European Working Group on Sarcopenia in Older People 2010 (EWGSOP1) and 2019 (EWGSOP2) criteria or slowness: which is the best predictor of mortality risk in older adults?

Objectives: to analyse the accuracy of grip strength and gait speed in identifying mortality; to compare the association between mortality and sarcopenia defined by the EWGSOP1 and EWGSOP2 using the best cut-off found in the present study and those recommended in the literature and to test whether slowness is better than these two definitions to identify the risk of death in older adults. / Methods: a longitudinal study was conducted involving 6,182 individuals aged 60 or older who participated in the English Longitudinal Study of Ageing. Sarcopenia was defined based on the EWGSOP1 and EWGSOP2 using different cut-off for low muscle strength (LMS). Mortality was analysed in a 14-year follow-up. / Results: compared with the LMS definitions in the literature (<32, <30, <27 and < 26 kg for men; <21, <20 and < 16 kg for women), the cut-off of <36 kg for men (sensitivity = 58.59%, specificity = 72.96%, area under the curve [AUC] = 0.66) and < 23 kg for women (sensitivity = 68.90%, specificity = 59.03%, AUC = 0.64) as well as a low gait speed (LGS) ≤0.8 m/s (sensitivity = 53.72%, specificity = 74.02%, AUC = 0.64) demonstrated the best accuracy for mortality. Using the cut-off found in the present study, probable sarcopenia [HR = 1.30 (95%CI: 1.16–1.46)], sarcopenia [HR = 1.48 (95%CI: 1.24–1.78)] and severe sarcopenia [HR = 1.78 (95%CI: 1.49–2.12)] according to EWGSOP2 were better predictors of mortality risk than EWGSOP1. LGS ≤0.8 m/s was a better mortality risk predictor only when LMS was defined by low cut-off. / Conclusions: using LMS <36 kg for men and < 23 kg for women and LGS ≤ 0.8 m/s, EWGSOP2 was the best predictor for mortality risk in older adults

Molecular characterization of short-term primary cultures and comparison with corresponding tumor tissue of Brazilian glioblastoma patients

Background: Glioblastoma, the most frequent and malignant adult brain tumor, has been extensively studied. However, there is no effective treatment, and to overcome this challenging scenario, it is essential to improve preclinical biological models. This study aimed to molecularly characterize short-term glioblastoma primary cultures and to compare them with patient tumor profiles. Methods: Glioblastoma cell lines were established from Barretos Cancer Hospital patients diagnosed with glioblastoma. The cells were cultured with DMEM (+)10% FBS (+)1% PS and were molecularly characterized using array CGH (aCGH), next-generation and Sanger sequencing. Results: We established four short-term glioblastoma cultures and we found that the primary cells exhibited a diversity of chromosomal aberrations, with gain of chromosome 7 and loss of chromosomes 10, 13 and 17p being the most frequent alterations. Mutation profiling showed that hotspot TERT promoter mutations were present in 3/4 cases, followed by mutations in TP53 (2/4) and in the RB1, BRAF and PTEN (1/4) genes. A similar chromosomal and mutation pattern was observed in all short-term cultures and matched frozen tumors. Conclusions: Herein, short-term glioblastoma primary cultures were successfully characterized and had genetic make-ups that were similar to those of patient tumors, suggesting that short-term primary cultures are suitable in vitro models for studies of glioblastoma biology.Universal/CNPq (475358/2011-2-Reis RM), FAPESP (2012/19590-0-Reis RM) and the MCTI/CNPq No. 73/2013 (Reis RM) grants. Bidinotto LT was a recipient of the FAPESP fellowship (2011/08523-7 and 2012/08287-4)info:eu-repo/semantics/publishedVersio

Sex Differences in Vitamin D Status as a Risk Factor for Incidence of Disability in Instrumental Activities of Daily Living: Evidence from the ELSA Cohort Study

