Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status.

ATP citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy-fed mice, and improved locomotion in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.

H2S serves as the immunoregulatory essence of apoptotic cell death.

Apoptosis supports tissue homeostasis and prevents immune disorders by removing damaged and functionally aberrant cells. Here, Ou et al. utilized genetic, pharmacological, and proteomic approaches focused on sulfur amino acid catabolism to discover that hydrogen sulfide (H2S) release during apoptosis suppresses Th17 cell differentiation, thus providing therapeutic targets for autoimmune diseases.

Telephone-Cardiopulmonary Resuscitation Guided by a Telecommunicator: Design of a Guiding Algorithm for Telecommunicators.

BACKGROUND: Out-of-hospital cardiac arrest is considered a global problem. In the last few years, there has been a growing interest in telephone-cardiopulmonary resuscitation guided by a telecommunicator. Indeed, several studies have demonstrated that it increases the chances of survival rate. This study focuses on the key points the operator should follow when performing telephone-cardiopulmonary resuscitation. The main objective of this paper is to design an algorithm to improve the telephone-cardiopulmonary resuscitation response protocol. METHODS: The available evidence and the areas of uncertainty that have not been previously mentioned in the literature are discussed. All the information has been analyzed by two discussion groups. Later, a consensus was reached among all members. Finally, a response algorithm was designed and implemented in clinical simulation. RESULTS: All the witnesses were able to recognize the OHCA, call for emergency assistance, follow all the operator's instructions, move the victim, and place their hands in the correct position to perform CPR. DISCUSSION: The results of the pilot study provide us a basis for further experimental studies using randomization and experimental and control groups. CONCLUSIONS: No standardized recommendations exist for the operator to perform telephone-guided CPR. For this reason, a response algorithm was designed.

Colostrum Features of Active and Recovered COVID-19 Patients Revealed Using Next-Generation Proteomics Technique, SWATH-MS.

Colostrum performs nutritional, anti-inflammatory and anti-infective functions and promotes immune system formation and organ development. The new coronavirus, SARS-CoV-2, has generated concerns about viral transmission through human milk, with a lack of evidence about human milk's protective effects against the infection. This study aimed at analyzing presence of the virus and at identifying the protein expression profile of human colostrum in active and COVID-19-recovered patients. Colostrum samples were collected from women with COVID-19 (n = 3), women recently recovered from the infection (n = 4), and non-infected women (n = 5). The samples were analyzed by means of RT-qPCR to determine presence of the virus and using SWATH-MS for proteomic analysis. Proteomic results were then analyzed using bioinformatic methods. The viral tests were negative for SARS-CoV-2 in the colostrum from COVID-19 patients. The proteomic analysis identified 301 common proteins in all samples analyzed. Nineteen proteins were upregulated and 7 were downregulated in the COVID-19 group versus the control samples, whereas 18 were upregulated and 7 were downregulated when comparing the COVID-19 group to the recovered group. Eleven proteins were biomarkers of active COVID-19 infection. Ten were upregulated: ACTN1, CD36, FAM3B, GPRC5B, IGHA2, IGK, PLTP, RAC1, SDCBP and SERPINF1, and one was downregulated: PSAP. These proteins are mainly related to immunity, inflammatory response and protein transport. In conclusion, the results of this study suggest that colostrum is not a vehicle for mother-to-child SARS-CoV-2 transmission. Moreover, the colostrum's proteome of active and recuperated patients indicate that it could provide immune benefits to infants.

Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging.

ATP-citrate lyase is a central integrator of cellular metabolism in the interface of protein, carbohydrate, and lipid metabolism. The physiological consequences as well as the molecular mechanisms orchestrating the response to long-term pharmacologically induced Acly inhibition are unknown. We report here that the Acly inhibitor SB-204990 improves metabolic health and physical strength in wild-type mice when fed with a high-fat diet, while in mice fed with healthy diet results in metabolic imbalance and moderated insulin resistance. By applying a multiomic approach using untargeted metabolomics, transcriptomics, and proteomics, we determined that, in vivo, SB-204990 plays a role in the regulation of molecular mechanisms associated with aging, such as energy metabolism, mitochondrial function, mTOR signaling, and folate cycle, while global alterations on histone acetylation are absent. Our findings indicate a mechanism for regulating molecular pathways of aging that prevents the development of metabolic abnormalities associated with unhealthy dieting. This strategy might be explored for devising therapeutic approaches to prevent metabolic diseases.

