Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht²/Z₅₀) and impedance ratio of high and low frequency (Z₂₅₀/Z₅) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht²/Z₅₀)) + (−55.24 × (Z₂₅₀/Z₅)) + (−10,940 × (1/Z₅₀)) + 51.33 for men, and ALM = (0.6144 × (Ht²/Z₅₀)) + (−36.61 × (Z₂₅₀/Z₅)) + (−9332 × (1/Z₅₀)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht²) in these participants were 6.8 and 5.7 kg/m² in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Introduction: maxillary hypoplasia and mandibular asymmetry may be corrected with orthognathic surgery at the completion of growth. Many patients require segmental Le Fort I osteotomies to obtain the most stable results. Unfortunately, if Invisalign is chosen for pre-surgical preparation, ClinCheck © software does not allow for prediction when these complex surgeries are planned. The objective of this paper was to show the potential of aligners beyond its software in most complex cases like multiple-piece maxillary osteotomies in cleft and non-cleft patients. Method: Thirteen patients who underwent pre-surgical treatment with clear aligners-Invisalign (study group) were matched in terms of diagnosis, surgical procedure, and orthodontic complexity with thirteen patients treated using fixed appliances (control group). A technique based on simple superimposition was devised to enhance the software for creating a suitable occlusion for segmental pre-surgical treatments. Virtual curves following the lower arch were employed to guide the correct pre-surgical positions of the upper teeth. The amount of impressions required in both groups to achieve satisfactory pre-surgical alignment of the segmented arches was compared. Results: one or no refinement phase were needed in the Invisalign group to reach an acceptable pre-surgical occlusion while the amount of pre-surgical impressions taken in order to reach adequate coordination with fixed appliance treatment was slightly higher. The average overall treatment duration did not show a statistically significant variation between the groups. Conclusions: it appears that clear aligner could serve as an effective treatment for individuals with skeletal discrepancies, including cleft and craniofacial anomalies, necessitating segmental Le Fort I osteotomies when aided by the suggested superimposition approach during digital pre-surgical movement simulations. More sophisticated softwares will certainly be implemented in the future.

Introduction. Autopsy is a medical procedure that consists of the corpse’s examination to determine the cause of death and obtain information on pathological conditions or injuries present in the body. In recent years there has been a reduction in hospital autopsies and an increase in forensic autopsies. Material and methods. A retrospective observational study was conducted on the reports of all the 645 hospital autopsies performed at Polyclinic of Bari from 2006 to 2021.Results. Group A, 2006-2009, 174 cases were studied: 58% male, 58% adults, 55% neonatology, pulmonary disease was the cause of death in 23%, and 55% of discrepancy between clinical and autopsy diagnosis. Group B, 2010-2013, comprised 119 cases: 52% male, 46% infants, 48% neonatology, pulmonary disease was the cause of death in 25%, and 56% of discrepancy between clinical and autopsy diagnosis. Group C, 2014-2017, comprised 168 cases: gender equality, 37% infants, 25% gynecology, pulmonary disease was the cause of death in 24%, and 58% of discrepancy between clinical and autopsy diagnosis. Group D, 2018-2021 comprised 184 cases: 56% male, 38% adult, 32% gynecology, pulmonary disease was the cause of death in 27%, and 58% discrepancy between clinical and autopsy diagnosis.Conclusion. The study of hospital autopsies at the Polyclinic of Bari shows that the discrepancy between clinical and autopsy diagnosis is around 56.75%. Thus, the hospital autopsy is helpful in the modern age, especially for diagnosing fetal and neonatal diseases.

The modification of proteins by small ubiquitin-related modifier (SUMO) molecules, SUMOylation, is a key post-translational modification involved in a variety of biological processes such as chromosomes organization, DNA replication and repair, transcription, nuclear transport, and cell signaling transduction. In recent years, emerging evidence has shown that SUMOylation regulates the development and homeostasis of the skeletal system, with its dysregulation causing skeletal diseases, suggesting that SUMOylation pathways may serve as a promising therapeutic target. In this review, we summarize the current understanding of the molecular mechanisms by which SUMOylation pathways regulate skeletal cells in the physiological and disease contexts.

Although fragility fractures, osteoporosis, sarcopenia and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral bone and muscle physiology the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently before. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass – FFM), grip strength and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and expressed as the percentage of body weight (FFM%) or divided by body mass index (FFM_BMI). Adjusted mean grip strength, FFM%, FFM_BMI, and BMD were calculated according quintiles of dietary magnesium, correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women respectively of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFM_BMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and have relevance for population prevention strategies for sarcopenia, osteoporosis and fractures.

Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Pharmacological and genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Senescent cells have an altered secretome, which may have an autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton. The review was written following an extensive literature survey of published studies, mostly excluding articles published on pre-print servers. The review discusses potential therapeutics targeting cellular senescence and the senescent secretome as underlying pathogenesis of an aging bone.

Time series ground deformation monitoring and reservoir parameter inversion are crucial for the dynamic assessment of oilfield resources and sustainable exploitation in an oilfield. As one of the regions with the richest oil reserves in China, the oilfield areas in the western Qaidam Basin are selected as a typical study area. Firstly, we used SAR images collected by the Sentinel-1A satellite from January 2021 to December 2022 and applied the Multidimensional Small Baseline Subset (MSBAS) method to obtain vertical and east-west deformation measurements. On this basis, a nonlinear Bayesian inversion method was applied to model the shallow reservoir in a series of complex deformation areas, based on a single-source model and a multi-source model, respectively. As a result, the ground deformation monitoring results obtained by long time series InSAR clearly reflect the uneven ground deformation caused by the oil extraction and water injection operation process. There is slight subsidence in the Huatugou oilfield, while significant uplift deformation occurred in the Ganchaigou oilfield and the Youshashan oilfield, with a maximum uplift rate of 48 mm/year. Further analysis indicates that the introduction of the 2D deformation field helps to improve the robustness of oilfield reservoir parameter inversion. Moreover, the dual-source model is more suitable than the single-source model for inverting complex deformation reservoir parameters. This study not only fills the blank of InSAR deformation monitoring for the oilfields in the western Qaidam Basin but also provides a theoretical reference for model and method selection of reservoir parameter inversion in other oilfields.

Sensory integration is an essential function of human life, and its decline causes difficulties in the quality of life, especially in older adults. In this study, we proposed an arm-reaching task based on a virtual reality head-mounted display (VR-HMD) system to assess sensory integration in daily life, and examined whether reaching task performance was associated with age and resting-state functional connectivity (rsFC) between the brain regions of interest involved in sensory integration. We hypothesized that performance during a reaching task with multiple cognitive loadings would be affected by aging. The gap angle between the reaching hand and target positions was compared between older and middle-aged adults as a measure of sensory integration function. In addition, rsFC, which was significantly correlated with the gap angles of individual participants in the older adult group, was identified using resting-state functional magnetic resonance imaging data. The mean gap angle was significantly larger in the older adults than in the middle-aged group and was also significantly correlated with connections between the left primary motor area and the left inferior temporal gyrus, temporo-occipital part. Because the connectivity between the areas is known to be related to visuomotor integration, the results suggest the involvement of visuomotor integration in the decline of sensory integration function in old age and the validity of the gap angle during the proposed VR-HMD task as an index for the decline in function.

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤32 weeks of gestational age (GA) within 24 hours of birth. Materials and Methods: It is a prospective study conducted from March 15, 2022, to November 15, 2023, in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n=44) and non-surfactant (n=44) subgroups. Results: 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler Score at 24 hours of life (1-RR = 1-0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p=0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p=0.0178) pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p=0.0210) post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p=0.0336). There were no significant changes in ductus arteriosus parameters at 24 hours of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤32 weeks of gestational age at 24 hours of life.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

Prenatal maternal feeding plays an important role in fetal development and has potential to cause long-lasting epigenetic modifications. MicroRNAs (miRNAs) are non-coding, single-stranded RNAs that serve as one epigenetic mechanism. Though miRNAs have crucial roles in fetal programming, growth, and development, there are limited data regarding maternal diet and sheep miRNA expression. Therefore, weanalyzed high and low maternal dietary protein for miRNA expression in sheep fetal longissimus dorsi. Pregnant ewes were fed an isoenergetic high-protein (HP, 160–270 g/day), low-protein (LP, 73–112 g/day), or standard protein diet (SP, 119–198 g/day) during pregnancy. miRNA expression profiles were evaluated using the Affymetrix GeneChip miRNA 4.0 Array. Twelve up-regulated, differentially expressed miRNAs (DE miRNAs) were identified targeting 65 genes. The oar-3957-5p miRNA was highly up-regulated in LP and SP compared to HP. Previous transcriptome analysis identified integrin and non-receptor protein tyrosine phosphatase genes targeted by miRNAs detected in the current experiment. A total of 28 GO terms and 10 pathway-based gene sets were significantly (padj < 0.05) enriched in target genes. Most genes targeted by identified miRNAs are involved in immune and muscle disease pathways. Our study shows dietary protein intake during pregnancy affects fetal skeletal muscle epigenetics via miRNA expression.

