[Epidemiological, clinical, and functional characteristics of patients older than 75 years admitted to a tertiary hospital during the first wave of the SARS-CoV-2 pandemic]. / Características epidemiológicas, clínicas y funcionales de los pacientes mayores de 75 años ingresados en un hospital terciario durante la primera ola pandémica por SARS-CoV-2.

BACKGROUND: The objective of the present study is to analyze the epidemiological, clinical and functional characteristics of patients admitted to the University Hospital of Navarra due to SARS-CoV-2 infection, as well as the predictors of mortality, during the first wave of the pandemic caused by this virus. METHODOLOGY: An observational, retrospective study was performed, including all hospitalized patients older than 75 years. Information has been obtained on multiple variables, among which it is worth mentioning previous geriatric syndromes or those that have appeared during hospitalization, or past medical history considered relevant in SARS-CoV-2 infection. A descriptive analysis of the data, comparisons according to various factors of interest and multivariate analysis to analyze factors associated with mortality were carried out. RESULTS: Data have been obtained from a total of 426 patients with a mean age of 83.2 years (52.6% men). 34.7% died in hospital and 4.5% within 1 month after hospital discharge. The factors related to mortality were: worse baseline functional status, chronic kidney disease, and fever or dyspnea as forms of presentation. The most frequent typical symptoms were: fever, dyspnea, cough, asthenia and hyporexia. Up to 42.1% presented delirium as a symptom of atypical onset. We observed a functional deterioration that was not recover after a month of follow-up (baseline Barthel index 81.12; 70.08 at discharge; 75.55 after a month). CONCLUSIONS: SARS-CoV-2 infection has caused high mortality rates in older adults. In this age group, the atypical presentation of this disease and functional deterioration during hospitalization are frequent. In the present study, a worse previous functional status has been identified as a predictor of mortality. More studies are needed to evaluate the impact that the disease and hospitalization have on the older patient, with the aim of implementing preventive, diagnostic and therapeutic measures that are necessary to avoid functional deterioration and adverse health events related to it.

Effects of a 12-week Vivifrail exercise program on intrinsic capacity among frail cognitively impaired community-dwelling older adults: secondary analysis of a multicentre randomised clinical trial.

INTRODUCTION: The World Health Organisation recently defined the construct of intrinsic capacity (IC), a function-based marker of older adult's health encompassing all mental and physical capacities of the individual. Multicomponent physical exercise (MCE) is a potential intervention capable to maintain/increase IC at older age; however, evidence is scarce on the effects of MCE on IC in cognitively impaired pre-frail/frail older adults. METHODS: Secondary analyses of a randomised clinical trial. One hundred and eighty-eight older outpatients (age = 84.06 ± 4.77, 70.2% women) presenting with pre-frailty/frailty (according to Fried Criteria) and mild cognitive impairment (MCI)/mild dementia were recruited in the Geriatric clinics of three tertiary hospitals in Spain. Subjects were randomised to participate in the 12-week home-based individualised Vivifrail MCE or usual care. An IC index was created based on the z-score of the locomotion (Short Physical Performance Battery), cognitive (Montreal Cognitive Assessment), psychology (15-item Geriatric Depression Scale Yesavage) and vitality (handgrip strength) domains. RESULTS: After the 3-month intervention, linear mixed models showed significant between-group differences in the evolution of the IC composite score (ß=0.48; 95% confidence interval [CI] = 0.24, 0.74; P < 0.001), IC Locomotion (ß = 0.42; 95% CI = 0.10, 0.74; P < 0.001), IC Cognition (ß = 0.45; 95% CI = 0.03, 0.87; P < 0.05) and IC Vitality domains (ß = 0.50; 95% CI = 0.25, 0.74 at 3-month) favouring the MCE group. CONCLUSIONS: The 12-week Vivifrail multicomponent exercise program is an effective strategy to enhance IC, especially in terms of locomotion, cognition and vitality IC domains in community-dwelling older adults with pre-frailty/frailty and MCI/mild dementia, compared to usual care.

Effect of a multicomponent exercise program and cognitive stimulation (VIVIFRAIL-COGN) on falls in frail community older persons with high risk of falls: study protocol for a randomized multicenter control trial.

