rapid-acting antidepressant ketamine has presented an early increase in blood BDNF concentration. Although evidence has pointed to increased levels of BDNF after antidepressant therapy, several factors, such as heterogeneous results, low sample size, publication bias, and different BDNF measurements (serum or plasma), pose a challenge in the interpretation of the relation between peripheral blood BDNF and MDD. These potential gaps in the literature have not been properly addressed in previous narrative reviews. In this review, current evidence regarding BDNF function, genetics and epigenetics, expression, and results from clinical trials is summarized, putting the literature into a translational perspective on MDD. In general, blood BDNF cannot be recommended for use as a biomarker in clinical practice. Moreover, future studies should expand the evidence with larger samples, use the serum or serum: whole blood concentration of BDNF as a more accurate measure of peripheral BDNF, and compare its change upon different treatment modalities of MDD.
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http://dx.doi.org/10.3389/fnbeh.2021.626906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906965PMC
February 2021

Dementia in Latin America: Paving the way toward a regional action plan.

Alzheimers Dement 2021 02 20;17(2):295-313. Epub 2020 Nov 20.

Hospital Geral de Fortaleza, University of Fortaleza, Brazil.

Across Latin American and Caribbean countries (LACs), the fight against dementia faces pressing challenges, such as heterogeneity, diversity, political instability, and socioeconomic disparities. These can be addressed more effectively in a collaborative setting that fosters open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking, and translational research) and align them to current global strategies to translate regional knowledge into transformative actions. Then we characterize key sources of complexity (genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions), map them to the above challenges, and provide the basic mosaics of knowledge toward a KtAF. Finally, we describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF.
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http://dx.doi.org/10.1002/alz.12202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984223PMC
February 2021

The effect of a multicomponent exercise protocol (VIVIFRAIL©) on inflammatory profile and physical performance of older adults with different frailty status: study protocol for a randomized controlled trial.

BMC Geriatr 2021 01 29;21(1):83. Epub 2021 Jan 29.

Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status.

Methods/design: This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change in physical performance using the Short Physical Performance Battery, handgrip strength, fatigue, gait speed, dual-task gait speed, depressive symptoms, FRAIL-BR and SARC-F scores, and quality of life at the 12-week period of intervention and after 3 months of follow-up.

Discussion: We expect a reduction in inflammatory interleukins or an increase in anti-inflammatory mediators in those who performed the VIVIFRAIL© protocol. The results of the study will imply in a better knowledge about the effect of a low-cost intervention that could be easily replicated in outpatient care for the prevention and treatment of frailty, especially regarding the inflammatory and anti-inflammatory pathways involved in its pathophysiology.

Trial Registration: Brazilian Registry of Clinical Trials (RBR-9n5jbw; 01/24/2020). Registred January 2020. http://www.ensaiosclinicos.gov.br/rg/RBR-9n5jbw/ .
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http://dx.doi.org/10.1186/s12877-021-02030-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844975PMC
January 2021

Depression as a determinant of frailty in late life.

Aging Ment Health 2020 Dec 11:1-7. Epub 2020 Dec 11.

Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Objectives: Accumulating evidence shows depression as a risk factor for frailty, but studies are mainly population-based and widely differ in their assessment of either depression or frailty. We investigated the association between depression and frailty among geriatric outpatients using different assessment instruments for both conditions.

Method: Among 315 geriatric outpatients (mean age 72.1 years, 68.3% female sex) participating the MiMiCS-FRAIL cohort study, major and subthreshold depression were measured with psychiatric diagnostic interview according to DSM-5 criteria (SCID-5) as well as with instruments to screen and measure severity of depressive symptoms (GDS-15 and PHQ-9). Frailty was assessed according to a screening instrument (FRAIL-BR) and a multidimensional Frailty Index (FI-36 items). Multiple logistic and linear regression were performed to assess the association between depression (independent variable) and frailty (dependent variable) adjusted for confounders.

Results: Frailty prevalence in patients with no, subthreshold or major depressive disorder increases from either 14.5%, 46.5% to 65.1% when using the FRAIL-BR questionnaire, and from 10.2%, 20.9%, to 30.2% when using the FI-36 index. These association remain nearly the same when adjusted for covariates. Both the FRAIL-BR and the FI-36 were strongly associated with major depressive disorder, subthreshold depression, and depressive symptoms by PHQ-9 and GDS-15.