This Special Issue of Humanities comes at a time when the viability of the humanities are challenged on numerous fronts. On the one hand, the humanities face material threats as the politics of austerity continues throughout Europe and the United States, diminishing public support and making profit margin and “job creation” the primary measure of value or the basis of state university funding decisions. On the other, the humanities face conceptual, theoretical and ethical challenges, as the emergence of post-racial and post-humanist discourses signal what Foucault called “a change in the fundamental arrangements of knowledge.” The defining boundaries of constructs such as “race” and “human” have been radically called into question, challenging us to rethink the classificatory systems that found hierarchical relationships between, for example, the “fully human” and sub-human or non-human others. Despite dominant nations’ professed commitment to a universal human rights paradigm, racialized identities are still often the targets of disenfranchisement and dehumanization, while the exploitation and destruction of the natural world continues in the name of “progress” and profits.

Skeletal metastases of unknown primary (SMUP) represent a clinical challenge dealing with patients diagnosed with bone metastases. The management have improved significantly in the past years, however fraught with lack of evidences, approach to these patients held out hope for more systematic and tailored treatment—and some patients can achieve impressive gains. Nevertheless, in real-life practice the outlook at the beginning of the take in charge of SMUP is decidedly more somber. An incomplete translational relevance of pathological and clinical data on the mortality and morbidity rate has had unsatisfactory consequences for SMUP patients and their physicians. We examined several approaches to confront the available evidences and highlighted three key points that emerge. The characterization of the SMUP biologic profile is essential to drive clinical decisions, integrating genetic and molecular profile into a multi-step diagnostic work-up. Nonetheless, pragmatic investigation plan and therapy of SMUP cannot follow a single template; it must be adapted to different pathophysiological dynamics and coordinated with efforts of a systematic algorithm and high-quality data derived from statistically powered clinical trials within. This review argues that greater efforts are required to face the unmet need dealing with SMUP patients in oncology. Finally, we provide an original functional network analysis, identifying novel therapeutic targets.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

Neuronal cells are believed to rely on autophagy to maintain cellular homeostasis. Nevertheless, autophagy may be a therapeutic target for neurodegenerative diseases because of the role it plays in neuronal cell death. Despite Beclin 1 association with autophagy and apoptosis, the molecular mechanisms that underlie Tau-induced vesicular pathology and Tau protein aggregates in humans remain poorly understood. Here, we set out to examine the role of three genes-ATG14L, Beclin 1 and VPS34- in autophagy nucleation failure-associated Tau disorders in fruit fly models. We found that either reduced ATG14L levels improve neuronal outcomes, or transgenic expression of ATG6/Beclin 1 greatly reduced age-dependent neurodegeneration and Tau pathology; whereas, the loss of Beclin 1 exacerbated these effects. Prior to p-Tau accumulation, the neuronal Beclin 1 network is critical for reducing p-Tau accumulation, indicating that the loss of Beclin 1 causes Tau pathology and neurodegeneration. As neurodegeneration progressed, glial cells showed an upregulation of vesicular Beclin 1 immunoreactivities. The reduced VPS34 also resulted in p-Tau accumulation, suggesting that neurons require both Beclin 1 and VPS34 to reduce p-Tau accumulation. Our results provide mechanistic insight into the molecular pathways that cause age-dependent Tau pathology and neurodegeneration due to an excess of autophagy nucleation processes and autophagy activity, and we derive novel inferences on the therapeutic possibilities of rebalanced Beclin 1 network by reducing autophagic specific nucleation component of ATG14L.

A population dynamics epidemic model is developed that incorporates age of infection and age of vaccination. The model analyzes pre-symptomatic and symptomatic periods of an infected individual in terms of infection age. The model analyzes the efficacy of vaccination in terms of vaccination age. The model is applied to the 2003 SARS epidemic in Taiwan and the current COVID-19 epidemic in New York State.

Functional connectivity (FC) is a potential candidate that can increase the performance of brain-computer interfaces (BCIs) in the elderly because of its compensatory role in neural circuits. However, it is difficult to decode FC by current machine learning techniques because of a lack of its physiological understanding. To investigate the suitability of FC in BCI for the elderly, we propose the decoding of lower- and higher-order FCs using a convolutional neural network (CNN) in six cognitive-motor tasks. The layer-wise relevance propagation (LRP) method describes how age-related changes in FCs impact BCI applications for the elderly compared to younger adults. Seventeen younger (24.5±2.7 years) and twelve older (72.5±3.2 years) adults were recruited to perform tasks related to hand-force control with or without mental calculation. CNN yielded a six-class classification accuracy of 75.3% in the elderly, exceeding the 70.7% accuracy for the younger adults. In the elderly, the proposed method increases the classification accuracy by 88.3% compared to the filter-bank common spatial pattern (FBCSP). LRP results revealed that both lower- and higher-order FCs were dominantly overactivated in the prefrontal lobe depending on task type. These findings suggest a promising application of multi-order FC with deep learning on BCI systems for the elderly.

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

Abstract Although we know something about single cell neuromuscular junction, It is still mysterious how multiple skeletal muscle cells coordinate to complete the intricate spatial curve movement. Here I propose a hypothesis that skeletal muscle cell populations with action potentials are alligned according to a curved manifolds on space(a curved shape on space) and the skeletal muscle also moves according to this corresponding shape(manifolds) when an specific motor nerve impulses are transmitted. the action potential of motor nerve fibers has the characteristics of time curve manifold and this time manifold curve of motor nerve fibers come from visual cortex in which a spatial geometric manifolds are formed within the synaptic connection of neurons. This spatial geometric manifolds of the synaptic connection of neurons orginate from spatial geometric manifolds in outside nature that are transmitted to brain through the cone cells and ganglion cells of the retina.Further,the essence of life is that life is an object that can move autonomously and the essence of life's autonomous movement is the movement of proteins. theoretically, due to the infinite diversity of geometric manifold shapes in nature, the arrangement and combination of 20 amino acids should have infinite diversity, and the geometric manifold formed by protein three-dimensional spatial structure should also have infinite diversity.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

Cells are influenced by several biomechanical aspects of their microenvironment, such as substrate geometry. According to the literature, substrate geometry influences the behavior of muscle cells; in particular, the curvature feature improves cell proliferation. However, the effect of the substrate geometry on the myogenic differentiation process is not clear and needs to be further investigated. Here, we show that the 3D co-printing technique allows the realization of substrates. To test the influence of the co-printing technique on cellular behavior we realized linear polycaprolactone substrates with channels in which a fibrinogen-based hydrogel loaded with C2C12 cells was deposited. Cell viability and differentiation were investigated up to 21 days in culture. The results suggest that this technology significantly improves the differentiation at 14 days. Therefore, we investigate the substrate geometry influence by comparing three different co-printed geometries – linear, circular, and hybrid structures (linear and circular features combined). Based on our results, all structures exhibit optimal cell viability (> 94%) but the linear pattern allows to increase the in-vitro cell differentiation, in particular after 14 days of culture. This study proposes an endorsed approach for creating artificial muscles for future skeletal muscle tissue engineering applications.

Purpose: Physical activity (PA) is likely the most important modifiable element for the growth of skeletal muscle. However, a detailed investigation of PA’s impact on preschoolers’ of skeletal muscle development is lacking. This study aimed to determine whether PA level is related to skeletal muscle thickness among preschool children. Methods: 275 healthy preschoolers between the ages 4–6 were instructed to wear an accelerometer for 4 consecutive days. The daily steps and minutes spent in moderate-to-vigorous PA (MVPA) and total PA (TPA) were examined. Muscle thickness (MT) was measured by B-mode ultrasonography. The MT was measured at the anterior (AT) and posterior thigh (PT) and the anterior (AL) and posterior lower leg (PL). Results: Boys were more physically active and engaged in significantly more TPA and MVPA on weekdays compared with girls. Compared with that on the weekends, more physical activity, and significantly greater number of daily steps and higher TPA and MVPA were recorded for both boys and girls on the weekdays. Multivariable regression analyses, after adjusting for daylight duration, indicated that a daily increase in the TPA and MVPA would lead to higher muscle size in AT (β=1.11 and β=1.37, p<0.05), and PL (β=1.18 and β=0.94, p<0.05) among preschool children. Conclusions: The time spent involved in most of the different categories of MVPA was significantly higher for boys than for girls on the weekdays and weekends. MVPA was positively correlated with greater skeletal muscle development in the lower body.

NIRS uses the relative absorption of light at 850nm and 760nm, to determine skeletal muscle oxygen saturation. Previous studies have used the ratio of both signals to report muscle oxygen saturation. Purpose: To evaluate the different approaches used to represent muscle oxygen saturation, and to evaluate the pulsations of the O₂heme and Heme signal. Method: Twelve participants, ages 20-29years were tested on the forearm flexor muscles using continuous wave NIRS at rest. Measurements were taken during 2-3mins rest, during physiological calibration (5-minuts Ischemia) and during reperfusion. Results: There was a significant difference in pulse size between O₂heme and Heme signal at the three locations (p < 0.05). Resting oxygen saturation was 58.8+9.2%, 69.6+3.9%, and 89.2+6.9% when calibrated using O₂heme, TSI, and Heme, respectively. Conclusion: The difference in magnitude of O₂heme and Heme pulse with each heartbeat might suggest different anatomical locations of these signals, which propose calibrating with just one of the signals instead of the ratio of both. Calculations of physiological calibration must account for increased blood volume in the tissue, because of the changes in blood volume which appear to be primarily from the O₂heme signal. Resting oxygen levels calibrated with Heme agrees with theoretical oxygen saturation.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Introduction: The purpose of this study was to determine the normative values of muscles’ contractile properties, lateral symmetry, and the impact of aging on muscle contractility in gymnastics. Materials and Methods: A survey of 81 athletes from different disciplines was undertaken: MAG (n = 26), WAG (n = 28), and RG (n = 27). The athletes’ average age was 15.41 ± 5.03 years. We try to establish the normative values for contraction time (muscle pairs) in gymnastics for Slovenian athletes for ten skeletal muscles. Results: Athletes’ age affects contractility in a negative way. Differences between the duration of contractility and age were found in all disciplines: m. BF (r = 0.48, p < 0.001), m. TB (r = 0.37, p < 0.013), m. ES (r = 0.17, p < 0.025), m. VL (r = 0.36, p < 0.00) and m. VM (r = 0.40, p < 0.000) at a statistical significance of p < 0.05. Conclusions: A comparison between the left and right sides shows little asymmetry in WAG and that the occurrence of injuries is in the middle range. In RG we see a bigger deviation, which could trigger the emergence of pain or injury in m. BF (13%) and m. GL (14.5%), but in MAG the deviation is greater in m. BB (12%), m. BF (11%) and m. GM (13%).