Vitamin D deficiency compromises elements underlying the disability process; however, there is no evidence demonstrating the association between vitamin D deficiency and the incidence of disability in instrumental activities of daily living (IADL). We investigated the association between vitamin D deficiency and the risk of incidence of IADL disability separately in men and women. A total of 4768 individuals aged ≥50 years from the English Longitudinal Study of Aging (ELSA) and without IADL disability according to the Lawton scale were available. Vitamin D was evaluated at baseline by serum 25(OH)D concentrations and classified as sufficient (>50 nmol/L), insufficient (>30 to ≤50 nmol/L) or deficient serum (≤30 nmol/L). IADL were reassessed after 4 years. Poisson models stratified by sex and controlled by covariates demonstrated that deficient serum 25(OH)D was a risk factor for the incidence of IADL disability in men (IRR: 1.43; 95% CI 1.02, 2.00), but not in women (IRR: 1.23; 95% CI 0.94, 1.62). Men appear to be more susceptible to the effect of vitamin D deficiency on the incidence of IADL disability, demonstrating the importance of early clinical investigation of serum 25(OH)D concentrations to prevent the onset of disability

Combination of dynapenia and abdominal obesity affects long-term physical performance trajectories in older adults: Sex differences

BACKGROUND: There is little epidemiological evidence of sex differences in the association between dynapenic abdominal obesity and the decline in physical performance among older adults. OBJECTIVE: The aims of the present study were to investigate whether the decline in physical performance is worse in individuals with dynapenic abdominal obese and whether there are sex differences in this association. METHODS: Out of 6,183 individuals aged 60 years or older from the English Longitudinal Study of Ageing, 2,308 participants with missing data were excluded. Therefore, a longitudinal analysis was conducted with 3,875 older adults. Abdominal obesity was determined based on waist circumference (>102 cm for male and >88 cm for female) and dynapenia was based on grip strength (<26 kg for male <16 kg for female). The sample was divided into four groups: non-dynapenic/non-abdominal obesity (ND/NAO), non-dynapenic/abdominal obesity (ND/AO), dynapenic/non-abdominal obesity (D/NAO) and dynapenic/abdominal obesity (D/AO). Decline in physical performance in an eight-year follow-up period was analyzed using generalized linear mixed models. RESULTS: At baseline, both male (-1.11 points; 95% CI: -1.58, -0.65; p <0.001) and female (-1.39 points; 95% CI: -1.76, -1.02; p <0.001) with D/AO had worse performances on the Short Physical Performance Battery (SPPB) than their counterparts in the ND/NAO group. Over the eight-year follow-up, male with D/AO had a faster rate of decline in the SPPB performance compared to male in the ND/NAO group (-0.11 points per year; 95% CI: -0.21, -0.01; p = 0.03). CONCLUSION: D/AO is associated with a stronger decline in physical performance in male but not female. The identification and management of dynapenic abdominal obesity may be essential to avoiding the first signs of functional impairment in older male

Is dynapenic abdominal obesity a risk factor for cardiovascular mortality? A competing risk analysis

BACKGROUND: Dynapenic abdominal obesity has been shown as a risk factor for all-cause mortality in older adults. However, there is no evidence on the association between this condition and cardiovascular mortality. OBJECTIVE: We aimed to investigate whether dynapenic abdominal obesity is associated with cardiovascular mortality in individuals aged 50 and older. METHODS: A longitudinal study with an 8-year follow-up was conducted involving 7,030 participants of the English Longitudinal Study of Ageing study. Abdominal obesity and dynapenia were respectively defined based on waist circumference (> 102 cm for men and > 88 cm for women) and grip strength (< 26 kg for men and < 16 kg for women). The sample was divided into four groups: non-dynapenic/non-abdominal obesity (ND/NAO), non-dynapenic/abdominal obesity (ND/AO), dynapenic/non-abdominal obesity (D/NAO) and dynapenic/abdominal obesity (D/AO). The outcome was cardiovascular mortality. The Fine-Grey regression model was used to estimate the risk of cardiovascular mortality as a function of abdominal obesity and dynapenia status in the presence of competing events controlled by socio-demographic, behavioural and clinical variables. RESULTS: The risk of cardiovascular mortality was significantly higher in individuals with D/AO compared with ND/NAO (SHR 1.85; 95% CI: 1.15-2.97). D/NAO was also associated with cardiovascular mortality (SHR: 1.62; 95% CI: 1.08-2.44). CONCLUSION: Dynapenic abdominal obesity is associated with cardiovascular mortality, with a larger effect size compared to dynapenia alone in individuals older than 50 years. Thus, prevention strategies and clinical interventions that enable mitigating the harmful effects of these conditions should be adopted to diminish such risk

A design of experiments (DoE) approach to optimize cryogel manufacturing for tissue engineering applications

