Background: The control of energy metabolism is fundamental for cell growth and function, and anomalies are implicated in complex diseases and ageing. It is important for cells to carefully tune metabolic pathways to optimize their function in response to different nutrient or physiological conditions. Metabolism in yeast cells can be easily manipulated by supplying different carbon sources: on glucose yeast rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. The growth medium and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in key energy metabolism pathways were coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that the acetyl-CoA synthase, rather than the citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. Conclusions: These systematic and targeted analyses provide a rich framework of the genetic and regulatory basis of fundamental metabolic states to guide future studies on energy metabolism in fission yeast and beyond. Our study pinpoints weaknesses of commonly used auxotroph mutants for investigating energy metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

A proportion of osteoarthritis (OA) patients are unsatisfied with post-operative outcomes following total joint replacement surgery (TJR), with insufficient pain relief or poor functional improvement. Predicting those will have poor outcomes would be beneficial for patients and clinicians. The aim of this study was to determine the relationship between baseline anthropometric data and the concentration of pre-operative serum and peri-operative synovial fluid (SF) cytokines with 7-month post-operative outcomes in a cohort of knee and hip OA patients. 160 OA patients were recruited who were scheduled for TJR. The concentration of 24 cytokines were measured in blood and SF by multiplex assay. EQ5Dindex health status was assessed pre-operatively and at 7-months post-operatively. 13% of patients were identified as non-responders based on EQ5Dindex. Compared to responders, non-responders were of higher BMI, had greater waist and hip circumference and had higher levels of SF leptin but lower levels of SF Resistin (p<0.05). Linear regression analysis found a significant relationship between pre-operative body weight and post-operative response (ΔEQ5Dindex; r=0.222, p=0.049). The combination of body weight with SF amphiregulin and SF IL-6 provided an improved predictive model of post-operative response (r=0.470, p=0.035).

(1) Background The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated applying data from older cognitively healthy adults living in the US, Ireland and Australia (the norming sample) The study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI) and dementia (1), and to cross-validate the new norms for detecting MCI and dementia (2) in a community sample of older adults with clinical diagnoses; (2)Methods: The validation sample included 142 older adults (mean age=87.7, SD=3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia through a consensus diagnosis as well as by the SKT; (3)Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 60.1% for all three diagnostic groups. The correlation between the SKT and the Addenbrooke’s Cognitive Examination III (ACE-III), a well validated measure of cognitive ability in older adults, was r = 0.3;. (4) Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

Background: Telemonitoring systems in cardiology have shown potential in improving chronic cardiovascular disease (CVD) management. This study aims to evaluate the impact of telemonitoring, mainly through mobile applications, on patient outcomes such as self-care, blood pressure control, quality of life, and hospitalization. Methods: We systematically reviewed studies assessing telemonitoring methods for patients with chronic CVD. The analysis included studies from various geographic regions and healthcare settings, focusing on qualitative outcomes without performing a meta-analysis. Results: Telemonitoring was found to aid in maintaining blood pressure and significantly enhance self-care abilities. Improvements in quality of life were observed in some studies, though results varied. Most studies indicated telemonitoring could effectively manage blood pressure and reduce hypertension-related complications. However, the heterogeneity of interventions and outcomes measured across trials posed challenges for a comprehensive meta-analysis. Conclusions: Integrating telemonitoring systems into routine care can significantly improve disease management and patient outcomes for chronic CVD patients. Future research should standardize telemonitoring interventions and outcome measures, conduct long-term studies, and evaluate the cost-effectiveness of these systems. Greater blindness in future randomized controlled trials and more studies on atrial fibrillation are also necessary. Significant potential exists for telemonitoring to improve patient outcomes and assist in managing chronic illnesses.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

The emphasis in the automotive industry towards sustainable mobility has led to a significant interest in hybrid-electric propulsion systems with high energy density batteries. Addressing the needs of this strategy, the battery market is exploring new technologies to improve the safety and lifespan of electric vehicles. To this end, there is a focus on the all-solid-state battery (ASSB) technology for its cycle capabilities. Filling the current void in the literature pertaining to accurate ageing models for ASSBs, in this work, we present an enhanced version of the numerical ageing model, originally developed for liquid electrolyte based batteries, to forecast the development of the solid electrolyte interface layer that is the major cause of battery capacity fading. The model has been tested on prototype batteries and reveals an accuracy of 99%. The capacity fade in ASSBs has been investigated under different conditions, and the enhanced ageing model has been validated using experimental data from these batteries. The findings suggest that there is potential for solid-state batteries to be commercialized, although significant work is needed to match the manufacturing level of lithium-ion batteries with liquid electrolytes.

Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

Vitamin A, or retinol, is one of the most effective anti-ageing molecules, but it presents issues with photo-sensitivity and irritation. Retinol-like alternatives are emerging, but have so far been less effective. Here, we present a Silibum marianum extract (SME) as a retinol-like ingredient providing both safety and efficacy. SME was compared to the reference compound, retinol, and to the main alternative, bakuchiol. In ex vivo tests, skin explants from a 58-year-old donor were treated with pure retinol (0.1%), bakuchiol (0.2%) or SME (0.8%). After 5 days, collagen and hyaluronic acid levels were analysed. A placebo-controlled study involving 57 volunteers (ages 45-73 years) was also conducted, with products applied twice-daily for 56 days. Results were measured by AEVA-HE and VISA. Levels of collagen III were significantly increased by SME, by 23% and 16% compared to bakuchiol and retinol, respectively. Compared to bakuchiol, SME treatment increased hyaluronic acid production by 36%. In clinical tests, SME had a significantly stronger anti-wrinkle effect than bakuchiol – reducing the number of wrinkles on the forehead by 21%, and their circumference by 17% – producing effects similar to retinol, and better than bakuchiol. In the self-assessment, 43% of volunteers reported discomfort while using retinol, as compared to 0% for the SME formulation. By enhancing levels of collagen III – the youth collagen – and hyaluronic acid in the skin, SME paves the way for the maturation of collagen I fibrils and skin plumping. With its stronger efficacy compared to bakuchiol and enhanced safety profile compared to retinol, SME may be the next-generation of natural alternatives to retinoids.

Background: CCL11 (eotaxin) is a chemokine with an important role in allergic conditions. Recent evidence indicates that CCL11 plays a role in brain disorders as well. Aims: This paper reviews the associations between CCL11 and aging, neurodegenerative, neuroinflammatory and neuropsychiatric disorders.Methods: Electronic databases were searched for original articles examining CCL11 in neuropsychiatric disorders.Results: CCL11 is rapidly transported from the blood to the brain through the brain-blood barrier. Age-related increases in CCL11 are associated with cognitive impairments in executive functions, episodic and semantic memory and, therefore, this chemokine was described as an “endogenous cognition deteriorating chemokine” (ECDC) or “accelerated brain-aging chemokine” (ABAC). In schizophrenia, increased CCL11 is not only associated with impairments in cognitive functions, but also with key symptoms including formal thought disorders. Some patients with mood disorders and premenstrual syndrome show increased plasma CCL11 levels. In diseases of old age, CCL11 is associated with lowered neurogenesis and neurodegenerative processes and, as a consequence, increased CCL11 increases risk towards Alzheimer's Disease. Polymorphisms in the CCL11 gene are associated with stroke. Increased CCL11 also plays a role in neuroinflammatory disease including multiple sclerosis. In animal models, neutralization of CCL11 may protect against nigrostriatal neurodegeneration. Increased production of CCL11 may be attenuated by glucocorticoids, minocycline, resveratrol and anti-CCL11 antibodies.Conclusion: Increased CCL11 production during inflammatory conditions may play a role in human disease including age-related cognitive decline, schizophrenia, mood disorders and neurodegenerative disorders. Increased CCL11 production is a new drug target in the treatment and prevention of those disorders.

The age-related loss of muscle mass and strength is referred to as “sarcopenia”. The combined effect of sarcopenia and osteoporosis is a devastating threat to the old adult, accounting for reduced mobility, risk for falls and subsequent fractures. In previous studies, we observed a high degree of inter-individual variability of paraspinal muscle fatty infiltration, one most relevant index of muscle wasting. This aspect solicited us to develop a computerized method to quantitatively characterize muscle fatty infiltration in aging and diseases. Magnetic resonance images of paraspinal muscles from 58 women of different age (age range 23-85 years) and physio-pathological status (healthy young, pre-menopause, post-menopause, and os-teoporosis), were used to set up the method. It is based on fractal analysis of lean muscle area (contractile muscle) to estimate muscle fatty infiltration. In particular, lacunarity was computed by parameter β from our hyperbola model function, used to fit the GBA (gliding box algorithm) curvilinear plot. Succolarity was estimated by parameter µ, for the four main directions, through an algorithm implemented on purpose. Results show that fractal lacunarity, by quantifying muscle fatty infiltration, can discriminate be-tween osteoporosis and healthy aging while succolarity can separate the other three groups showing similar lacunarity. Therefore, fractal features of contractile muscle, by measuring fatty infiltration, can represent good indices of sarcopenia in aging and disease.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately leads to recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from continued presence of the initial trigger, or dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults including centenarians is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death [1–3]. Hence inflammation has been described as one of seven pillars of ageing. Age-associated sterile, chronic, and low-grade inflammation is commonly termed inflammageing - it is not simply a consequence of increasing chronological age, but is also a marker of biological ageing, multimorbidity and mortality risk. While inflammageing was initially thought to be caused by “continuous antigenic load and stress”, reports from the last two decades describe a much more complex phenomenon also involving cellular senescence and ageing of the immune system. In this review, we explore the sources and consequences of inflammageing and highlight potential interventions. In particular, we assess the contribution of cellular senescence to age-associated inflammation, identify patterns of pro- and anti-inflammatory markers characteristic of inflammageing, describe alterations in the ageing immune system that lead to elevated inflammation, and finally assess the ways that diet, exercise and pharmacological interventions can reduce inflammageing and thus improve later life health.

In this paper, the authors seek to discuss some of the complexities involved in cross-cultural working in relation to the communication and management of pain in older people. Specifically, the paper addresses the culture construction of ageing and how pain is often constructed as a natural part of ageing. The authors also suggests that with the rise of the ideology of active-ageing many older people who are disabled or living in chronic pain, may feel a moral imperative to hide pain and ill-health. The discussion extends into looking at the impact of culture and the communication of pain, including specific idioms of distress, somaticize and the lay-management of pain through stoicism.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

This study presents the utilization of the Microwave InfraRed Thermography (MIRT) technique to identify and analyze the defects in the carbon-fiber-reinforced polymer (CFRP) composite rein-forcement of concrete specimens. At first, a set of the numerical models was created, comprising of the broadband pyramidal horn antenna and the analyzed specimen. The utilization the system operating at a power of 1000W in a continuous mode, operating at frequency of 2.45 GHz was analyzed. The specimen under examination comprised a compact concrete slab that was covered with an adhesive layer, thereafter, topped with a layer of CFRP. An air gap represented a defect at the interface between the concrete and CFRP within the adhesive layer. In the modelling stage the study investigated three separate scenarios: a sample with no defects, a sample with a defect located at the center, and a sample with a numerous additional random defects located at the rim of the CFRP matte, to analyze the effect of the natural reinforcement degradation in this area. The next phase of the study involved conducting experiments to confirm the results obtained from nu-merical modeling. In the experiments the concrete sample aged for 10 years with the defect in the center and naturally developed defects at the CFRP rim was used. The study employed numerical modeling to explore the phenomenon of microwave heating in complex structures. The aim was to assess the chosen antenna design and identify the most effective experimental setup. These con-clusions were subsequently confirmed through experimentation. The observations made during the heating process were particularly remarkable, since they deviated from earlier studies that solely conducted measurements of the sample post-heating phase. The findings demonstrate that MIRT has the capacity to be employed as a technique for detecting flaws in concrete structures reinforced with CFRP.

