Search

Background: There is no gold standard definition of sarcopenic obesity (SO). Our objective is to evaluate the benefit of using the new definition proposed by the European Association for the Study of Obesity (EASO) in older people., Methods: Data from the Toledo Study of Healthy Aging, a study based on a cohort of community-dwelling older adults, were used. SO was defined according to the EASO and by a composite of the Foundation for the National Institute of Health (FNIH) for the diagnosis of sarcopenia and the WHO's criteria for obesity (Body Mass Index, BMI ≥ 30 kg/m 2 ; waist circumference, >88 cm for women and >102 cm for men). Frailty [Frailty Phenotype (FFP) and Frailty Trait Scale-5 (FTS5)] and disability (Katz Index) statuses were assessed at baseline and at the follow-up (median 2.99 years). Mortality at a 5-year follow-up was also assessed. The Logistic and Cox regression models were used to assess the associations., Results: Of the 1559 subjects (age 74.79 ± 5.76 years; 45.54% men), 30.15% (EASO/ESPEN) vs. 16.36% (FNIH) met the SO criteria (Kappa = 0.42). SO was associated with the prevalence of frailty by both the EASO's [OR(95%CI): FFP: 1.70 (1.33-2.16); FTS-5 binary: 2.29 (1.60-3.27); β(95%CI): FTS-5 continuous 3.63 (3.00-4.27)] and FNIH+WHO's criteria [OR (95%CI): 2.20 (1.61, 3.00)]. The FNIH + WHO's criteria were cross-sectionally associated with disability [OR: 1.52 (1.07, 2.16); p -value 0.018], while the EASO's criteria were not. The EASO's criteria did not show any association at the follow-up, while the FNIH + WHO's criteria were associated with incident frailty., Conclusions: The EASO's new criteria for sarcopenic obesity demonstrate moderate agreement with the traditional definition and are cross-sectionally associated with adverse events, but they do not effectively predict the outcomes generally associated with sarcopenic obesity in older adults. Therefore, the performance of the EASO's criteria in older people raises the need for refinement before recommending it for generalized use in this population.

Background: The prevention and treatment of bone loss and osteoporotic fractures is a public health challenge. Combined with normobaric hypoxia, whole-body vibration has a high clinic potential in bone health and body composition. The effect of this therapy may be mediated by its action on bone marrow mesenchymal stem cells (MSCs). Objectives: Evaluate the effects of cyclic low-vibration stimuli and/or hypoxia on bone marrow-derived human MSC differentiation. Methods: MSCs were exposed four days per week, two hours/day, to hypoxia (3% O 2 ) and/or vibration before they were induced to differentiate or during differentiation into osteoblasts or adipocytes. Gene and protein expression of osteoblastic, adipogenic, and cytoskeletal markers were studied, as well as extracellular matrix mineralization and lipid accumulation. Results: early osteoblastic markers increased in undifferentiated MSCs, pretreated in hypoxia and vibration. This pretreatment also increased mRNA levels of osteoblastic genes and beta-catenin protein in the early stages of differentiation into osteoblasts without increasing mineralization. When MSCs were exposed to vibration under hypoxia or normoxia during osteoblastic differentiation, mineralization increased with respect to cultures without vibrational stimuli. In MSCs differentiated into adipocytes, both in those pretreated as well as exposed to different conditions during differentiation, lipid formation decreased. Changes in adipogenic gene expression and increased beta-catenin protein were observed in cultures treated during differentiation. Conclusions: Exposure to cyclic hypoxia in combination with low-intensity vibratory stimuli had positive effects on osteoblastic differentiation and negative ones on adipogenesis of bone marrow-derived MSCs. These results suggest that in elderly or frail people with difficulty performing physical activity, exposure to normobaric cyclic hypoxia and low-density vibratory stimuli could improve bone metabolism and health.