The interplay between Diffuse Idiopathic Skeletal Hyperostosis (DISH) and the gut microbiota represents a compelling area of research, offering insights into the relationship between spinal degenerative diseases and the gut's microbial inhabitants. This comprehensive review seeks to unravel the complex connection, shedding light on its implications for human health and potential therapeutic avenues. A crucial section dives into the world of gut microbiota (GM), exploring its impact on human health, featuring its defining characteristics, and highlighting its role in metabolism, immunomodulation, host interaction, and how its composition changes over time. The subsequent portion delves into the relationship between microbiome composition and pathological bone development, including the link between Intervertebral Disc Degeneration (IDD) and gut inflammation, emphasizing how gut inflammation and GM dysbiosis play pivotal roles. Further dissecting the interconnections, various axes of influence, including the gut-spine axis, gut-bone axis, gut-joint axis, gut-disc axis (specific to DISH), gut-ligament axis, and gut-muscle axis, are discussed. Of particular interest is the section on the impact of GM on DISH-derived pain, addressing a critical aspect of the condition's manifestation. The review discusses the potential of GM modulation as a treatment for DISH, providing hope for therapeutic advancements. Additionally, it highlights the positive impact of lifestyle interventions, such as dietary modifications, sleep optimization, and exercise regimens, in mitigating GM dysbiosis and potentially improving DISH outcomes. Lastly, the intriguing prospect of fecal microbiome transplant and its implications for DISH management is examined, opening new avenues for research and therapeutic interventions. In conclusion, this comprehensive review underscores the intricate interplay between DISH and the gut microbiota, offering a fresh perspective on the impact of GM on spinal degenerative diseases. It emphasizes the potential for innovative treatments, such as GM modulation and lifestyle interventions, and presents fecal microbiome transplant as an exciting area for future exploration.

The proliferation and differentiation of mammalian skeletal muscle satellite cells (MuSCs) are highly complicated. Apart from the regulatory signaling cascade driven by the protein-coding genes, non-coding RNAs like microRNAs (miRNA) and circular RNAs (circRNAs) play essential roles in this biological process. However, circRNA functions in MuSCs proliferation and differentiation remain largely to be elucidated. Here, we screened for an exonic circTCF4 based on our previous RNA-Seq data, specifically expressed during the development of the longest dorsal muscle in goats. Subsequently, the circular structure and whole sequence of circTCF4 were verified using Sanger sequencing. Besides, circTCF4 was spatiotemporally expressed in multiple tissues from goats but strikingly enriched in muscles. Furthermore, circTCF4 suppressed MuSCs proliferation and differentiation, independent of AGO2 binding. Finally, we conducted Poly(A) RNA-Seq using cells treated with small interfering RNA targeting circTCF4 and found that circTCF4 would affect multiple signaling pathways, including insulin signaling pathway and AMPK signaling pathway related to muscle differentiation. Our results provide additional solid evidence for circRNA regulating skeletal muscle formation.

Views of aging include peoples’ assessment of their own aging process and their subjective age. Positive aging views relate to good psychological well-being which predicts better physical and mental health. While these were substantially studied, the moderating roles of self-aging attitudes and psychological well-being in the subjective age-age discrimination connection have been much less explored. The current study used a convenience sample of 568 participants (mean = 66.21y, SD = 11.95, age range 50-95), 55.8% women, 67.1% employed. In line with the hypotheses, young subjective age and psychological well-being were connected to less age discrimination in the workplace and higher psychological well-being mitigated the subjective age-age discrimination at work connection. When the perception of old age as a period of loss was added to the model, adults who perceived old age as a period of loss and reported lower levels of psychological well-being, demonstrated the strongest relationship between an increase in subjective age and an increase in age-related discrimination at work. The findings emphasize the importance of the psychological well-being of older employees as a resource for improving their attitudes to their last years at work.

Introduction: Childhood obesity is becoming an emerging public health issue as it is associated with increased morbidity and premature deaths. Determinants like the child’s household characteristics, maternal weight before the preconception stage, and maternal weight in childhood are studied. There is no study available to understand the association between overweight women of reproductive age and overweight children under five years of age. Studying these determinants to understand the problem can help in framing policies to intervene in the issue. Methods: The data for the study was collected from the National Family Health Survey 5 (NFHS5). It has been sub-grouped into urban and rural categories. The percentage of women with high-risk Waist-Hip-Ratio (WHR) and the percentage of overweight women were independent variables whereas the percentage of overweight under-five children was dependent. Simple linear regression, multiple linear regression, and Pearson correlation coefficient analysis were done for the collected data. Results: Study shows the percentage of overweight women has increased by 4.1%, and the percentage of overweight children has increased by 2% during the NFHS5 (2019-21) compared to NFHS4 (2015-16). Pearson correlation coefficient (R) is 0.5662 and Ꞵ-coefficient for multiple linear regression is 0.1397 for central obesity in women (%) and percentage of overweight children. Conclusion: Central obesity in women is more common than the overweight. Overweight in women as well as in children under five is increasing. Central obesity in women shows a moderate positive relation with overweight in children under five years.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.

Background: According to EWGSOP2, the diagnosis of sarcopenia is confirmed when in addition to low muscle strength, low muscle quantity or quality is present. Echo intensity (EI) determined by muscle ultrasound (US) has been proposed as an efficient method for the assessment of muscle quality. The effect of changing various US parameter settings on EI remains unclear. Therefore, the aim of this study was to assess the differences between EI values obtained by adjusting parameter settings over their entire range in a sample of middle-aged healthy subjects. Methods: Thirty-two repeated US scans of rectus femoris (RF) and rectus abdominis (RA) muscles were taken in eight men and three women with a portable Mindray M7 premium US machine, working in an Extended field-of-view, B-Mode setup, equipped with a linear 5.0-10.0 MHz transducer. The following US parameters and settings were fixed: gain 60dB, depth 6.5cm, and frequency 10 MHz. Readily adjustable parameters were dynamic range (DR), gray map (GM), line density, persistence, and IClear. A default setting DR65 was chosen as the reference setting. For each of the parameters, the settings of one single parameter of interest was changed over its entire range following a standardized protocol. The EI values were calculated using the open-source software ImageJ. Repeated measures analyses were performed to evaluate the effect of parameter settings on EI. Linear interpolation was used to determine non-significant ranges across a given parameter. Results: For the RF muscle, the EI values were significantly different across DR (p<0.001), GM (p<0.001), and IClear (p<0.001). Post hoc analysis confirmed the differences within these three settings. Echo intensity values within the range of DR55 to DR80 were not significantly different. For the RA muscle, the EI values were significantly different across DR (p=0.004) and GM (p=0.030). Post hoc pairwise comparisons revealed no significant difference with the default setting, except for DR150 (p=0.042). Conclusion: We showed that EI values differ across the DR and GM range, especially in the RF. We suggest using a DR setting within its midrange to minimize the effect of machine setting-dependent factors on EI values. These findings reconfirm the need for standardization of ultrasound echo intensity settings when applied for diagnostic purposes of muscle quality.

The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent regulators of muscle mass, with a decrease in mechanical loading leading to a decrease in muscle mass. This concept has been supported by a plethora of of human- and animal-based studies during the last 100 years and has resulted in the commonly used term of “disuse atrophy”. These same studies have also provided a great deal of insight into the structural adaptations that mediate disuse-induced atrophy. For instance, disuse results in radial atrophy of fascicles, and this is driven, at least in part, by radial atrophy of the muscle fibers. However, the ultrastructural adaptations that mediate these changes remain far from defined. Indeed, even the most basic questions, such as whether the radial atrophy of muscle fibers is driven by the radial atrophy of myofibrils and/or myofibril hypoplasia, have yet to be answered. In this review, we thoroughly summarize what is known about the macroscopic, microscopic, and ultrastructural adaptations that mediated disuse-induced atrophy and highlight some of the major gaps in knowledge that need to be filled.