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid-responsiveness via passive leg-raising maneuver (PLR) before spontaneous breathing trial (SBT) associated with less extubation failure in ventilated patients with high fluid balance, admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Postoperative fluid balance was +4476 [3697,5722] mL. PLRs were conducted at ICU admission (T1) and pre-SBT (T2). Cardiac index (CI) changes were recorded before and after SBT (T3). Seven patients were fluid responsive at T1, and 12 at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 [2.8,3.7] to 3.7 [3.4,4.1] mL/min/m2 (p= 0.045). All fluid-responsive patients at T2 were extubated after SBT and consolidated extubation. Two out of three of fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post-LT may start weaning earlier and achieve successful extubation despite high postoperative fluid balance. This highlights the profound impact of personalized assessment of cardiovascular state on critical surgical patients.

Active ageing is defined as the process of optimizing opportunities for physical, social and mental health to enable older people to take an active part in society without discrimination and to enjoy an independent and good quality of life. The World Health Organization assumed this as a process for increasing and maintaining an individual’s participation in activities to enhance his/her quality of life. In this survey, the authors addressed the following question: “Is assistive technology (AT) for mobility contributing to enhancement of lifelong capacity and performance?”. From June 2015 until February 2016, 96 community dwelling adults, AT users for mobility (powered wheelchairs, manual wheelchairs, lower limb prostheses, walkers, crutches and canes), aged 45-97, mean 67.02 +/- 14.24 years old, 56.3% female, were interviewed using the Psychosocial Impact of Assistive Devices Scale (P-PIADS), the Activities and Participation Profile related to Mobility (APPM) and demographics, clinical and questions about AT use and training. The participants’ profiles revealed moderate limitation and restrictions in participation, measured by the APPM (2.03). Most participants showed positive impact of AT; average scores obtained from the P-PIADS subscales were: Self-esteem 0.62, Competency 1.11 and Adaptability 1.10. P-PIADS total was 0.96, with the powered wheelchair users scoring the highest (1.53) and the walker users scoring the lowest (0.73). All subscales and P-PIADS total were positively correlated with the activities and participation profile. There was no relation between age and the psychosocial impact of AT or activities and participation profile. These results encourage the authors to follow these participants up for a lifelong intervention. To accomplish that aim, currently, the protocol is implemented at the AT prescribing centers in Coimbra, Portugal in order to assess the impact of AT on participation in society, one of the domains of the Active Ageing Index, a new analytical tool to help policy makers in developing policies for active and healthy ageing.

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. T2DM condition increases the risk of micro and macro-vascular complications as well as the risk of geriatric syndromes as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the cli-nician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycate haemoglobin target according to functional and cognitive status comorbidities, life ex-pectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be cathegorized in three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for the glycemic control is different, also according to the type of treatment drug. The therapeutic ap-proach should always begin with lifestyle changes; after that, several lines of therapies are available, with different mechanism of action and potential effect other than glucose level reduction. Partic-ular interest is growing around sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review we evaluate the therapeutic options available for the treat-ment of older diabetic patients, to ensure a correct treatment approach

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

The normal ageing process significantly affects resistance arteries, leading to various biological and physiological consequences. Systolic hypertension is a common occurrence in ageing individuals, accompanied by increased large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, there is a progressive elevation in mean arterial pressure, supported by clinical and epidemiological evidence as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. Dysregulation of calcium entry channels (T-type, L-type, TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to age-related dysregulation of myogenic tone. Flow-mediated vasodilatation, a hallmark of endothelial function, is compromised in ageing. This result of endothelial dysfunction is related to oxidative stress, lower nitric oxide bioavailability and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall, often seen in conjunction with outward remodeling (in normotension), but can also present as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of extracellular matrix fiber proteins and actin cytoskeletal components. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation, often referred to as "inflammaging”, play substantial roles in age-related vascular dysfunction. Due to its role in regulation of vascular tone as well as structural proteins, the RhoA/Rho-kinase pathway becomes a new target in age-related vascular dysfunction and associated diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance overall vascular health.

Abstract Aims: We aimed to present successful endoscopic retrograde cholangiopancreatography (ERCP) applications and results in our pregnant cases. Method: The data of 14 successful ERCP applications in our pregnant patients between 2016 and 2022 were evaluated retrospectively. ERCP procedure was performed by endoscopists experienced in biliary endoscopy while the patients were on the left decubitus position. Fluoroscopy was performed using methods to reduce fetal radiation exposure. Short-term fluoroscopy were used during the procedure. Fluoroscopy times applied to the patient were recorded. Results: ERCP and sphincterotomy were applied to 14 pregnant women who presented with cholestasis findings. Two of the procedures were performed aproprate trimesters in whole patients. The mean maternal age in our pregnant women was 24.8±5.6 (19-38), mean gestational age was 17.8 weeks (10-34w). The fluoroscopy time was 0.16 min (0-35sec). Fetal radiation exposure was negligible in 10 pregnant women (10 sec) and between 10-14 seconds in 4 pregnant women. The estimated fetal radiation exposure of the two women was between 30 and 35 seconds. Procedure-related complications were one minimal bleeding after sphincterotomy, two hyperamylasemia after ERCP, and one acute respiratory distress syndrome. Cholecystitis developed in one pregnant woman two days after ERCP. Conclusion: When necessary precautions are taken under the control of a multidisciplinary team, ERCP can be safely applied during pregnancy, and successful results can be obtained.

This paper is introducing KABADA (Knowledge Alliance of Business Idea Assessment: Digital Approach) unique tool, together with opinions of young people about entrepreneurship, their skills and experience with this tool. The focus is on non-business students who study natural sciences, engineering and other areas at the Faculty of Forestry and Wood Technology at Mendel University in Brno, Czech Republic. KABADA tool has been developed and tested by a team of international experts. It can be used to improve forester management. This structured, Web-based, platform which is based on theoretical research, relevant statistics, and artificial intelligence insights, guides entrepreneurs through every step of the way including what challenges and opportunities lie ahead. The research included survey answers from 60 university students before and after using KABADA tool. The results show that students are interested in entrepreneurship but do not have the knowledge, experience and support from curriculum. Majority of students had no or very low experience with entrepreneurship nor any entrepreneurship training or study course before. After using the tool, students declared to have higher knowledge of entrepreneurship and the number of students who intended to become an entrepreneur increased. The tool is available on-line, free of charge.

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted a metabolomic analysis of brain, heart, kidney, liver, lung and spleen in young (9-10 weeks) and old (96-104 weeks) wild type (mixed genetic background of 129/J and C57BL/6) mice using NMR spectroscopy. We found differences in metabolic fingerprints of all tissues and identified several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to age determine the age of biologic tissues and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level.

Sensory processing is a crucial function of the nervous system that significantly affects a large portion of the population, particularly older individuals who may be dealing with different forms of dementia. The global population of people aged 65 or older has reached a substantial count of around 703 million, representing approximately 9% of the total global population. Within this demographic, an estimated 5-8% of those aged 60, highlighting the growing need to address sensory modulation challenges for healthy aging. Sensory diet, derived from sensory integration theory, provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain. Recent neuroimaging studies have revealed intricate structural and functional alterations in the brain associated with the implementation of sensory diets. Furthermore, the integration of the Metaverse, augmented reality, and virtual reality has opened up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. This article offers a comprehensive exploration of the effectiveness of sensory diets in enhancing attentional control, self-regulation, and alleviating sensory-related distress among the healthy aging and dementia population. By employing precise quantitative evaluations such as sensory processing scales and advanced neuroimaging methodologies, it presents solid evidence of the tangible impact of these interventions. Emphasizing the importance of interdisciplinary cooperation and leveraging technological advancements, the article underscores the crucial need for customized sensory diets to optimize sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia.

Astringency is an important sensory characteristic of food and beverages containing polyphenols. However, astringency perception in elderly people has not been documented. The aim of the present work was to evaluate sensitivity to astringency as a function of age and salivary flow. Fifty-four panellists, including 30 elderly people (age=75±4.2 years) and 24 young people (age=29.4±3.8 years), participated in this study. Astringency sensitivity was evaluated by the 2-alternative forced choice (2-AFC) procedure using tannic acid solutions. Whole saliva was collected for 5 min before and after sensory tests. The results showed that the astringency threshold was significantly higher in the elderly group than in the young group. Moreover, a negative correlation between salivary flow and threshold was observed in the young group only. These results showed a difference in oral astringency perception as a function of age for the first time. This difference can be linked to salivary properties that differ as a function of age.

According to current literature and preliminary data, hydroxychloroquine (HCQ) seems potentially effective in the treatment of patients with Covid-19 pneumonia. The concentrations of HCQ in lungs might be well above that of plasma. Most likely, this property of HCQ provides effective drug concentrations in lungs. HCQ has a gradual onset of action in the treatment of rheumatic diseases. This could be valid for the treatment of Covid-19 pneumonia. It was suggested that regular HCQ administration in animals for a certain time might result in gradual accumulation of HCQ in tissues. Reduced perfusion, somewhat distorted architecture of lung tissue, edema and, suggested gradual accumulation of HCQ in lung tissue might cause reduced HCQ concentrations in pneumonic areas of the lungs in Covid-19 pneumonia. Patients with Covid-19 pneumonia and extensive lung involvement might have less HCQ concentrations in their lungs than patients having limited lung involvement. Furthermore, patients with Covid-19 pneumonia and extensive lung involvement might have more viral load than patients having limited lung involvement. That’s why treatment of patients with advanced Covid-19 pneumonia using HCQ might result in treatment failure, however HCQ might be effective in the treatment of patients with mild and moderate Covid-19 pneumonia. Using HCQ in Covid-19 pneumonia prophylaxis seems logical since providing enough accumulation of HCQ in the healthy lungs, before the arrival of the SARS-CoV-2 virus, might prevent Covid-19 pneumonia. However, the purpose of this paper is not to recommend using or not using HCQ for the treatment or for the prophylaxis of Covid-19 pneumonia. The purpose of this paper is only to try to bring a new perspective on the role of HCQ in the treatment or in the prophylaxis of Covid-19 pneumonia. This paper proposes only hypotheses, which need further researches to be confirmed.

Flanders (Belgium) is ageing at a rapid pace. Elderly people will continue to live at home in large numbers, partly because this is encouraged by the government. However, many homes are not adapted to reduced mobility. For example, it is not possible to circulate with a wheelchair. But also the living environment poses challenges for the elderly. Flanders is known for a far-reaching spread of housing and facilities, with the result that daily facilities can often only be reached by car. As a result of this spatial fragmentation, the elderly themselves often live for care providers in unreachable places. This ensures, among other things, that the in-home help travels several car kilometers. And research shows that so-called informal care is not self-evident either. Because what about the elderly who don't have children living nearby? Or with the residents who only see their next neighbor hundreds of meters away, who is also often a little mobile peer? The (untouched) appropriateness of the home, the presence or absence of facilities or neighbors, all of which belongs to what we can call the spatial capital of an environment. If this is not present, an autonomous life for a less mobile elderly person is not possible. The argument is that without sufficient spatial capital, the policy options are to allow the elderly to live in their homes for as long as possible or caring neighborhoods dead ends.

Traumatic pneumothorax (PTX) occurs in up to 50% of patients with severe polytrauma and chest injuries. Patients with traumatic PTX with clinical signs of tension physiology and hemodynamic instability are typically treated with an urgent decompressive thoracostomy, tube thoracostomy, or needle decompression. There is recent evidence that non-breathless patients with hemodynamically stable traumatic PTX can be managed conservatively through observation or a percutaneous pigtail catheter. We present here a 52-year-old woman who presented to the emergency department with 55 mm traumatic PTX. Following aspiration of 1500 ml of air, clinical improvement was immediately observed, allowing the patient to be discharged shortly thereafter. In hemodynamically stable patients with posttraumatic PTX, without specific risk factors or oxygen desaturation, observation or simple needle aspiration can be a reasonable approach. We aimed in this article to review the available literature on needle aspiration and conservative treatment of traumatic pneumothorax. A total of 12 studies were selected out of 190 articles on traumatic PTX, where conservative treatment versus chest tube decompression was compared. Our case report demonstrated that even a large PTX in a hemodynamically stable patient without other risk conditions, can be successfully treated conservatively with simple needle aspiration to avoid tube thoracostomy complications.

