Background
The associations between free‐living physical activity (PA) and sedentary behaviour (SB) and sarcopenia in older people and its determinants are controversial. Self‐reporting, the use of ...one‐size‐fits‐all cut‐points for intensity categorization when using accelerometers and the absence of a clear sarcopenia definition hampered explorations. The aim of this study is to describe the associations between objectively measured PA patterns and sarcopenia and its determinants.
Methods
Subjects aged >65 with valid accelerometry and sarcopenia‐related measures from Toledo Study of Healthy Aging (TSHA) were included. Muscle mass (MM) was estimated by dual‐energy X‐ray absorptiometry. Handgrip strength (HS) was measured by dynamometry. Physical performance assessment relied on gait speed (GS). Sarcopenia presence was ascertained using Foundation for the National Institutes of Health (FNIH) criteria. PA and SB were estimated by ActiTrainer worn for 1 week and classified into time spent in SB and different PA intensity bands light PA (LPA) and moderate‐to‐vigorous PA (MVPA) using age‐specific cut‐points. Different multivariate linear and logistic regression models (i) single‐parameter, (ii) partition, and (iii) isotemporal substitution models were used for estimating associations between PA, SB, and sarcopenia determinants and sarcopenia rates, respectively. All models adjusted for age, sex, co‐morbidities (Charlson index), and functional ability (Katz and Lawton indexes).
Results
Five hundred twelve subjects from the TSHA had available data (78.08 ± 5.71 years of age; 54.3% women). FNIH sarcopenia assessment was performed in 497 subjects (23.3% were sarcopenic). In the linear regression, the single‐parameter model showed an association between MVPA and all sarcopenia determinants. In the partition model, MVPA was associated with greater MM and GS. The isotemporal substitution showed that reallocating 1 h/day of MVPA displacing SB was associated with greater values in MM β = 0.014; 95% confidence interval (CI) = 0.004, 0.024; P < 0.01, GS (β = 0.082; 95% CI = 0.054, 0.110; P < 0.001), and HS (β = 0.888; 95% CI = 0.145, 1.631; P < 0.05). In the logistic regression, the single‐parameter model yielded a significant association between 1 h/day increase in MVPA and sarcopenia reduction odds ratio (OR) = 0.522; 95% CI = 0.367, 0.726; P < 0.001, as did the partition model (OR = 0.555; 95% CI = 0.376, 0.799; P < 0.01). The reallocation of 1 h/day SB only yielded a significant lower sarcopenia risk by almost 50% when it was substituted with MVPA, whereas the substitution of 15 min/day yielded a significant lower sarcopenia risk by 15% (P < 0.001) but did not show any association when it was substituted with LPA.
Conclusions
An increase in MVPA replacing SB and LPA was associated with a reduction in sarcopenia prevalence and better performance across its determinants (MM, GS, and HS). LPA did not show any significant effect.
The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not ...considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.
The Middle-to-Upper Paleolithic transition in Europe covers the last millennia of Neanderthal life together with the appearance and expansion of Modern Human populations. Culturally, it is defined by ...the Late Middle Paleolithic succession, and by Early Upper Paleolithic complexes like the Châtelperronian (southwestern Europe), the Protoaurignacian, and the Early Aurignacian. Up to now, the southern boundary for the transition has been established as being situated between France and Iberia, in the Cantabrian façade and Pyrenees. According to this, the central and southern territories of Iberia are claimed to have been the refuge of the last Neanderthals for some additional millennia after they were replaced by anatomically Modern Humans on the rest of the continent. In this paper, we present the Middle-to-Upper Paleolithic transition sequence from Cova Foradada (Tarragona), a cave on the Catalan Mediterranean coastline. Archaeological research has documented a stratigraphic sequence containing a succession of very short-term occupations pertaining to the Châtelperronian, Early Aurignacian, and Gravettian. Cova Foradada therefore represents the southernmost Châtelperronian-Early Aurignacian sequence ever documented in Europe, significantly enlarging the territorial distribution of both cultures and providing an important geographical and chronological reference for understanding Neanderthal disappearance and the complete expansion of anatomically Modern Humans.
