Resting metabolic rate in relation to incident disability and mobility decline among older adults: the modifying role of frailty.

BACKGROUND: Alterations in resting metabolic rate (RMR), the largest component of daily total energy expenditure, with aging have been shown in various studies. However, little is known about the associations between RMR and health outcomes in later life. AIMS: To analyze whether RMR is associated with incident disability and mobility decline in a 10-year longitudinal study, as well as the moderating role of frailty in these associations. METHODS: Data from 298 older adults aged 70 and over from the Frailty and Dependence in Albacete (FRADEA) study in Spain were used, including a baseline measurement in 2007-2009 and a follow-up measurement 10 years later. RMR was measured by indirect calorimetry. Outcomes were incident disability in basic activities of daily living (BADL, Barthel Index), incident disability in instrumental ADL (IADL, Lawton index), and mobility decline (Functional Ambulation Categories scores). Fried's frailty phenotype was used as an indicator of frailty. Logistic regression analyses were conducted. RESULTS: Fully adjusted and stratified analyses revealed that only in the pre-frail/frail group, a higher RMR was associated with a lower risk of incident BADL disability (OR = 0.47, 95% CI = 0.23-0.96, p = 0.037), incident IADL disability (OR = 0.39, 95% CI = 0.18-0.84, p = 0.017), and mobility decline (OR = 0.30, 95% CI = 0.14-0.64, p = 0.002). CONCLUSIONS: To our knowledge, this is the first study looking at the associations between RMR and functional health using a longitudinal research design. The results suggest that RMR could be used as an early identifier of a specific resilient group within the pre-frail and frail older population, with a lower risk of further health decline.

Psychological and Functional Impact of COVID-19 in Long-Term Care Facilities: The COVID-A Study.

OBJECTIVE: To analyze the psychological and functional sequelae of the COVID-19 pandemic among older adults living in long term care facilities (LTCFs). DESIGN: Cohort longitudinal study SETTING ANT PARTICIPANTS: A total of 215 residents ≥ 65 years without moderate-to-severe cognitive impairment, living in five LTCFs in Albacete (Spain). MEASUREMENTS: Baseline on-site data were collected between March - June 2020 and three-month follow-up between June to September 2020. Symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), and sleep disturbances were measured as psychological variables. Disability in basic activities of daily living (BADL), ambulation and frailty were assessed as functional variables. Differences were analyzed in relation to level of comorbidity and test positivity for COVID-19. RESULTS: At baseline, residents with COVID-19 presented worse functionality, higher frailty levels and malnutrition risk compared to non-COVID-19 residents. At three-month follow-up, higher rates of clinically significant depressive symptoms (57.7%), anxiety symptoms (29.3%), PTSD symptoms (19.1%) and sleep disturbances (93.0%) were found among residents regardless of COVID status. Thus, among 215 residents, 101 (47%) experienced a decline in BADL from baseline to the 3-month follow-up (median functional loss = 5 points in Barthel Index). In multivariate analyses, COVID-19 status did not explain either the functional or the ambulation loss. By contrast, residents with low comorbidity and COVID-19 presented higher PTSD symptoms (effect 2.58; 95% CI 0.93 to 4.23) and anxiety symptoms (effect 2.10; 95% CI 0.48 to 3.73) compared to the low comorbidity/non-COVID19 group. CONCLUSION: COVID-19 pandemic was associated, after three-months, with high psychological impact in older adults in LTCFs., specifically with higher post-traumatic stress and anxiety symptoms. Functional decline did not differ in relation to COVID-19 status but could be related to isolation strategies used for pandemic control.

Energy Deposition around Swift Carbon-Ion Tracks in Liquid Water.

Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion's path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion's path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak.

Frailty, depression risk and 10-year hospitalization in older adults. The FRADEA study.

OBJECTIVES: To determine whether the interaction between frailty status and depression risk is associated with hospitalization density in older adults. METHODS: Ongoing cohort study in 794 subjects aged over 70 years from Albacete (Spain). Data were collected on depression risk, frailty, hospitalizations, and covariates. Participants were categorized into six groups. RESULTS: Adjusted hospitalization risk was higher for groups of prefrail/-non depression risk (HR 1.48; 95% confidence interval (CI) 1.16-1.89), prefrail/depression risk (HR 1.73; 95% CI 1.29-2.30), frail/non depression risk (HR 1.79; 95% CI 1.22-2.62), and frail/depression risk (HR 2.12; 95% CI 1.49-3.02), compared with robust/non depression risk group (p<0.01). Frail and prefrail groups presented increased hospitalization density in the first four follow-up years. CONCLUSIONS: Depression risk changes the yearly probabilities of hospitalization in prefrail and frail groups, increasing them in the first years. Depression risk should be monitored in prefrail and frail older adults as an independent risk factor for hospitalization.