Congenital deafness is a major pediatric problem, affecting about 1.5-3 per 1000 newborns. The early treatment through cochlear implantation and auditory rehabilitation has been a historic milestone. Early diagnosis of congenital deafness is an essential requirement to obtain the best results, which is achieved through neonatal screening, a diagnostic practice that we began systematically at the Hospital Clínico in Valencia (Spain) 30 years ago.

In the article, the results of research on a NiTi alloy with a high nickel content (51.7 at.%), produced using the additive technology SLM method and subjected to isothermal aging after so-lution annealing, are presented. The study involved the determination of the sequence of phase transformations occurring using differential scanning calorimetry (DSC), and the determination of the temperature range of these transformations. In parallel, the phase composition was determined using the XRD method; hardness and the Young’s modulus were also determined. The analysis of the DSC results obtained indicates the following characteristic features of the NiTi alloy, which change with ageing time: (1) during cooling (from +1500C to -500C), the type of transformation changes from a one-step transformation after solution annealing to a two-step transformation after the ageing process over 1, 20 and 100 hours at 500°C; (2) during heating (from -500C to +1500C) for all the samples, regardless of the ageing time, only a one-step transformation from martensite M(B19’) to austenite A(B2) is observed; (3) the temperature at which the transformation starts increases with the ageing time, (4) the width of the total temperature range of the transformation M(B19’)  A(B2) during heating changes from large (∆T=49,7°C), after solution annealing, to narrow (∆T=19.3°C and ∆T=17.9°C after 20 h and 100 h of ageing) and, most importantly, (5) a comparison with literature data shows that, irrespective of the composition of the NiTi alloy and the manufacturing technology of the alloy samples (regardless of the fact whether this was traditional or additive technology), a sufficiently long ageing process period leads to the occurrence of the martensite  austenite transformation in the same temperature range.

The effects of post-treatment temperature-based methods on 1D single PLA filaments after FFF have been studied. This lets to decouple the variables related to the 3D structure (layer height, raster angle, infill density, and others) from the variables solely related to the material (molecular weight, molecular orientation, crystallinity, and others). PLA 1D filaments have been aged at 20, 39, 42, 51, 65, 75 and 80 ºC in a water-bath-inspired process in which the hydrolytic degradation of the PLA has been minimised for the ageing temperatures of interest. The evolution of the thermal and mechanical properties of the PLA filaments at different temperatures was recorded. Differential scanning calorimetry (DSC) was used to evaluate thermal and physical properties, in which the glass transition, enthalpic relaxation, crystallisation and melting reactions were analysed. Tensile tests were performed to evaluate the tensile strength and elastic modulus. The flow-induced molecular orientation, the degradation, the logistic fitting and the so-called summer effect –stabilisation of properties at higher temperatures– are discussed for assessing the safeness of accelerating ageing.

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is often linked to deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.

Neuropsychiatric manifestations of COVID-19 include delirium, general malaise, headache, and psychiatric symptoms. These manifestations are related to the neuroinflammatory response to viral antigens and proinflammatory mediators/immune cells. Tetracyclines, such as minocycline, have antibacterial and anti-inflammatory properties. Saiko-keishi-to, a traditional Japanese Kampo medicine, also has anti-inflammatory properties. Given the anti-inflammatory properties of minocycline and Saiko-keishi-to, we describe two cases of COVID-19 with prolonged headaches and general malaise successfully treated with these medications.

Background: Lipoprotein lipase (LPL) deficiency is a genetic condition. Affected individuals typically develop symptoms before age 10 with severe hypertriglyceridemia. No pharmacological treatment has lowered triglyceride levels in LPL deficiency patients successfully. The purpose of this study is to report on clinical outcomes of patients with LPL deficiency who responded to dietary therapy with successful reduction of their triglyceride (TG) levels with a long-chain triglyceride (LCT)-restricted, medium-chain triglyceride (MCT)-supplemented diet. Methods: A single-center retrospective case review study of LPL deficiency patients who met the inclusion criteria and were evaluated at the Hospital of Sick Children between January 2000 to December 2022. Data collected include demographic and clinical data, biochemical profiles at diagnosis and after dietary treatment initiation, and molecular results. Results: The study included seven patients with a suspected diagnosis of LPL deficiency (hypertriglyceridemia > 20 mmol/L). Six patients had a confirmed molecular diagnosis of LPL deficiency, and one had a Glycogen storage disease 1a (GSD1a) diagnosis. After presenting with hypertriglyceridemia, an LCT-restricted and MCT-supplemented diet was initiated, resulting in immediate and sustained TG reduction in all LPL deficiency patients that adhered to the diet. Additionally, they all maintained excellent growth and development. LPL deficiency-related complications were not observed under the MCT-enriched diet, except for increased pancreatic enzymes in one patient after dietary error. As expected, the diet failed to treat hypertriglyceridemia in the GSD1 patient. Conclusions: The dietary restriction of LCT in combination with MCT supplementation was feasible and effective in the long-term management of patients with LPL deficiency. In our experience, this treatment eliminated LPL-related complications and led to good clinical outcomes.

The research paper comprehensively and consistently addresses all relevant theoretical areas related to the topic and includes an extensive empirical analysis of the absorption of EU funds and their impact on the sustainable development of Croatia, Slovenia, Hungary, and Poland. The analysis aims to investigate the efficiency of the absorption of funds from the EU, the impact of these funds on regional development of countries, as well as the reasons for such impacts. The "Regional Development Model Based on EU Funds" was tested with the aim of applying the model to the Republic of Croatia, countries in the region, and other European countries to achieve a higher level of absorption of financial resources from the available EU funds. Data for the empirical analysis were collected using a highly structured survey questionnaire on a sample of 244 respondents involved in the preparation and implementation of EU-funded projects. The contribution of economic science in theoretical terms arises from the development of scientific knowledge and ideas about the importance of increasing the number of development projects that will increase the absorption of funds from the European Union, thereby increasing economic activities in Croatia and the region. The expected contribution of economic science in the applied sense is based on the formulation of the "Regional Development Model Based on EU Funds," which is based on the application of knowledge, good practices, and stakeholder experiences, considering relevant indicators from available sources. The greatest contribution is demonstrated through testing the "Regional Development Model Based on EU Funds," which is applicable to the Republic of Croatia, countries in the region, and other European countries over a longer period. Finally, research of the impact of EU funds on the regional development of recipient countries is considerably less represented and very modest, only in the "upswing" of systematic scientific research. The research aims to fill the gaps in research and encourage thinking of key stakeholders responsible for regional development, who should eventually realize the importance of defining a regional policy aimed at EU funds as a key to regional development and reducing regional disparities within countries.

: As antibiotic resistance undermines efforts to treat bacterial infections, phage therapy is being increasingly considered as an alternative in clinical settings and agriculture. However, a major concern in using phages is that pathogens will develop resistance to the phage. Due to the constant evolutionary pressure by phages, bacteria have evolved numerous mechanisms to block infection. If we determine the most common among them, we could use this knowledge to guide phage therapeutics. Here we compile data from 88 peer-reviewed studies where phage resistance was experimentally observed and linked to a bacterial gene, then assessed these data for patterns. In total, 141 host genes were identified to block infection against one or more of 80 phages (representing five families of the Caudovirales) across 16 microbial host genera. These data suggest that bacterial phage resistance is diverse, but even well-studied systems are understudied, and there are gaping holes in our knowledge of phage resistance across lesser-studied regions of microbial and viral sequence space. Fortunately, scalable approaches are newly available that, if broadly adopted, can provide data to power ecosystem-aware models that will guide harvesting natural variation towards designing effective, broadly applicable phage therapy cocktails as an alternative to antibiotics.

Historical legacy of Eastern European and Balkans’ health systems was mutually interdependent and shaped by local socioeconomic circumstances. Three distinctive systems of risk sharing and health financing to develop since the late XIX century were the Bismarck, Beveridge, and Semashko systems. Modern day healthcare systems in these countries are challenged by population ageing, accelerated innovation in medical technology, growing purchasing power and rising demand for healthcare services. Supply side changes contribute to demand side efficiency bottlenecks in financing, driving the costs of the already expensive medical care up. All of the nations have a large share of citizens experiencing difficulty with affordability and access to medical care, particularly in rural and remote areas. Network of Health technology assessment agencies have mushroomed over the past three decades. Principles of health economics theory and cost-effective resource allocation are slowly gaining ground in governing authorities’ mindset and decision-making process. For many years to come, pharmaceuticals and medical services will remain dependent on out-of-pocket spending. Currently accelerating and spreading 4.0 Industrial Revolution, together with the Belt and Road Initiative, are likely to substantially impact the further economic development of this vast region. Post-Pandemic ‘Green’ Recovery strategies adopted by many of the Eastern European governments shall also make this transition towards sustainable development more difficult and challenging given the large dependency of all these economies upon traditional carbon fuels.

Seed quality is crucial for the success of crop production, as it affects germination capacity, emergence potential, and seedling growth. This study investigated the impact of extended stor-age on the germination capacity, oleoresin and essential oil contents of black cumin seeds from three black cumin varieties in Ethiopia: "Aden", "Dershaye", and "Darbera". Seeds were stored for up to three years, and germination studies were conducted using a Completely Randomized De-sign. Results showed that storage period significantly affected various germination parameters, with a decrease in germination percentage observed with increasing storage period. However, variety and the interaction between storage period and variety had no statistically significant effect on germination percentage. The study also provides valuable insights into the correlations between different germination indices. Additionally, as black cumin seeds age, their oleoresin and essential oil contents decrease across all three varieties. Proper seed storage practices are essential in maintaining the germination potential of black cumin seeds, particularly over ex-tended storage periods. Overall, this study provides insights into the impact of extended seed storage on black cumin seed quality and germination potential, highlighting the importance of proper seed management practices to support sustainable crop production.

A new intervention model for promoting healthy ageing grounded on integrated value-based care was developed and tested in the city of Valencia (Spain). Its implementation raised relevant barriers for older adults in their access to health, health promotion, and health self-management linked with their health and digital literacy. This new intervention model included several aspects. On the one hand, researchers together with older adults and their informal caregivers participating in the study, designed personalised care plans, based on older adults’ specific needs, to be implemented with the support of a digital solution. On the other hand, researchers and health and social professionals implemented a series of six workshops in different locations of the city to encourage the sense of community among participants, reinforcing their trust in the new care model and increasing their adherence. Social activities were at the core of the workshops to understand older people’s interaction with the health and social services provided in the neighbourhood. Qualitative and quantitative methods were combined to extract information from older participants on how to engage them as active actors of their own health and understanding their values and preferences. Qualitative results show that after a post-pandemic situation, they were more concerned about social isolation and desired face-to-face contact with their professional care team; however, feelings of loneliness and/or sadness were not considered amongst the reasons to visit health professionals. Some of the conclusions reveal that the use of technology as a supportive tool is well received but with a stress on its role as “supportive”, and not replacing the close contact with healthcare professionals. Professionals recognised the benefits of this new approach but required more time and incentives to dedicate the effort needed.