Objectives: Insulin resistance determined by Homeostasis Model of Insulin Resistance (HOMA-IR) has been associated with functional decline in non-diabetic older subjects. However, insulin is not routinely assessed. The study evaluated the predictive value of non-insulin-dependent IR surrogates on functional decline in non-diabetic older men and women., Design and Participants: Prospective cohort study over 5 years. The study included 615 older participants from the Toledo Study of Healthy Aging., Methods: Frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 5 years follow-up. 193 subjects experienced functional decline (2.5-point reduction in the FTS-5 score). Multivariate regression models analysed the effect of five described IR surrogates on functional decline considering potential confounders., Results: Among evaluated IR proxies, triglyceride glucose-body mass index (TyG-BMI) and HOMA-IR were significantly associated with an increased risk of functional decline (odd ratio (95% confidence interval) TyG-BMI: 1.16 (1.05, 1.28), p = 0.0035 and HOMA-IR: 1.59 (1.15, 2.21), p = 0.0056) among all participants. When stratified by gender, HOMA-IR was related to functional decline in men [2.02 (1.13, 3.59), p = 0.0173] and TyG-BMI in women [1.19 (1.05, 1.35), p = 0.0057]., Conclusions: Only TyG-BMI index mimics the predictive capacity of insulin-based IR marker. The predictive ability of IR indexes is gender-specific, being TyG-BMI the only index able to predict functional decline in women and HOMA-IR in men., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Supplementation with β-hydroxy β-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease., Objectives: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM)., Methods: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables., Results: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty., Conclusions: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures., Methods: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia., Results: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women ( p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm 2 and 3.66 cm 2 for CSA, 32.57 mm and 40.21 mm for the X -axis, and 7.85 mm and 10.4 mm for the Y -axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women., Conclusions: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice., Competing Interests: G.G.R. and A.M are full employees of Abbott Laboratories. None of the remaining authors have any conflicts of interest. The authors declare that the project was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Circadian variations in the timing of the onset of stroke symptoms have been described, showing a morning excess of cardiovascular risk. To date, no differences have been found between stroke subtype and time distribution throughout the day. The present study aims to compare the seasonal and circadian rhythm of symptoms onset in ischemic, hemorrhagic, and stroke mimic patients., Methods: This study was conducted prospectively at a hospital and involved a cohort of stroke alert patients from 2018 to 2021. Stroke subtypes were classified as ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimic. Clinical variables were recorded, and each patient was assigned to a 4-h interval of the day according to the time of onset of symptoms; unwitnessed stroke patients were analyzed separately. Seasonal changes in stroke distribution were analyzed at 3-month intervals., Results: A total of 2,348 patients were included in this analysis (ischemic 67%, ICH 13%, mimic 16%, and TIA 3%). Regardless of stroke subtype, most of the patients were distributed between 08-12 h and 12-16 h. Significant differences were found in the time distribution depending on stroke subtype, with ICH predominating in the 4-8 h period (dawn), most of which were hypertensive, TIA in the 12-16 h period (afternoon), and stroke mimic in the 20 h period (evening). The ischemic stroke was evenly distributed throughout the different periods of the day. There were no differences in the seasonal pattern between different stroke subtypes, with winter being the one that accumulated the most cases., Conclusion: The present study showed different circadian patterns of stroke subtypes, with a predominance of ICH at dawn and stroke mimic in the afternoon. The stroke circadian rhythm resembles previous studies, with a higher incidence in the morning and a second peak in the afternoon., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Menéndez Albarracín, Valls Carbó, Rabaneda Lombarte, Yugueros Baena, Carbonell Gisbert, Flores-Pina, Larrañaga De Bofarull, Martínez Sánchez, Hernández-Pérez, Bustamante Rangel, Dorado Bouix, Gomis Cortina, Millán Tornè and Pérez de la Ossa.)

Background: Frailty is a key element in healthy ageing in which muscle performance plays a main role. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation has shown favourable effects in modulating protein synthesis, improving muscle mass and function in interventional studies. Decreased age-related endogenous HMB levels have been shown in previous studies. The aim of the present study is to assess whether there is an association between endogenous plasma HMB levels and frailty., Methods: Data from 1290 subjects (56.98% women; mean ± standard deviation age 74.6 ± 5.95 years) from the Toledo Study for Healthy Aging were obtained. Participants had their frailty status qualified according to Fried's Frailty Phenotype (FFP) score and the Frailty Trait Scale in its 12-domain version (FTS-12). Plasma HMB levels were analysed by an ultrahigh-performance liquid chromatography tandem mass spectrometry. Differences between groups (frail vs. non-frail) were tested using Mann-Whitney U test, Kruskal-Wallis test and chi-squared test. The association between HMB and frailty was assessed by multivariate linear and logistic regressions when frailty was analysed as continuous and binary, respectively. Models were adjusted by age, gender, comorbidity, body composition and protein intake., Results: HMB levels were lower in those aged ≥75 years than in those aged 65-74 years, with an inverse linear relationship between age and HMB levels (β = -0.031; P = 0.018), mainly accounted by males (β = -0.062; P = 0.002). HMB levels were higher in men (0.238 ± 0.065 vs. 0.193 ± 0.051 ng/mL; P ≤ 0.001). HMB levels were significantly lower in frail than in non-frail individuals: 0.204 ± 0.058 versus 0.217 ± 0.063 ng/dL (P = 0.001) according to the FFP and 0.203 ± 0.059 versus 0.219 ± 0.063 ng/mL (P < 0.001) according to FTS-12. These differences showed a dose-dependent profile when we compared them by quintiles of HMB (P for trend: 0.022; 0.012 and 0.0004, respectively, for FFP, FTS-12 binary and FTS-12 continuous). Variables associated with low HMB levels were body mass index, strength, exhaustion and weight loss. Frailty was associated with HMB levels in all the adjusted models, including the fully adjusted ones, no matter the tool used (odds ratio: 0.45 [0.26, 0.77] for FFP and 0.36 [0.20, 0.63] for FTS-12 binary; β = -4.76 [-7.29, -2.23] for FTS-12 score). This association was also observed when the analyses were done by quintiles, showing such association since Q4 (FFP), Q2 (FTS-12 binary) and Q3 (FTS-12 score). The associations were observed in the whole sample and in each gender., Conclusions: There is an inverse association between HMB levels and frailty status. These findings support the design of targeted clinical trials to evaluate the effect of HMB supplementation in older frail people with low HMB levels., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Olive tree ( Olea europaea ) leaf extract (OELE) has important antioxidant and anti-inflammatory properties, supporting its use in human clinical practice. We recently designed an amorphous hydrogel called EHO-85 (EHO indicates olive leaf extract in Spanish) containing OELE for skin ulcer treatments. Yet, its effectiveness has not been previously compared with other products used in routine clinical practice. This is necessary to evaluate its potential translation to the human clinic. Thus, in this study, the effect of EHO-85 on healing was evaluated in comparison with treatments containing Indian/Asiatic pennywort ( Centella asiatica ), hyaluronic acid, or dexpanthenol in a rat model. The speed of wound closure and histological parameters after seven and 14 days were analyzed. All treatments accelerated wound closure, but there were differences between them. Dexpanthenol after seven days produced the highest epithelialization and the lowest inflammation and vascularization. EHO-85 also promoted epithelialization and reduced vascularization. After 14 days, wounds treated with EHO-85 showed less inflammation and higher levels of collagen in the extracellular matrix. This indicates a higher degree of maturity in the regenerated tissue. In conclusion, the effect of EHO-85 on healing was equal to or superior to that of other treatments routinely used in human clinical practice. Therefore, these results, together with previous data on the effects of this hydrogel on ulcer healing in humans, indicate that EHO-85 is a suitable, low-cost, and efficient therapeutic option for wound healing.