COVID-19 and female immigrant caregivers in Spain: Cohabiting during lockdown.

From a gender perspective, female immigrant domestic caregivers have been particularly impacted during the COVID-19 pandemic: first, as female immigrants, and second, due to their work within the domestic care sector, which has been so badly affected in this pandemic. This study investigates the emotions and experiences of 15 female Latin American immigrant domestic workers, caregivers in five Andalusian cities (Seville, Cádiz, Málaga, Huelva and Córdoba) (Spain) who were cohabiting with their employees/patients during the COVID-19 pandemic lockdown, using qualitative research through in-depth interviews and life stories. The results show the moral debt accrued by the caregivers with the family who employ them, while worsening the physical and psychological health of many of the caregivers, due to both work overload and fear of the global pandemic.

Calcitriol-Mediated Hypercalcemia, Somatostatin Receptors Expression and 25-Hydroxyvitamin D3-1α- Hydroxylase in GIST Tumors.

Hypercalcemia is a common complication in cancer patients Mainly caused by Parathyroid hormone-related protein (PTHrP) secretion and metastasis. Calcitriol secretion is a rare source of hypercalcemia in solid tumors, especially in gastrointestinal stromal tumors (GIST). We present a case report of a female patient with a 23 cm gastric GIST that expressed somatostatin-receptors and presented with severe hypercalcemia due to calcitriol secretion. Calcium control was achieved with medical treatment before the use of targeted-directed therapies. Surgery was performed and allowed complete tumor resection. Two years later, patient remains free of disease. Molecular analysis revealed the mRNA expression of 25-hydroxyvitamin D3-1-hydroxylase (1αOHase) and vitamin-D receptors in the tumor cells, confirming the calcitriol-mediated mechanism. Furthermore, the expression of the endotoxin recognition factors CD14 and TLR4 suggests an inflammatory mediated mechanism. Finally, the expression of somatostatin-receptors, especially SST2 might have been related with clinical evolution and prognosis in this patient.

Thyroid hormones in diabetes, cancer, and aging.

Thyroid function is central in the control of physiological and pathophysiological processes. Studies in animal models and human research have determined that thyroid hormones modulate cellular processes relevant for aging and for the majority of age-related diseases. While several studies have associated mild reductions on thyroid hormone function with exceptional longevity in animals and humans, alterations in thyroid hormones are serious medical conditions associated with unhealthy aging and premature death. Moreover, both hyperthyroidism and hypothyroidism have been associated with the development of certain types of diabetes and cancers, indicating a great complexity of the molecular mechanisms controlled by thyroid hormones. In this review, we describe the latest findings in thyroid hormone research in the field of aging, diabetes, and cancer, with a special focus on hepatocellular carcinomas. While aging studies indicate that the direct modulation of thyroid hormones is not a viable strategy to promote healthy aging or longevity and the development of thyromimetics is challenging due to inefficacy and potential toxicity, we argue that interventions based on the use of modulators of thyroid hormone function might provide therapeutic benefit in certain types of diabetes and cancers.

Cultural stereotypes in care contexts.

INTRODUCTION: The main goal of the present study was to examine the stereotype content model (SCM) assumption for universality and to test whether the mediating role of cultural views about older adult caregivers is maintained in other health care contexts. METHODS: One hundred and sixty professionals and volunteers who worked with older adults in day care centers (DCCs) and senior citizen centers (SCCs) and 1,151 participants from a representative sample of the Spanish population were examined using the SCM questionnaire; older adult and personnel functioning were assessed through an observation procedure with two subscales of the Evaluation Scale from the Sistema de Evaluación de Residencias de Ancianos. RESULTS: The results showed that the context does not seem to influence the cultural views about older adults held by caregivers. All results support the cultural stereotype pattern in which members of the older adult group are viewed with high warmth (HW) and low competence (LC) as posited by the SCM model. With respect to the mediation of cultural stereotypes on caregivers/older adult functioning, this has not been supported in this study. Neither cultural views of warmth (predicted by the SCM) nor views of competence (from our previous studies) influence either caregiver functional behaviors or older adult functioning. CONCLUSION: Two post hoc hypotheses can be inferred: 1) there is more variability in competence and warmth in DCCs and SCCs and 2) although we did not find significant differences in the pattern of competence and warmth in perceived cultural stereotypes about older adults, more healthy environments could reduce the influence of cognitive views on behavior.