Recently, many independent research project focus on the study of the molecular basis of aging processes. I parallel, the different progression of many diseaes between sex is a hot topic research area. These studies require many data, models and tools for inferring aging and sex specific molecular machinaries. Among the others, the Genotype-Tissue Expression (GTEx) database is one of the preminent resources for the analysis of expression data related to tissues, sex and age. The current version of the database has a lot of querying interface that enable many analysis centered on the expression of genes on tissues. Despite this the database lacks on the analysis at sex/age level, thus the researcher has to download data and then write queries by hand. Nevertheless it lacks on the integration with existing protein interaction data. Therefore, the need for the introduction of tools enabling easy access and powerful analysis capabilities (i.e. state of the art network based analysis and integration), arises. We here present NOMA-DB a framework for the analysis of age related genes based on the GTEx database that enable easy querying at sex/age level, network based analysis. The framework is based on wrapping the GTEx database and on building an application logic level on top of existing data. The current version enables the analysis of genes by tissue, gene and age, thus it may be used in potentially future directions of analysis towards better comprehension of aging/sex-related molecular machineries based on the analysis of expression dat

Paediatric supraventricular tachycardia (SVT) is a common arrhythmia of great clinical significance. If not treated promptly, it can cause heart failure and cardiogenic shock. Depending on the patient’s condition SVT treatment involves vagal manoeuvres, pharmacological or direct current cardioversion. The goal of acute SVT management is to immediately convert SVT to normal sinus rhythm (NSR) and prevent its recurrence. Adenosine is recommended as first-line treatment for stable SVT by the European Resuscitation Council (ERC) and American Heart Association (AHA) guidelines when vagal manoeuvres have proven ineffective. ERC and AHA guidelines recommend the intravenous route of administration. Intraosseous (IO) administration technique is also possible, but still relatively unknown. The aim of this paper is to describe a 3.5-year old child with SVT which was converted to NSR following IO administration of adenosine. Successful conversion was achieved in the second attempt with the adenosine dose. In the described case, there was no recurrence of SVT.

Bioelectrochemical systems (BES) encompass a group of biobased technologies capable of directly converting organic matter into electricity. In these systems, which are derived from conventional electrochemical systems, the ion exchange membrane represents a key element because of its influence on the economic feasibility and on the performance of BES. This study examines the impact of long-term operation of a BES on the mechanical, chemical and electrochemical properties of five different kind of cation exchange membranes (Nafion-117, CMI-7001, Zirfon UTP 500, FKE and FKB) through several techniques: (i) scanning electron microscopy (SEM) and atomic force microscopy (AFM) to assess the changes on the membranes surface, (ii) thermogravimetric analysis (TGA) to evaluate the structural stability of the membranes, and (iii) ion exchange capacity (IEC) to monitor any change in their electrochemical properties. Results confirmed that there is not an ideal membrane for BES. While Nafion and CMI-7000 exhibited the strongest chemical structure, they also underwent the highest fouling as revealed by a fast increase in surface roughness.

Shiga-like toxin producing Escherichia coli (STEC) is a well-known cause of foodborne acute diarrheic diseases especially in children and the elderly. The potentially fatal complications associated with toxin production range from bloody diarrhoea and ischemic colitis to kidney failure, haemolytic-uremic syndrome (HUS) and colon perforation. We describe a case and literature review of STEC – induced colitis, highlighting the clinical features, and the necessary tools for the best diagnosis approach and management. Facing challenging differential diagnosis ranging from ischemic colitis, inflammatory bowel disease, to infectious process due to a pathogenic or opportunistic agent, we practiced a step-by-step exploration. Beginning with bacteriological investigation, imagistic screening, and colonoscopy, we could rule out some of initial suppositions and reach the final diagnosis, also considering the pathological results. Although antibiotics are not indicated in this pathology, our patient did receive antibiotics, given the risk of translocation and colon perforation, without associating any complications, as HUS or peritonitis. Detailed and rigorous investigations along with a multi-speciality team are required for a prompt medical support. Coping the symptoms and refraining from further complications are the mainstem of the treatment.

This study investigated whether metabolomic fingerprints of bovine embryo growth media improve the prediction of successful embryo implantation. In this prospective cohort study, the metabolome from in vitro produced Day 7 blastocysts with successful implantation (n=11), blas-tocysts with failed implantation (n=10), and plain culture media without embryos (n=5) was in-cluded. Samples were analyzed using AbsoluteIDQ® p180 Targeted Metabolomics Kit with LC-MS/MS, and a total of 189 metabolites were analyzed from each sample. Blastocysts that re-sulted in successful embryo implantation had significantly higher levels of methionine sulfoxide (p<0.001), DOPA (p<0.05), spermidine (p<0.001), acetylcarnitine to free carnitine ratio (p<0.05), C2+C3 to free carnitine ratio (p<0.05), and lower levels of threonine (nep<0.001) and phosphati-dylcholine PC ae C30:0 (p<0.001) compared to control media. However, when compared to embryos that failed to implant, only DOPA, spermidine, C2/C0, (C2+C3)/C0 and PC ae C30:0 levels differentiated significantly. In summary, our study identifies a panel of differential metabolites in the culture media of bovine blastocysts that could act as potential biomarkers for the selection of viable blastocysts before embryo transfer.

Dengue virus infections are a serious public health problem worldwide. Aedes aegypti is the primary vector of dengue in Cuba. Since there is no vaccine or specific treatment, the control efforts are directed to reduce mosquito populations. The indiscriminate use of pesticides can lead to increase insecticide resistance as well as adverse effects on human health. The sterile insect technique is a species-specific and environmental friendly method of insect control based on the release of large numbers of sterile males. The success of this technique in sustainable control of agricultural pests has encouraged its evaluation for mosquito control. Here, we describe an open field trial to evaluate the effect of the release of irradiated males on a wild population of Aedes aegypti. The case-control study was performed in a suburb of Havana, and compared the mosquito population before and after the intervention, in both control and treated areas. The wild population was monitored by an ovitrap network, recording frequency and density of eggs as well as their hatch rate. A significant induced sterility was observed in the field population, compared to the control. The ovitrap index and the mean eggs/ trap declined dramatically after an expected lag period of twelve and five weeks, respectively. For the last three weeks, no egg was collected in the treated area, evidencing a significant suppression of the wild population. We conclude that the sterile males released competed successfully, and induced enough sterility to suppress the local Aedes aegypti population.

Poly(vinyl acetate) (PVAC) is a ubiquitous polymer in various industrial applications, including paints and adhesives. While extensive research has focused on understanding the degradation mechanisms of PVAC-based paint, under different environmental conditions, limited attention has been paid to the long-term stability of PVAC-based white glues, especially when used in artworks. This study investigates the accelerated degradation of a commercial PVAC-based white glue considered as representive of this class of materials as used in contemporary artworks, to predict its durability and assess its behavior in art objects. Through accelerated aging experiments and comparison with natural aging observed in artworks, the study reveals the formation of chromophores and the release of plasticizer as key degradation processes. Despite minimal structural modifications in PVAC, the loss of plasticizer leads to an increase in glass transition temperature, affecting the adhesive's cohesive strength and contributing to detachment of materials in artworks. The findings underscore the importance of preventive conservation measures to mitigate degradation issues in PVAC-based artworks.

In the present work, the effects of ageing treatment on the microstructures of a near-β Ti alloy (TC18) are studied. The influence of ageing treatment on the tensile properties and failure mechanisms are systematically analyzed. It is found that the size and morphology of the primary α (αp) phases are insensitive to ageing temperature and time. Furthermore, the ageing temperature and time dramatically influence the precipitation of the secondary α (αs) phases. Massive αs phases precipitate and gradually coarsen, and finally weave together with increasing the ageing temperature or extending the ageing time. The thickness of αs phases is responsible for the material strengths, while the content of α phases can enhance the material ductility. The ductile characteristics of the alloy with coarser αs phases are more obvious than those with thinner αs phases. Therefore, the ageing treatment is helpful for the precipitation and homogeneous distribution of αs phases, which is essential for balancing the strengths and ductility of the studied Ti alloy.

Introduction: The primary objective of researchers in the biology of ageing is to gain a comprehensive understanding of the ageing process while developing practical solutions that can enhance the quality of life for older individuals. This involves a continuous effort to bridge the gap between fundamental biological research and its real-world applications. Purpose: In this narrative review, we attempt to link research findings concerning the hormetic relationship between neurons and germ cells, and translate these findings into clinically relevant concepts. Methods: We conducted a literature search using PubMed, Embase, PLOS, Digital Commons Network, Google Scholar and Cochrane Library from 2000 to 2023, analyzing studies dealing with the relationship between hormetic, cognitive, and reproductive aspects of human ageing. Results: The process of hormesis serves as a bridge between the biology of neuron-germ cell interactions on one hand, and the clinical relevance of these interactions on the other. Details concerning these processes are discussed here, emphasizing new research which strengthens the overall concept. Conclusions: This review presents a scientifically and clinically relevant argument, claiming that maintaining a cognitively active lifestyle may decrease age-related degeneration, and improve overall health in ageing.

Standard evolutionary theory, supported by mathematical modelling of outbred, dispersed populations predicts that ageing is not an adaptation. We recently argued that in clonal, viscous populations, programmed organismal death could promote fitness through social benefits and has, in some organisms (e.g. Caenorhabditis elegans), evolved to shorten lifespan. Here we review previous adaptive death theory, including consumer sacrifice, biomass sacrifice, and defensive sacrifice types of altruistic adaptive death. In addition we discuss possible adaptive death in semelparous fish, coevolution of reproductive and adaptive death, and adaptive reproductive senescence in C. elegans. We also describe findings from recent tests for the existence of adaptive death in C. elegans using computer modelling. Such models have provided new insights into how trade-offs between fitness at the individual and colony levels mean that senescent changes can be selected traits. Exploring further the relationship between adaptive death and social interactions, we consider examples where adaptive death results more from action of kin than from self-destructive mechanisms and, to describe this, introduce the term adaptive killing of kin.

In this review, several cost-effective thin-film coating methods which include dip-coating, spin-coating, spray-coating, blade-coating, and roll-coating are presented. Each method has its set of advantages and disadvantages depending on the type of application. Not all of them are appropriate for large-scale production due to their certain limitations. That is why the coating method should be selected based on the type and size of substrate including the resolution of the required thin-films. The sol-gel method offers several benefits, such as simplicity in fabrication, excellent film uniformity, the capacity to cover surfaces of any size and over vast areas, and a low processing temperature. Nevertheless, these coating methods are somewhat economical and well managed in low-budget laboratories. Moreover, the produced thin-films are homogeneous and have low-surface roughness. Furthermore, some other thin-film deposition methods such as physical vapor deposition (PVD) and chemical vapor deposition (CVD) are also discussed. Since CVD is not restricted to line-of-sight deposition, a characteristic shared by sputtering, evaporation, and other PVD processes, many manufacturing methods favor it. However, these techniques require sophisticated equipment and cleanroom facility. We aim to provide the pros and cons of thin-film coating methods and let the readers decide the suitable technique for their specific application.

Differences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum from 36 MHO and 34 MUO women, who participated in a lifestyle intervention for weight loss were analyzed using an untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical and dietary intake parameters were assessed at both time points. Both groups showed differential metabolites profile at baseline and sixth month. Seven metabolites including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline and tyrosine significantly changed between group post-intervention, in which all showed a decreasing pattern in MHO. Significant reduction in body weight and BMI in the MUO correlated with changes in carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. Changes in carnitine and tyrosine levels in MUO correlated with weight loss, suggesting potential targets for therapeutic intervention.