Excitation and ionisation cross-sections in condensed-phase biomaterials by electrons down to very low energy: application to liquid water and genetic building blocks.

Electronic excitations and ionisations produced by electron impact are key processes in the radiation-induced damage mechanisms in materials of biological relevance, underlying important medical and technological applications, including radiotherapy, radiation protection in manned space missions and nanodevice fabrication techniques. However, experimentally measuring all the necessary electronic interaction cross-sections for every relevant material is an arduous task, so it is necessary having predictive models, sufficiently accurate yet easily implementable. In this work we present a model, based on the dielectric formalism, to provide reliable ionisation and excitation cross-sections for electron-impact on complex biomolecular media, considering their condensed-phase nature. We account for the indistinguishability and exchange between the primary beam and excited electrons, for the molecular electronic structure effects in the electron binding, as well as for low-energy corrections to the first Born approximation. The resulting approach yields total ionisation cross-sections, energy distributions of secondary electrons, and total electronic excitation cross-sections for condensed-phase biomaterials, once the electronic excitation spectrum is known, either from experiments or from a predictive model. The results of this methodology are compared with the available experimental data in water and DNA/RNA molecular building blocks, showing a very good agreement and a great predictive power in a wide range of electron incident energies, from the large values characteristic of electron beams down to excitation threshold. The proposed model constitutes a very useful procedure for computing the electronic interaction cross-sections for arbitrary biological materials in a wide range of electron incident energies.

Electronic excitation spectra of cerium oxides: from ab initio dielectric response functions to Monte Carlo electron transport simulations.

Nanomaterials made of cerium oxides CeO2 and Ce2O3 have a broad range of applications, from catalysts in automotive, industrial or energy operations to promising materials to enhance hadrontherapy effectiveness in oncological treatments. To elucidate the physico-chemical mechanisms involved in these processes, it is of paramount importance to know the electronic excitation spectra of these oxides, which are obtained here through high-accuracy linear-response time-dependent density functional theory calculations. In particular, the macroscopic dielectric response functions  of both bulk CeO2 and Ce2O3 are derived, which compare remarkably well with the available experimental data. These results stress the importance of appropriately accounting for local field effects to model the dielectric function of metal oxides. Furthermore, we reckon the energy loss functions Im(-1/) of the materials, including the accurate evaluation of the momentum transfer dispersion from first-principles calculations. In this respect, by using Mermin-type parametrization we are able to model the contribution of different electronic excitations to the dielectric loss function. Finally, from the knowledge of the electron inelastic mean free path, together with the elastic mean free path provided by the relativistic Mott theory, we carry out statistical Monte Carlo (MC) electron transport simulations to reproduce the major features of the reported experimental reflection electron energy loss (REEL) spectra of cerium oxides. The good agreement with REEL experimental data strongly supports our approach based on MC modelling, whose main inputs were obtained using ab initio calculated electronic excitation spectra in a broad range of momentum and energy transfers.

Angular and energy distributions of electrons produced in arbitrary biomaterials by proton impact.

We present a simple method for obtaining reliable angular and energy distributions of electrons ejected from arbitrary condensed biomaterials by proton impact. Relying on a suitable description of the electronic excitation spectrum and a physically motivated relation between the ion and electron scattering angles, it yields cross sections in rather good agreement with experimental data in a broad range of ejection angles and energies, by only using as input the target composition and density. The versatility and simplicity of the method, which can be also extended to other charged particles, make it especially suited for obtaining ionization data for any complex biomaterial present in realistic cellular environments.

Simulation of depth-dose curves and water equivalent ratios of energetic proton beams in cortical bone.

