The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are of those over 65 years of age with a 23-fold greater risk of death. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes, obesity and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms. Here, we present the molecular differences between the young, middle-aged and elderly that may determine whether COVID-19 is a mild or life-threatening illness. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

Abstract: The Inconel 625 is a nickel-based alloy has been widely used in the high-temperature application. The Inconel 625 exhibits unstable plastic flow at elevated temperature characterized by serrated yielding, known as Portevin-Le Chatelier effect. The aim of this work is to evaluate the mechanical properties at high temperatures of the Inconel 625. The tensile tests were performed in the temperature range of room temperature until 1000 °C and strain rate of 2x10^-4 to 2x10^-3 s^-1. The creep tests were performed in the temperature range of 600-700 °C, in the stress range of 500-600 MPa in a constant load mode. The surface fracture was observed by optical and scanning electron microscopy. Serrated stress-strain behavior was observed in the curves obtained at 200 to 700 °C, which was associated with the dynamic strain aging effect. The yield strength and the elongation values show an anomalous behavior as a function of the test temperature. An intergranular cracking was observed specimen tensile tested at 500 °C that can be attributed to the decohesion of the carbides along the grain boundaries. The fracture surface of the specimen tensile tested at 700 °C showed the predominance of transgranular cracking with tear dimples with a parabolic shape.

Skin disease is a very common disease for humans. In the medical industry detecting skin disease and recognizing its type is a very challenging task. Due to the complexity of human skin texture and the visual closeness effect of the diseases, sometimes it is really difficult to detect the exact type. Therefore, it is necessary to detect and recognize the skin disease at its very first observation. In today's era, artificial intelligence (AI) is rapidly growing in medical fields. Different machine learning (ML) and deep learning(DL) algorithms are used for diagnostic purposes. These methods drastically improve the diagnosis process and also speed up the process. In this paper, a brief comparison between the machine learning process and the deep learning process was discussed. In both processes, three different and popular algorithms are used. For the machine Learning process Bagged Tree Ensemble, K-Nearest Neighbor (KNN), and Support Vector Machine(SVM) algorithms were used. For the deep learning process three pre-trained deep neural network models

It is a significant task to assess the safety of the aging offshore jacket platform in order to extend the service life. This paper analyzes the multiple risk factors of an aging jacket platform in Bohai Bay, China and builds the safety evaluation index system, which includes three levels, namely, the target layer, the first-grade indicators layer and the second-grade indicators layer. The target layer consists of three first-grade indicators: ocean environments, structure status, and human and organizational factors. Each first-grade indicator is divided into three second-grade indicators. The weight of each indicator is calculated by analytic hierarchy process to weaken subjective effect. Grey clustering method is applied to estimate the failure risk of the platform in Bohai Bay qualitatively and quantitatively. The assessment standard is divided into five grades and the whitening function of each grey cluster is determined by the assessment scheme. The grey evaluation weight vector of each second-grade indicator is calculated by the table dispatching method. Through layer by layer calculation, the grey assessment value of the target layer is finally estimated by making the grey assessment weight vector single-value and the grey grade is determined according to the maximum principle. The evaluation results show quantitatively that the failure risk grade of the jacket platform in Bohai Bay is medium and the safety assessment method is reasonable and feasible.

Current instrumental technology in evaluating performance of skin care creams is still rather limited and there are no industrial standard testing equipment, method and performance specifications for it. In this paper, we report our attempt in using an instrument called PhabrOmeter for this purpose. PhabrOmeter is a commercialized instrument for sensory performance evaluation of textiles, leather, paper and nonwoven and has been designated by American Association of Textile Chemists and Colorists (AATCC) as a standard test method for textiles, AATCC TM 202 in 2013. By adopting artificial skin samples treated with skin care creams, we have developed a procedure to apply this instrument for evaluation of skin care creams from sample preparation, measurement to data analysis and interpretation. The results using commercial skin care creams to demonstrate the feasibility and advantages of this instrument are provided.

With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.

POH (Peri Orbital Hyperpigmentation) represents a minor clinical entity that attracts immense aesthetic damages and it generates social integration difficulties. This review focuses on the etiopathogenic causes of this entity, differentiating and reclassifying this defect as having, on the one hand, genetic causes of melanic hyperproduction – for Fitzpatrick cutaneous phototypes IV and V – and, on the other hand, both genetic and acquired vascular causes, in individuals with light-coloured skin phototypes. Hence, there is a big difference in the field of pathogenic treatment, for the two entities. In addition, this study notes the direct relationship between skin aging and POH, especially for aquired vascular causes. In this reasoning, other aesthetic deficiencies of the skin in the palpebral area should be also considered, like: blepharochalasis, wrinkles, the anatomical causes of the lower eyelid shading, symmetrical or asymmetric suborbital oedema. All of these issues will complicate the therapeutic decision and subsidiary, the pharmaceutical advice. In this context, the review shows the guidelines for a honest councelling of the patients, pointing the efficiency limit for the topical pharmaceutical medication (depigmentants, exfoliants) versus the necessity of minimally invasive or/ and surgical treatments (in blefarochalasis).