Nucleic acid amplification diagnostics offer outstanding features of sensitivity and specificity. However, they still lack speed and robustness, require extensive infrastructure, and are neither ...affordable nor user-friendly. Thus, they have not been extensively applied in point-of-care diagnostics, particularly in low-resource settings. In this work, we have combined the loop-mediated isothermal amplification (LAMP) technology with a handheld portable device (SMART-LAMP) developed to perform real-time isothermal nucleic acid amplification reactions, based on simple colorimetric measurements, all of which are Bluetooth-controlled by a dedicated smartphone app. We have validated its diagnostic utility regarding different infectious diseases, including Schistosomiasis, Strongyloidiasis, and COVID-19, and analyzed clinical samples from suspected COVID-19 patients. Finally, we have proved that the combination of long-term stabilized LAMP master mixes, stored and transported at room temperature with our developed SMART-LAMP device, provides an improvement towards true point-of-care diagnosis of infectious diseases in settings with limited infrastructure. Our proposal could be easily adapted to the diagnosis of other infectious diseases.
Aqueous and methanolic extracts of several microalgae (Ankistrodesmus sp., Spirogyra sp., Euglena cantabrica, and Caespitella pascheri) and cyanobacteria (Nostoc sp., Nostoc commune, Nodularia ...spumigena, Leptolyngbya protospira, Phormidiochaete sp., and Arthrospira platensis) were screened for their radical scavenging activity against the stable radical 1,1-diphenyl-2-picrylhydrazyl. Despite the fact that water was a more efficient solvent to extract greater amount of extractable substances, it seems that methanol was more efficient to extract a selected group of compounds with a higher antioxidant activity. In addition, the identification of 4 simple phenolics (gallic, syringic, protocatechuic, and chlorogenic acids) and the flavonoids (+) catechin and (-) epicatechin was carried out by using reverse phase high performance liquid chromatography. The strain Euglena cantabrica showed the highest concentration of phenolic compounds, particularly gallic and protocatechuic acids (5.87 and 2.97 mg per gram of dried biomass, resp.). Aqueous and methanolic extracts of microalgae Euglena cantabrica also exhibited the highest antioxidant activity, probably due to the presence of the high contents of phenolics.
Background
Physical activity (PA) is a recognized contributor to healthy aging. However, the majority of studies exploring its associations with adverse outcomes in cohorts of older adults use ...single‐time PA estimates, which do not consider its dynamic nature. The aim of the present study is to explore the presence of different PA trajectories in the Toledo Study of Healthy Aging and their association with adverse outcomes. Our hypothesis is that prospectively maintaining or increasing PA is associated with a reduced risk of adverse outcomes.
Methods
We used data from 1679 participants enrolled in the Toledo Study of Healthy Aging. Trajectories based on the Physical Activity Scale for the Elderly were identified using group‐based trajectory modelling. Cox and logistic regression were used to investigate associations between PA trajectories and mortality and hospitalization, and incident and worsening disability, respectively. Mortality was ascertained by linkage to the Spanish National Death Index; disability was evaluated through the Katz Index; and hospitalization was defined as the first admission to Toledo Hospital. Models were adjusted by age, sex, smoking, Charlson Index, education, cognitive impairment, polypharmacy, and Katz Index at Wave 2.
Results
We found four PA‐decreasing and one PA‐increasing trajectories: high PA‐consistent (n = 566), moderate PA‐mildly decreasing (n = 392), low PA‐increasing (n = 237), moderate PA‐consistent (n = 191), and low PA‐decreasing (n = 293). Belonging to the high PA‐consistent trajectory group was associated with reduced risks of mortality as compared with the low PA‐decreasing group hazard ratio (HR) 1.68; 95% confidence interval (CI) = 1.21–2.31 and hospitalization compared with the low PA‐increasing and low PA‐decreasing trajectory groups (HR 1.24; 95% CI = 1.004–1.54 and HR 1.25; 95% CI = 1.01–1.55, respectively) and with lower rates of incident odds ratio (OR) 3.14; 95% CI = 1.59–6.19 and worsening disability (OR 2.16; 95% CI = 1.35–3.45) in relation to the low PA‐decreasing trajectory group and at follow‐up. Increasing PA during late life (low PA‐increasing group) was associated with lower incident disability rates (OR 0.38; 95% CI = 0.19–0.82) compared with decreasing PA (low PA‐decreasing group), despite similar baseline PA.