Doxorubicin (Dox) is a commonly used chemotherapeutic that can adversely affect skeletal muscle, including causing muscle atrophy. Dox is known to induce an event known as mitochondrial permeability transition (MPT) in cardiac muscle and this plays an important role in Dox-mediated cardiac toxicity. Further to this, recent evidence identifies MPT as a mechanism of atrophy in skeletal muscle, suggesting that MPT may underlie some of the Dox-related toxicity in skeletal muscle. To test this hypothesis, we used cultured human primary myotubes, C2C12 myotubes, and single adult mouse flexor digitorum brevis (FDB) muscle fibers in experiments involving Dox treatment with or without inhibitors of MPT. Dox treatment of myotubes caused myonuclear translocation of the mitochondrial protein apoptosis inducing factor (AIF) and increased mitochondrial reactive oxygen species (mROS), consistent with the known consequences of MPT. Furthermore, Dox caused atrophy in C2C12 myotubes grown on patterned plates, human primary myotubes, and single muscle fibers from adult mice. Notably, Dox-induced atrophy could be prevented by a wide variety of agents that inhibit MPT, as well as by inhibiting mROS or Caspase 3. In conclusion, our results indicate that MPT plays an important role in driving Dox-mediated skeletal muscle atrophy.

Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.

Due to its time effective, joint friendly and highly customizable character whole-body-electromyostimulation (WB-EMS) is regarded as a feasible solution for a large variety of training issues particularly in the area of non-athletic application. To identify gaps in research and summarize prevalent evidence we conducted an evidence map on outcomes addressed by WB-EMS trials in middle-aged to older, non-athletic adults. Based on a comprehensive systematic search in five databases and two study registers according to PRISMA, 54 projects published in 80 articles were included. More than 90% of the studies reported outcomes related to the physical fitness or function domain. Body composition parameters were addressed by two thirds of the projects. Health-related outcomes addressed by WB-EMS included cancer/neoplasm (n=7), endocrine regulation (n=8), glucose metabolism (15), nervous system diseases (n=2), cardiovascular system diseases (n=22), non-specific chronic low back pain (n=4), osteopenia (n=5) and diseases of the renal system (n=12). Outcomes related to inflammation were addressed 18 times. Of importance, no studies reported clinically relevant adverse effects related to the WB-EMS intervention. In summary, while considerable evidence on outcomes related to fitness/function and body composition is prevalent, evidence gaps of WB-EMS research were particular evident for diseases of the nervous and cerebrovascular system.

Generative artificial intelligence (AI), in particular large language models such as ChatGPT have reached public consciousness with a wide-ranging discussion of their capabilities and suitability for various professions. Following the printing press and internet, generative AI language models are the third transformative technological invention with truly cross-sectoral impact on knowledge transmission. While the printing press allowed for the transmission of knowledge that is independent of the physical presence of the knowledge holder with publishers acting as gatekeepers, the internet added levels of democratization allowing anyone to publish, along with global immediacy. The development of social media resulted in an increased fragmentation and tribalization of on-line communities on their ways of knowing, resulting in alternative truths propagated in echo chambers. It is against this background that generative AI language models have entered public consciousness. Using strategic foresight methodology, this paper will examine the polemic proposition that the age of generative AI will emerge as an age of public ignorance.

Type 2 diabetes mellitus (T2DM) has emerged as a major health care concern in modern society, primarily due to lifestyle changes and dietary habits. Obesity-induced insulin resistance is considered as the major pathogenic factor in T2DM. In this study, we have investigated the effect of vindoline, an indole alkaloid of Catharanthus roseus on insulin resistance, oxidative stress and inflammatory responses in high glucose induced insulin resistant L6-myoblast cells, and dexamethasone (IR inducer)/1L-β (inflammation inducer) induced dysfunctional 3T3-L1 adipocytes. Results showed that dexamethasone induced dysfunctional 3T3-L1 adipocytes treated with different concentrations of vindoline significantly enhanced basal glucose consumption, accompanied by increased expression of GLUT-4, IRS-1 and adiponectin. Vindoline treatment significantly suppressed the ROS production and upregulated pro-inflammatory mediators in IL-1β induced dysfunctional adipocytes. Similarly, vindoline treated insulin resistant L6 myoblasts exhibited significantly enhanced glycogen content accompanied with upregulation of IRS-1 and GLUT-4. Thus, in vitro studies of vindoline in insulin resistant skeleton muscle and dysfunctional adipocytes confirmed that vindoline treatment significantly mitigate insulin resistance in myotubes and improves functional status of adipocytes. These results demonstrated that vindoline has the potential to be used as a therapeutic agent to ameliorate obesity-induced T2DM associated insulin resistance profile in adipocytes and skeletal muscles.

Background The link between age at marriage and first birth in explaining completed family size is not always direct, due to heterogeneity in circumstances, that compel individual women to marry or initiate childbearing at a particular age. We analyzed data for 1020 women aged 45-49 in 2014 of the 1965-1969 birth cohort from the 2013-14 Zambia Demographic and Health Survey (ZDHS). Methods We fitted a bivariate and multivariate multinomial logistic regression to establish the relationship between a mother’s age at first marriage and at first birth on completed family size (CFS). Chi-square test of proportions measuring differences in proportions and relative risk ratios (RRR) with confidence intervals at 95% are reported. Results Our results show that the average CFS was 6.7 (95% CI: 6.5 – 6.9) among women completing their reproductive span in 2014 with mean age at first marriage and birth being 18.3 years (95% CI: 18.0 – 18.5) and 18.9 years (95% CI: 18.7 – 19.1) respectively. Women marrying at younger ages and having their first birth at younger ages were more likely (RRR: 1.187; 95% CI: 1.138-1.239 and RRR: 0.195; 95% CI: 0.074-0.511 respectively) to have higher CFS than their compatriots that initiated both marriage and childbearing at or after age 22 controlling for covariates as presented in the controlled model. The independent effects model shows that the risk of having 1-3 children compared to 6 or more children was lower (RRR: 0.073; 95% CI: 0.009-0.611; RRR: 0.136; 95% CI: 0,046-0.402 and RRR: 0.421; 05% CI: 0.135-1.312) for women whose ages at first marriage were <15, 15-18 and 19-21 respectively relative to 22+. Women with 1-3 children were 2.5 times more likely to use contraception than women with 6 or more children. Conclusion Having no education, being a rural resident and having a medium household wealth all increase the risk of having higher CFS. Women that marry before age 19 have a higher likelihood of having 6 or more children by the end of their reproductive period. The study concludes that apart from a woman’s age at first marriage and first birth, a complex network of factors interact to determined CFS.

Round bodies in spirochete cultures have been a controversial subject since their description seven decades ago. We report the existence of round bodies (spherical cells) in cultures of Mucispirillum schaedleri, a spiral bacterium phylogenetically distant from spirochetes. Furthermore, when grown in biofilms, M. schaedleri demonstrates a unique morphology known as cording, which has been previously described only in mycobacteria. Thus, M. schaedleri has two distinct features, each previously thought to be unique to two different phylogenetically distant groups of bacteria.

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

The facultative loss of muscle mass and function during aging (sarcopenia) poses a serious threat to our independence and health. Much of what we know about sarcopenia derive from studies on small rodents which serve as models for the human condition. Here we used outbred male rats to study the natural history of sarcopenia with the aim to compare behavioral motor deficits with degree of muscle wasting and to find processes underlying the preclinical phase of sarcopenia. Selected metrics were validated in female rats. We used the soleus muscle because of its long duty cycles in everyday life and significance for postural control. The results show that gait and coordination remain intact through middle age (12-18 months; 40%-60% of median lifespan) when muscle mass relative to body weight is largely maintained. The muscle, however, show multiple signs of remodeling with a shift in myofiber-type composition towards type I, increased number of hybrid fibers and fibers expressing embryonic myosin. In parallel with the shift in fiber type prevalence, fiber type clustering increased. The latter combined with a transcriptional upregulation of nicotinic acetylcholine receptor subunit  (CHRN ), NCAM and Myogenin (MYOG) suggests a remodeling driven by myofiber denervation. Additional stigmata were increased number of central nuclei, transcriptional upregulation of Smad3, FBXO32, and MuRF1mRNAs; unaltered density of satellite cells (SC) and Catenin mRNA. In early (25-month-old) and advanced (30-month-old) aging, gait and coordination deteriorate as loss of muscle mass progresses. In late middle age and early aging because of a type II atrophy (>50%), followed by type I atrophy (>50%). Number of myofiber did not correlate with this process. At advance age, the atrophy is accompanied by a decrease in SC and Catenin mRNA while several transcripts upregulated earlier-on were downregulated. In contrast, glial-derived nerve growth factor (GDNF) mRNA abundance peaked at endpoint. We conclude that sarcopenia in the rat as in humans, has a long preclinical phase where the muscle undergoes extensive remodeling to preserve muscle mass and function. The data supports the notion that myofiber denervation is the instigating mechanism, initially affecting large type II motor units (MUs) and at more advanced stage also the smaller type I MUs.

Purpose: The aim of this article is to analyze the incidence of undiagnosed obstructive sleep apnea OSA in patients affected by dento-skeletal malformation. We also evaluated the patterns most affected by the condition and calculated the post surgical changes. Methods: We conducted a retrospective cohort study on 71 patients including 35 men and 36 women. Patients were evaluated with Polysomnography before surgery and at least 6 months after surgery to assess any improvement or worsening of the apnea hypopnea index AHI index. Regarding AHI evaluation criteria an AHI > 5 was considered indicative of OSA, 4 5, com-pared to 20.5% described in the Italian population. Conclusion: In patients who receive orthognathic surgery the presence of Obstructive Sleep Apnea is significantly higher than in the general population. When planning the surgical correction of a dentoskeletal malformation, the surgeon must aim not only to the aesthetics results, but also to a proper stomatognathic and respiratory function, this cannot be done without taking poly-somnography information into account.