Conclusion: Late life depression and frailty are associated in a dose-dependent manner, irrespective of the used definitions. Nonetheless, to avoid residual confounding, future research on underlying biological mechanisms should preferably be based on formal psychiatric diagnoses and objectively assessment frailty status.
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http://dx.doi.org/10.1080/13607863.2020.1857689DOI Listing
December 2020

Design and protocol of the multimorbidity and mental health cohort study in frailty and aging (MiMiCS-FRAIL): unraveling the clinical and molecular associations between frailty, somatic disease burden and late life depression.

BMC Psychiatry 2020 12 1;20(1):573. Epub 2020 Dec 1.

Institute and Department of Psychiatry, University of São Paulo, São Paulo, Brazil.

Background: To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression and their interconnectedness.

Methods: MiMiCS-FRAIL is an ongoing observational cohort study of geriatric outpatients in Brazil, with an extensive baseline assessment and yearly follow-up assessments. Each assessment includes a comprehensive geriatric assessment to identify multimorbidity and geriatric syndromes, a structured psychiatric diagnostic interview and administration of the PHQ-9 to measure depression, and several frailty measures (FRAIL, Physical Phenotype criteria, 36-item Frailty Index). Fasten blood samples are collected at baseline to assess circulating inflammatory and anti-inflammatory cytokines, leukocytes' subpopulations, and to perform immune-metabolic-paired miRome analyses. The primary outcome is death and secondary outcomes are the number of falls, hospital admissions, functional ability, well-being, and dementia. Assuming a 5-year mortality rate between 25 and 40% and a hazard rate varying between 1.6 and 2.3 for the primary determinants require a sample size between 136 and 711 patients to detect a statistically significant effect with a power of 80% (beta = 0.2), an alpha of 5% (0.05), and an R between the predictor (death) and all covariates of 0.20. Local ethical board approved this study.

Discussion: Frailty might be hypothesized as a final common pathway by which many clinical conditions like depression and chronic diseases (multimorbidity) culminate in many adverse effects. The MiMiCS-FRAIL cohort will help us to understand the interrelationship between these variables, from a clinical perspective as well as their underlying molecular signature.
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http://dx.doi.org/10.1186/s12888-020-02963-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706060PMC
December 2020

Frailty in geriatric psychiatry inpatients: a retrospective cohort study.

Int Psychogeriatr 2020 Nov 16:1-9. Epub 2020 Nov 16.

Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Objective: We aimed to evaluate the prevalence, clinical determinants, and consequences (falls and hospitalization) of frailty in older adults with mental illness.

Design: Retrospective clinical cohort study.

Setting: We collected the data in a specialized psychogeriatric ward, in Boston, USA, between July 2018 and June 2019.

Participants: Two hundred and fourty-four inpatients aged 65 years old and over.

Measurements: Psychiatric diagnosis was based on a multi-professional consensus meeting according to DSM-5 criteria. Frailty was assessed according to two common instruments, that is, the FRAIL questionnaire and the deficit accumulation model (aka Frailty Index [FI]). Multiple linear regression analyses were conducted to evaluate the association between frailty and sample demographics (age, female sex, and non-Caucasian ethnicity) and clinical characteristics (dementia, number of clinical diseases, current infection, number of psychotropic, and non-psychotropic medications in use). Multiple regression between frailty assessments and either falls or number of hospital admissions in the last 6 and 12 months, respectively, were analyzed and adjusted for covariates.

Results: Prevalence of frailty was high, that is, 83.6% according to the FI and 55.3% according to the FRAIL questionnaire. Age, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty identified by the FRAIL. Dementia, current infection, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty according to the FI. Falls were significantly associated with both frailty instruments. However, we found only a significant association for the number of hospital admissions with the FI.

Conclusion: Frailty is highly prevalent among geriatric psychiatry inpatients. The FRAIL questionnaire and the FI may capture different forms of frailty dimensions, being the former probably more associated with the phenotype model and the latter more associated with multimorbidity.
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http://dx.doi.org/10.1017/S1041610220003403DOI Listing
November 2020

Could Frailty be an Explanatory Factor of the Association between Depression and Other Geriatric Syndromes in Later Life?