Silver in different forms is used for medical purposes from ancient times. It is not yet well known, which form of silver is more biocompatible and less toxic. Here we considered silver nanoparticles and silver citrate. Also, the relationships of neurotoxicity of silver compaunds with ageing factor is not yet described. To assess the role of nanoform in neurotoxicity of silver and role of ageing a long-term experiment was conducted. We had four control groups of intact mice and four experimental groups which were exposed to silver nanoparticles and silver citrate for two months. Four groups of mice were introduced into the experiment since the age of five months to assess ageing factors. It was shown that the nanoform does play a certain role in neurotoxicity of silver. Silver citrate seems to be a more preferable silver compound. Ageing can be regarded as a positive factor that neutralizes toxic action of silver compounds. It may be due to the development of physiological/cognitive functions with the age as well as adaptation to unnatural content in the individual cages that is definitely stressful for mice.

Distribution System Operators (DSOs) are adapting to changing energy demands and the shift toward renewable and decentralized energy. Circularity is increasingly relevant for DSOs as their distribution systems age and need replacing. Taking circular action, however, is generally regarded as challenging as the current circular economy (CE) landscape is highly fragmented and rarely touches the implementation level. A longitudinal case study at Dutch DSO Liander on the circu-larity of distribution transformers was used to understand empirical success factors for taking circular action and to generate prescriptive knowledge on the operationalization of circularity. Six design propositions for circular action were formulated that suggest to 1) initiate small-scale cir-cularity experiments, 2) involve technical and strategic experts, 3) synergize circularity with more urgent, primary goals 4) translate circular initiatives bottom-up and top-down, 5) collaborate with other DSOs, and 6) create multidisciplinary teams. At DSO Liander, selecting the right interventions depending on the changing context contributed to operationalizing circularity for distribution transformers and achieving circularity targets. The generalizable design propositions could assist other DSOs in optimizing their strategy toward circular action.

Cesarean section is a challenge intervention in patients treated with dual antiplatelet therapy. We present case of 32 years old pregnant woman experiencing large acute myocardial infarction (MI) of anterolateral wall complicated by cardiogenic shock in the 38th week of pregnancy treated with drug-eluting stent implantation and dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor. Less than 24 hours after MI delivery started, urgent Caesarean section was indicated. As multiplate aggregometry testing showed a relatively insufficient level of ticagrelor platelet inhibition and a moderate level of aspirin platelet inhibition, Caesarean section was performed without discontinuation of ticagrelor, which was decided due to the need for emergency surgery. Local hemostatic measures including administration of tranexamic acid were applied. The patient did not experience excessive bleeding. A healthy male baby was born. To the best of our knowledge, this is the first reported case of surgery in pregnant women treated with DAPT without ticagrelor discontinuation.

The challenge of accessing finance by entrepreneurs from traditional financial sources is pervasive. The COVID-19 pandemic further exacerbated the problem of limited access to finance from banks. Against this backdrop, the objective of the study was to determine the factors driving crowdfunding success during the COVID-19 pandemic in Africa. The ordinary least squares (OLS) and probit regression models were estimated to analyse 216 crowdfunding projects in Africa. The results of the study documented that targeted amount (TA), and COVID-19 pandemic were negative and significant drivers of crowdfunding success. Furthermore, comments (CMM) and duration (DRN) were negative and significantly affected crowdfunding success. Conversely, images (IM), videos (VD), backers (BCK), and updates (UPD) were positive and significantly affected crowdfunding success. The study contributes to the body knowledge by investigating the drivers of crowdfunding success during the COVID-19 pandemic period which hitherto had not been researched on extenisvely.

The main purpose of this work is to contribute to understanding the mechanism of oxidation of the polymeric components of common disposable masks used during the COVID-19 pandemic to offer the chemical basis to predict their long-term behaviour under typical environmental conditions. Artificial ageing of representative mask layers under isothermal conditions (110℃) or accelerated photoageing showed that all the PP-made components underwent a fast oxidation process, following the typical hydrocarbon oxidation mechanism. In particular, yellowing and the melting temperature drop are early indicators of their diffusion-limited oxidation. Morphology changes also induced a loss of mechanical properties, observable as embrittlement of the fabric fibres. Results were validated through preliminary outdoor ageing of masks, which allows us to predict they will suffer fast and extensive oxidation only in the case of contemporary exposure to sunlight and relatively high environmental temperature, leading to their extensive breakdown in the form of microfiber fragments, i.e., microplastics.

The following are three successful case studies that affected humanity during the COVID-19 pandemic. The key to their success was their swift adaptability to the new confinement regulations and the unyielding determination of those carrying out their plans. Various extraordinary and prompt efforts were required to make the essential logistical preparations and practice for distance learning a reality. The research activities were also reorganized so the thesis students might carry out a few simple experiments at home under the strict supervision of their advisers and supervisors. The findings revealed that the students who participated in these projects applied all the abilities they had gained before the epidemic. In addition, they included crucial knowledge about the project, problem-based, and research-based learning. Furthermore, because they were the primary implementers of the trials, they learned by planning and performing experiments. The culmination of these efforts was displayed in three scientific publications that were published in index journals with a high level of impact. This latter factor is essential for the prestige and visibility of the university, in addition to the acquisition of financing and grants for scientific research.

Introducing children to sustainable and healthy school meals can promote a long-term dietary shift to lower climate impact and improve population health. The aim of the OPTIMAT study was to optimize meals for minimum deviation from the current food supply while reducing greenhouse gases and ensuring nutritional adequacy without increasing cost. Optimized menus were tested in four primary schools in Sweden and effects on daily food consumption and waste evaluated. Pupils received their usual menu plan for three weeks and then the isocaloric optimized menu plan for another three weeks. Nutritional recommendations for a school lunch and a maximum of 500 grams of CO2eq/meal were applied as constraints during linear programming. Pulses, Cereals, Meat and Eggs increased, while Fats and Oils, Dairy, Sauces and Seasonings decreased. The amount of ruminant meat was reduced in favor of other meat products. The new menu was 28% lower in greenhouse gas emissions and slightly less costly than the original. No significant changes in mean food consumption or plate waste were found in interrupted time series analysis between the two periods. This pragmatic approach for combining linear optimization with meal planning could accelerate sustainable development of the meal sector in Sweden and abroad.

Over the last three decades, special economic zones (SEZs) have given new impetus to the ever-growing export-oriented industrialization in developing countries. Where various economies have benefited from SEZs, many zones have ended up becoming enclaves with trifling advantage. The SEZs in Pakistan have experienced the same fate and failed to contribute to exports, employment and creating linkages with the domestic economy. Recently under China Pakistan Economic Corridor (CPEC), SEZs are proposed to be set up in Pakistan; with a hope to fuel the stuttering economy. However, it is pertinent to first understand the local context and device policies considering stakeholders' perspectives. This study aims to identify the factors for the successful implementation of SEZs derived from the regional context of Pakistan. In-depth interviews are conducted from most relevant stakeholders, who have been involved in the development of SEZs. The results pointed towards the removal of political influence over zones and government taking the lead role in deciding the types of industry to be invited in these zones. Each zone should have a clear vision of development based on its regional advantage. The zone promotions should be based on competitiveness rather than fiscal incentives. Joint ventures and PPP to be encouraged inside the zones for sustainable operations.

As the global aging trend continues to intensify, there will inevitably be more complex and diverse aging problems in the future. There is no doubt that designers have the responsibility to explore the possibilities of the future and solve the problems that will be faced in the future. Based on the Future Cone, the Double Diamond Model and the IDEO Method Cards, this study proposes a new model to guide the design practice of future aging issues in the context of aging. With the aim of validating and refining the framework, an ageing designer workshop was held where participants were asked to imagine, explore and express ideas about future ageing issues. The workshop was used to refine the proposed model. More specifically, the model includes a future concept, a design guidance process based on the Double Diamond Model, and tools that can be applied at all stages of design, which can help designers generate ideas and solutions for future aging problems, and collectively lead society to a more desirable future. Moreover, this study also explores broader directions for the development of the model and provides a reference for continued research on this topic in the future.

Studies have shown the benefits of endovascular treatment (EVT) in adult stroke cases, but its application in pediatric stroke remains controversial. Despite evidence of improved outcomes in adults, there are no established recommendations for EVT in children. Conducting individual case reports and case series is vital to understanding its potential advantages and disadvantages in this context. This case report presents a 9-year-old boy who experienced basilar artery occlusion leading to a stroke and was effectively treated with mechanical thrombectomy.

Present experimental study assesses the mechanical properties of glass/carbon/glass hybrid composite laminates after exposure to moisture and elevated temperatures for extended periods. The top and bottom layers of the hybrid laminates are glass fiber reinforced and the middle layer is carbon fiber reinforced with the matrix specified as a polymer material. The hybrid laminates were manufactured using the resin transfer molding method and their compressive and tensile properties were determined using a tensile testing machine. The material parameters such as the storage modulus, the loss modulus, and the damping factors of the laminates were identified using dynamic mechanical analysis as a function of the temperature and the vibration frequency. The experimental results on compressive and tensile properties revealed slight variations when the hybrid laminates were kept at low temperatures for extended periods. This might occur due to the increasing molecular cross-linking of the polymer network. As the temperature increased, compressive, tensile, storage modules, loss modulus, and damping factors decreased. This might occur due to the increasing mobility of the binder material. Particularly, the highest stiffness parameters were obtained on -80°C/GCG (Glass/Carbon/Glass) laminates due to the presence of beta transition on the glassy region. The relationships between the glass transitions and the targeted frequencies were characterized. The values of the glass transition shift towards higher temperatures as the frequency increases. This might occur due to a reduction in the gaps between the crosslinking of the epoxy network when the frequency increases. The accuracy of the storage modulus results was compared with the empirical models. The model based on the Arrhenius law provided the closest correlation. Meanwhile, another model was observed that was not accurate enough to predict when gamma and beta relaxations occur under a glassy state.

The widespread use of renewable energy sources has considerably expanded distributed generation. An unbalanced load on distribution cables may also result from the recent increase in novel appliances and electric vehicles, the reverse power flow may create short-term overloads. These transient overloads increase the temperature for a short time beyond the limit, which causes degradation. However, the temperature distribution on the cable is not even. Therefore, the cable components are not degraded evenly and similarly. This publication describes the change in electrical properties of low-voltage cables caused by short-term cyclic artificial ageing to track the impact of these brief temperature rises. This study examines how cable structure affects the dielectric characteristics of cable specimens. Four cable samples, each measuring 50 cm in length (SZAMKAM 0.6/1 kV 16 mm2× 4 manufactured by Prysmian MKM Kft, Hungary) put through an accelerated ageing test in a temperature-controlled oven after changing their structures by removing their layers. Three rounds, each of six hours, accelerated thermal ageing were applied. After each round of ageing, the dielectric parameter tanδ and capacitance were measured by Dirana Dielectric Response Analyzer in the laboratory at room temperature 24±0.5∘C. Furthermore, the polarization and depolarization currents were also studied. The results show that changing the cable structure impacts the dielectric parameters, especially the effect of belting layer is significant. From point of view of aging the PVC belting layer protects the diffusion of plasticizers of inner structure.

Although pollination is one of the most crucial biological processes that ensures plant reproduction, its mechanisms are poorly understood. Especially in insect-mediated pollination, a pollen undergoes several attachment and detachment cycles when being transfered from anther to insect and from insect to stigma. The influence of the surface properties of pollen, insect and floral surfaces on the adhesion forces that mediate pollen transfer are poorly studied. Here, we investigate the adhesive properties of Hypochaeris radicata pollen and their dependence on pollen ageing by quantifying the pull-off forces from glass slides using centrifugation and atomic force microscopy. We found that the properties of the pollenkitt – the viscous, lipid liquid on the surface of most pollen grains – influences the forces necessary to detach a pollen from hydrophilic surfaces. Our results show that aged H. radicata pollen form weaker adhesions to hydrophilic glass than fresh ones. On the other hand, when a pollen grain ages in contact with glass, the adhesion between the two surfaces increases over time. This study shows for the first time the pollen ageing effect on the pollination mechanism.