DPP4 may play a relevant role in MSC differentiation into osteoblasts or adipocytes. Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4i), such as sitagliptin and vildagliptin, are used as antidiabetic drugs. However, vildagliptin is not a specific DPP4i and also inhibits DPP8/9, which is involved in energy metabolism and immune regulation. The aim of this study is to evaluate how sitagliptin, vildagliptin or 1G244 (a DPP8/9 specific inhibitor) may influence cell viability, as well as osteogenic and adipogenic differentiation in human mesenchymal stem cells (MSC). Viability, apoptosis, osteoblastogenesis and adipogenesis markers, as well as protein synthesis of β-catenin, were studied in MSC cultures induced to differentiate into osteoblasts or adipocytes in the presence or absence of sitagliptin, vildagliptin or 1G244. The two tested DPP4i did not affect MSC viability, but 1G244 significantly decreased it in MSC and osteoblast-induced cells. Additionally, 1G244 and vildagliptin inhibited osteogenesis and adipogenesis, unlike sitagliptin. Therefore, inhibition of DPP4 did not affect MSC viability and differentiation, whereas inhibition of DPP8/9 negatively affected MSC. To the best of our knowledge, these results show for the first time that DPP8/9 have an important role in the viability and differentiation of human MSC. This data can be considered for human clinical use of drugs affecting DPP8/9 activity.

Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, and traumatic fractures require effective treatments that favor bone formation and regeneration. Among these, cell therapy based on mesenchymal stem cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part on their paracrine properties. These are mainly mediated by extracellular vesicle (EV) secretion. EV modulates regenerative processes such as inflammation, angiogenesis, cell proliferation, migration, and differentiation. Thus, MSC-EV are currently an important tool for the development of cell-free therapies in regenerative medicine. This review describes the current knowledge of the effects of MSC-EV in the different phases of bone regeneration. MSC-EV has been used by intravenous injection, directly or in combination with different types of biomaterials, in preclinical models of bone diseases. They have shown great clinical potential in regenerative medicine applied to bone. These findings should be confirmed through standardization of protocols, a better understanding of the mechanisms of action, and appropriate clinical trials. All that will allow the translation of such cell-free therapy to human clinic applications.

The use of mesenchymal stem-cells (MSC) in cell therapy has received considerable attention because of their properties. These properties include high expansion and differentiation in vitro , low immunogenicity, and modulation of biological processes, such as inflammation, angiogenesis and hematopoiesis. Curiously, the regenerative effect of MSC is partly due to their paracrine activity. This has prompted numerous studies, to investigate the therapeutic potential of their secretome in general, and specifically their extracellular vesicles (EV). The latter contain proteins, lipids, nucleic acids, and other metabolites, which can cause physiological changes when released into recipient cells. Interestingly, contents of EV can be modulated by preconditioning MSC under different culture conditions. Among them, exposure to hypoxia stands out; these cells respond by activating hypoxia-inducible factor (HIF) at low O 2 concentrations. HIF has direct and indirect pleiotropic effects, modulating expression of hundreds of genes involved in processes such as inflammation, migration, proliferation, differentiation, angiogenesis, metabolism, and cell apoptosis. Expression of these genes is reflected in the contents of secreted EV. Interestingly, numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia. In this review, we show the implications of hypoxia responses in relation to tissue regeneration. In addition, hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV, with a high potential for clinical use in regenerative medicine that can be applied to different pathologies., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Many caregivers are insufficiently prepared, and little is known about measures that can be employed to enhance their preparedness., Aim: The aim of this study was to explore the factors associated with caregiver preparedness and establish a predictive model including the relationship between preparedness, burden, resilience and anxiety., Design: A cross-sectional design was used., Methods: The sample included 172 family caregivers who were selected from one private hospital and daytime nursing centres. Caregivers were recruited from 2018 to 2019; they completed assessments for caregiver preparedness, anxiety, resilience and burden. A multiple linear regression analysis was performed to identify the factors associated with preparedness., Results: Preparedness was significantly associated with high levels of resilience and a low level of burden, while it was not associated with anxiety. Caregivers' gender, experience and cohabitation status were the main predictors. Resilience is an explanatory factor for caregiver preparedness in the predictive model., Conclusion: The demographic variables related to preparedness can be used to guide efforts to meet the needs of vulnerable caregivers. A caregiver's preparedness depends on their level of burden and resilience. Nursing interventions focused on these aspects could make the caregiver's role easier and improve the quality of care provided., (© 2022 The Authors. International Journal of Nursing Practice published by John Wiley & Sons Australia, Ltd.)