Clin Gerontol 2021 Mar-Apr;44(2):143-153. Epub 2020 Oct 25.

Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo , São Paulo, Brazil.

Objectives: This study aimed to investigate whether frailty could be an explanatory factor of the association between depression and the number of geriatric syndromes.

Methods: Cross-sectional baseline data from a cohort study (MiMiCS-FRAIL) were analyzed in a sample of 315 older adults. Depression was measured according to DSM-5 criteria and a self-report questionnaire (PHQ-9). Frailty was assessed according to the FRAIL questionnaire and a 30-item Frailty Index (FI). We considered six geriatric syndromes. Multiple linear regression analyses were performed and adjusted for potential confounders.

Results: Multiple linear regression analyses yielded significant associations between depression and geriatric syndromes. These associations decreased substantially in strength when frailty was added to the models. Findings were consistent for different definitions of depression and frailty.

Conclusions: Among depressed patients, frailty may be hypothesized as a causal pathway toward adverse health outcomes associated with depression. Longitudinal studies should explore the causality of this association.

Clinical Implications: Frailty should be treated or prevented in order to minimize the impact of other geriatric syndromes among depressed older adults. Screening for frailty would be of utmost importance in mental health care, as frailty is neglected especially in this field. Integrated care models are crucial for clinical practice in mental illness care.
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http://dx.doi.org/10.1080/07317115.2020.1836106DOI Listing
October 2020

Relationship between affective temperament and major depressive disorder in older adults: A case-control study.

J Affect Disord 2020 12 11;277:949-953. Epub 2020 Sep 11.

Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil; Geriatrics Division, Department of Internal Medicine, Faculty of Medicine of Jundiaí, Jundiaí, Brazil.

Background: In clinical practice it is often challenging to determine whether mood disturbances should be considered a state or trait characteristics. This study is important to understand the influence of temperaments in the diagnosis of depression. The objective of the present study was to compare the frequency of three types of affective temperament (dysthymia, hyperthymia and cyclothymia) among older adults with major depression compared to non-psychiatric control patients.

Methods: A case-control study comparing 50 patients with major depression aged 65 years or above with a comparison group of 100 non-psychiatric controls. Affective temperaments were assessed using the TEMPS-A questionnaire. The 17-item Hamilton Depression Rating Scale and the Young mania Rating Scale were used for the assessment of symptoms of depression and mania, respectively.

Results: In the sample 80% had an affective temperament, most commonly hyperthymia (67.3%). In depressive patients 48% had criteria for hyperthymic temperament against 77% of the controls (OR= 0.3, 95%CI 0.1-0.7). 38.8% of these patients presented cyclothymic temperament, whereas among controls, 12% fulfilled criteria (OR= 2.9, 95%CI 1.1-7.2).

Limitations: The sample was relatively small, and their educational level was very low.

Conclusion: A cyclothymic temperament may predict major depression unlike hyperthymia. Whether the effectiveness of mood stabilizers in unipolar disorder is moderated by a cyclothymic temperament and should be explored in future randomized controlled trials.
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http://dx.doi.org/10.1016/j.jad.2020.09.038DOI Listing
December 2020

Diagnostic Accuracy of Usual Cognitive Screening Tests Versus Appropriate Tests for Lower Education to Identify Alzheimer Disease.

J Geriatr Psychiatry Neurol 2021 May 24;34(3):222-231. Epub 2020 Sep 24.

67791Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, Brazil.

Introduction: The accuracy of commonly used screening tests for Alzheimer's disease (AD) has not been directly compared to those that could be more appropriate for lower schooling.

Objective: To compare the diagnostic accuracy of usual screening tests for AD with instruments that might be more appropriate for lower schooling among older adults with low or no literacy.

Methods: The study included a clinical sample of 117 elderly outpatients from a Geriatric Clinic classified as literate controls (n = 39), illiterate controls (n = 30), literate AD (n = 30) and illiterate AD (n = 18). The tests were compared as follows: Black and White versus Colored Figure Memory Test; Clock Drawing Test versus Clock Reading Test; Verbal Fluency (VF) animal versus grocery category; CERAD Constructional Praxis versus Stick Design Test.