Conclusions
Our results suggest that sustaining higher PA levels during aging might lead to healthy aging, characterized by a reduction in adverse outcomes. Our study supports the need for enhancing PA participation among older populations, with the goal of reducing personal and economic burden in a worldwide aging population.
Some of the Sima de los Huesos (SH) humeri have been previously studied and described elsewhere. Here we present an updated inventory and a review of the specimens recovered to the present day. The ...morphological key traits of the adult and subadult specimens are described, discussed, and illustrated. The SH humeri share with Neandertals many traits usually considered to be Neandertal specializations, thus, most of this morphological pattern is not exclusive to them. The variation found within fossil samples stresses the frequential nature of all these traits and in the specific case of the SH humeri, most of the traits considered as phylogenetically relevant are retained by their descendants, the Neandertals. Some traits are plesiomorphic for the entire genus Homo or are present in European hominins since the early Pleistocene. Finally, some other traits display high variability within the SH sample or different hominin samples and are of uncertain phylogenetic value. Altogether, this evidence is consistent with the hypothesis based on the overall cranial and postcranial morphology that the SH hominins are a sister group to the later Neandertals.
Current knowledge of the evolution of the postcranial skeleton in the genusHomois hampered by a geographically and chronologically scattered fossil record. Here we present a complete characterization ...of the postcranium of the middle Pleistocene paleodeme from the Sima de los Huesos (SH) and its paleobiological implications. The SH hominins show the following: (i) wide bodies, a plesiomorphic character in the genus Homo inherited fromtheir early hominin ancestors; (ii) statures that can be found in modern human middle-latitude populations that first appeared 1.6–1.5 Mya; and (iii) large femoral heads in some individuals, a trait that first appeared during the middle Pleistocene in Africa and Europe. The intrapopulational size variation in SH shows that the level of dimorphism was similar to modern humans (MH), but the SH hominins were less encephalized than Neandertals. SH shares many postcranial anatomical features with Neandertals. Although most of these features appear to be either plesiomorphic retentions or are of uncertain phylogenetic polarity, a few represent Neandertal apomorphies. Nevertheless, the full suite of Neandertal-derived features is not yet present in the SH population. The postcranial evidence is consistent with the hypothesis based on the cranial morphology that the SH hominins are a sister group to the later Neandertals. Comparison of the SH postcranial skeleton to other hominins suggests that the evolution of the postcranium occurred in a mosaic mode, both at a general and at a detailed level.
The excellent fossil record from Sima de los Huesos (SH) includes three well‐known complete adult femora and several partial specimens that have not yet been published in detail. This fossil record ...provides an opportunity to analyze the morphology of European pre‐Neandertal adult femur and its variation with different evolution patterns. Currently, there are a minimum of five adult individuals (males or females). In this study, we compiled previously published basic anatomical and biometric characteristics of SH adult femora, emphasizing the most relevant features compared to other recent and fossil hominins. The SH femora exhibited a primitive morphological pattern common to all non‐Homo sapiens femora, as well as most of the Neandertal traits. Therefore, the complete Upper Pleistocene Neandertal pattern was well‐established in Middle Pleistocene ancestors long before the proper Neandertals appeared. Additionally, we highlight that the SH and Neandertal femora share some morphological traits and proportions with modern humans that hold sexual significance in our species, regardless of size. Keeping this in mind, we discussed the sex determination of the complete SH specimens and re‐evaluated sex allocation in two of them.
Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer ...malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic. Keywords: Cancer, Metastasis, EMT, Non-coding RNA, Molecular mechanisms
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