Dipeptidyl peptidase IV (DPP4) is a ubiquitous protease that can be found in membrane-anchored or soluble form. Incretins are one of the main DPP4 substrates. These hormones regulate glucose levels, by stimulating insulin secretion and decreasing glucagon production. Because DPP4 levels are high in diabetes, DPP4 inhibitor (DPP4i) drugs derived from gliptin are widespread used as hypoglycemic agents for its treatment. However, as DPP4 recognizes other substrates such as chemokines, growth factors and neuropeptides, pleiotropic effects have been observed in patients treated with DPP4i. Several of these substrates are part of the stem-cell niche. Thus, they may affect different physiological aspects of mesenchymal stem-cells (MSC). They include viability, differentiation, mobilization and immune response. MSC are involved in tissue homeostasis and regeneration under both physiological and pathological conditions. Therefore, such cells and their secretomes have a high clinical potential in regenerative medicine. In this context, DPP4 activity may modulate different aspects of MSC regenerative capacity. Therefore, the aim of this review is to analyze the effect of different DPP4 substrates on MSC. Likewise, how the regulation of DPP4 activity by DPP4i can be applied in regenerative medicine. That includes treatment of cardiovascular and bone pathologies, cutaneous ulcers, organ transplantation and pancreatic beta-cell regeneration, among others. Thus, DPP4i has an important clinical potential as a complement to therapeutic strategies in regenerative medicine. They involve enhancing the differentiation, immunomodulation and mobilization capacity of MSC for regenerative purposes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG / RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide.

Background: Brief interventions (BI) for risky drinkers in primary healthcare have been demonstrated to be cost-effective but they are still poorly implemented. Digital BI seems to be a complementary strategy to overcome some barriers to implementation but there is a scarcity of studies in clinical environments. We present the results of a randomized controlled non-inferiority trial which tests the non-inferiority of facilitated access to a digital intervention (experimental condition) for risky drinkers against a face-to-face BI (control condition) provided by primary healthcare professionals., Method: In a non-inferiority randomized controlled trial, unselected primary healthcare patients (≥ 18 years old) were given a brief introduction and asked to log on to the study website to fill in the 3-item version of the Alcohol Use Disorders Identification Test. Positively screened patients (4+ for women and 5+ for men) received further online assessment (AUDIT, socio-demographic characteristics and EQ-5D-5L) and were automatically randomized to either face-to-face or digital BI (1:1). The primary outcome was the proportion of patients classified as risky drinkers by the digitally administered AUDIT at month 3. A multiple imputation approach for the missing data was performed., Results: Of the 4499 patients approached by 115 healthcare professionals, 1521 completed the AUDIT-C. Of the 368 positively screened patients, 320 agreed to participate and were randomized to either intervention. At month 3, there were more risky drinkers in the experimental group (59.8%) than in the control group (52%), which was similar to the distribution at baseline and less than the pre-specified margin of 10%. The difference was not significant when accounting for possible confounders., Conclusion: Digital BI was not inferior to face-to-face BI, in line with previous findings and the a priori hypothesis. However, the low power of the final sample, due to the low recruitment and loss to follow-up, limits the interpretation of the findings. New approaches in this field are required to ensure the effective implementation of digital interventions in actual practice., Competing Interests: AG has received honoraria, research grants and travel grants from Lundbeck and D&A Pharma, which had no bearing on the research of this study. HL-P has received travel grants from Lundbeck, and Otsuka, and honoraria from Lundbeck which had no bearing on the research of this study. The other authors do not provide any competing interests., (© 2021 Published by Elsevier B.V.)

Nutritional management of patients with intestinal failure often includes the use of oligomeric formulas. Implementing the use of oligomeric formulas in surgical patients with maldigestion or malabsorption could be a nutritional strategy to be included in clinical protocols. We aim to generate knowledge from a survey focused on the effectiveness of nutritional therapy with oligomeric formulas with Delphi methodology. Each statement that reached an agreement consensus among participants was defined as a median consensus score ≥7 and as an interquartile range ≤3. The use of oligomeric formulas in surgical patients, starting enteral nutrition in the post-operative phase in short bowel syndrome and in nonspecific diarrhea after surgical procedures, could improve nutritional therapy implementation. Stakeholders agreed that early jejunal enteral nutrition with oligomeric formula is more effective compared to intravenous fluid therapy and it is useful in patients undergoing upper gastro-intestinal tract major surgery when malabsorption or maldigestion is suspected. Finally, oligomeric formulas may be useful when a feeding tube is placed distally to the duodenum. This study shows a practical approach to the use of oligomeric formulas in surgical patients with intestinal disorders and malabsorption, and it helps clinicians in the decision-making process.