BACKGROUND: Falls represent important drivers of intrinsic capacity losses, functional limitations and reduced quality of life in the growing older adult's population, especially among those presenting with frailty. Despite exercise- and cognitive training-based interventions have shown effectiveness for reducing fall rates, evidence around their putative cumulative effects on falls and fall-related complications (such as fractures, reduced quality of life and functional limitations) in frail individuals remains scarce. The main aim of this study is to explore the effectiveness program combining an individualized exercise program and an executive function-based cognitive training (VIVIFRAIL-COGN) compared to usual care in the prevention of falls and fall-related outcomes over a 1-year follow-up. METHODS: This study is designed as a four-center randomized clinical trial with a 12-week intervention period and an additional 1-year follow-up. Three hundred twenty frail or pre-frail (≥ 1 criteria of the Frailty Phenotype) older adults (≥ 75 years) with high risk of falling (defined by fall history and gait performance) will be recruited in the Falls Units of the participating centers. They will be randomized in a 1:1 ratio to the intervention group (IG) or the control group (CG). The IG will participate in a home-based intervention combining the individualized Vivifrail multicomponent (aerobic, resistance, gait and balance and flexibility) exercise program and a personalized executive function-based cognitive training (VIVIFRAIL-COGN). The CG group will receive usual care delivered in the Falls Units, including the Otago Exercise Program. Primary outcome will be the incidence of falls (event rate/year) and will be ascertained by self-report during three visits (at baseline, and 6 and 12 weeks) and telephone-based contacts at 6, 9 and 12 months after randomization. Secondarily, effects on measures of physical and cognitive function, quality of life, nutritional, muscle quality and psychological status will be evaluated. DISCUSSION: This trial will provide new evidence about the effectiveness of an individualized multidomain intervention by studying the effect of additive effects of cognitive training and physical exercise to prevent falls in older frail persons with high risk of falling. Compared to usual care, the combined intervention is expected to show additive effects in the reduction of the incidence of falls and associated adverse outcomes. TRIAL REGISTRATION: NCT04911179 02/06/2021.

Characterisation of the pathophysiology of neuropathy and sensory dysfunction in a mouse model of recessive dystrophic epidermolysis bullosa.

ABSTRACT: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic condition in which mutations in the type VII collagen gene ( COL7A1 ) lead to decreased expression of this anchoring protein of the skin, causing the loss of stability at the dermo-epidermal junction. Most patients with RDEB experience neuropathic pain and itch due to the development of a small fibre neuropathy, characterised by decreased intraepidermal innervation and thermal hypoaesthesia. To understand the physiopathology of this neuropathy, we used a mouse model of RDEB (Col7a1 flNeo/flNeo ) and performed a detailed characterisation of the somatosensory system. Col7a1 flNeo/flNeo mice showed a decrease in heat sensitivity, an increase in spontaneous scratching, and a significant decrease in intraepidermal nerve fibre density in the hindpaw; these changes were distal because there was no significant loss of unmyelinated or myelinated fibres in the nerve trunk. Of interest, we observed a decrease in axon diameter in both myelinated and unmyelinated fibres. This axonal damage was not associated with inflammation of the dorsal root ganglion or central projection targets at the time of assessment. These results suggest that in RDEB, there is a distal degeneration of axons produced by exclusive damage of small fibres in the epidermis, and in contrast with traumatic and acute neuropathies, it does not induce sustained neuroinflammation. Thus, this animal model emphasizes the importance of a healthy cutaneous environment for maintenance of epidermal innervation and faithfully replicates the pathology in humans, offering the opportunity to use this model in the development of treatments for pain for patients with RDEB.

Effects of Vivifrail multicomponent intervention on functional capacity: a multicentre, randomized controlled trial.

BACKGROUND: Physical exercise is an effective strategy for preserving functional capacity and improving the symptoms of frailty in older adults. In addition to functional gains, exercise is considered to be a cornerstone for enhancing cognitive function in frail older adults with cognitive impairment and dementia. We assessed the effects of the Vivifrail exercise intervention for functional capacity, cognition, and well-being status in community-dwelling older adults. METHODS: In a multicentre randomized controlled trial conducted in three tertiary hospitals in Spain, a total of 188 older patients with mild cognitive impairment or mild dementia (aged >75 years) were randomly assigned to an exercise intervention (n = 88) or a usual-care, control (n = 100) group. The intervention was based on the Vivifrail tailored multicomponent exercise programme, which included resistance, balance, flexibility (3 days/week), and gait-retraining exercises (5 days/week) and was performed for three consecutive months (http://vivifrail.com). The usual-care group received habitual outpatient care. The main endpoint was change in functional capacity from baseline to 1 and 3 months, assessed with the Short Physical Performance Battery (SPPB). Secondary endpoints were changes in cognitive function and handgrip strength after 1 and 3 months, and well-being status, falls, hospital admission rate, visits to the emergency department, and mortality after 3 months. RESULTS: The Vivifrail exercise programme provided significant benefits in functional capacity over usual-care. The mean adherence to the exercise sessions was 79% in the first month and 68% in the following 2 months. The intervention group showed a mean increase (over the control group) of 0.86 points on the SPPB scale (95% confidence interval [CI] 0.32, 1.41 points; P < 0.01) after 1 month of intervention and 1.40 points (95% CI 0.82, 1.98 points; P < 0.001) after 3 months. Participants in the usual-care group showed no significant benefit in functional capacity (mean change of -0.17 points [95% CI -0.54, 0.19 points] after 1 month and -0.33 points [95% CI -0.70, 0.04 points] after 3 months), whereas the exercise intervention reversed this trend (0.69 points [95% CI 0.29, 1.09 points] after 1 month and 1.07 points [95% CI 0.63, 1.51 points] after 3 months). Exercise group also obtained significant benefits in cognitive function, muscle function, and depression after 3 months over control group (P < 0.05). No between-group differences were obtained in other secondary endpoints (P > 0.05). CONCLUSIONS: The Vivifrail exercise training programme is an effective and safe therapy for improving functional capacity in community-dwelling frail/prefrail older patients with mild cognitive impairment or mild dementia and also seems to have beneficial effect on cognition, muscle function, and mood status.

