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.

Frailty identification and management among Brazilian healthcare professionals: a survey.

BACKGROUND: National and international guidelines on frailty assessment and management recommend frailty screening in older people. This study aimed to determine how Brazilian healthcare professionals (HCPs) identify and manage frailty in practice. METHODS: An anonymous online survey on the assessment and management of frailty was circulated virtually through HCPs across Brazil. RESULTS: Most of the respondants used non-specific criteria such as gait speed (45%), handgrip strength (37.6%), and comprehensive geriatric assessment (33.2%). The use of frailty-specific criteria was lower than 50%. The most frequently used criteria were the Frailty Index (19.1%), Frailty Phenotype (13.2%), and FRAIL (12.5%). Only 43.5% felt confident, and 40% had a plan to manage frailty. In the multivariate-adjusted models, training was the most crucial factor associated with assessing frailty, confidence, and having a management plan (p < 0.001 for all). Those with fewer years of experience were more likely to evaluate frailty (p = 0.009). Being a doctor increased the chance of using a specific tool; the opposite was true for dietitians (p = 0.03). Those who assisted more older people had a higher likelihood of having a plan (p = 0.011). CONCLUSION: Frailty assessment was heterogeneous among healthcare professions groups, predominantly using non-specific criteria. Training contributed to frailty assessment, use of specific criteria, confidence, and having a management plan. This data informs the need for standardized screening criteria and management plans for frailty, in association with increasing training at the national level for all the HCPs who assist older people.

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.

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.

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.

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.

Photon Energy Storage in Strained Cyclic Hydrazones: Emerging Molecular Solar Thermal Energy Storage Compounds.

The generally small Gibbs free energy difference between the Z and E isomers of hydrazone photoswitches has so far precluded their use in photon energy storing applications. Here, we report on a series of cyclic and acyclic hydrazones, which possess varied degrees of ring strain and, hence, stability of E isomers. The photoinduced isomerization and concurrent phase transition of the cyclic hydrazones from a crystalline to a liquid phase result in the storage of a large quantity of energy, comparable to that of azobenzene derivatives. We demonstrate that the macrocyclic photochrome design in combination with phase transition is a promising strategy for molecular solar thermal energy storage applications.

The long-term course of cognition in bipolar disorder: a systematic review and meta-analysis of patient-control differences in test-score changes.

Neuropsychological impairment represents a key aspect of bipolar disorder (BD) that is evident even in early-course patients and is a strong predictor of functional outcomes among those affected. Previous meta-analyses of longitudinal studies suggest that BD-related cognitive deficits may not progress along the course of the disorder. However, short test-retest periods were used in most primary studies and comparisons with healthy controls were limited. The aim of this review was to synthesize the findings of research reports comparing long-term neurocognitive trajectories between BD patients and healthy individuals. PubMed, PsycINFO, and Scopus databases were searched from inception through July 2021. Publications were considered for inclusion if they reported cognitive test scores of BD patients and healthy controls at two different time points, with a minimum test-retest interval of 5 years. Fifteen studies compared the long-term course of cognition in BD patients with that of healthy controls. Ten of these were included in the quantitative analysis and involved 540 BD patients and 644 healthy individuals (mean follow-up period: 8.9 years). Patient-control effect sizes (standardized mean differences) were calculated for test-score changes in 24 neuropsychological variables and combined by means of meta-analytic procedures. No significant differences were found between patients and controls regarding long-term cognitive outcomes. These findings are consistent with previous shorter-term longitudinal meta-analyses and do not provide evidence for progressive cognitive deterioration in most bipolar individuals. Future studies should address the longitudinal course of cognition in different subgroups of BD patients and its prognostic and therapeutic value.

Frailty in geriatric psychiatry inpatients: a retrospective cohort study.

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.

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

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 (n = 30), remitted depression (n = 43) and healthy controls (n = 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.

Number of ideas in spontaneous speech predicts cognitive impairment and frailty in community-dwelling older adults nine years later.

OBJECTIVE: To investigate the associations between linguistic parameters in spontaneous speech at baseline and cognitive impairment and frailty nine years later. METHODS: A prospective analysis was carried out on data of the Frailty in Brazilian Older People Study (FIBRA) Study, a population-based study on frailty. From a probabilistic sample of 384 individuals aged 65 and older at baseline (2008-2009), 124 aged 73 years and older at follow-up were selected, as they had scored above the cutoff values of cognitive screening for dementia adjusted by years of schooling at baseline and had answered to the question What is healthy aging and had no frailty at baseline. Verbal responses were submitted to content analysis and had its ideas and words counted. Number of ideas corresponded to the frequency of meaning categories and number of words to all identified significant textual elements in the text constituted by the sample answers to that question. RESULTS: Multivariate logistic regression analyses, controlling for the effects of age, sex, and education, showed that individuals with a high number of ideas at baseline had lower chance of having cognitive impairment (OR = 0.39; 95% CI 0.22 - 0.69) and frailty (OR 0.66; 95% CI 0.44 - 0.99) nine years later than those with low number of ideas. CONCLUSIONS: Higher number of ideas, but not number of words, in spontaneous speech seems to be associated to a more positive prognosis in mental and physical health nine years later. Linguistic markers may be used to predict cognitive impairment and frailty in older individuals.

Fundamental studies to emerging applications of pyrrole-BF2 (BOPHY) fluorophores.

BF2-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 BF2-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.

Multistage Reversible Tg Photomodulation and Hardening of Hydrazone-Containing Polymers.

The glass transition temperature (Tg) of a series of polyacrylate- and polymethacrylate-based polymers having bistable hydrazone photoswitches as pendants increases upon photoisomerization. The ensuing photohardening of the polymeric network was corroborated using nanoindentation measurements. The bistability of the switch allowed us to lock-in and sustain multiple Tg values in the same polymeric material as a function of the hydrazone switch's Z/E isomer ratio, even at elevated temperatures.

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

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.

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

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 (HRFI  = 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 (HRFI  = 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.

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.

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/ .

New molecular switch architectures.

In this paper we elaborate on recently developed molecular switch architectures and how these new systems can help with the realization of new functions and advancement of artificial molecular machines. Progress in chemically and photoinduced switches and motors is summarized and contextualized such that the reader may gain an appreciation for the novel tools that have come about in the past decade. Many of these systems offer distinct advantages over commonly employed switches, including improved fidelity, addressability, and robustness. Thus, this paper serves as a jumping-off point for researchers seeking new switching motifs for specific applications, or ones that address the limitations of presently available systems.

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

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%, p =.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.

Depression as a determinant of frailty in late life.

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.

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

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.