Aim: To psychometrically test the Spanish version of the Caregiver Preparedness Scale (CPS) and document the preparedness level of caregivers., Design: A descriptive and validation study., Method: Purposive sampling method was used to select 171 family caregivers Spain. The scale was cross-culturally adapted through a process that included translation, comparison with versions in other languages and back-translation, review, pre-testing and validity, and reliability tests., Results: The Spanish family caregivers are mainly female (79%) and married (75%). The Spanish version of the CPS presents changes with respect to the original. Confirmatory factor analysis supported the single-factor model. Analysis of internal consistency yielded a Cronbach's α of 0.89. Significant correlations (p < .01) with other scales supported convergent validity. A descriptive analysis of the validated scale showed average levels of preparation (2.16 out of 4). Caregivers felt better prepared to attend to the patient's physical needs than emotional or spiritual needs., (© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: Mesenchymal stem cells (MSC) of bone marrow are the progenitor of osteoblasts and adipocytes. MSC tend to differentiate into adipocytes, instead of osteoblasts, with aging. This favors the loss of bone mass and development of osteoporosis. Hypoxia induces hypoxia inducible factor 1α gene encoding transcription factor, which regulates the expression of genes related to energy metabolism and angiogenesis. That allows a better adaptation to low O 2 conditions. Sustained hypoxia has negative effects on bone metabolism, favoring bone resorption. Yet, surprisingly, cyclic hypoxia (CH), short times of hypoxia followed by long times in normoxia, can modulate MSC differentiation and improve bone health in aging., Aim: To evaluate the CH effect on MSC differentiation, and whether it improves bone mineral density in elderly., Methods: MSC cultures were induced to differentiate into osteoblasts or adipocytes, in CH (3% O 2 for 1, 2 or 4 h, 4 d a week). Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes, respectively. In addition, gene expression of marker genes, for osteogenesis or adipogenesis, have been quantified by quantitative real time polymerase chain reaction. The in vivo studies with elderly (> 75 years old; n = 10) were carried out in a hypoxia chamber, simulating an altitude of 2500 m above sea level, or in normoxia, for 18 wk (36 CH sessions of 16 min each). Percentages of fat mass and bone mineral density from whole body, trunk and right proximal femur (femoral, femoral neck and trochanter) were assessed, using dual-energy X-ray absorptiometry., Results: CH (4 h of hypoxic exposure) inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes, respectively. However, both parameters were not significantly affected by the other shorter hypoxia times assessed. The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation, in MSC induced to differentiate into osteoblasts. Interestingly, osteocalcin (associated to energy metabolism) was upregulated. Vascular endothelial growth factor an expression and low-density lipoprotein receptor related protein 5/6/dickkopf Wnt signaling pathway inhibitor 1 (associated to Wnt/β-catenin pathway activation) increased in osteoblasts. Yet, they decreased in adipocytes after CH treatments, mainly with the longest hypoxia times. However, the same CH treatments increased the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio in both cell types. An increase in total bone mineral density was observed in elderly people exposed to CH, but not in specific regions. The percentage of fat did not vary between groups., Conclusion: CH may have positive effects on bone health in the elderly, due to its possible inhibitory effect on bone resorption, by increasing the osteoprotegerin / receptor activator for nuclear factor kappa B ligand ratio., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Several studies have shown differences in the motivational processes that lead to excessive alcohol consumption among adolescents. The paper focuses on the analysis of the reasons for alcohol consumption among minors, and compare the differences according to sex, age, and level of consumption., Method: A representative sample (N = 2,865) of adolescents aged 12 to 18 years (mean age 14.24, dt = 1.33) was collected. The variables abuse, binge drinking and drinking motives were evaluated using a questionnaire designed ad hoc, which identified the Cooper's four categories of motives., Results: The analyses (ANOVA, Pearson correlation, and logistic regression) showed that there were no differences between young men and women regarding consumption or binge drinking. Minors who abused alcohol experience consumption as pleasurable in itself, as an important source of intrinsic reinforcement. Conformity predicted the problematic consumption of alcohol among boys and a decrease in the frequency of binge drinking among girls. In addition, the larger group showed more presence of enhancement and social motives., Conclusions: This study suggests that it would not be of interest to focus prevention on the negative consequences of consumption, but rather on the training of specific skills.

This study explored the relationship between religion, religiosity and alcohol consumption in a sample of 2.890 adolescents (ages 12-18) in Madrid, Spain. Results showed that non-believers were the group that consume and abuse alcohol the most, as opposed to Catholics. Besides, religiosity was related to a lower alcohol use. Therefore, religion and religiosity in Spanish adolescents appear to be related to a low alcohol use. This contribution may help to clarify the risk and protection factors for alcohol consumption by adolescents and contribute to strengthening the preventive actions.