Marine origin polymers represent a sustainable and natural alternative to mammal counterparts regarding the biomedical application due to their similarities with proteins and polysaccharides present in extracellular matrix (ECM) in humans and can reduce the risks associated with zoonosis and overcoming social- and religious-related constraints. In particular, collagen-based biomaterials have been widely explored in tissue engineering scaffolding applications, where cryogels are of particular interest as low temperature avoids protein denaturation. However, little is known about the influence of the parameters regarding their behavior, i.e., how they can influence each other toward improving their physical and chemical properties. Factorial design of experiments (DoE) and response surface methodology (RSM) emerge as tools to overcome these difficulties, which are statistical tools to find the most influential parameter and optimize processes. In this work, we hypothesized that a design of experiments (DoE) model would be able to support the optimization of the collagen-chitosan-fucoidan cryogel manufacturing. Therefore, the parameters temperature (A), collagen concentration (B), and fucoidan concentration (C) were carefully considered to be applied to the Boxâ Behnken design (three factors and three levels). Data obtained on rheological oscillatory measurements, as well as on the evaluation of antioxidant concentration and adenosine triphosphate (ATP) concentration, showed that fucoidan concentration could significantly influence collagen-chitosan-fucoidan cryogel formation, creating a stable internal polymeric network promoted by ionic crosslinking bonds. Additionally, the effect of temperature significantly contributed to rheological oscillatory properties. Overall, the condition that allowed us to have better results, from an optimization point of view according to the DoE, were the gels produced at −80ºC and composed of 5% of collagen, 3% of chitosan, and 10% fucoidan. Therefore, the proposed DoE model was considered suitable for predicting the best parameter combinations needed to develop these cryogels.This research was funded by the Portuguese Foundation for Science and Technology (FCT) for Ph.D. fellowship (D.N.C.) under the scope of the doctoral program Tissue Engineering, Regenerative Medicine and Stem Cells, ref. PD/BD/143044/2018, for postdoctoral fellowship (C.G.), ref. SFRH/BPD/94277/2013. This work has been partially funded by ERDF under the scope of the Atlantic Area Program through project EAPA_151/2016 (BLUEHUMAN)

Karyotypic divergence reveals that diversity in the Oecomys paricola complex (Rodentia, Sigmodontinae) from eastern Amazonia is higher than previously thought.

The genus Oecomys (Rodentia, Sigmodontinae) is distributed from southern Central America to southeastern Brazil in South America. It currently comprises 18 species, but multidisciplinary approaches such as karyotypic, morphological and molecular studies have shown that there is a greater diversity within some lineages than others. In particular, it has been proposed that O. paricola constitutes a species complex with three evolutionary units, which have been called the northern, eastern and western clades. Aiming to clarify the taxonomic status of O. paricola and determine the relevant chromosomal rearrangements, we investigated the karyotypes of samples from eastern Amazonia by chromosomal banding and FISH with Hylaeamys megacephalus (HME) whole-chromosome probes. We detected three cytotypes for O. paricola: A (OPA-A; 2n = 72, FN = 75), B (OPA-B; 2n = 70, FN = 75) and C (OPA-C; 2n = 70, FN = 72). Comparative chromosome painting showed that fusions/fissions, translocations and pericentric inversions or centromeric repositioning were responsible for the karyotypic divergence. We also detected exclusive chromosomal signatures that can be used as phylogenetic markers. Our analysis of karyotypic and distribution information indicates that OPA-A, OPA-B and OPA-C are three distinct species that belong to the eastern clade, with sympatry occurring between two of them, and that the "paricola group" is more diverse than was previously thought

Are Serum 25-Hydroxyvitamin D Deficiency and Insufficiency Risk Factors for the Incidence of Dynapenia?