Using BAMLET complex in a functional spreadable cheese elaborated with bovine colostrum.

BAMLET is a bioactive complex formed by the interaction between α-Lactoalbumin (α-LA) and oleic acid which exhibits cytotoxic activity against cancer cells. BAMLET is selectively cytotoxic to malignant cells while sparing the healthy ones. There are, however, no reports about its application in a food matrix. The objective of this work was to synthetize the BAMLET complex from oleic acid and bovine colostrum from the second and third milkings which naturally contain α-LA to prepare two functional spreadable cheeses. The complex was successfully formed and retained in the cheeses as verified through SDS-PAGE applied to the whey obtained. The spreadable cheese from the second milking had a higher protein content (13.56 ± 0.02%) and a higher yield (40%) than the product obtained from the third milking. Even though the cheeses did not show any significant differences (p > 0.05) in the inhibition of the angiotensin-converting enzyme 1, their inhibitory activities were good, as a 0.5 g portion of the cheese from the second milking was sufficient to inhibit 57.52 ± 9.17%, while the cheese from the third milking inhibited 51.48 ± 1.07% of the enzyme. The sensory analysis showed a good acceptance for both spreadable cheeses.

Effect of a multicomponent exercise programme (VIVIFRAIL) on functional capacity in frail community elders with cognitive decline: study protocol for a randomized multicentre control trial.

BACKGROUND: The benefit of physical exercise in ageing and particularly in frailty has been the aim of recent research. Moreover, physical activity in the elderly is associated with a decreased risk of mortality, of common chronic illnesses (i.e. cardiovascular disease or osteoarthritis) and of institutionalization as well as with a delay in functional decline. Additionally, very recent research has shown that, despite its limitations, physical exercise is associated with a reduced risk of dementia, Alzheimer disease or mild cognitive decline. Nevertheless, the effect of physical exercise as a systematic, structured and repetitive type of physical activity, in the reduction of risk of cognitive decline in the elderly, is not very clear. The purpose of this study aims to examine whether an innovative multicomponent exercise programme called VIVIFRAIL has benefits for functional and cognitive status among pre-frail/frail patients with mild cognitive impairment or dementia. METHODS/DESIGN: This study is a multicentre randomized clinical trial to be conducted in the outpatient geriatrics clinics of three tertiary hospitals in Spain. Altogether, 240 patients aged 75 years or older being capable of and willing to provide informed consent, with a Barthel Index ≥ 60 and mild cognitive impairment or mild dementia, pre-frail or frail and having someone to help to supervise them when conducting the exercises will be randomly assigned to the intervention or control group. Participants randomly assigned to the usual care group will receive normal outpatient care, including physical rehabilitation when needed. The VIVIFRAIL multicomponent exercise intervention programme consists of resistance training, gait re-training and balance training, which appear to be the best strategy for improving gait, balance and strength, as well as reducing the rate of falls in older individuals and consequently maintaining their functional capacity during ageing. The primary endpoint is the change in functional capacity, assessed with the Short Physical Performance Battery (1 point as clinically significant). Secondary endpoints are changes in cognitive and mood status, quality of life (EQ-5D), 6-m gait velocity and changes in gait parameters (i.e. gait velocity and gait variability) while performing a dual-task test (verbal and counting), handgrip, maximal strength and power of the lower limbs as well as Barthel Index of independence (5 points as clinically significant) at baseline and at the 1-month and 3-month follow-up. DISCUSSION: Frailty and cognitive impairment are two very common geriatric syndromes in elderly patients and are frequently related and overlapped. Functional decline and disability are major adverse outcomes of these conditions. Exercise is a potential intervention for both syndromes. If our hypothesis is correct, the relevance of this project is that the results can contribute to understanding that an individualized multicomponent exercise programme (VIVIFRAIL) for frail elderly patients with cognitive impairment is more effective in reducing functional and cognitive impairment than conventional care. Moreover, our study may be able to show that an innovative individualized multicomponent exercise prescription for these high-risk populations is plausible, having at least similar therapeutic effects to other pharmacological and medical prescriptions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03657940 . Registered on 5 September 2018.