Results: The means of literate and illiterate controls did not differ in the Black and White Figure Memory Test (immediate recall), Colored Figure Memory Test (delayed recall), Clock Reading Test and VF animals and grocery categories. The means of the clinical groups (controls versus AD), in the 2 schooling levels, differed significantly in most of the tests, except for the CERAD Constructive Praxis and the Stick Design Test. Diagnostic accuracy was not significantly different between the compared tests.

Conclusion: Commonly used screening tests for AD were as accurate as those expected to overcome the education bias in a sample of older adults with lower or no education.
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http://dx.doi.org/10.1177/0891988720958542DOI Listing
May 2021

Identifying and managing frailty in Brazil: a scoping review protocol.

JBI Evid Synth 2020 04;18(4):849-856

Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Nottingham, UK.

Objective: The objective of this review is to scope the evidence on how researchers, health, and social care professionals in Brazil currently identify and manage frailty in older adults.

Introduction: The rapidly aging population and associated increased healthcare usage by older people with frailty are challenging the sustainability of healthcare for older people in Brazil. Understanding how frailty is identified, measured, categorized, and managed in Brazil is an important part of building a response to the challenge.

Inclusion Criteria: This scoping review will consider studies that included older Brazilian adults (≥60 years old) recruited from different settings (community, primary care, health care centers, hospital, and long-term care institutions). Studies will be included if they involved any kind of frailty assessment (tools, scales, and measures) and/or interventions. This review will consider all study designs, regardless of their rigor. National policies for older people will be also be considered for analysis.

Methods: Indexed and gray literature in English or Portuguese from 2001 to the present will be considered. The searches will be conducted using bibliographic databases, university repositories, and the Brazilian Government official database. The studies will be independently screened according to the inclusion criteria by two reviewers based on their title, abstract, and full text. In case of disagreement, a third reviewer will be consulted. A customized data extraction form will be used to extract data from the included studies. The results will be presented in tabular form, accompanied by a narrative summary related to the objective of the present scoping review.
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http://dx.doi.org/10.11124/JBISRIR-D-19-00188DOI Listing
April 2020

PORTUGUESE VERSION OF THE SNAQ QUESTIONNAIRE: TRANSLATION AND CULTURAL ADAPTATION.

Arq Gastroenterol 2020 Apr-Jun;57(2):178-181

Universidade de São Paulo, Faculdade de Saúde Pública, São Paulo, SP, Brasil.

Background: Poor appetite is common through the aging process and increases the risk of weight loss, protein-energy malnutrition, immunossupression, sarcopenia and frailty. The Simplified Nutritional Appetite Questionnaire (SNAQ) has the aim to monitor appetite and identify older adults at risk of weight loss.

Objective: To describe the process of translation and cultural adaptation to Brazilian Portuguese of the SNAQ.

Methods: The translation and cultural adaptation was developed in five steps: translation (by three of the authors of the manuscript and assembled by consensus), backtranslation (by an English native speaker), semantic evaluation (by one verontologist and one nutritionist), comprehension of content (by nutrition specialists and by a group of older persons), pre-test and the SNAQ final version development.

Results: The SNAQ Portuguese version maintained the original version meaning and referral. To achieve this feature, the process required some modifications to improve the understanding of older persons, such as inclusion of other options to the answers of some questions, rewritten of one question and inclusion of a meal definition.

Conclusion: SNAQ questionnaire has been successfully translated and adapted to Portuguese. As our next step, we are validating this tool in different clinical settings in Brazil.
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http://dx.doi.org/10.1590/S0004-2803.202000000-33DOI Listing
September 2020

Subtypes of Late-Life Depression: A Data-Driven Approach on Cognitive Domains and Physical Frailty.

J Gerontol A Biol Sci Med Sci 2021 01;76(1):141-150

University Center of Psychiatry and Interdisciplinary Center Psychopathology and Emotion Regulation, University Medical Center Groningen, The Netherlands.

Background: With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life-related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance, and physical frailty.

Methods: A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout, and mortality at 2-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty.

Results: A latent profile analysis model with five classes best described the data, yielding two subgroups suffering from pure depression ("mild" and "severe" depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labeled as "amnestic depression," "frail-depressed, physically dominated," and "frail-depressed, cognitively dominated." The prospective analyses showed that patients in the subgroup of "mild depression" and "amnestic depression" had the highest remission rates, whereas patients in both frail-depressed subgroups had the highest mortality rates.