Epidemiological evidence showing the association between low 25(OH)D and age-related reduction in neuromuscular strength (dynapenia) is a paucity and controversial and, to date, the effect of osteoporosis and vitamin D supplementation on these associations has not been measured. Thus, we analyze whether serum 25(OH)D deficiency and insufficiency are risk factors for the incidence of dynapenia in individuals aged 50 or older and whether osteoporosis or vitamin D supplementation modify these associations. For that, 3205 participants of the ELSA study who were non-dynapenic at baseline were followed for 4 years. Vitamin D was measured at baseline by the serum concentration of 25(OH)D and classified as sufficient (> 50 nmol/L), insufficient (≥ 30 and ≤ 50 nmol/L) or deficient (< 30 nmol/L). The incidence of dynapenia was determined by a grip strength < 26 kg for men and < 16 kg for women at the end of the 4-year follow-up. Poisson regression models were adjusted by sociodemographic, behavioral, clinical and biochemical characteristics. Serum 25(OH)D deficient was a risk factor for the incidence of dynapenia (IRR = 1.70; 95% CI 1.04-2.79). When only individuals without osteoporosis and those who did not use vitamin D supplementation were analyzed, both serum 25(OH)D deficiency (IRR = 1.78; 95% CI 1.01-3.13) and insufficiency (IRR = 1.77; 95% CI 1.06-2.94) were risk factors for the incidence of dynapenia. In conclusion, a serum level of 25(OH)D < 30 nmol/L is a risk factor for the incidence of dynapenia. Among individuals without osteoporosis and those who do not take vitamin D supplementation, the threshold of risk is higher (≤ 50 nmol/L)

Chromosomal Signatures Corroborate the Phylogenetic Relationships within Akodontini (Rodentia, Sigmodontinae).

Comparative chromosome-painting analysis among highly rearranged karyotypes of Sigmodontinae rodents (Rodentia, Cricetidae) detects conserved syntenic blocks, which are proposed as chromosomal signatures and can be used as phylogenetic markers. In the Akodontini tribe, the molecular topology (Cytb and/or IRBP) shows five low-supported clades (divisions: "Akodon", "Bibimys", "Blarinomys", "Oxymycterus", and "Scapteromys") within two high-supported major clades (clade A: "Akodon", "Bibimys", and "Oxymycterus"; clade B: "Blarinomys" and "Scapteromys"). Here, we examine the chromosomal signatures of the Akodontini tribe by using Hylaeamys megacephalus (HME) probes to study the karyotypes of Oxymycterus amazonicus (2n = 54, FN = 64) and Blarinomys breviceps (2n = 28, FN = 50), and compare these data with those from other taxa investigated using the same set of probes. We strategically employ the chromosomal signatures to elucidate phylogenetic relationships among the Akodontini. When we follow the evolution of chromosomal signature states, we find that the cytogenetic data corroborate the current molecular relationships in clade A nodes. We discuss the distinct events that caused karyotypic variability in the Oxymycterus and Blarinomys genera. In addition, we propose that Blarinomys may constitute a species complex, and that the taxonomy should be revised to better delimit the geographical boundaries and their taxonomic status

Chromosomal phylogeny and comparative chromosome painting among Neacomys species (Rodentia, Sigmodontinae) from eastern Amazonia

Abstract: Background: The Neacomys genus is predominantly found in the Amazon region, and belongs to the most diverse tribe of the Sigmodontinae subfamily (Rodentia, Cricetidae, Oryzomyini). The systematics of this genus and questions about its diversity and range have been investigated by morphological, molecular (Cytb and COI sequences) and karyotype analysis (classic cytogenetics and chromosome painting), which have revealed candidate species and new distribution areas. Here we analyzed four species of Neacomys by chromosome painting with Hylaeamys megacephalus (HME) whole-chromosome probes, and compared the results with two previously studied Neacomys species and with other taxa from Oryzomyini and Akodontini tribes that have been hybridized with HME probes. Maximum Parsimony (MP) analyses were performed with the PAUP and T.N.T. software packages, using a non-additive (unordered) multi-state character matrix, based on chromosomal morphology, number and syntenic blocks. We also compared the chromosomal phylogeny obtained in this study with molecular topologies (Cytb and COI) that included eastern Amazonian species of Neacomys, to define the phylogenetic relationships of these taxa. Results: The comparative chromosome painting analysis of the seven karyotypes of the six species of Neacomys shows that their diversity is due to 17 fusion/fission events and one translocation, pericentric inversions in four syntenic blocks, and constitutive heterochromatin (CH) amplification/deletion of six syntenic autosomal blocks plus the X chromosome. The chromosomal phylogeny is consistent with the molecular relationships of species of Neacomys. We describe new karyotypes and expand the distribution area for species from eastern Amazonia and detect complex rearrangements by chromosome painting among the karyotypes. Conclusions: Our phylogeny reflects the molecular relationships of the Akodontini and Oryzomyini taxa and supports the monophyly of Neacomys. This work presents new insights about the chromosomal evolution of this group, and we conclude that the karyotypic divergence is in accord with phylogenetic relationships