Antibodies are important tools for the study of membrane proteins in biological, biophysics and structural analyses. However, the production of purified membrane proteins is still a formidable challenge due to the amphipathic character and inherent instability of these proteins. In this work, we tested a strategy for producing antibodies against an ATP-Binding Cassette (ABC) transporter without the need to produce the full membrane complex. Instead, just the extra cytoplasmic regions of the ABC-type transporter Rv1819c from Mycobacterium tuberculosis were presented in the RAD-display, a scaffold system based on the engineered Pyrococcus furiosus RadA protein developed for exposition of peptides. The RadA scaffold protein is highly stable, can tolerate long insertions and easy to produce in Escherichia coli. Based on the three-dimensional structure of Rv1891c, we selected two versions of the main extracellular loops of the permease to use as test cases for this approach. Rv1819c-derived peptides displayed on RAD display system were used for immunization of mice and production of polyclonal antibodies. These antibodies were able to recognize the transporter in M. tuberculosis cell extracts, on intact cells by flow cytometry and as purified protein. The results showed the approach can be a useful tool for in vitro analyses, screening, and evaluation of different epitopes in membrane proteins.

This single case study aims to address a gap in literature regarding the establishment of microenterprises for people with physical disability in Vietnam. Semi-structured interviews were conducted with seven people with physical disability including the Director of a non-government organisation supporting six entrepreneurs with physical disability who were engaged in teaching English to school aged children after school. Data was analysed utilising Lingelbach, De La Vina and Asel’s (2005) three characteristics that improve probability of entrepreneurial success in developing countries. This framework aided in examining the approach of establishing microenterprises by the non-government organisation. The entrepreneurs with physical disability reported earnings above average wages and feeling empowered by participating in the microenterprises. These feelings of empowerment were reportedly associated with greater independence, increased self-efficacy and a confidence in planning for their futures.

The key challenges to treating glioblastoma multiforme (GBM) are the heterogenous and complex nature of the GBM tumour microenvironment (TME) and difficulty of drug delivery across the blood-brain barrier (BBB). The TME is composed of various neuronal and immune cells, as well as non-cellular components including metabolic products, cellular interactions, and chemical compositions, all of which play a critical role in GBM development and therapeutic resistance. In this review, we aim to unravel the complexity of the GBM TME, evaluate current therapeutics targeting this microenvironment, and lastly identify potential targets and therapeutic delivery vehicles for the treatment of GBM. Specifically, we explore the potential of aptamer-targeted delivery as a successful approach to treating brain cancers. Aptamers have emerged as promising therapeutic drug delivery vehicles with the potential to cross the BBB and deliver payloads to GBM and brain metastases. By targeting specific ligands within the TME, aptamers could potentially improve treatment outcomes and overcome the challenges associated with larger therapies such as antibodies.

This paper provides an overview of current literature on community-led development initiatives in urban contexts, their role in addressing urban inequality, and the challenges they face. This study examines effective strategies of community-led initiatives, such as empowering communities, building partnerships, mobilizing resources, focusing on local needs, and participatory design methods. Case studies from around the world demonstrate how successful community-led development initiatives have been able to overcome obstacles to create more inclusive and equitable urban environments. Institutional support, including technical assistance, capacity building, and regulatory frameworks, are crucial for promoting the success and sustainability of these initiatives. Challenges to community-led initiatives include limited resources, capacity building needs, inadequate infrastructure, lack of institutional support, and lack of trust among community members. Therefore, the paper suggests that it is essential to address these challenges to enable the success of community-led development initiatives. Furthermore, this study recommends that future research should explore how emerging technologies and innovative approaches can effectively support community-led development initiatives and advance more just and sustainable urban development.

The importance of frailty in older people is getting constant recognition as an important aspect both in terms of public health, as well in personal level for the appropriate management of an older person health condition. This is reflected by the continuously increasing number of research studies carried out in several settings across different countries. Sometimes this is very solid, but in other cases there is a considerable gap in terms of accurate and well grounded documentation of frailty status. This is the case in Greece, where we are missing clinically validated tools to approach frailty. We are missing frailty screening tools, such as for instance PRISMA 7, the gold standard tool of Fried criteria is somehow problematic since the question referring to physical activity originates from a questionnaire that has not been translated and validated, while Clinical Frailty Scale has been validated for the translation but not for the capacity to detect frailty. Aim of this study is to validate these tools for their accuracy to detect frailty by using a measurable index of frailty, previously proposed for use in clinical studies: the Short Physical Performance Battery (SPPB). 74 male and female participants have been evaluated for their frailty status using different tools. We observed that PRISMA 7 translation detects frailty only when one question is removed at a cut-off of ≥ 2 and indicated a sensitivity of 88.1%, and specificity of 99.9% with a good correlation with SPPB measurements (r = 0.858; p &lt; 0.001). When CFS was validated using SPPB it demonstrated a very good correlation (r = -0.838; p &lt; 0.001 respectively) as it was the case for the modified Fried Criteria (r = -0.725; p &lt; 0.001). All items demonstrated a good correlation between them. We can here propose that we can accurately assess frailty status in the community setting by using a modified version of Fried criteria, Clinical Frailty Scale translation in Greek and we can screen for frailty by using the Greek translation of PRISMA 7 only after removing the item 6 of the questionnaire.

Background: Availability of large longitudinal population health and aging studies, such as the English Longitudinal Study on Ageing, hold many opportunities for the examination of the development of Frailty over time. Lacking are psychometrically robust longitudinal measurement of the concepts of frailty required for accurate and reliable estimates and identification of frail individuals. Objectives. Development of a psychometrically robust longitudinal research tool of Frailty. The tool is to be easy to replicate for future use in health and aging research. Participants/Measurements. Data comes from four waves of ELSA (2014-2017); N=39,528. Six domains of health status deficits that may measure frailty were used: Mobility, Daily Function, Self-rated general health, Self-rated pain, Depression, Self-report doctor diagnoses of health. Design. Exploratory factor analysis (EFA) of common-self-reported deficits available across four waves of longitudinal data were compared to determine which deficits were a best fit for a research-based frailty index. Standardized regression factor scores were calculated to represent individual’s placement in factors identified from EFA. Cross-sectional validation and reliability are reported. Results. Five-Factors of Frailty found were consistent across ELSA waves. Mobility/Severe Pain, Planning/Self Care, Depression, Moderate Pain/Movement/Arthritis and Cardio-Metabolic. The variable make-up of each factor differed between males and females. Psychometric properties of the five factor frailty model were taken into account at each stage of development (factorability/sampling adequacy, cross-sectional replicability, internal consistency, low interdeterminacy, relations with age).Conclusions. Five distinct factors of an accumulation of deficits approach to frailty were found. Use and development of the five factors of frailty research tool are outlined. This research tool will aid researchers in determining the complex risk factors and outcomes of empirically derived components of frailty in ELSA.

Background: Active ageing is a multidimensional, relative, and context-dependent concept with different paths and outcomes. The purpose of this qualitative study was to explore personal active ageing strategies in a specific context. Method: Following a directed content analyze procedure, we conduct semi structured individual interview with 39 elder (men and women) between the ages of 60-97 years that selected with purposeful sampling .data collection and analysis were concurrent. We analyzed the data from interviews, written narratives, and field notes using directed content analyze. The Reliability of data was fulfilled in accordance Lincoln and Guba criteria. We stopped data collection when no new concept was added and data saturation occurred. Results: Based on the experience of elders, we identified 5 categories: 1) Preventive 2) Coping 3) Internal self-control 4) Coherence maintenance strategies 5) Opportunity exploiting strategies. These described the active ageing strategies when encountering with age related change. Utilizing these strategies, the elder accompanied the life time. Conclusion: The finding suggests that active ageing is a continuous process in confronting age related change. The identified strategies can help to promote active ageing by familiarizing older with opportunities of life and training them in how to use these strategies.

Advanced paternal age increases the risk of transmitting de novo germline mutations, particularly missense mutations activating the receptor tyrosine kinase (RTK) signaling pathway, exemplified by the FGFR3 mutation linked to achondroplasia (ACH). This risk is attributed to the expansion of spermatogonial stem cells carrying the mutation, forming sub-clonal clusters in the ageing testis, thereby increasing the frequency of mutant sperm and the number of affected offspring from older fathers. While prior studies proposed a correlation between sub-clonal cluster expansion in the testis and elevated mutant sperm production in older donors, limited data exist on the universality of this phenomenon. Our study addresses this gap by examining the testis expansion patterns, as well as increases of mutations in sperm for two FGFR3 variants: c.1138G>A (p.G380R) and c.1948A>G (p.K650E)- associated with ACH or thanatophoric dysplasia (TDII), respectively. Unlike the ACH mutation, which showed sub-clonal expansion events in an aged testis and a significant increase of mutant sperm with the donor’s age, the TDII mutation formed sub-clonal clusters, but exhibited reduced transmission into sperm and no significant age-related increase. The mechanism behind this divergence remains unclear, suggesting potential pleiotropic effects of aberrant RTK signaling in the male germline, possibly hindering differentiation requiring meiosis. This study provides further insights into transmission risks of micro-mosaics associated with advanced paternal age in the male germline.

Aluminium bronzes possess a unique combination of high strength and wear and corrosion resistance in aggressive environments; thus, these alloys find wide application in marine, shipbuilding, aviation, railway, offshore platform applications and other fields. Iron-aluminium bronzes (IABs) are the cheapest and most widely used. When the aluminium content is above 9.4 wt%, IAB is biphasic (i.e. it undergoes -transformation) and can be subjected to all heat-treatment types depending on the desired operating behaviour of the bronze component. This article presents correlations (mathematical models) between the primary mechanical characteristics (yield limit, tensile strength, elongation, hardness and impact toughness) and the ageing temperature and time of quench at 920°C in water Cu-11Al-6Fe bronze, obtained using the centrifugal casting method. The microstructure evolution was evaluated depending on the ageing temperature and time changes. Overall, the research was conducted in three successive inter-related stages: a one-factor-at-a-time study, planned experiment, and optimisations. Four optimisation tasks, which have the greatest importance for practice, were formulated and solved. The defined multiobjective optimisation tasks were solved by searching for the Pareto-optimal solution approach. The decisions were made through a nondominated sorting genetic algorithm (NSGA-II) using QstatLab. The optimisation results were verified experimentally. Additional samples were made for this purpose, quenched at 920°C in water and subjected to subsequent ageing with the optimal values of the governing factors (ageing temperature and time) for the corresponding optimisation task. The comparison of the results for the mechanical characteristics with the theoretical optimisation results presents good agreement.

The prevention, mitigation and treatment of movement impairments, ideally, requires early diagnosis or identification. As the human movement system has physiological and functional redundancy, movement limitations do not promptly arise at the onset of physical decline. A such, prediction of movement limitations is complex: it is unclear how much decline can be tolerated before movement limitations start and how humans select compensatory movement strategies for a task. Adding to the challenge is the lack of general applicable and consensus terminology on movement limitations. Currently, the term ‘homeostatic reserve’ or ‘physiological reserve’ is used to refer to the redundancy of the human biological system, but this does not describe the redundancy in the muscle architecture of the human body. This article therefore proposes CaReMoOC, a framework incorporating neuromusculoskeletal capacity (accumulation of neuromusculoskeletal resources over the lifespan), reserve (task-specific difference between capacity and task demand), movement objectives (considerations made to plan a movement), and compensation (use of NMSK resources to respond to the task demand). Two forms of compensation are Compensation for Capacity, when capacity does not meet the task demands, and Compensation for Movement Objectives, when the movement is changed due to for example a fear of falling. This article demonstrates the framework for healthy ageing, providing an overview of age-related capacity decline (neural, skeletal, muscular system) and shifted weighting of movement objectives (energy, pain, stability, speed) relevant for experimental and modelling research in biomechanics and motor control. CaReMoOC provides a means to communicate hypotheses and theories on movement impairments and limitations. To predict movement limitations, we need to find ways to quantify NMSK reserve.