The normal growth and development of skeletal muscle is essential for the health of the body. The regulation of skeletal muscle by intestinal microorganisms and their metabolites has been continuously revealed. Acetate is the predominant short-chain fatty acid synthesized by gut microbiota through the fermentation of dietary fiber, however, the underlying molecular mechanisms governing the interaction between acetate and skeletal muscle during rapid growth stage remain to be further elucidated; Here, specific pathogen-free (SPF) mice, germ-free (GF) mice, and germ-free mice supplemented with sodium acetate (GS) were used to evaluate the effects of acetate on skeletal muscle growth and development of young mice with gut microbiota deficiency; We found the concentration of serum acetate, body mass gain, succinate dehydrogenase activity and expression of myogenesis maker gene of skeletal muscle in the GS group was higher than GF group following sodium acetate supplement. Furthermore, the transcriptome analysis revealed that acetate activated biological processes regulating skeletal muscle growth and development in GF group that are inhibited due to gut microbiota deficiency. In vitro experiment, we proved that acetate up-regulated Gm16062 to promote skeletal muscle cell differentiation; Overall, our findings proved that acetate promote skeletal muscle growth and development in young mice via increase Gm16062 expression.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined by in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was totally stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs were closer to those in humans than to those in mice.

School-aged children may benefit from education interventions focused on healthy eating and physical activity to improve their quality of life. This article aims to review scientific evidence on food and nutrition education (FNE) in Spanish-speaking countries for the prevention of overweight and obesity in school-aged children (6-12 y). Articles were searched between April and August 2021. The searches were conducted using MEDLINE, Google Scholar, and SciELO. The primary search for articles focused on the experience of FNE interventions in Spanish-speaking countries. Overall, 518 articles were found and 33 studies were eligible for data extraction. Forty-two percent of the studies had a focus on FNE and 64% were focused on describing the eating habits of schoolchildren. Nutritional assessments (anthropometric) were found frequently with 91% and 30% of the studies focused on physical activity. All interventions focused on preventing or reducing overweight and obesity in school-age children. Educational, cognitive, dietary, and physical activity practices were described, whit being educational the most frequent intervention. Interventions reported positive effects of FNE interventions to improve knowledge and practices of healthy lifestyles in school-age children.

Two Iron Age settlements, Tuzusai and Taldy Bulak 2 (ca. 500 BCE to 1 CE), located in Southeastern Kazakhstan on the Talgar alluvial fan north of the Tian Shan range, have yielded a small collection of bone, antler/horn, bronze, and stone artifacts with affinity to nomadic art of the first millennium BCE. Both settlements date within the period of late Saka culture. Two pieces have decorative ornamentations with zoomorphic imagery: a small carved fragment of a with carved images of a wing and an ear and a perforated bone disk with the carving of three birds’ heads. The other artifacts include objects associated with Saka weaponry or nomadic economy such as the two antler/horn psalia (cheek pieces) and a bronze amulet. A carnelian bead will also be described as an imported object. These special finds are found on the occupation floors of mud brick houses and pit houses of settlements, not in grave or burial contexts. The objects are placed in stratigraphic sequence in the settlement sites. Then the method for placing these objects within the chronological framework of “animal-style art” is through comparisons with similar objects found throughout Eurasia—a method used in Soviet and Post-Soviet archaeology. The results show that functional and stylistic elements of the six objects indicate that the Talgar settlements were part of a larger world-system of trade and communication along the early Silk Route(s).

Background and Aim: It is generally accepted that oxidative stress mediators play an important role in ischemia-reperfusion injury(I/R), although the exact mechanism is not fully elucidated. While the impact of silymarin on I/R injury in several tissues, including the myocardial, cerebral, gastric and liver tissue, has been examined, the present state of research on this topic remains insufficient to provide a widely accepted understanding. For this purpose, our objective was to examine the effect of silymarin on muscle tissue in rats subjected to lower extremity I/R injury. Method: After ethics committee approval, 18 male Wistar albino rats weighing between 225-275 g were used. The rats were divided into three groups containing six mice each, Control,Ischemia-Reperfusion and Silymarin-Ischemia/Reperfusion groups. Silymarin was administered intraperitoneally 30 minutes before the procedure.( 100 mg/kg-1 ) In the I/R groups, an atraumatic microvascular clamp was placed in the infrarenal abdominal aorta. After 120 minutes, the clamp was removed and reperfusion was achieved for 120 minutes. In muscle tissue samples taken at the end of the reperfusion period; Malondialdehyde (MDA) levels, catalase (CAT) enzyme activity levels and histopathological parameters were compared. Results: In the histopathological examination, no degeneration was observed in the muscle fibers in the control group, while findings of striated muscle damage such as muscle atrophy hypertrophy, muscle degeneration-congestion, internal of the muscle nucleus-oval-central nucleus, fragmentation-hyalinization and leukocyte cell infiltration were observed in the I/R group. In the S-I/R group, muscle atrophy hypertrophy, internal of the muscle nucleus-oval-central nucleus, fragmentation-hyalinization and leukocyte cell infiltration were observed to improve these damaged areas compared to the I/R group. MDA levels in the I/R group were found to be significantly higher than in the control and S-I/R groups. CAT enzyme activity was found to be significantly higher in the I/R group than in the control group. Conclusion:Our study revealed that the administration of silymarin at a dosage of 100 mg/kg-1 by intraperitoneal injection 30 minutes before ischemia in rats effectively decreased lipid peroxidation and oxidative stress. Additionally, it successfully reduced the injury caused by ischemia/reperfusion in muscle histology.

BACKGROUND: Lower limb skeletal muscle ischemia-reperfusion (IR) injury associated with increased morbidity and mortality is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. METHODS: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups of six each. (Group Control-C, Group Ischemia-Reperfusion -IR, Group Ischemia-Reperfusion and Proanthocyanidin-IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 minutes before laparotomy and 1-hour ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. RESULTS: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than group control and group IR-proanthocyanidin. Besides, oval-central nucleus standardization was significantly higher in the IR and proanthocyanidin group than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-proanthocyanidin groups while, catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR and proanthocyanidin groups. CONCLUSION: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.

TMEM16A is a Ca2+-activated Cl- channel expressed in various species and tissues. In mammalian skeletal muscle precursors, the activity of these channels is still poorly investigated. Here, we characterized TMEM16A channels and investigated if the pharmacological activation of Piezo1 channels could modulate the TMEM16A currents in mouse myogenic precursors. Whole-cell patch-clamp recordings combined with the pharmacological agents Ani9, T16inh-A01 and Yoda1 were used to characterize TMEM16A-mediated currents and the possible modulatory effect of Piezo1 activity on TMEM16A channels. Western blot analysis was also carried out to confirm the expression of TMEM16A and Piezo1 channel proteins. We found that TMEM16A channels were functionally expressed in fusion-competent mouse myogenic precursors. The pharmacological blockage of TMEM16A inhibited myocyte fusion into myotubes. Moreover, the specific Piezo1 antagonist Yoda1 positively regulated TMEM16A currents. The findings demonstrate, for the first time, a sarcolemmal TMEM16A channel activity and its involvement at the early stage of mammalian skeletal muscle differentiation. In addition, the results suggest a possible role of mechanosensitive Piezo1 channels in the modulation of TMEM16A currents.

This paper examines some of the largely neglected areas of opportunity to utilize skeletal space structure systems in support of modular, industrialized, economical, sustainable and digital future of the construction industry. In this context, the feasibility of future use of skeletal space structures is studied for a few classes of engineering structures, namely, residential apartment buildings, and offshore platforms, along with their suitability for reconstruction, renovation, modernization and retrofit of damaged buildings and urban areas of cultural heritage significance. Finally, the particulars of lean project management of space structures are discussed with emphasis on engineering and economic factors, production management, environmental aspects, quality management, and reliability, maintainability and sustainability considerations. This article concludes that skeletal space structures can fulfil many of the essential construction requirements of modern societies, especially those facing environmental challenges, all while allowing for design flexibility and mass customization.

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy and well-being of elderly individuals emerges as a critical imperative, serving not only individual interests but also broader societal goals. This review investigates various interventions designed to optimize the health and independence of aging populations, offering insights into effective strategies for promoting healthy aging and mitigating the societal burdens associated with an aging demographic.

The ability to express and recognize emotion via facial expressions is well known to change with age. The present study investigated the differences in the facial recognition and facial expression of the elderly (n = 57) and the young (n = 115) and measure how each group uses different facial muscles for each emotion with Facial Action Coding System (FACS). In facial recognition task, the elderly did not recognize facial expressions better than young people and reported stronger feelings of fear and sad from photographs. In making facial expression task, the elderly rated all their facial expressions as stronger than the younger, but in fact, they expressed strong expressions in fear and anger. Furthermore, the elderly used more muscles in the lower face when making facial expressions than younger people. These results help to understand better how the facial recognition and expression of the elderly change, and show that the elderly do not effectively execute the top-down processing concerning facial expression.

Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. The skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited the proliferation and promoted apoptosis of BSCs, and promoted mitophagy in a time and dose-dependent manner in BSCs. In addition, 1mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA(mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated, and the results showed that 1mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway, while the addition of PP242, an inhibitor of the mTOR signaling pathway, also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1, and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. In conclusion, NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.