We have determined the depth-dose curve, penetration range, and water equivalent ratio for proton beams of clinical energies in cortical bone by means of a detailed and accurate simulation that combines molecular dynamics and Monte Carlo techniques. The fundamental input quantities (stopping power and energy loss straggling) for the simulation were obtained from a reliable electronic excitation spectrum of the condensed-phase target, which takes into account the organic and mineral phases that form it. Our simulations with these inputs, which are in excellent agreement with the scarce data available for a cortical bone target, deviate from simulations performed using other stopping quantities, such as those provided by the International Commission on Radiation Units and Measurements in its widely used Report No. 49 [M. J. Berger et al., Stopping powers and ranges for protons and alpha particles, International Commission on Radiation Units and Measurements, Bethesda, Maryland, 1993]. The results of this paper emphasize the importance of an accurate determination of the stopping quantities of cortical bone to advance towards the millimetric precision for the proton penetration ranges and deposited dose needed in radiotherapy.

A 12-week multicomponent exercise program enhances frailty by increasing robustness, improves physical performance, and preserves muscle mass in older adults with HIV: MOVIhNG study.

Background: Our aim was to analyze the effects of a multicomponent exercise program (MEP) on frailty and physical performance in older adults with HIV (OAWH) since exercise can reverse frailty in the older population overall, but there is no data for OAWH. Methods: A prospective longitudinal study with intervention and control group was designed. Sedentary adults 50 or over with and without HIV were included. The intervention was a 12-week home-based MEP. Dependent variables were frailty (frailty phenotype), physical performance (Senior Fitness Test), muscle mass (ASMI) by bioimpedance. Pre- and postintervention measurements were analyzed using McNemar's test for categorical variables and the Wilcoxon signed-rank test for quantitative variables. Results: 40 OAWH and 20 OA without HIV. The median age was 56.5 years. 23.3% were women. The prevalence of frailty was 6.6% with no frail HIV-negative participants. Three of the four frail HIV-participants transitioned two (50%) from frail to prefrail and one (25%) to robust after the MEP. In participants with an adherence ≥50%, physical performance was significantly improved [basal vs. 12 week]: upper extremity strength [13 (13-15) vs. 16 (15-19), p = 0.0001], lower extremity strength [13 (11-16) vs. 15 (13-16), p = 0.004], aerobic endurance [62 (55-71) vs. 66 (58-80), p = 0.005]. Participants with low adherence experienced a significant worsening in ASMI [8.35 (7.44-9.26) vs. 7.09 (6.08-8.62), p = 0.03]. Conclusion: A 12-week MEP enhances frailty by increasing robustness in OAWH, and improves physical performance, and preserves muscle mass in older adults with good adherence to the MEP independently of HIV status.

Development of Continuous Assessment of Muscle Quality and Frailty in Older Patients Using Multiparametric Combinations of Ultrasound and Blood Biomarkers: Protocol for the ECOFRAIL Study.

BACKGROUND: Frailty resulting from the loss of muscle quality can potentially be delayed through early detection and physical exercise interventions. There is a demand for cost-effective tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessments. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional, and microstructural muscle properties, while biological assays derived from blood samples are associated with functional information. OBJECTIVE: This study aims to assess multiparametric combinations of ultrasound and blood-based biomarkers to offer a cross-sectional evaluation of the patient frailty phenotype and to track changes in muscle quality associated with supervised exercise programs. METHODS: This prospective observational multicenter study will include patients aged 70 years and older who are capable of providing informed consent. We aim to recruit 100 patients from hospital environments and 100 from primary care facilities. Each patient will undergo at least two examinations (baseline and follow-up), totaling a minimum of 400 examinations. In hospital environments, 50 patients will be measured before/after a 16-week individualized and supervised exercise program, while another 50 patients will be followed up after the same period without intervention. Primary care patients will undergo a 1-year follow-up evaluation. The primary objective is to compare cross-sectional evaluations of physical performance, functional capacity, body composition, and derived scales of sarcopenia and frailty with biomarker combinations obtained from muscle ultrasound and blood-based assays. We will analyze ultrasound raw data obtained with a point-of-care device, along with a set of biomarkers previously associated with frailty, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Additionally, we will examine the sensitivity of these biomarkers to detect short-term muscle quality changes and functional improvement after a supervised exercise intervention compared with usual care. RESULTS: At the time of manuscript submission, the enrollment of volunteers is ongoing. Recruitment started on March 1, 2022, and ends on June 30, 2024. CONCLUSIONS: The outlined study protocol will integrate portable technologies, using quantitative muscle ultrasound and blood biomarkers, to facilitate an objective cross-sectional assessment of muscle quality in both hospital and primary care settings. The primary objective is to generate data that can be used to explore associations between biomarker combinations and the cross-sectional clinical assessment of frailty and sarcopenia. Additionally, the study aims to investigate musculoskeletal changes following multicomponent physical exercise programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294757; https://clinicaltrials.gov/ct2/show/NCT05294757. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50325.