Background: Stress hyperglycemia (SH) is common is patients with ST-elevation myocardial infraction (STEMI). The aims of the study were to analyze the impact of SH on the incidence of all-cause mortality and major adverse cardiovascular events (MACE-cardiovascular death, non-fatal reinfarction, target vessel revascularization and stroke) in STEMI patients without diabetes mellitus (DM) who have been treated successfully with primary PCI (pPCI). Method: we analyzed 2,362 STEMI patients treated with successful pPCI (post-procedural flow TIMI=3) and without DM and cardiogenic shock at admission. SH was defined as plasma glucose level above 7.8mmol/L at admission. The follow-up period was 8 years. Results: Incidence of SH was 26.9%. Eight-year all-cause mortality and MACE rates were significantly higher in patients with SH, as compared to patients without SH (9.7% vs 4.2%, p<0.001 and 15.7% vs 9.4%, p<0.001). SH was an independent predictor of short and long-term all-cause mortality (HR 2.19, 95%CI 1.16-4.18 and HR 1.99, 95%CI 1.03-3.85) and MACE (HR 1.49, 95%CI 1.03-2.03 and HR 1.35, 95%CI 1.03-1.89). Conclusion: Despite successful revascularization, SH at admission was an independent predictor of short-term and long-term (up to eight years) all-cause mortality and MACE, but its negative prognostic impact was stronger in short-term follow-up.

A retrospective cohort study was performed to determine the likelihood of malignant stroke after mechanical thrombectomy via ASPECTS-PASS score(A-P score), a novel scoring system using ASPECT score and number of arterial-passes. This prediction score is designed to help clinicians take early measures. Malignant stroke is defined as a large MCA infarct with mass effect that develops during the first 5 days following presentation and is associated with approximately 80% mortality. Previous studies have shown an association of low ASPECTS and high number of passes with poor outcome.We performed a retrospective cohort analysis on 78 patients with anterior circulation stroke who underwent mechanical thrombectomy at our hospital. We analyzed the likelihood of developing malignant stroke post thrombectomy in the first 5 days following successful recanalization (TICI ≽ 2b). Malignant stroke is defined as severe symptoms secondary to edema as evidenced by midline shift, cistern engorgement, and hemorrhagic conversion with edema. Patients with ASPECTS of 0-5 were excluded. We used two variables to predict the outcome: ASPECT score and number-of-passes. We used the equation ASPECT score minus number-of-passes (A-P) to arrive at a single number to predict the risk of malignant stroke. A-P scoring scale ranged from 0-9. Our study showed a statistically significant inverse relationship of A-P score and risk of malignant stroke. Approximately 90% of patients with A-P score < 5 developed malignant stroke in our study. A-P score can help predict malignant stroke post thrombectomy even after successful recanalization. Thus, A-P score of ≤ 5 suggests very high risk. (A-P) Score can assist clinicians to take early measures, and thereby prevent worse outcomes.

Integrating a grid-connected battery into a Renewable Energy Community boosts Collective-Self-Consumption of photovoltaic produced energy and allow to perform Energy Arbitrage in the day-ahead and intraday electricity market. However, is it a cost-effective investment? The proposed analysis relay on Net Present Value assessment. Ageing affects are integrated and sensitivity analyses are conducted: considering community customers number, electricity mar-ket prices, battery cost, size and the decision to engage in energy arbitrage. Each scenario under-goes a 20-year hourly simulation using an ageing aware rolling-horizon 24-hours-looking-ahead scheduling, optimized with Mixed-integer linear Programming. Forecast errors, provid-ing of ancillary services, real time control and grid constrains are not taken into account. Simulations conducted on the Italian market indicates that a battery dedicated solely to collec-tive self-consumption is not economically appealing. However, integrating Energy Arbitrage, despite impact on battery lifespan, halves the payback period and enhances the attractiveness of larger battery investments. The Net Present Value is contingent upon battery size, customer number and market prices. However, if battery cost does not exceed 200 €/kWh the investment become cost-effective across all scenarios.

This case report presents a critical clinical scenario involving a 55-year-old patient who developed severe Plasmodium falciparum malaria with renal complications despite receiving doxycycline prophylaxis while travelling in a malaria-endemic region. The case emphasizes the potential failure of doxycycline prophylaxis and highlights the importance of considering malaria in patients with a history of travel to endemic areas, even if they have adhered to prophylactic treatment. The patient's clinical presentation included fever, extreme fatigue, and loss of consciousness, leading to hospitalization. Laboratory findings revealed severe anaemia, elevated liver enzymes, and impaired renal function, consistent with the criteria for severe malaria. The diagnosis was confirmed by the presence of Plasmodium falciparum parasites on blood smears. Due to limited access to parenteral antimalarial medications, the patient received oral artemether-lumefantrine, resulting in clinical improvement. Supportive care and dialysis played a vital role in the patient's recovery. This case report underscores the need for increased awareness of prophylaxis failure, the challenges of managing severe malaria in non-endemic countries, and the importance of timely and appropriate interventions to improve outcomes in severe malaria cases, particularly those with renal involvement. Further research is warranted to evaluate alternative preventive strategies in regions with drug-resistant malaria strains.

For most professionals to be successful in the current job market, they need some entrepreneurial skills (ES). This study aimed to describe and systematize these skills, considering the current globalization and digital transformation phenomena. The documental analysis and the critical reflection on the collected data allowed us to identify the socio-economic and socio-cultural reasons for the relevance of this problem. Consequently, to elaborate a frame of reference that is intended to be adequate to the needs of the professionals of the current global and digital era. The results pointed to a tripartite ES model - to be open to novelty, to create solutions to emerging problems, and to communicate effectively - which integrates the following skills: creativity and innovation, the spirit of initiative, self-efficacy and resilience, strategic planning, and evaluation, resolution of problems and decision-making, transformational leadership, clear and visual communication, teamwork and networking, and digital communication. In the continuation of this study, an ES scale will be created and validated according to this model, which will make it possible to measure the degree of development of these competencies.

In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due to diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable of identifying proteins exhibiting structural differences in complex proteomes. PLF applied to published young and aged intervertebral disc (IVD) MS datasets (posterior, lateral and anterior regions of the annulus fibrosus), identified 268 proteins with age-related structural differences. For several ECM assemblies (collagens I, II and V and aggrecan), these differences were markedly conserved between degeneration-prone (posterior and lateral) and resistant (anterior) regions. Significant differences in peptide yields, observed within collagen I, II and V α-chains (COL1A2, COL2A1, COL5A1), were located within their triple helical regions and/or cleaved C-terminal propeptides, indicating potential accumulation of damage and impaired maintenance in ageing. Several proteins (COL5A1, COL2A1 and aggrecan) also exhibited tissue region (lateral)-specific differences in structure between aged and young, suggesting that some ageing mechanisms may act locally within tissues. This study not only provides evidence of age-related changes in ECM protein structures which are tissue-region specific, but also highlights the ability of PLF to identify potential protein biomarkers of localised tissue remodelling.

In healthy ageing, capacity declines in the neural, muscular, and skeletal systems, and each system decline has its effect on the execution of complex motor tasks. This decline in capacity can result in the inability to stand up (sit-to-stand, sit-to-walk), which is a key movement for independence. The mechanisms leading to mobility limitations or inabilities are complex, overlapping, and interdependent and the complementary fields of biomechanics, motor control, and physiology need to be combined to understand these mechanisms. The aim of this review is to provide an overview of the current knowledge of age-related compensation in standing up and to consider the limitations of these results when analysing standing up in daily life using the Capacity, Reserve, Movement Objectives, and Compensation (CaReMoOC) framework that combines biomechanics, motor control, and physiology. A literature search was performed in the search engine Scopus, using the keywords and their synonyms: strateg*(approach, technique, way) AND, sit-to-walk OR sit-to-stand OR rise (raise, arise, stand, stand-up) AND chair (seat). Inclusion criteria were: biomechanics or motor control on sit-to-stand or sit-to-walk in healthy and/or frail adults (<60y) and elderly (>60y), and/or osteoarthritis patients as a specific case of ageing related decline. The review shows that movement compensations in standing up manifest as changes in planned trajectory (Compensation by Selection) and in muscle recruitment (Compensation by Reorganisation). However, as most studies in the literature typically use standardized experimental protocols where movement compensation is restricted, these studies cannot be directly translated to functional tasks, such as the mobility of the elderly in their homes, communities, and clinic. Compensation must be included in future studies in order to facilitate clinical translation. Specifically, future studies in the standing up task should 1) determine the effect of varying arm use strategies (e.g., armrests, knees, chair, cane) on trunk and both lower limb and upper limb joint loading, 2) analyse control strategies in elderly people, 3) determine the biomechanical implications of asymmetry, and 4) incorporate assessments of age-related physical and neural decline as well as changes in psychological priorities.

OpenAI has managed to turn 100 million heads in two months towards their new Language model tool (LM) ChatGPT. The third generation Generative Pretrained Transformer (GPT-3) has the capacity to tackle simple to complex and sophisticated problems, while providing reasoning behind its generated answers. ChatGPT can be used to increase productivity and improve efficiency and face challenging problems. Programming mobile applications is a challenging task that requires professional software engineers, skills and abilities to be developed. The following paper takes a case study approach to assess how novice app developers can use ChatGPT to generate Java scripts that will be used in Android studio to create a functional application. The results after, many iterations and ongoing conversations with ChatGPT managed to create an application for the anticipated function. Important insights have been drawn from the case study that could set the ground for any novice user seeking to create applications using Java scripting and Android Studio.

Golf courses have a significant environmental impact. High water demands and the intensive use of agricultural chemicals have been a concern for decades and are therefore in the focus of efforts to make golf courses more environmentally sustainable. Products based on modifying or using plant-associated microbiota are one of the fastest growing sectors in agriculture, but their application on turfgrasses on golf courses is so far negligible. In this review, we summarize the limited knowledge on microbiomes of golf turf ecosystems and show that the lack of holistic studies addressing structure and function of golf turf microbiomes, including their responses to intense turf management procedures, is currently the main bottleneck for development and improvement of reliable, well-functioning microbial products. We further highlight the endosphere of turfgrasses, which is easily accessible for microbial cultivation through constant mowing, as the most stable and protected micro-environment. Many grass species do possess endophytic bacteria and fungi that have shown to improve the plants’ resistance towards microbial pathogens and insect pests, and several products using endophyte-enhanced grass varieties are commercially successful. We anticipated that this trend would tee-off on golf courses, too, once a more comprehensive understanding of golf turf microbiomes is available.

Invasion ecology has a long tradition of searching for traits distinguishing alien invasive and non-invasive plants. Surprisingly, this approach has been so far poorly used to understand why some arable weeds are abundant and widespread while others are rare and narrowly distributed. In the present study, we focused on the characteristics of successful weeds occurring in maize fields, one of the most import crop worldwide. Two national weed surveys conducted in France were used to identify increasing and decreasing species based on 175 and 484 surveyed fields in the 1970s and the 2000s, respectively. Weed trait values related to regional frequency, local abundance and specialization to maize were identified with Phylogenetic Generalized Least-Squares (PGLS). We found a positive relationship between regional frequency and local abundance, i.e. the most widespread weeds were also locally more abundant. We highlighted that weeds with the C4 photosynthetic pathway and summer emergence were more abundant, more frequent and more specialized to maize crops. More generally, we highlighted two successful strategies: on the one hand, traits related to a general weediness syndrome with rapid resource acquisition (high SLA and Ellenberg-N) and high colonization capacity (seed longevity, fecundity and wind dispersal), on the other hand, traits related to specific adaptation to spring cultivation (thermophilous species with summer emergence, late flowering and C4 photosynthetic pathway). Deviations from the abundancy-frequency relationships also indicated that species of the Panicoideae sub-family, species with Triazine-resistant populations and neophyte species were more abundant than expected by their regional frequency. To some extent, it is therefore possible to predict which species can be troublesome in maize crops and use this information in weed risk assessment tools to prevent new introductions or favor early detection and eradication. This study showed how tools developed in functional and macro-ecology can be used to improve our understanding of weed ecology and to develop more preventive management strategies.