Conclusions: Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according to the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy, and augmentation with geriatric rehabilitation.
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http://dx.doi.org/10.1093/gerona/glaa110DOI Listing
January 2021

Sarcopenia and cognitive impairment: Possible physiopathological causation or just a spurious association?

Clin Nutr 2020 05 29;39(5):1622. Epub 2020 Mar 29.

School of Arts, Sciences and Humanities of the University of São Paulo, SP, Brazil.

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http://dx.doi.org/10.1016/j.clnu.2020.03.027DOI Listing
May 2020

The Future of Molecular Machines.

Authors:
Ivan Aprahamian

ACS Cent Sci 2020 Mar 3;6(3):347-358. Epub 2020 Mar 3.

6128 Burke Laboratory, Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States.

Artificial molecular machines have captured the imagination of scientists and nonscientists alike for decades now, given their clear potential to transform and enhance all aspects of human life. In this Outlook, I use a bicycle as an analogy to explain what a molecular machine is, in my opinion, and work through a representative selection of case studies to specify the significant accomplishments made to date, and the obstacles that currently stand between these and the field's fulfillment of its great potential. The hope of this intentionally sober account is to sketch a path toward a rich and exciting research trajectory that might challenge current practitioners and attract junior scientists into its fold. Considering the progress we have witnessed in the past decade, I am positive that the future of the field is a rosy one.
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http://dx.doi.org/10.1021/acscentsci.0c00064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099591PMC
March 2020

Visualizing intracellular particles and precise control of drug release using an emissive hydrazone photochrome.

Chem Sci 2020 Feb 25;11(11):3016-3021. Epub 2020 Feb 25.

Thayer School of Engineering, Dartmouth College Hanover New Hampshire 03755 USA

The spatiotemporal control over the structure of nanoparticles while monitoring their localization in tumor cells can improve the precision of controlled drug release, thus enhancing the efficiency of drug delivery. Here, we report on a photochromic nanoparticle system (), assembled from fluorescent bistable hydrazone photoswitch-modified amphiphilic copolymers. The intrinsic emission of the hydrazone switch allows for the visualization of particle uptake, as well as their intracellular distribution. The → photoswitching of the hydrazone switch within the nanoparticle leads to the expansion of the nanoparticles (, drug release) accompanied by emission quenching, the degree of which can function as an internal indicator for the amount of drug released. The bistability of the switch enables the kinetic trapping of particles of different sizes as a function of irradiation time, and allows for the exhibition of light-dependent cell cytotoxicity in MDA-MB-231 cells using loaded with doxorubicin.
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http://dx.doi.org/10.1039/c9sc05321bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157519PMC
February 2020

Planarization-Induced Activation Wavelength Red-Shift and Thermal Half-Life Acceleration in Hydrazone Photoswitches.

ChemistryOpen 2020 02 3;9(2):191-194. Epub 2020 Feb 3.

Department of Chemistry Dartmouth College, 6128 Burke Laboratory Hanover New Hampshire 03755 USA.

The optimization and modulation of the properties of photochromic compounds, such as their activation wavelengths and thermal relaxation half-lives ( ), are essential for their adaptation in various applications. In this work, we studied the effect of co-planarization of the rotary fragment of two photochromic hydrazones with the core of the molecule on their switching properties. The and isomers of both compounds exhibit red-shifted absorption bands relative to their twisted versions, allowing for their photoswitching using longer wavelengths of light. Additionally, the thermal half-lives of both hydrazones are drastically shortened from hundreds of years to days.
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http://dx.doi.org/10.1002/open.201900340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996581PMC
February 2020

Ultrafast processes triggered by one- and two-photon excitation of a photochromic and luminescent hydrazone.

Beilstein J Org Chem 2019 15;15:2438-2446. Epub 2019 Oct 15.

LENS - European Laboratory for Non-linear Spectroscopy, via N. Carrara 1, 50019 Sesto Fiorentino (FI), Italy.