The role of perceived discrimination on active aging.

Among older adults, perceived age discrimination is highly associated with unhealthy outcomes and dissatisfaction. Active aging is a multidimensional concept described by a set of characteristics, particularly health, positive mood and control; most importantly, active aging is currently at the core of public policies. The aim of the present study was to test to what extent perceived discrimination influences active aging. Methods A total of 2005 older adults in three representative samples from regions of Germany, Mexico and Spain participated; they were tested on active aging and perceived discrimination. First, active aging was defined as high reported health, life satisfaction and self-perception of aging. Second, authors introduced the assumption that, in the total sample, structural equation modelling would confirm the hypothesis of a direct negative link between perceived age discrimination and active aging. Finally, multiple group comparison performed through structural equation modelling also provided support for the negative association between perceived discrimination and active aging proposed. In spite of the differences found among the three countries in both active aging variables and age discrimination perception, multiple group comparison indicates that regardless of the culture, perceived discrimination is a negative predictor of active aging.

Effectiveness of non-pharmacological interventions for the prevention and management of psychological and social morbidity in women who have an elective abortion: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to synthesize the best available evidence on the effectiveness of non-pharmacological interventions for the prevention and management of psychological and social morbidity in women who have an elective abortion.The specific review question that will be addressed is: In women (aged 13 years or more) with unwanted pregnancies who decide to have an elective abortion, which non-pharmacological interventions should be provided before, during and after the elective abortion procedure both in community and hospital environments to prevent and manage psychological and social morbidity?

Active aging promotion: results from the vital aging program.

Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished.

Cognitive plasticity in normal and pathological aging.

The main goal of the present study is to examine to what extent age and cognitive impairment contribute to learning performance (cognitive plasticity, cognitive modifiability, or learning potential). To address this question, participants coming from four studies (Longitudinal Study of Active Aging, age range, 55-75 years, N = 458; Longitudinal Study in the very old [90+], age range, 90-102, N = 188, and Cognitive Plasticity within the Course of Cognitive Impairment, 97 "Normal", 57 mild cognitive impairment [MCI], and 98 Alzheimer's disease [AD] patients) were examined through a measure of verbal learning (developed from Rey). The results show that all age, MCI, and AD groups learned across the five learning trials of that test, but significant differences were found due to age, pathology, and education. The effects of pathology (MCI and AD) can be expressed in a metric of "years of normal decline by age"; specifically, being MCI means suffering an impairment in performance that is equivalent to the decline of a normal individual during 15 years, whereas the impact of AD is equivalent to 22.7 years. Likewise, the improvement associated with about 5 years of education is equivalent to about 1 year less of normal aging. Also, the two pathological groups significantly differed from "normal" groups in the delayed trial of the test. The most dramatic difference is that between the "normal" group and the AD patients, which shows relatively poorer performance for the AD group in the delayed trial than in the first learning trial. The potential role of this unique effect for quick detection purposes of AD is assessed (in the 75-89 years age range, sensitivity and specificity equal 0.813 and 0.917, respectively).

Actividades cognitivas y funcionamiento cognitivo en personas muy mayores / Cognitive activities and cognitive functioning in the elderly

Introducción. El objetivo de esta investigación ha sido analizar si la actividad es un factor protector del declive intelectual y, concretamente, examinar si la actividad intelectual, respecto de otro tipo de actividades, es un predictor del mantenimiento del funcionamiento cognitivo en un grupo de personas mayores de 90 años, independientes en las actividades básicas de la vida diaria y que tienen preservada su capacidad cognitiva. Material y métodos. Esta muestra fue seleccionada para el estudio biopsicosocial sobre personas independientes de 90 años y más. Se trata de un estudio longitudinal en el que participaron 188 personas, 67 varones y 121 mujeres. Se tomaron medidas del funcionamiento cognitivo y del nivel de actividad y se volvieron a repetir pasados entre 6 y 14 meses; se realizaron análisis inferenciales en la línea base y en el seguimiento. Resultados. En la línea base encontramos una fuerte asociación entre el nivel de actividad y el funcionamiento cognitivo. Y más aún, la realización de actividades intelectuales en la línea base predice un mejor funcionamiento cognitivo en el seguimiento. La realización de actividades intelectuales y el mantenimiento del funcionamiento cognitivo son dos entidades que, en ausencia de deterioro cognitivo, se dan asociadas en ancianos muy mayores. Conclusiones. Estos resultados tienen implicaciones importantes para la comunidad científica a la hora de encontrar índices predictivos y estrategias preventivas, pero también para el individuo al encontrar factores de cambio personal sobre los que poder actuar paliando problemas asociados a la edad(AU)