In the next decade, further digitalisation of the entire wind energy project lifecycle is expected to be a major driver for reducing project costs and risks. In this paper, a literature review on the challenges related to implementation of digitalisation in the wind energy industry is first carried out, showing that there is a strong need for new solutions that enable co-innovation within and between organisations. Therefore, a new collaboration method called the WeDoWind Ecosystem is developed and demonstrated. The method is centred around specific "challenges", which are defined by "challenge providers" within a topical "space" and made available to participants via a digital platform. The data required in order to solve a particular "challenge" is provided by the "challenge providers" under the confidentiality conditions they specify. The method is demonstrated via a case study, the EDP Wind Turbine Fault Detection Challenge. Six submitted solutions using diverse approaches are evaluated. Two of the methods perform significantly better than EDP’s existing method in terms of Total Prediction Costs (saving up to €120,000). The WeDoWind Ecosystem is found to be a promising solution for enabling co-innovation in wind energy, providing a number of tangible benefits for both challenge and solution providers.

In the realm of power delivery to end-users, transformers are indispensable, with their malfunctions leading to substantial economic, safety, and environmental repercussions. The need for persistent surveillance is accentuated for in-situ oil-filled transformers, given the potential degradation of oil and the emergence of related ageing by-products. As the focus tilts towards online detection methodologies for transformer oil ageing, bypassing challenges associated with traditional offline methods such as sample contamination and misinterpretation, fiber optic sensors are gaining trac-tion due to their compact nature, cost-effectiveness, and resilience to electromagnetic disturbances typical in high-voltage environments. This work delves into the sensitivity analysis of intensi-ty-modulated plastic optical fiber sensors. The investigation encompasses key determinants such as the influence of optical source wavelengths, noise response dynamics, ramifications of varying sensing lengths, and repeatability assessments. Findings underscore that elongating the sensing length detrimentally affects both the linearity response and repeatability, largely attributed to the diminished resistance to external noise. Additionally, the choice of the optical source wavelength proved to be a critical variable in assessing sensor sensitivity.

The worldwide population is undergoing a fundamental change in its age structure, which challenges the health and social services system. The need to migrate towards a more person-centered and coordinated model of care that supports the optimization of abilities and capacities for older people has to be matched. In this sense, eHealth technologies can play a fundamental role. In this paper, through a questionnaire-based data collection on 30 primary (older people) and 32 secondary (informal caregivers) end-users, we share the sustainable way to develop a product optimizing the user experience and ensuring adoption. Both older adults and caregivers consider the use of smartphone and smartwatch to be very important, but also the use of digital devices for healthcare can be helpful. Seniors care about self-monitoring of health parameters using wearable devices, regardless of their health status, and would like to be included in the process of making good health decisions, because they need to feel in control of their healthcare process. Digital solutions in health and care can support the wellbeing of older adults in many areas of their daily lives at home and in their communities, but only if such innovation is designed around the natural voice of the intended target.

Beef dry aging consist in a selection of unpackaged primal cuts that are placed in a refrigerator room with controlled environment for several weeks. The goals are the concentration of flavor, like nutty and beefy and tenderness improvement. In this study it was intended verify the microbiological and physicochemical behavior and the meat sensorial perception during a process example of meat dry aging. Twelve beef loins were selected for 90 days of dry aging and placed in a refrigerator room with average temperature, relative humidity and forced air 3.17 ± 0.68 °C, 60.65 ± 4.23 % and 0.5-2 m/s, respectively. On 1, 14, 21, 35, 60 and 90 days of dry aging, were taken two samples, crust and lean meat for microbiological counts, pH, aw, color L*a*b* and sensorial analysis. During drying, there weren´t any pathogenic bacteria counts and the average counts were higher for the crust. The aw and pH had an average of 0.98 ± 0.02 and 5.77± 0.015, with a slightly decrease and increase respectively (P&lt;0.05) along aging days. The dry aging process practices, with room refrigeration at RH&lt;65.00% and temperature &lt;4.00 °C can be the reason for aw&lt;0.98 and meat pH&lt;6.00 and therefore for the absence of pathogenic bacteria. The lower microbial counts on the lean meat and the overall acceptability assessed by the sensory panel confirm the importance of the good trimming and storage practices for the dry aged beef.

Although the universal health coverage (UHC) is pursued by many countries, not all countries with UHC include dental care as their benefits. Japan, with its long-held tradition of UHC, has covered dental care as essential benefit and majority of dental care services are provided to all patients with minimal copayment. Being under the UHC, the scope of services as well as prices are regulated by the uniform fee schedule and dentists submit claims according to the uniform format and fee schedule. The author analyzes the publicly available dental health insurance claims data as well as a sampling survey on dental hygiene and illustrates how Japan’s dental care is responding to the challenges of the population ageing.

Ageing may be characterized by progressive loss of cognitive function as well as decrease in physical activities, in addition to change in appearance. Previously, we reported that intracerebroventricular transplantation of a human neural stem cell (NSC) line (F3) over-expressing choline acetyltransferase (F3.ChAT) gene, an enzyme responsible for acetylcholine synthesis, markedly improved cognitive function and physical activity of aged animals by enhancing acetylcholine and growth factors (GFs) and neurotrophic factors (NFs). In the present study, 10-month-old F344 rats were intravenously transplanted with F3 or F3.ChAT NSCs (1 x 106 cells) once a month to 21st month of age when the cumulative mortality reached 20%, and physical activity and learning/memory function were investigated, in addition to the analyses of brain acetylcholine concentration, and cholinergic and dopaminergic system restoration. Neuroprotective and neuroregenerative activities of stem cells were also confirmed by analyzing oxidative damages, neuronal skeletal protein, angiogenesis, brain and muscle weights, and proliferating host stem cells. Stem cells markedly improved both the cognitive (passive avoidance and water-maze performances) and physical (locomotor and rota-rod activities) functions, in parallel with the elevation of acetylcholine levels in cerebrospinal fluid and in muscles, in which F3.ChAT cells were superior to F3 parental cells. Stem cell transplantation down-regulated CCL11, leading to restoration of microtubule-associated protein 2 as well as functional markers of cholinergic and dopaminergic systems, and preserved brain and muscular capillaries, recovering muscle mass. In addition, stem cells enhanced antioxidative capacity, attenuating oxidative damage of multiple organs including muscles and the brain. The results indicate that NSCs over-expressing ChAT gene improve cognitive function and physical activity of ageing animals by protecting and recovering functions of multiple organs including cholinergic and dopaminergic systems as well as muscles from oxidative injuries through secretion of acetylcholine and GFs/NFs, increased antioxidant elements, and enhanced blood flow.

NK population is characterized by distinct NK cell subsets which respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e. resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.

The anthropogenic deterioration of aquatic ecosystems affects water resources due to agricultural malpractices, pollution from domestic septic tanks, recreational activities, and poor watershed management, among others. This study examines the management of Las Curias Reservoir (176,974 m2), San Juan, Puerto Rico, post the 2016 arrival of the invasive aquatic fern Salvinia molesta. In December 2019, a community-led initiative introduced the Cyrtobagous salviniae weevil, an effective biological control agent for S. molesta, and commenced a mechanical removal campaign using an aquatic harvester. Limnological sampling (September 2019 to March 2022) and drone flights were employed to measure physicochemical and floating plant cover changes, respectively, in the reservoir. Monitoring of weevils in the reservoir demonstrated a rapid establishment and dispersal, which resulted in visible damage including browning of plants and eventually sinking of entire mats. By January 29, 2021, 71% (125,652 m2) of the reservoir surface was covered by salvinia. In 2022, the reservoir recorded an average dissolved oxygen concentration of 2.38 mg/L -1 (± 0.021, n = 144), the highest in the study period and indicative of ecosystem recovery. After three years of control efforts, dissolved oxygen, pH, and specific conductance returned to levels recorded prior to Salvinia molesta introduction. This ecosystem recovery, a first in Puerto Rico, could be attributed to an early use of mechanical control and a long-term impact of biological control.

Disseminated or military tuberculosis (TB) is defined as the presence of at least two non-contiguous sites of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation and spread of a latent focus or due to iatrogenic origin. Disseminated TB represents a life-threatening condition, especially in at-risk children and when the diagnosis and treatment are delayed. We report on a case of a 3-year old boy who presented with long-lasting unrecognised disseminated TB that was successfully managed in a low-resource setting.

There is growing evidence on the relevance of self-efficacy for well-being and functioning among individuals with psychotic disorders, but specific self-efficacy for coping with stress has rarely been investigated. This study explored the outcomes of an intervention for the improvement of coping resources based on a training in coping skills and coping with stress self-efficacy (CSSE). Fourteen adult volunteers who were diagnosed with schizophrenia (n=12) or schizoaffective disorder (n=2) were matched in clinical and sociodemographic characteristics and randomly assigned to the study groups. The intervention group received the training along with their pharmacological therapy; the control group received their prescribed drug therapy. Participants completed self-reports on CSSE, perceived successful daily functioning based on coping skills, and clinical status (BPRS-E). Trained patients showed a significant increase in CSSE and reported greater successful functioning status, and significant improvements in their clinical status were also observed. All these enhancements remained at 3-month and 6-month follow-ups. Control participants showed no significant changes. Moreover, the intervention condition interacted with CSSE and perceived coping functioning in explaining improvements in clinical status: in the treatment group, greater CSSE translated into enhanced daily functioning, and this improvement predicted better clinical status. These findings stress the relevance of promoting coping resources in psychotic disorders and provide preliminary evidence for the potential benefits of CSSE.

In this letter we investigate if SARS-CoV-2 RNA is involved in the increased ageing of alveolar cells. Our in silico study is explorative. With the results we are able to outline experiments with AEC2 repair of bleomycin damaged alveolar cells. If AEC2 repair capability is diminished by spike RNA then perhaps this result provides a first step on a route to treat immortal lung cancer cells.

The current state of biological knowledge contains an unresolved paradox: life as a continuity in the face of the phenomena of ageing. In this manuscript I propose a theoretical framework that offers a solution for this apparent contradiction. The framework proposed is based on a rethinking of what ageing is at a molecular level, as well as on a rethinking of the mechanisms in charge of the flow of information from one generation to the following ones. I propose an information-based conception of ageing instead of the widely accepted damage-based conception of ageing and propose a full recovery of the chromosome theory of inheritance to describe the intergenerational flow of information. Altogether the proposed framework allows a precise and unique definition of what life is: a continuous flow of biological information. The proposed framework also implies that ageing is merely a consequence of the way in which epigenetically-coded phenotypic characteristics are passed from one generation to the next ones.

The potential advantages of plant-based interventions in decreasing the incidence and lessening the morbidity and mortality of COVID-19 are yet to be widely acknowledged. Nevertheless, recent publications propose that these interventions could be effective. Our cardiology center conducted an interventional study in which we incorporated plant-based foods and provided supplementation to 3470 elderly COVID-19 patients with multiple comorbidities. We pay close attention to the precise selection of food items, the application of appropriate processing methods, and the provision of nourishing meals to our patients. Our outcome was highly successful as we achieved a zero mortality rate, and none of our patients experienced worsening conditions or required hospitalization. In this review article we present the mechanisms how plant-based and supplement interventions can mitigate COVID-19 disease severity and mortality. And experts have validated our hypotheses very recently. The measures and methods used to address the ongoing SARS-CoV-2 pandemic through plant-based interventions and supplements are effective and may help prevent or manage future pandemics.