Semiempirical model for the ion impact ionization of complex biological media.

We present a semiempirical model for calculating the electron emission from any organic compound after ion impact. With only the input of the density and composition of the target we are able to evaluate its ionization cross sections using plausible approximations. Results for protons impacting in the most representative biological targets (such as water or DNA components) show a very good comparison with experimental data. Because of its simplicity and great predictive effectiveness, the method can be immediately extended to any combination of biological target and charged particle of interest in ion beam cancer therapy.

Limits of stability and falls during a multicomponent exercise program in faller older adults: A retrospective cohort study.

BACKGROUND/OBJETIVES: Multicomponent exercise programs have been demonstrated to prevent falls in older adults. However, the underlying responsible mechanisms are not clear. We aimed to analyze the association between changes in the limits of stability (LOS) as a relevant balance component, and falls occurrence during a multicomponent physical exercise program. METHODS: Retrospective study, including ninety-one participants who had experienced a fall in the previous year, and were attended in a falls unit. All of them were included in a twice-a-week multicomponent exercise program during 16 weeks. Pre- and post-program measurements were collected for leg press, gait speed, the short physical performance battery (SPPB), and LOS (point of excursion [POE] and maximal excursion [MEX]) with posturography. Falls occurrence was assessed between the beginning and the completion of the exercise program (16 week). RESULTS: The mean age was 77.2 years, and 72 were female. Thirty-two participants fell at least once during the exercise period. The global baseline POE was 47.6 %, and the MEX was 64.7 %, and there were no differences between fallers and nonfallers. Nonfallers presented greater improvements in POE (6.3 % versus 1.3 %; p < .05) and MEX (9.2 % versus 3.0 %; p < .01) than fallers. The POE and MEX were independently associated with a reduced probability of having had a fall, OR: 0.95 (95 % CI: 0.91 to 0.99) and 0.94 (95 % CI: 0.90 to 0.99), respectively. Changes in SPPB results or leg press strength were not associated with decreased falls. Adjusted probability of fall occurrence decreased by 5 % and 6 % per 1 % improvement in absolute values in POE and MEX, respectively. CONCLUSIONS: Improvements in LOS after a multicomponent physical exercise program in older adults with previous falls may be associated with a decreased occurrence of falls.

Relative Role of Physical Mechanisms on Complex Biodamage Induced by Carbon Irradiation.

The effective use of swift ion beams in cancer treatment (known as hadrontherapy) as well as appropriate protection in manned space missions rely on the accurate understanding of the energy delivery to cells that damages their genetic information. The key ingredient characterizing the response of a medium to the perturbation induced by charged particles is its electronic excitation spectrum. By using linear-response time-dependent density functional theory, we obtained the energy and momentum transfer excitation spectrum (the energy-loss function, ELF) of liquid water (the main constituent of biological tissues), which was in excellent agreement with experimental data. The inelastic scattering cross sections obtained from this ELF, together with the elastic scattering cross sections derived by considering the condensed phase nature of the medium, were used to perform accurate Monte Carlo simulations of the energy deposited by swift carbon ions in liquid water and carried away by the generated secondary electrons, producing inelastic events such as ionization, excitation, and dissociative electron attachment (DEA). The latter are strongly correlated with cellular death, which is scored in sensitive volumes with the size of two DNA convolutions. The sizes of the clusters of damaging events for a wide range of carbon-ion energies, from those relevant to hadrontherapy up to those for cosmic radiation, predict with unprecedented statistical accuracy the nature and relative magnitude of the main inelastic processes contributing to radiation biodamage, confirming that ionization accounts for the vast majority of complex damage. DEA, typically regarded as a very relevant biodamage mechanism, surprisingly plays a minor role in carbon-ion induced clusters of harmful events.

[Frailty prevalence in hospitalized older adults. A systematic review.] / Prevalencia de fragilidad en adultos mayores hospitalizados. Revisión sistemática.