Manganese (Mn) oxidation increases intracellular Mn in Pseudomonas putida GB-1.

Bacterial manganese (Mn) oxidation plays an important role in the global biogeochemical cycling of Mn and other compounds, and the diversity and prevalence of Mn oxidizers have been well established. Despite many hypotheses of why these bacteria may oxidize Mn, the physiological reasons remain elusive. Intracellular Mn levels were determined for Pseudomonas putida GB-1 grown in the presence or absence of Mn by inductively coupled plasma mass spectrometry (ICP-MS). Mn oxidizing wild type P. putida GB-1 had higher intracellular Mn than non Mn oxidizing mutants grown under the same conditions. P. putida GB-1 had a 5 fold increase in intracellular Mn compared to the non Mn oxidizing mutant P. putida GB-1-007 and a 59 fold increase in intracellular Mn compared to P. putida GB-1 ∆2665 ∆2447. The intracellular Mn is primarily associated with the less than 3 kDa fraction, suggesting it is not bound to protein. Protein oxidation levels in Mn oxidizing and non oxidizing cultures were relatively similar, yet Mn oxidation did increase survival of P. putida GB-1 when oxidatively stressed. This study is the first to link Mn oxidation to Mn homeostasis and oxidative stress protection.

Laryngoscopic, acoustic, perceptual, and functional assessment of voice in rock singers.

OBJECTIVE: The present study aimed to vocally assess a group of rock singers who use growl voice and reinforced falsetto. METHOD: A group of 21 rock singers and a control group of 18 pop singers were included. Singing and speaking voice was assessed through acoustic, perceptual, functional and laryngoscopic analysis. RESULTS: No significant differences were observed between groups in most of the analyses. Acoustic and perceptual analysis of the experimental group demonstrated normality of speaking voice. Endoscopic evaluation showed that most rock singers presented during singing voice a high vertical laryngeal position, pharyngeal compression and laryngeal supraglottic compression. Supraglottic activity during speaking voice tasks was also observed. However, overall vocal fold integrity was demonstrated in most of the participants. Slightly abnormal observations were demonstrated in few of them. Singing voice handicap index revealed that the most affected variable was the physical sphere, followed by the social and emotional spheres. CONCLUSIONS: Although growl voice and reinforced falsetto represent laryngeal and pharyngeal hyperfunctional activity, they did not seem to contribute to the presence of any major vocal fold disorder in our subjects. Nevertheless, we cannot rule out the possibility that more evident vocal fold disorders could be found in singers who use these techniques more often and during a longer period of time.

Population abundance of Frankliniella occidentalis (Thysanoptera: Thripidae) and natural enemies on plant hosts in central Chile.

Populations of the invasive Frankliniella occidentalis (Pergande) are serious pests of agricultural crops in the Aconcagua Valley of central Chile. An extensive survey was conducted of 55 plant species in 24 families to identify plant hosts of F. occidentalis and to determine its relative abundance on each host during each season. A more intensive study was conducted on selected plant species serving as reproductive hosts to determine the population dynamics of F. occidentalis and to evaluate the potential importance of Orius species and other natural enemies for controlling F. occidentalis. Adults of F. occidentalis were active during each season of the year inhabiting the flowers of 91% of the sampled plant species in 22 families, and 86% of these plant species in 19 families served as reproductive hosts. The number of host plant species used was greatest in the spring and least in the winter. All of the hosts except Medicago sativa L. were used only when flowering. Populations of F. occidentalis were significantly aggregated in M. sativa in the terminal buds over the leaves when the host was not flowering, and in the flowers, followed by the terminal buds, followed by the leaves when the host was flowering. Larvae were 1.3-2.3 times more abundant on dates when M. sativa was flowering. There were no identifiable patterns in plant hosts based on endemicity or plant family. Most of the plant species used by F. occidentalis were inferior quality hosts where populations either declined or were stable. Populations of F. occidentalis on low-quality hosts generally escaped predation by Orius species and competition by other species of thrips. Only 25% of the food hosts and 28% of the reproductive hosts for F. occidentalis in the extensive survey, respectively, were host plants for Orius. Parasitoids and other predators were not found to be important in suppressing thrips on any of the plant hosts. Populations of F. occidentalis increased on only a few hosts, including M. sativa and Sisymbrium officinale L. Scop. These apparently are major sources of F. occidentalis adults invading crops. We conclude that F. occidentalis is established in central Chile and that it has replaced and possibly displaced the native Frankliniella australis (Morgan) as the most common thrips species.