Objective: Understanding the impact of Level of Information and Communication Technology Use, computer self-efficacy and perceived product usability of healthcare professionals regarding an alcohol consumption reduction website on facilitated access defined as referring patients to the webpage., Methods: 52 nurses and 41 general practitioners were assessed before patient recruitment started, using a questionnaire designed to assess socio-demographic characteristics, professional engagement to the website, Level of Information and Communication Technology Use, Computer self-efficacy ("the judgment of one's capability to use a computer") and Perceived product usability ("the extent to which a product can be used by specified users to achieve specified goals with effectiveness, efficiency, and satisfaction in a specified context of use"). Dependent variable was the self-report of number of brochures distributed to patients., Results: Professionals' engagement with facilitated access measured by brochures handed out was not predicted by Perceived product usability, Level of Information and Communication Technology Use or Computer self-efficacy. Professionals who had actively engaged with the website (customization) provided significantly more brochures compared with those who had not (Coefficient B 15.7 CI95% 3.5-27.8). Professional's socio-demographic characteristics did not predict engagement in facilitated access., Conclusion: Professionals' Perceived product usability, Level of Information and Communication Technology Use and Computer self-efficacy were not associated to facilitated access. Active early engagement of health professionals with the website (customization) is a key predictor of subsequent engagement with facilitated access., Practice Implications: Computer Self-Efficacy, Level of Information and Communication Technology Use and Perceived Product Usability are irrelevant for facilitated access and efforts should be focused on taking time to collaborate with providers and convincing them about the usefulness of the intervention (including customization). Website customization by health care professionals is a promising predictor of engagement., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: To test if training and support, financial reimbursement and option of referring screen-positive patients to an internet-based method of giving advice (eBI) can increase primary health-care providers' delivery of Alcohol Use Disorders Identification Test (AUDIT)-C-based screening and advice to heavy drinkers., Design: Cluster randomized factorial trial with 12-week implementation and measurement period., Setting: Primary health-care units (PHCU) in different locations throughout Catalonia, England, the Netherlands, Poland and Sweden., Participants: A total of 120 PHCU, 24 in each of Catalonia, England, the Netherlands, Poland and Sweden., Interventions: PHCUs were randomized to one of eight groups: care as usual, training and support (TS), financial reimbursement (FR) and eBI; paired combinations of TS, FR and eBI, and all of FR, TS and eBI., Measurements: The primary outcome measure was the proportion of eligible adult (age 18+ years) patients screened during a 12-week implementation period. Secondary outcome measures were proportion of screen-positive patients advised; and proportion of consulting adult patients given an intervention (screening and advice to screen-positives) during the same 12-week implementation period., Findings: During a 4-week baseline measurement period, the proportion of consulting adult patients who were screened for their alcohol consumption was 0.059 per PHCU (95% CI 0.034 to 0.084). Based on the factorial design, the ratio of the logged proportion screened during the 12-week implementation period was 1.48 (95% CI = 1.13-1.95) in PHCU that received TS versus PHCU that did not receive TS; for FR, the ratio was 2.00 (95% CI = 1.56-2.56). The option of referral to eBI did not lead to a higher proportion of patients screened. The ratio for TS plus FR was 2.34 (95% CI = 1.77-3.10), and the ratio for TS plus FR plus eBI was1.68 (95% CI = 1.11-2.53)., Conclusions: Providing primary health-care units with training, support and financial reimbursement for delivering Alcohol Use Disorders Identification Test-C-based screening and advice to heavy drinkers increases screening for alcohol consumption. Providing primary health-care units with the option of referring screen-positive patients to an internet-based method of giving advice does not appear to increase screening for alcohol consumption., (© 2016 Society for the Study of Addiction.)

Background: Brief interventions in primary healthcare are cost-effective in reducing drinking problems but poorly implemented in routine practice. Although evidence about implementing brief interventions is growing, knowledge is limited with regard to impact of initial role security and therapeutic commitment on brief intervention implementation., Methods: In a cluster randomised factorial trial, 120 primary healthcare units (PHCUs) were randomised to eight groups: care as usual, training and support, financial reimbursement, and the opportunity to refer patients to an internet-based brief intervention (e-BI); paired combinations of these three strategies, and all three strategies combined. To explore the impact of initial role security and therapeutic commitment on implementing brief interventions, we performed multilevel linear regression analyses adapted to the factorial design., Results: Data from 746 providers from 120 PHCUs were included in the analyses. Baseline role security and therapeutic commitment were found not to influence implementation of brief interventions. Furthermore, there were no significant interactions between these characteristics and allocated implementation groups., Conclusions: The extent to which providers changed their brief intervention delivery following experience of different implementation strategies was not determined by their initial attitudes towards alcohol problems. In future research, more attention is needed to unravel the causal relation between practitioners' attitudes, their actual behaviour and care improvement strategies to enhance implementation science., Trial Registration: ClinicalTrials.gov: NCT01501552.

Aims: To determine the relation between existing levels of alcohol screening and brief intervention rates in five European jurisdictions and role security and therapeutic commitment by the participating primary healthcare professionals., Methods: Health care professionals consisting of, 409 GPs, 282 nurses and 55 other staff including psychologists, social workers and nurse aids from 120 primary health care centres participated in a cross-sectional 4-week survey. The participants registered all screening and brief intervention activities as part of their normal routine. The participants also completed the Shortened Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ), which measure role security and therapeutic commitment., Results: The only significant but small relationship was found between role security and screening rate in a multilevel logistic regression analysis adjusted for occupation of the provider, number of eligible patients and the random effects of jurisdictions and primary health care units (PHCU). No significant relationship was found between role security and brief intervention rate nor between therapeutic commitment and screening rate/brief intervention rate. The proportion of patients screened varied across jurisdictions between 2 and 10%., Conclusion: The findings show that the studied factors (role security and therapeutic commitment) are not of great importance for alcohol screening and BI rates. Given the fact that screening and brief intervention implementation rate has not changed much in the last decade in spite of increased policy emphasis, training initiatives and more research being published, this raises a question about what else is needed to enhance implementation., (© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