BACKGROUND: Theres is uncertain evidence regarding the prevalence, measurement tools, outcomes, and efficacy of the interventions on frailty in hospitalized older adults. For this reason, we present the results of a systematic review about Frailty and Hospital, following the PRISMA methodology. METHODS: We found 2,050 articles published in PubMed. After an initial assessment of titles and abstracts, complete comprehensive text lecture, and meta-analysis review, we finally included in the systematic review 246 originals. RESULTS: The main result of the systematic review is that from the 246 articles, 179 described frailty prevalence in hospital older adults, with a pooled prevalence of 41.4% (95% CI 38.4% to 44.4%; range 4.7% to 92.5%). The most frequent type of studies were those observational prospectives 166 (67.5%), being the rest observtcional retrospectives or cross-sectional 64 (26.2%) or randomized clinical trials 15 (6.1%). The most frequent healthcare levels where the studies took place were the Hospital/Hospitalization in 125 (50.8%), Geriatric Department in 41 (16.7%), Surgical Units in 23 (9.3%), Cardiology Department in 18 (7.3%), Emergency Department in 15 (6.1%), and other in 24 (9.8%). The most frequent used measurement tolos were the Clinical Frailty Scale in 69 works (28%), the frailty phenotype in 41 (15.9%), the Frailty Index in 39 (15.9%) and the FRAIL scale in 27 (11.0%). In several papers, more than one instrument was used, and in many of them, scales and cut-off points were arbitrarely determined, producing a great results heterogeneity. CONCLUSIONS: The prevalence of frailty in hospitalized older adults is very high. It is necessary to improve frailty measure homogenity and to realize randomized clinical trials in this population.

OBJETIVO: Existe escasa evidencia sobre la prevalencia, herramientas de medición, resultados de salud y eficacia de las intervenciones sobre la fragilidad en adultos mayores en medio hospitalario. Por ello, presentamos los resultados de una revisión sistemática de la Fragilidad en adultos mayores en medio hospitalario, siguiendo la metodología de la declaración PRISMA. METODOS: Se encontraron 2.050 artículos en PubMed. Tras la valoración inicial de los títulos y resúmenes, lectura de texto completo y revisión de los meta-análisis, al final se incluyeron en la revisión sistemática 246 originales. RESULTADOS: El principal resultado fue que, de los 246 originales revisados, 179 describían la prevalencia de fragilidad en adultos mayores en el hospital, siendo el porcentaje combinado del 41,4% (IC 95% 38,4% a 44,4%; rango 4,7% a 92,5%). Por tipo de estudios predominaron los observacionales prospectivos 166 (67,5%), observacionales retrospectivos o transversales 64 (26,2%) y ensayos clínicos 15 (6,1%). Los dispositivos asistenciales más frecuentes fueron el Hospital en general/Hospitalización 125 (50,8%), Geriatría 41 (16,7%), Unidades quirúrgicas 23 (9,3%), Cardiología 18 (7,3%), Urgencias/emergencias 15 (6,1%) y otros dispositivos médicos 24 (9,8%). Las herramientas de valoración de la fragilidad más empleadas fueron la Clinical Frailty Scale en 69 artículos (28%), fenotipo de fragilidad en 41 (16,7%), Frailty Index en 39 (15,9%) y herramienta FRAIL en 27 (11,0%). En varios artículos se emplearon dos o más de las herramientas descritas, y en muchos, las escalas y los puntos de corte fueron arbitrariamente modificados por los autores, generando una gran heterogeneidad en los resultados. CONCLUSIONES: La prevalencia de fragilidad en adultos mayores en el hospital es muy alta, pero es necesaria una mayor uniformidad en su medición y la implementación de ensayos clínicos para evaluar intervenciones.

JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality.

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.

Multiscale simulation of the focused electron beam induced deposition process.

Focused electron beam induced deposition (FEBID) is a powerful technique for 3D-printing of complex nanodevices. However, for resolutions below 10 nm, it struggles to control size, morphology and composition of the structures, due to a lack of molecular-level understanding of the underlying irradiation-driven chemistry (IDC). Computational modeling is a tool to comprehend and further optimize FEBID-related technologies. Here we utilize a novel multiscale methodology which couples Monte Carlo simulations for radiation transport with irradiation-driven molecular dynamics for simulating IDC with atomistic resolution. Through an in depth analysis of [Formula: see text] deposition on [Formula: see text] and its subsequent irradiation with electrons, we provide a comprehensive description of the FEBID process and its intrinsic operation. Our analysis reveals that simulations deliver unprecedented results in modeling the FEBID process, demonstrating an excellent agreement with available experimental data of the simulated nanomaterial composition, microstructure and growth rate as a function of the primary beam parameters. The generality of the methodology provides a powerful tool to study versatile problems where IDC and multiscale phenomena play an essential role.