Objectives: Multicentric Osteolysis, Nodulosis, and Arthropathy (MONA) syndrome is a rare genetic skeletal dysplasia. Its diagnosis can be deceptively similar to childhood-onset genetic skeletal dysplasias and juvenile idiopathic arthritis. We aimed to report the syndrome’s clinical and radiologic features with emphasis on skeletal manifestations. And establish relevant phenotype-genotype correlations. Methods: We evaluated two boys, 4-and-7-years-old with MONA syndrome. Both patients had consanguineous parents. We verified the diagnosis by correlating the outcomes of clinical, radiologic and molecular analysis. We specifically evaluated the craniofacial morphology and clinical and radiographic skeletal abnormalities. We contextualized the resultant phenotype-genotype correlations to publications on MONA and its differential diagnosis. Results: Skeletal manifestations were the presenting symptoms and mostly restricted to hands and feet in terms of fixed extension deformity of the metacarpophalangeal and flexion deformity of the interphalangeal joints with extension deformity of big toes. There were arthritic symptoms in the older patient especially of the wrists and minute pathologic fractures. The skeletal radiographs showed osteopenia/dysplastic changes of hands and feet. Both patients had variants in the matrix metalloproteinase2 gene which conformed to phenotype of previously reported literature in one patient while the other had a novel variant which conformed to MONA phenotype. Craniofacial abnormalities were present. However, minimal extra-skeletal manifestations. Conclusion: Overall, there is an emerging distinctive skeletal pattern of involvement in terms of both clinical and radiographic features. This includes age of onset and location of presenting skeletal manifestations, chronological order of joint affection, longitudinal disease progression, specifics of skeletal radiographic pathology and craniofacial features. Nevertheless, physicians are cautioned against differential diagnosis of similar genetic skeletal dysplasias and juvenile idiopathic arthritis.

In some cases, the human impact on ancient landscapes has been so profound that local soils still remain significantly affected even after hundreds and thousands of years after ending impact. We studied the Late Bronze Age Muradymovo settlement located in Urals, Russia, aiming to estimate the consequences of the ancient people activity for environment. Despite the present humid climate, the modern soils inside the cultural layer of the study site contain more than 27% of gypsum at a depth of just 10 cm from the surface, and a microrelief of the study site is typical of a gypsum desert. The nearby background Chernozems are gypsum-free to a depth of 2 meters. According to the archaeological data, the ancient people belonged to the ‘Srubno-Alakul’ archaeological culture (1750–1350 yrs BC cal) and had a tradition of building their houses from gypsum rocks. At the present time, this area is still unsuitable for human settlement. The properties of modern soils inside the cultural layer of the study site are directly affected by the Late Bronze Age human activities. It has been identified on soil morphology, micromorphology and chemical properties of soils developed inside the cultural layer of the settlement.

Coccidioides spp are thermally dimorphic fungi found in geographically defined areas of the Western Hemisphere. The primary portal of entry is respiratory, with a symptomatic pneumonic disease as the most common presentation. Subsequent pulmonary complications as well as extrapulmonary metastatic infection may occur, either of which may be the presenting disease manifestation. Cavitary lung disease may be found incidentally or when investigating symptoms such as cough or hemoptysis. This study aims to explore the spectrum of coccidioidal cavities and the evaluation and management in a cohort of patients seen at Kern Medical over the last 12 years.

Environmental studies, metabolic research, and state of the art neurobiology point towards the reduced amount of natural day and sunlight exposure of the developing child’s organism as the consequence of increasingly long hours spent indoors online as the single unifying source of a whole set of health risks identified worldwide, as is made clear in this review of the current literature. Over exposure to digital environments, from abuse to addiction, now concerns even the youngest (ages 0 to 2), and triggers, as argued on the basis of clear examples herein, a chain of interdependent negative and potentially long-term metabolic changes. This leads to a deregulation of the serotonin and dopamine neurotransmitter pathways in the developing brain, currently associated with online activity abuse and/or internet addiction, and akin to that found in severe substance abuse syndromes. A general functional working model is proposed under the light of evidence brought to the forefront in this review.

The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses’ mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.

Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). 8 PanNENs patients developed BMets, and 107 remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BM-PanNENs patients vs. non-BM-PanNENs patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated BM-PanNENs from non-BM-PanNENs patients; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. Based on CBMs metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125 and CY18 combination 93/90%, respectively. The useful CBMs for BM-PanNENs patients detection were CA125, CY18, and B2M. They seem to have the diagnostic capacity as a fair single biomarker and CA125&CY18 combination panel for the detection of BMets.

Calorie restriction (CR), defined as a reduction of the total calorie intake of 30% to 60% without malnutrition, is the only nutritional strategy that has proven to extend lifespan, prevent or delay the onset of age-associated diseases, and delay the functional decline in a wide range of species. However, little is known about the effects of CR when started early in life. We sought to analyze the effects of CR in the skeletal muscle of young Wistar rats. For this, 3-month-old male and female rats were subjected to 40% CR or fed ad libitum for 3 months. Gastrocnemius muscles were used to extract RNA and total protein. Western blot and RT-qPCR were performed to evaluate the expression of key markers/pathways modulated by CR and affected by aging. CR decreased body and skeletal muscle weight in both sexes. No differences were found in most senescence, antioxidant, and nutrient sensing pathways analyzed. However, we found a sexual dimorphism in markers of oxidative stress, inflammation, apoptosis, and mitochondrial function in response to CR. Our data show that young female rats treated with CR exhibit similar expression patterns of key genes/pathways associated with healthy aging when compared to old animals treated with CR, while in male rats these effects are reduced. Additional studies are needed to understand how early or later life CR exerts positive effects on health- and lifespan.

Recently, fasting has been spotlighted from a healthcare perspective. However, the de-tailed biological mechanisms and significance by which the effects of fasting confer health benefits are not yet clear. Due to certain advantages of zebrafish, as a vertebrate model widely utilized in biological studies, we used mRNA-sequencing and bioinformatics analysis to examine comprehensive gene expression changes in skeletal muscle tissues during fasting-refeeding. Our results produced a novel set of nutrition-related genes under a fasting-refeeding protocol. We found five dramatically upregulated genes in each fasting (for 24 hours) and refeeding (after 3 hours), exhibiting a rapid response to the provided conditional changes. The assessment of the gene length revealed, the gene set whose expression was elevated only after 3 hours of refeeding had a shorter length, suggesting that nutrition-related gene function is associated with gene length. Taken together, our results from bioinformatics analyses provide new insights into biological mechanisms induced by fasting-refeeding conditions within zebrafish skeletal muscle.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.

In individuals with spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre-and post-intervention. The results revealed a preservation of muscle CSA in the Comb-NMES group compared to a control group receiving transcutaneous electrical nerve stimulation and passive movements. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI can attenuate inflammatory pathways linked to muscle atrophy and potentially promote muscle repair, advocating for its inclusion in early rehabilitation efforts. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

Epitranscriptomics refers to post-transcriptional regulation of gene expression via RNA modifications and editing that affect RNA functions. Many kinds of modifications of mRNA have been described, among which N6-Methyladenosine (m6A), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (Ψ), 5-methylcytidine (m5C). They alter mRNA structure and consequently stability, localization and translation efficiency. Perturbation of the epitranscriptome is associated with human diseases, thus opening the opportunity for potential manipulations as therapeutic approach. In this review, we overview the functional roles of epitranscriptomic marks in the skeletal muscle system, in particular in embryonic myogenesis, muscle cell differentiation and muscle homeostasis processes. Further, we explored high throughput epitranscriptome sequencing data to identify RNA chemical modifications in muscle-specific genes and we discuss the possible functional role and the potential therapeutic applications.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Japan has the world’s largest old population ratio, and aging is an urgent societal issue. As global trends seem to be following Japan’s social changes, there is an emphasis on municipalities becoming more age-friendly. Hence, we examine the age-friendliness of 135 Japanese municipalities, selecting 240 resident architectural designers and constructors to assess their municipalities, using the Age-Friendly Cities and Communities Questionnaire (AFCCQ). The findings indicate that Japan lacks “outdoor spaces and buildings.” Additionally, the evaluation of “housing,” “community support and health services,” and “transportation” in populated municipalities in the past five years is significantly higher than those in depopulated ones. Age-friendliness is significantly affected in the AFCCQ total score (hereafter, Score) based on “housing,” “social participation,” “community support and health services,” “transportation” and “financial situation” evaluations. High specificity (0.939) was found when the Score was treated as a marker of depopulation and, therefore, an age-friendly approach is a necessary condition to prevent depopulation. Furthermore, a lack of “communication and information” is observed in municipalities with a higher rate of single-person households aged 65 years and above. Therefore, resident architectural designers’ and constructors’ assessments, combined with the AFCCQ can be a powerful tool in evaluating the age-friendliness of municipalities.

Generative models for images, audio, text and other low-dimension data have achieved great success in recent years. Generating artificial human movements can also be useful for many applications, including improvement of data augmentation methods for human gesture recognition. The object of this research is to develop a generative model for skeletal human movement, allowing to control the action type of generated motion while keeping the authenticity of the result and the natural style variability of gesture execution. We propose to use a conditional Deep Convolutional Generative Adversarial Network (DC-GAN) applied to pseudo-images representing skeletal pose sequences using Tree Structure Skeleton Image format. We evaluate our approach on the 3D-skeleton data provided in the large NTU RGB+D public dataset. Our generative model can output qualitatively correct skeletal human movements for any of its 60 action classes. We also quantitatively evaluate the performance of our model by computing Frechet Inception Distances, which shows strong correlation to human judgement. Up to our knowledge, our work is the first successful class-conditioned generative model for human skeletal motions based on pseudo-image representation of skeletal pose sequences.