The perioperative management of patients undergoing abdominal surgery has been based on traditional concepts and often not supported by scientific evidence. Recently there have been several scientific studies showing that some traditional procedures for the perioperative management of patients as preoperative fasting, bowel preparation, use of naso-gastric tubes, placement of intra-abdominal drainage, postoperative fasting etc. They are unnecessary and sometimes counterproductive. Perioperative management protocols ERAS or Fast-Track (Enhanced Recovery After Surgery) are based on the use in the perioperative period of measures that are supported by current scientific evidence. Since 2000 appear in the scientific literature several works that reflect the application of protocols ERAS or Fast- Track in surgery of the digestive system where it's shown uniformly, not only the security of your application but also, decreased complications and hospital stay. Although initially these protocols were described in colorectal surgery, due to the good results obtained, the application of these protocols has rapidly expanded to other surgical specialties such as thoracic surgery, Urology, Gynaecology, etc. In all these specialties has unanimously showing improved postoperative recovery with ERAS application protocols. The purpose of this paper is twofold. On the one hand examine the scientific evidence that exists today on the most important elements of an ERAS program and present preliminary results of the implementation of a program ERAS in our hospital.

Introduction: Early identification (EI) and brief interventions (BIs) for risky drinkers are effective tools in primary care. Lack of time in daily practice has been identified as one of the main barriers to implementation of BI. There is growing evidence that facilitated access by primary healthcare professionals (PHCPs) to a web-based BI can be a time-saving alternative to standard face-to-face BIs, but there is as yet no evidence about the effectiveness of this approach relative to conventional BI. The main aim of this study is to test non-inferiority of facilitation to a web-based BI for risky drinkers delivered by PHCP against face-to-face BI., Method and Analysis: A randomised controlled non-inferiority trial comparing both interventions will be performed in primary care health centres in Catalonia, Spain. Unselected adult patients attending participating centres will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Participants with positive results will be requested online to complete a trial module including consent, baseline assessment and randomisation to either face-to-face BI by the practitioner or BI via the alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 3 months and 1 year using the full AUDIT and D5-EQD5 scale. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis., Ethics and Dissemination: The protocol was approved by the Ethics Commmittee of IDIAP Jordi Gol i Gurina P14/028. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations., Trial Registration Number: ClinicalTrials.gov NCT02082990., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Antioxidant therapy has been proposed to improve the oxidative stress status of diabetic patients. Natural products are a source of substances such as carotenoids, with known antioxidant properties with possible benefits on diabetes. Among them, Dunaliella salina is a microalga with high content in carotenoids that can be extracted via an environmentally clean process such as supercritical fluid extraction with CO2. Five doses of D. salina extract with in vitro antioxidant properties were intragastrically administrated to adult male streptozotocin (STZ) diabetic rats. Urine fingerprints of control and diabetic rats, both with and without treatment, were obtained by capillary electrophoresis with two different modes (normal polarity and MEKC and reverse polarity and CZE). When the profiles were submitted together to pattern recognition techniques they showed the effects of D. salina extract on this acute and short-term treatment animal model in a rapid, simple and cost-effective way without identifying a single marker. In order to have a further biochemical knowledge of the effect, after treatment, rats were sacrificed and blood and liver glutathione, as well as plasma glucose, triglycerides, cholesterol, total protein, urea, acetoacetate, 3-hydroxybutyrate, lactate, pyruvate and urate, TBARS and urine 8-isoprostane were analysed. Vitamin E in plasma and liver was also measured. Twenty-seven parameters were individually assessed, and both univariate statistics (mean comparison after 1W-ANOVA) and multivariate data analysis were performed. D. salina extract induced changes showed up by the multivariate analysis. Results of the treatment from most of the parameters can be considered beneficial for diabetic animals; although an increase in hyperglycemia and 8-isoprostane excretion when STZ treated animals received the extract was observed.

Type I diabetes in humans and streptozotocin (STZ)-induced diabetes in rats has been associated with oxidative stress, but antioxidant therapy has given contradictory results, in part related to the absence of common conditions used to evaluate in-vivo antioxidant properties. This prompted the study of an experimental model of antioxidant therapy in STZ-treated rats. Adult female rats received STZ (50 mgkg(-1)) and were studied 7 or 14 days later. Adipose tissue weight progressively decreased with the time of treatment, whereas plasma triglycerides increased at 7 days, before returning to control values at 14 days after STZ treatment. STZ diabetic rats had increased plasma thiobarbituric acid reacting substances and alpha-tocopherol levels, but the latter variable was decreased when corrected for total lipids. STZ diabetic rats showed a higher GSSG/GSH ratio at Day 14 and lower GSH + GSSG at Day 7 in liver. To evaluate the effect of short-term antioxidant therapy, rats received 5 doses of vitamins C and E over 3 days before being killed on Day 14. Treatment with antioxidants decreased plasma lactic acid and thiobarbituric acid reacting substances, as well as urine 8-isoprostane, and decreased plasma uric acid in controls. Vitamins increased the plasma alpha-tocopherol/lipids ratio only in control rats, although the plasma and liver alpha-tocopherol concentration increased in both groups. STZ diabetic rats showed moderate oxidative stress and treatment with antioxidant vitamins caused a significant change in a selected group of oxidative stress markers, which reflected an improvement in some of the complications associated with this disease. The present experimental conditions can be used as a sensitive experimental model to study the responsiveness of diabetes to other antioxidant interventions.