Gait plasticity impairment as an early frailty biomarker.

BACKGROUND/OBJECTIVES: To assess whether gait plasticity and gait reserve, valid measures of gait adaptation to environmental stressors, are associated with frailty. DESIGN: Cross-sectional sub-analysis of the FISTAC study (Identification of the Physical Attributes of the Fear of Falling Syndrome). SETTING: Community-dwelling women from the Falls Unit of a Geriatrics Department. PARTICIPANTS: One hundred and twenty-nine women with an age ≥ 70 years old and presence of at least one previous fall in the last year. MEASURES: Age, comorbidity, nutritional status, cognitive status, depression, medications, disability, fear of falling, physical function, hand grip strength, 1RM leg-press strength, maximum and mean leg-press power were determined. Frailty was assessed using the frailty phenotype criteria. Gait plasticity parameters were measured by walking at normal pace, fast pace, and slow pace, and mean (left and right) stride velocity and stride variability (SD) for the three walks were determined independently and for the sum of the three walks. Gait reserve was calculated as the difference in stride velocity from normal to fast pace. ROC curves were constructed to determine the best association between gait plasticity parameters and frailty. RESULTS: The mean age of the participants was 79 years (SD 8.0). The median of normal, fast, slow and three-walks pace stride velocity were 68.9 cm/s (interquartile range [IQR 33.8]), 96.1 cm/s (IQR 38.3), 51.6 cm/s (IQR 19.8), and 72.7 cm/s (IQR 20.7) respectively. The median of normal, fast, slow and three-walks pace stride variability were 4.5 cm/s (IQR 3.3), 5.4 cm/s (IQR 3.8), 3.6 cm/s (IQR 2.3) and 15.9 cm/s (IQR 16.5) respectively. The median of gait reserve was 23 cm/s (IQR 46). Gait reserve and fast pace stride velocity were associated not only with frailty, but also with a lower age, disability, depression, physical function, muscle strength and power, and fear of falling, more than gait velocity. Areas under the curve (95% CI) for gait parameters with stronger association with frailty were fast pace stride velocity 0.801 (0.723-0.880), three-walk mean stride velocity 0.761 (0.678-0.845), three-walks stride variability 0.724 (0.635-0.81) and gait reserve 0.727 (0.635-0.818). CONCLUSIONS: Lower gait reserve and lower gait plasticity have a stronger association with frailty than gait speed in older women. Our results may support the use of these gait parameters to early identify frailty in community-dwelling older women.

COVID-19 outbreak in long-term care facilities from Spain. Many lessons to learn.

BACKGROUND/OBJECTIVES: To analyze mortality, costs, residents and personnel characteristics, in six long-term care facilities (LTCF) during the outbreak of COVID-19 in Spain. DESIGN: Epidemiological study. SETTING: Six open LTCFs in Albacete (Spain). PARTICIPANTS: 198 residents and 190 workers from LTCF A were included, between 2020 March 6 and April 5. Epidemiological data were also collected from six LTCFs of Albacete for the same period of time, including 1,084 residents. MEASUREMENTS: Baseline demographic, clinical, functional, cognitive and nutritional variables were collected. 1-month and 3-month mortality was determined, excess mortality was calculated, and costs associated with the pandemics were analyzed. RESULTS: The pooled mortality rate for the first month and first three months of the outbreak were 15.3% and 28.0%, and the pooled excess mortality for these periods were 564% and 315% respectively. In facility A, the percentage of probable COVID-19 infected residents were 33.6%. Probable infected patients were older, frail, and with a worse functional situation than those without COVID-19. The most common symptoms were fever, cough and dyspnea. 25 residents were transferred to the emergency department, 21 were hospitalized, and 54 were moved to the facility medical unit. Mortality was higher upon male older residents, with worse functionality, and higher comorbidity. During the first month of the outbreak, 65 (24.6%) workers leaved, mainly with COVID-19 symptoms, and 69 new workers were contracted. The mean number of days of leave was 19.2. Costs associated with the COVID-19 in facility A were estimated at € 276,281/month, mostly caused by resident hospitalizations, leaves of workers, staff replacement, and interventions of healthcare professionals. CONCLUSION: The COVID-19 pandemic posed residents at high mortality risk, mainly in those older, frail and with worse functional status. Personal and economic costs were high.