Pigs are susceptible to cold stress due to the absence of brown fat caused by the partial deletion of uncoupling protein 1 during their evolution. Some local pig breeds in China, exhibit potential cold adaptability, but research has primarily focused on fat and intestinal tissues. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, yet the molecular mechanism of cold adaptation in porcine skeletal muscle remains poorly understood. This study investigated the cold adaptability of two pig breeds, Mashen pigs (MS) and Large White pigs (LW), in a 4-day cold (4°C) or room temperature (25°C) environment. We recorded phenotypic changes and collected blood, and longissimus dorsi muscle for transcriptome sequencing. Finally, a candidate gene was randomly selected for functional exploration in porcine skeletal muscle satellite cells. A decrease in body temperature and body weight in both LW and MS pigs under cold stress, accompanied by increased shivering frequency and respiratory frequency. However, MS pigs demonstrated stable physiological homeostasis, indicating a certain level of cold adaptability. LW pigs primarily responded to cold stress by regulating heat production and Glycolipid energy metabolism. MS pigs exhibited a distinct response to cold stress, involving regulation of heat production, energy metabolism pathways, robust fatty acid oxidation ability, and stronger immune response. Furthermore, the functional exploration of PRSS8 in porcine skeletal muscle satellite cells revealed it affected cellular energy metabolism and thermogenesis by regulating ERK phosphorylation. These findings shed light on the diverse transcriptional responses of skeletal muscle in LW and MS pigs under cold stress, offering valuable insights into the molecular mechanisms underlying cold adaptation in pigs.

Orthognathic surgery is used to modify anomalies in maxillomandibular position; this process can significantly affect the anatomy of the airway and cause functional changes. This study aims to define the impact of mandibular maxillary movement on the airway of subjects with dentofacial deformity. A retrospective study was conducted on subjects with Angle class II (CII group) and Angle class III (CIII group) dentofacial deformities. The subjects were treated by bimaxillary surgery; for all of them, planning was performed with software and 3D printing. Cone beam computed tomography (CBCT) was obtained 21 days before surgery and 6 months after surgery and was used for planning and follow-up with the same conditions and equipment. Was used the superimposition technique to obtain the maximum and minimum airway areas, and total airway volume. The data were analyzed with the Shapiro-Wilk test and Student’s t-test, while Spearman's test was used to correlate the variables, considering a value of p&lt;0.05. Seventy-six subjects aged 18 to 55 years (32.38 ± 10.91) were included: 46 subjects were in CII group, treated with a maxillo-mandibular advancement, and 30 subjects were in the CIII group, treated with a maxillary advancement and a mandibular setback. In CII group, a maxillary advancement of +2.45 mm (±0.88) and a mandibular advancement of +4.25 mm (±1.25) were observed, with a significant increase in all the airway records. In the CIII group, a maxillary advancement of +3.42 mm (±1.25) and a mandibular setback of -3.62 mm (±1.18) was noted, with no significant changes in the variables measured for the airway (p&gt;0.05). It may be concluded that maxillo mandibular advancement is an effective procedure to augment the airway area and volume in the CII group. On the other hand, in subjects with mandibular prognathism and Angle class III operated with the maxillary advancement and mandibular setback lower than 4 mm it is possible to not reduce the areas and volume in the airway.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n=11) and patients with PDAC (n=24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using Ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Direct measurement of strain within muscle is important for understanding muscle function in health and disease. Current technology (kinematics, dynamometry, electromyography) provides limited ability to measure strain within muscle. Regional fiber orientation and length are related with active/passive strain within muscle. Currently, ultrasound imaging provides the only non-invasive means of observing regional fiber orientation within muscle during dynamic tasks. Previous attempts to automatically estimate fiber orientation from ultrasound are not adequate, often requiring manual region selection, feature engineering, providing low-resolution estimations (one angle per muscle), and deep muscles are often not attempted. Here, we propose deconvolutional neural networks (DCNN) for estimating fiber orientation at the pixel-level. Dynamic ultrasound images sequences of the calf muscles were acquired (25 Hz) from 8 healthy volunteers (4 male, ages: 25–36, median 30). A combination of expert annotation and interpolation/extrapolation provided labels of regional fiber orientation for each image. We then trained DCNNs both with and without dropout using leave one out cross-validation. Our results demonstrated robust estimation of regional fiber orientation with approximately 3° error, which was an improvement on previous methods. The methods presented here provide new potential to study muscle in disease and health.

Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.

In this work we report on our effort to design and implement an early introduction to basic robotics principles for children at kindergarten age. The humanoid robot Pepper, which is a great platform for human-robot interaction experiments, was presenting the lecture by reading out the contents to the children making use of its speech synthesis capability. One of the main challenges of this effort was to explain complex robotics contents in a way that pre-school children could follow the basic principles and ideas using examples from their world of experience. A quiz in a Runaround-game-show style after the lecture activated the children to recap the contents they acquired about how mobile robots work in principle. Besides the thrill being exposed to a mobile robot that would also react to the children, they were very excited and at the same time very concentrated. What sets apart our effort from other work is that part of the lecturing is actually done by a robot itself and that a quiz at the end of the lesson is done using robots as well. To the best of our knowledge this is one of only few attempts to use Pepper not as a tele-teaching tool, but as the teacher itself in order to engage pre-school children with complex robotics contents. We got very positive feedback from the children as well as from their educators.

Based on the demographic shift and the related challenges resulting from the growing number of elderly and persons with chronic diseases, the idea of smart home that supports its inhabitants in the daily life, gains importance. The purpose of this paper was to examine in a prototypic Ambient Assisted Living environment if users after interaction with different health-supporting applications intend to use such in the future. Two experimental studies exemplary show possible applications of home-integrated technology that can support, assist and accompany the target group in different contexts, and examine to what extent participants are willing to future use such sophisticated technology at home. The results show that people in general, but especially the old and chronically ill ones are quite fascinated of health-supporting ambient technology and the majority intends to use such ambient assistance in the future (study I). Moreover, serious games for healthcare are shown as a hedonic use of technology in smart homes that have a great potential to retain or improve the physical health, mobility and the overall well-being of the inhabitants (study II). The article provides two examples of ambient technology to leverage the demographic change and presents important user factors for facilitating high user acceptance.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes and an increase in collagen with aging, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a decrease in intermyofibrillar mitochondria, increased mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

The retinal pigment epithelium (RPE), which ensures the normal functioning of the neural retina, is a pigmented single-cell layer that separates the retina from the Bruch's membrane and the choroid. There are three main types of pigment granules in the RPE cells of the human eye: lipofuscin granules (LG) containing the fluorescent “age pigment” lipofuscin, melanoprotein granules (melanosomes, melanolysosomes) containing the screening pigment melanin and complex melanolipofuscin granules (MLG) containing simultaneously both types of pigments - melanin and lipofuscin. This review examines the functional role of pigment granules in the aging process and in the development of oxidative stress and associated pathologies in RPE cells. The focus is on the process of light-induced oxidative degradation of pigment granules caused by reactive oxygen species. The reasons leading to increased oxidative stress in RPE cells as a result of oxidative degradation of pigment granules are considered. A mechanism has been proposed to explain the phenomenon of age-related decline in melanin content in RPE cells. The essence of the mechanism is that when the lipofuscin part of the melanolipofuscin granule is exposed to light, reactive oxygen species are formed, which destroy its melanin part. As more melanolipofuscin granules are formed with age and the development of degenerative diseases, the melanin in pigmented epithelial cells ultimately disappears.

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness world-wide. We recently reported that polyethylene glycol (PEG) can activate the alternative pathway of the complement system and induce choroidal neovascularization (CNV) in mice. Currently, no other investigator has demonstrated CNV after PEG injection in the mouse eye. The aim of this article is twofold: we review the histologic changes in mouse retina and retinal pigmented epithelium (RPE) after treatment with PEG, and we summarize a model of wet and dry AMD pathogenesis in mice through subretinal PEG treatment of RPE cells and retinal layers. We injected (subretinal) male C57BL/6 mice with 2 μL of solution containing 0.5 mg and 1.0 mg of PEG or PBS in control groups. Eyes were harvested at day 1, 3 and 5 after injection and processed for analysis. Sections were immunohistochemically stained for complement component C3, mem-brane attack complex (MAC), and cytokeratin 18. Light and laser confocal microscopy was used for image capturing. PEG increased deposition of C3 and MAC on RPE cells and on all retinal layers after 1.0 mg injection. PEG induced loss of cellular contacts between RPE cells and migration of RPE cells in the subretinal space at day 1 after PEG injection. After 0.5 mg PEG injection, increased size of RPE cells was detected at day 3 and 5. Apoptotic bodies were observed in outer nuclear layer at day 3 and 5 after 0.5 mg PEG treatment. RPE cells with dark cytoplasm and condensed chromatin were observed. Higher doses of PEG induce CNV, encouraged RPE cell proliferation and death, and damage photoreceptors in mice. This simple and fast model may be useful to explore the pathogenesis of both dry and wet AMD.