In this work we apply a combination of steady state and time resolved luminescence and absorption spectroscopies to investigate the excited-state dynamics of a recently developed molecular photoswitch, belonging to the hydrazone family. The outstanding properties of this molecule, involving fluorescence toggling, bistability, high isomerization quantum yield and non-negligible two-photon absorption cross section, make it very promising for numerous applications. Here we show that the light induced isomerization occurs on a fast <1 ps timescale in both toluene and acetonitrile, while the excited state lifetime of the -form depends on solvent polarity, suggesting a partial charge transfer nature of its low lying excited state. Time-resolved luminescence measurements evidence the presence of a main emission component in the 500-520 nm spectral range, attributed to the isomer, and a very short living blue-shifted emission, attributed to the isomer. Finally, transient absorption measurements performed upon far-red excitation are employed as an alternative method to determine the two-photon absorption cross-section of the molecule.
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http://dx.doi.org/10.3762/bjoc.15.236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808199PMC
October 2019

Solution Phase and Surface Photoisomerization of a Hydrazone Switch with a Long Thermal Half-Life.

J Am Chem Soc 2019 11 24;141(44):17637-17645. Epub 2019 Oct 24.

Department of Chemistry and Applied Biosciences , ETH Zurich , Vladimir-Prelog-Weg 3 , Zurich CH 8093 , Switzerland.

Photoswitches can be employed for various purposes, with the half-life being a crucial parameter to optimize for the desired application. The switching of a photochromic hydrazone functionalized with a C6 alkyl thiolate spacer (C6 HAT) was characterized on a number of metal surfaces. C6 HAT exhibits a half-life of 789 years in solution. Tip-enhanced Raman spectroscopy (TERS) was used to study the photoisomerization of the C6 HAT self-assembled monolayers (SAMs) on Au, Ag, and Cu surfaces. The unique spectroscopic signature of the isomer at 1580 and 1730 cm in TER spectra allowed for its discrimination from the isomer. It was found that C6 HAT switches on Au and Cu surfaces when irradiated with 415 nm; however, it cannot isomerize on Ag surfaces, unless higher energy light is used. Based on this finding, and supported by density functional theory calculations, we propose a substrate-mediated photoisomerization mechanism to explain the behavior of C6 HAT on these different metal surfaces. This insight into the hydrazone's switching mechanism on metal surfaces will contribute to the further exploitation of this new family photochromic compounds on metal surfaces. Finally, although we found that the thermal isomerization rate of C6 HAT drastically increases on metal surfaces, the thermal half-life is still 6.9 days on gold, which is longer than that of the majority of azobenzene-based systems.
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http://dx.doi.org/10.1021/jacs.9b07057DOI Listing
November 2019

Serotonin receptor inhibitor is associated with falls independent of frailty in older adults.

Aging Ment Health 2021 02 11;25(2):219-224. Epub 2019 Oct 11.

Medical Investigation Laboratory on Ageing (LIM66), Division of Geriatrics, Department of Internal Medicine, University of São Paulo Medical School, São Paulo, Brazil.

Objectives: To evaluate whether fall risk in older adults is associated with the use of selective serotonin receptor inhibitor (SSRI) monotherapy among geriatric outpatients, and whether this association is moderated by the presence of depressive disorder and/or frailty.

Methods: Prospective cohort study with a 12-month follow-up and including 811 community-dwelling adults aged 60 or older from a university-based Geriatric Outpatient Unit. Major depressive disorder (MDD) was diagnosed according to DSM-5 criteria; subsyndromal depression as not meeting MDD criteria, but a Geriatric Depression Scale 15-item score ≥ 6 points. Frailty was evaluated with the FRAIL questionnaire. The association between SSRI use, depression, or both as well as the association between SSRI use, frailty, or both with falls were estimated through a generalized estimating equation (GEE) adjusted for relevant confounders.

Results: At baseline, 297 patients (36.6%) used a SSRI (82 without remitted depression) and 306 (37.7%) were classified as physically frail. Frailty was more prevalent among SSRI users (44.8% versus 33.7%, =.004). After 12 months, 179 participants had at least one fall (22.1%). SSRI use, depression as well as frailty were all independently associated with falls during follow-up. Nonetheless, patients with concurrent of SSRI usage and non-remitted depression had no higher risk compared to either remitted SSRI users or depressed patients without SSRIs. In contrast, concurrence of SSRI use and frailty increases the risk of falling substantially above those by SSRI usage or frailty alone.

Conclusion: SSRI usage was independently associated with falls. Especially in frail-depressed patients, treatment strategies for depression other than SSRIs should be considered.
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http://dx.doi.org/10.1080/13607863.2019.1675143DOI Listing
February 2021
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