Energy Spectra of Protons and Generated Secondary Electrons around the Bragg Peak in Materials of Interest in Proton Therapy.

The number and energy of secondary electrons generated around the trajectories of swift protons interacting with biological materials are highly relevant in proton therapy, due to the prominent role of low-energy electrons in the production of biodamage. For a given material, electron energy distributions are determined by the proton energy; and it is imperative that the distribution of proton energy at depths around the Bragg peak region be described as accurately as possible. With this objective, we simulated the energy distributions of proton beams of clinically relevant energies (50-300 MeV) at depths around the Bragg peak in liquid water and the water-equivalent polymer poly(methyl methacrylate) (PMMA). By using a simple model, this simulation has been conveniently extended to account for nuclear fragmentation reactions, providing depth-dose curves in excellent agreement with available experimental data. Special care has been taken to describe the electronic excitation spectrum of the target, taking into account its condensed phase nature. A predictive formula has been obtained for the mean value and the width of the proton energy distribution at the Bragg peak depth, quantities which are found to grow linearly with the initial energy of the beam, in good agreement with available data. To accurately characterize (in number and energy) the electrons generated around the proton paths, the energy distributions of the latter at each depth have been convoluted with the energy-dependent ionization inverse mean free paths. This results in a number of low-energy electrons around the Bragg peak larger than when only the proton beam average energy at the given depths is considered. The convoluted ionization inverse mean free path closely resembles the Bragg curve shape. The average energy of the secondary electrons is nearly constant (∼55 eV for liquid water and ∼43 eV for PMMA) in the plateau of the Bragg curve, independent of the proton incident energy and suddenly decaying once the Bragg peak is reached. These findings highlight the importance of a precise calculation of the proton beam energy distribution as a function of the target depth to reliably characterize the secondary electrons generated around the Bragg peak region.

Benefits of a multicomponent Falls Unit-based exercise program in older adults with falls in real life.

BACKGROUND/OBJECTIVES: Multicomponent exercise programs are the cornerstone in preventing gait and balance impairments and falls in older adults. However, the effects of these programs in usual clinical practice have been poorly analyzed. DESIGN: 4-Month, twice-a-week multicomponent exercise program cohort study in real-life. SETTING: Falls Unit, Complejo Hospitalario Universitario of Albacete, Spain. PARTICIPANTS: Sixty-seven participants who had experienced a fall in the previous year were included. MEASUREMENTS: Pre- and post-intervention measurements were collected for leg press, gait speed, the Short Physical Performance Battery (SPPB), the Falls Efficiency Scale International, fat mass percentage, body mass index, the Geriatric Depression Scale by Yesavage (GDS), the Mini Mental State Examination, and the number of falls. RESULTS: Fifty participants completed the program (adherence rate 75%, attendance 80%). Their mean age was 77.2 (SD 5.8) years; 39 were women. The participants reduced the mean number of frailty criteria from 2.1 to 1.3 (95%CI 0.4-1.1) and increased mean gait speed from 0.65 m/s to 0.82 m/s (95%CI 0.11-0.22), increasing their median SPPB scores from 8.5 to 10.0 points (p < 0.001), leg press strength from 62.5 kg to 80.0 kg (p < 0.001), and leg press power at 60% load from 76 W to 119 W (p < 0.001). There was also an improvement in GDS scores from 5.3 to 4.4 (95%CI 0.1-1.7). Body mass index did not change, but fat-free mass increased from 43.7 kg to 44.2 kg (95%CI 0.1-1.0), and fat mass percentage declined from 36.7% to 36.0% (95% CI 0.1-1.4). Seventeen patients (34%) had a fall during the six-month follow-up, and there was a reduction in the median number of falls from 3.0/year to 0.0/six months. CONCLUSIONS: A multicomponent Falls Unit-based exercise program as part of usual clinical practice in real life, improved physical function, reduced depressive symptoms, improved body composition and decreased the number of falls in older adults with previous falls.