Introduction. The aim of this study was to analyse whether the activity is a protective factor of intellectual decline, and specifically to examine whether intellectual activity versus other activities, is a better predictor for the maintenance of cognitive functioning in a group of people over 90 years, independent in basic daily living activities and having preserved cognitive capacity. Material and methods. This sample was selected from a bio-psycho-social longitudinal study of independent persons 90 and over. This is a longitudinal study involving 188 people, 67 males and 121 females. Measurements were taken of cognitive functioning and level of activity and repeated between 6 and 14 months; inferential analysis was performed at baseline and follow-up. Results. At base-line, there is a strong association between the level of activity and performance. Also, and most important, intellectual activities at baseline predict cognitive functioning at follow-up. According to our results, intellectual activities and the maintenance of cognitive functioning are associated with the absence of cognitive impairment in the very elderly. Conclusions. This has important implications for the scientific community in finding a predictive index and strategies, but also for the individual to identify factors of change on which to act to reduce problems associated with aging(AU)

[Cognitive activities and cognitive functioning in the elderly]. / Actividades cognitivas y funcionamiento cognitivo en personas muy mayores.

INTRODUCTION: The aim of this study was to analyse whether the activity is a protective factor of intellectual decline, and specifically to examine whether intellectual activity versus other activities, is a better predictor for the maintenance of cognitive functioning in a group of people over 90 years, independent in basic daily living activities and having preserved cognitive capacity. MATERIAL AND METHODS: This sample was selected from a bio-psycho-social longitudinal study of independent persons 90 and over. This is a longitudinal study involving 188 people, 67 males and 121 females. Measurements were taken of cognitive functioning and level of activity and repeated between 6 and 14 months; inferential analysis was performed at baseline and follow-up. RESULTS: At base-line, there is a strong association between the level of activity and performance. Also, and most important, intellectual activities at baseline predict cognitive functioning at follow-up. According to our results, intellectual activities and the maintenance of cognitive functioning are associated with the absence of cognitive impairment in the very elderly. CONCLUSIONS: This has important implications for the scientific community in finding a predictive index and strategies, but also for the individual to identify factors of change on which to act to reduce problems associated with aging.

Mortality and refusal in the longitudinal 90+ project.

Attrition is one of the most important threats for longitudinal studies on aging mainly due to refusal and mortality. This study deals with those individuals who were assessed in the base line of 90+ project but died, dropped out or were examined in the follow-up. Participants of the 90+ project baseline consist of a sample of 188 older than 90 years, independent individuals (mean age = 92.9; 67 men and 121 women) living in the community (n = 76) or in residences (n = 112). They were assessed through the European Survey on Aging Protocol (ESAP) by collecting anthropometric, health and life styles, bio-behavioral, psychological and social data. After 6-14 months from the baseline, 55% individuals were re-assessed, 11% died and 34% dropped out for several reasons. Comparisons between the individuals deceased, interviewed and those who dropped out yielded significant differences mainly due to contextual variables. The mortality rate of participants living in residences is three times greater than those of participants living in the community. Trying to determine the differences between these three groups due to bio-psycho-social variables, we found that regular physical activity, mental status, leisure activities, fitness, perceived control and openness assessed at the baseline differentiate our three groups. Finally, 90% of those individuals who died were identified at the baseline as "non successful agers", while more than a half of those who participated and a third of the non-participants were identified as "successful agers". It can be concluded that among those independent but very old people, mortality is less important than willing to participate and contextual, behavioral and psychological factors are relevant for distinguishing mortality, survival and participation.