The objective in much of the proteomics literature today is to establish the difference between healthy and disease states at the protein level using blood plasma. A critical component in this endeavor is to establish what is normal. The focus of the work reported here was to do this with oxidized proteins that might relate to oxidative stress and oxidative stress-related diseases. Oxidative stress is known to increase markedly in cancer, diabetes, heart disease, and neurodegenerative diseases. Since proteins are one of the targets of ROS, generated by oxidative stress, oxidized proteins are excellent biomarker candidates for these diseases. But first it is necessary to identify oxidized proteins that occur in the healthy state. Healthy rat plasma was used in this study as a source for the identification of naturally oxidized proteins. Freshly drawn blood was treated with biotin hydrazide to selectively derivatize carbonyl groups in oxidized proteins. Oxidized proteins thus biotinylated were separated from the other plasma proteins using avidin affinity chromatography. Affinity selected proteins were further fractionated on a C(8) RP column and fractions collected. The collected fractions were then tryptic digested and the peptides identified using a combination of LC/MS/MS and database searches. One hundred forty-six proteins were identified using 700 signature peptides from the tryptic digested chromatographic fractions. The most frequently encountered proteins in the samples were keratins. Brain and liver were among the organs contributing the most oxidized proteins to plasma followed by heart and kidney.

Adrenal myelolipomas are rare benign tumors comprising mature adipose tissue and diverse hematopoietic elements. These neoplasms are usually incidental findings, although bulky masses can generate abdominal pain as well as other symptoms related to compression of adjacent organs. Diagnosis is usually provided by ultrasonography or computed tomography. Asymptomatic patients with tumors with a maximum diameter of less than 6cm can benefit from periodic surveillance, whereas local compression symptoms and size larger than 6cm are indications for surgical treatment. We present a case of giant adrenal myelolipoma and provide a review of the literature., (Copyright © 2008 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.)

This review article addresses the different capillary electrophoretic methods that are being used for the study of both short-chain organic acids (including anionic catecholamine metabolites) and fatty acids in biological samples. This work intends to provide an updated overview (including works published until November 2004) on the recent methodological developments and applications of such procedures together with their main advantages and drawbacks. Moreover, the usefulness of CE analysis of organic acids to study and/or monitor different diseases such as diabetes, new-borns diseases or metabolism disorders is examined. The use of microchip devices and CE-MS couplings for organic acid analysis is also discussed.

The concept of functional food, about which scientific agreement is still lacking, springs from the field of Optimum Nutrition, aimed at modifying genetic and physiological aspects of human life and at the prevention and treatment of a growing number of diseases, far beyond merely covering nutritional requirements. From the European Union perspective, functional foods can be natural as well as industrially processed foods. The leading functional foods regarding which the soundest scientific evidence exists are probiotics, live microbial food ingredients represented mainly by fermented dairy products. Prebiotics, such as inulin-type fructans, are the trophic substrate of probiotics and potential intestinal microflora selectors. The combination of prebiotics and probiotics is termed synbiotic. Innumerable substances are known to have functional effects: soluble and insoluble fiber, phytosterols, phytoestrogens, monounsaturated and polyunsaturated fatty acids, phenol derivatives, vitamins and other phytochemicals. Functional foods exert their actions on different systems, especially the gastrointestinal, cardiovascular and immunological ones, acting too as enhancers of development and differentiation and positively modulating nutrient metabolism, gene expression, oxidative stress and the psychic sphere. The establishment of Health Claims must be firmly based upon scientific knowledge and legal regulation. Efficient biomarkers related to biological response must be found. Furthermore, it is essential to analyze possible diet or drug interactions as well as it is indispensable to conduct valid studies on humans. The prime objective must be the diet as a whole. Thus, the future challenge of a functional diet emerges.

Objectives: To assess reliability in terms of inter-observer agreement of blood pressure (BP) readings. Various health professionals and measuring systems. Influence of observer's experience., Design: Observational, descriptive, cross-sectional study., Setting: Urban health centre, Córdoba., Participants: 131 hypertensive, randomised patients, belonging to a functional care unit. 11 were excluded., Measurements: To reduce variability: course on the right way to take blood pressure, otoscope and verification of visual sharpness of observers, calibration and validation of measuring devices, limited time and blinding of measurements. 4 BP measurements per patient: 3 with mercury sphygmomanometer (2 simultaneously, one individual) and one with an automatic device. Descriptive, clinical and somatometric variables were gathered. Inter-observer agreement was evaluated through the intraclass correlation coefficient (ICC), the mean of differences method (MDM) and the simple concordance index (CI). An ICC > 0.75 was thought acceptable. A difference > 5 mmHg was thought clinically relevant (MDM and CI)., Main Results: Acceptable consistency for MDM: alone, systolic and diastolic pressure of OBS 1/ OBS 2, bi-auricular, -6.1/+8.9 mmHg and -6.8/+5.8 mmHg. Less favourable results: for systolic and diastolic pressure: OBS 1/AUTO -20.9/25.0 and -16.4/15.1; OBS 2/AUTO -22.8/24.4 and -16.6/15.2. Remaining intervals always > 10 mmHg; CI > 0.75 in all comparisons except diastolic pressure OBS 1/AUTO and diastolic pressure OBS 2/AUTO (0.69 in both cases). 41% of comparisons were > 5 mmHg. No differences in less expert professionals were found., Conclusions: Inaccuracy of the standard BP measurement method (mercury sphygmomanometer) for MDM and CI. Contradictory conclusions according to method of measurement. Differences not clinically acceptable.