The relationship between child psychology and the widespread usage of mobile devices in the modern day is examined in "The Mobile Dilemma: Child Psychology and the Era of Technological Dependence." The abstract serves as a brief synopsis of the work, highlighting its important ideas and arguments. Concerns concerning the effects of excessive time spent on mobile devices on children's mental health and development have arisen in this age of technology dependency. The essay opens by pointing out the importance of investigating the psychological effects of kids' exposure to mobile gadgets. The effects of mobile phone addiction on learning, memory, and social and emotional health are investigated. The neurodevelopmental implications are explored further in the abstract, with a focus on the impact of mobile technology on brain plasticity and the formation of the developing brain. It offers advice on how to establish appropriate limits for children's screen time, encourages the development of digital literacy, and promotes responsible behavior.The pros and cons of using mobile devices in the classroom are also examined, along with their effects on students' ability to study and the risks and difficulties that could arise from implementing such a strategy. The emotional and social impacts of mobile device addiction are discussed in the abstract. This includes the impact on one's social life, empathy, ability to communicate, and sense of self-worth. The abstract also stresses the importance of interdisciplinary efforts involving parents, teachers, psychologists, and legislators to combat mobile device addiction through intervention and preventative techniques. Future directions are highlighted, with a focus on topics such as mobile technology development, digital well-being, privacy protection, mental health implications, screen time limits, digital literacy, and the impact of cultural and socioeconomic variables.

Background: Little information exists regarding the differences in the clinical and laboratory characteristics of Kikuchi-Fujimoto disease (KFD) according to age. Objective: To evaluate the clinical and laboratory characteristics of KFD according to age. Methods: We retrospectively evaluated patients diagnosed with KFD at Pusan National University Hospital between 2010 and 2020. Results: Eighty patients (46 children and 34 adults) with a mean age of 21.5 ± 11.8 years (range, 3–49 years) were included in the study. Among children, the male sex ratio was higher, in adults, the female sex ratio was higher. Fever, tenderness in the lymph node, and skin rashes were more common in children, while myalgia and weight loss were more common in adults. In children, the recurrence rate was significantly higher among boys than among girls (15.8% vs 0.0%, P=0.001). EBV and ANA positivity rates were higher in boys than in girls. In adults, the recurrence rate was significantly higher in women than in men (18.2% vs 0.0%, P=0.005). ANA positivity rates were higher in women than in men. Conclusion: The clinical features, laboratory findings, and recurrence of KFD may differ depending on age and sex. Clinicians should be aware of this.

Abstract: The aim of the present study was to identify the age and sex-related associations between marital status with PA and TV time. We used data from Vigitel, an annual telephone survey started in 2006 in Brazil. We applied a complex sample logistic regression model to estimate the odds for PA and TV time comparing marital statuses according to age and sex subgroups, independent of obesity, hypertension, diabetes, self-assessed poor health, and smoking. Our sample included 561,837 individuals with a TV time &gt; 3 h/day (prevalence = 25.2%) and PA &gt; 150 min/week (prevalence = 35%). Compared to single individuals, married men and women were less likely to watch TV more than 3 h/day in participants &gt; 30 years old. When compared to single, married participants were less likely to do more than 150 min of PA/week at younger age groups. Married women older than 40 years were more likely to do more than 150 min of PA/week than the single ones, while there were no differences among married men by age group. In conclusion, married individuals are less likely to spend more than 3 hours a day watching TV than single individuals. Single men and women were more likely to do more than 150 min of PA/week at younger age groups and married women older than 40 years were more likely to do 150 min of PA/week than single women.

Egyptian mongoose (Herpestes ichneumon) is a medium-size carnivore that in Europe is restricted to Iberia. The bio-ecology of this species remains to be elucidated in several dimensions, including gut microbiota that is nowadays recognized as a fundamental component of mammals. In this work, we investigated the gut microbiota of this herpestid by single-molecule real-time sequencing of twenty paired male (n=10) and female (n=10) intestinal samples. This culture-independent approach enabled microbial profiling based on 16S rDNA and investigation of taxonomical and functional features. The core gut microbiome of the adult subpopulation was dominated by Firmicutes, Fusobacteria, Actinobacteria, and Proteobacteria. Eight genera were uniquely found in adults and five in non-adults. When comparing gut bacterial communities across sex, four genera were exclusive of females and six uniquely found in males. Despite these compositional distinctions, alpha- and beta-diversity analyses showed no statistically significant differences across sex or between adult and non-adult specimens. However, males presented a significantly higher abundance of amino acid and citrate cycle metabolic pathways, compared to the significant overrepresentation in females of galactose’ metabolic pathways. Adults showed a significantly higher abundance of cationic antimicrobial peptide resistance pathways, while non-adults bared a significant overrepresentation of two-component systems associated with antibiotic synthesis, flagellin production and chemotaxis control. This study adds new insights into mongoose bio-ecology palette, highlighting taxonomical and functional microbiome dissimilarities across sex and age classes, possibly related to primary production resources and life-history traits that impact on behavior, diet and gut ecosystem.

As times goes, the survival was improved attributed to target therapy and chemotherapy. Metastasis to skeletal muscle tissue is rare. Herein, we reported a case presenting with deep venous thrombosis but skeletal muscle metastasis. Though it was rare, oncologist shoud be keep in mind due to worse prognosis .

Limb girdle muscular dystrophies (LGMD), caused by mutations in 29 different genes, are the fourth most prevalent group of genetic muscle diseases, leading to progressive weakness and atrophy of the skeletal muscles. Although the link between LGMD and their genetic origins has been determined, LGMD still represent an unmet medical need. In this paper, we describe a platform for modeling LGMD based on the use of human induced pluripotent stem cells (hiPSC). Thanks to the self-renewing and pluripotency properties of hiPSC, this platform provides an alternative and renewable source of skeletal muscle cells (skMC) to primary, immortalized or overexpressing cells. We report that skMC derived from hiPSC express the majority of the genes and proteins causing LGMD. As a proof of concept, we demonstrate the importance of this cellular model for studying LGMDR9 by evaluating disease-specific phenotypes in skMC derived from hiPSC obtained from four patients.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

An increased risk of multiple sclerosis (MS) had been found when individuals had consumed large amounts of processed meat and sausages at young age (Lauer, 2014). Furthermore it was found in many studies that MS patients had acquired a number of common childhood infections at higher ages than controls. Therefore, MS patients from an epidemiological long-term investigation in Germany and different hospital controls, were evaluated for a statistical interaction of these two factors. 324 MS patients and 242 hospital controls were inquired. The study focussed on age 0 - 16. Subjects were tested for additive interaction by multiple linear regression analysis (Knol et al., 2007). There was an additive interaction of the age at any common childhood infection with the consumption of scalded sausages (regression estimate = 0.1370; standard error = 0.0603; p = 0.0239). In contrast, no such interaction could be shown for: animal fats; smoked meat (e.g. ham and bacon); and cold - smoked German salami. Thus there was a synergy of the intake of scalded sausages (e.g. frankfurters, bolognas, etc.) and age at common childhood infections, for the later risk of MS.

INTRODUCTION: With an increase in the aging population, the application of evidence-based practice in geriatric education can strengthen knowledge, skills, and clinical experience for healthcare students caring for older adults. Age Friendly Health Systems (AFHS) is one of the frameworks founded on providing evidence-based and low-risk care centered on what matters most to older adults, their families, and caregivers. Virtual Reality (VR) platforms are gaining popularity due to their ability to provide an immersive, hands-on learning experience resembling an actual medical practice or care setting. Immersive learning enhances students’ sensory perceptions, promoting an innovative and engaging way of acquiring concepts that are difficult to teach in real life. This study aimed to design, develop, implement, and evaluate a case-based training module highlighting AFHS and educating medical students on the 4Ms approach in geriatric care (What Matters, Medication, Mentation, and Mobility). METHODOLOGY: The project was a feasibility study completed in two phases. Phase one included planning and development of a case-based scenario incorporating 4Ms of AFHS. Phase two included implementing and evaluating the VR training module into the geriatric curriculum for medical students. RESULTS: The final VR case displays a hospital and post-acute setting where an elderly patient is admitted for a hip fracture. Students learn how to triage and treat patients from admission to discharge while demonstrating their knowledge of AFHS. Approximately 10% of students completed the evaluation survey, and preliminary results indicate significant knowledge change in pre-post scenario-based training on AFHS. CONCLUSION: The VR education platform and embedded scenario promise an innovative adaptation of technology in learning the concepts of the 4Ms of AFHS. However, future studies should explore VR education with clinical assessment evaluation to ensure competence in providing Age-Friendly care.

Pregnancy at advanced maternal age is considered a risk factor for adverse maternal, fetal, and neonatal outcomes. Here we investigated whether maternal age could be associated with differences in the blood levels of newborn screening (NBS) markers for inborn metabolic disorders on the Recommended Universal Screening Panel (RUSP). Population-level NBS data from screen-negative singleton infants were examined, which included blood metabolic markers and covariates such as gestational age, birth weight, age at blood collection, infant sex, parent-reported ethnicity, and maternal age at delivery. Marker levels were compared between maternal age groups (age range: 15-44 years) using effect size analyses, which controlled for group size differences and potential confounding from other covariates. Our results showed that 13% of the markers had maternal age-related differences including newborn metabolites with either increased (C14, C16, C18, C18:1, C3DC) or decreased (C5OH) levels at advanced maternal age group (≥35 years, absolute Cohen’s d ≥ 0.2). The increased C3DC levels in this group correlated with a higher false-positive rate in newborn screening for malonic acidemia (p-value < 0.001), while no significant difference in screening performance was seen for other markers. Maternal age at delivery is associated with inborn metabolic differences and should be considered together with other clinical variables in genetic disease screening.