Atomic force microscopy (AFM) has been extensively used for the nanoscale characterization of polymeric materials. The coupling of AFM with infrared spectroscope (AFM-IR) provides another advantage to the chemical analyses and thus helps to shed light upon the study of polymers. In this perspective paper, we review recent progress in the use of AFM-IR in polymer science. We describe first the principle of AFM-IR and the recent improvements to enhance its resolution. We discuss then the last progress in the use of AFM-IR as a super-resolution correlated scanned-probe IR spectroscopy for chemical characterization of polymer materials dealing with polymer composites, polymer blends, multilayers and biopolymers. To highlight the advantages of AFM-IR, we report here several results in studying crystallization of both miscible and immiscible blends as well as polymer aging. Then, we demonstrate how this novel technique can be used to determine phase separation, spherulitic structure and crystallization mechanisms at the nanoscale, which have never been achieved before. The review also discusses future trends in the use of AFM-IR in polymer materials, especially in polymer thin film investigation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

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

Batteries are called to be part of the electricity grid by providing ancillary services. Area regulation services seem to provide substantial revenues and profit. But Li-ion batteries are still too expensive to enter widely into this market. On the other hand, electric vehicle batteries are considered inappropriate for traction purposes when they reached a state of health of 80%. The reuse of these batteries offers affordable batteries for second life stationary applications. This study analyzes how batteries may provide services to a gas turbine cogeneration power plant and how long these batteries may last under different loads.

Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors and modification of telomere length. Such beneficial effects may inhibit or delay the emergence of neurodegenerative diseases, including Alzheimer’s disease (AD). This review is based on the hypothesis that irisin produced by physical exercise helps control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD. Although current and ongoing studies on irisin show promising results, further research is required to clarify its potential as a meaningful therapeutic target for treating human diseases.

The process of senescence (aging) is largely determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function of senescence, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood’s disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is described.

Optical tissue imaging has several advantages over the routine clinical imaging methods, including non-invasiveness (does not change the structure of tissues), remote operation (avoids infection) and ability to quantify the tissue condition by means of specific image parameters. Dermatologists and other skin experts need compact (preferably pocket-size), self-sustained and easy-to-use imaging devices. The operational principles and designs of ten portable in-vivo skin imaging prototypes developed at the Biophotonics Laboratory of Institute of Atomic Physics and Spectroscopy, University of Latvia during the recent five years are presented in this paper. Four groups of imaging devices are considered. Multi-spectral imagers offer possibilities for distant mapping of specific skin parameters, so facilitating better diagnostics of skin malformations. Autofluorescence intensity and photobleaching rate imagers show a promising potential for skin tumor identification and margin delineation. Photoplethysmography video-imagers ensure remote detection of cutaneous blood pulsations and can provide real-time information on cardiovascular parameters and anesthesia efficiency. Multimodal skin imagers perform several of the above-mentioned functions by taking a number of spectral and video images with the same image sensor. Design details of the developed prototypes and results of clinical tests illustrating their functionality are presented and discussed.

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

Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) signaling promotes health and longevity in diverse model organisms. Over the past decade, excitement has built over the possibility that treatment with the mTORC1 inhibitor rapamycin can be utilized to treat or prevent age-related disease in humans. However, concerns over the side effects of rapamycin on immunity and metabolism have precluded the routine use of rapamycin as a geroprotective therapy. Here, we discuss the evidence that these negative side effects of rapamycin are largely mediated by off-target inhibition of a second mTOR Complex (mTORC2). Further, we discuss how intermittent treatment with rapamycin, specific dietary regimens, and new molecules may provide routes to the safer and more selective inhibition of mTORC1. We conclude that the time is ripe for the development of therapies based on the safe and selective inhibition of mTORC1 for the treatment or prevention of diseases of aging.

There is a skin allergy epidemic in the western world, and the rate of deterioration has increased significantly in the past 5-10 years. It is probable that there are many environmental contributing factors, yet some studies have linked it primarily to the rise in the use of synthetic chemical ingredients in modern cosmetics. Our challenge, therefore, was to find a mechanism to determine the effect these substances have on skin health, and whether they really are a primary cause of long term damage to the skin. The first problem is the lack of any definitive way to measure skin health. Motivated by the overwhelming evidence for a link between deficient gut flora and ill health, we decided to look at whether our skin microbiota could similarly be used as an indicator of skin health. Our research illustrates how it is microbiota diversity alone that can predict whether skin is healthy or not, after we revealed a complete lack of conclusive findings linking the presence or abundance of particular species of microbe to skin problems. This phenomenon is replicated throughout nature, where high biodiversity always leads to healthy ecosystems. ‘Caveman’ skin, untouched by modern civilisation, was far different to ‘western’ skin and displayed unprecedented levels of bacterial diversity. The less exposed communities were to western practices, the higher the skin diversity, which is clear evidence of an environmental factor in the developed world damaging skin. For the first time we propose benchmark values of diversity against which we can measure skin to determine how healthy it is. This gives us the ability to be able to predict which people are more likely to be prone to skin ailments, and start to test whether cosmetic ingredients and products are a main cause of the skin allergy epidemic.

Alkali Silica Reaction (ASR) is known to be a serious problem for concrete worldwide, especially in high humidity and high temperature regions. ASR is a slow process that develops over years to decades and it is influenced by changes in environmental and loading conditions of the structure. The problem becomes even more complicated if one recognizes that other phenomena like creep and shrinkage are coupled with ASR. This results in synergistic mechanisms that can not be easily understood without a comprehensive computational model. In this paper, coupling between creep, shrinkage and ASR is modeled within the Lattice Discrete Particle Model (LDPM) framework. In order to achieve this, a multi-physics formulation is used to compute the evolution of temperature, humidity, cement hydration, and ASR in both space and time, which is then used within physics-based formulations of cracking, creep and shrinkage. The overall model is calibrated and validated on the basis of experimental data available in the literature. Results show that even during free expansions (zero macroscopic stress), a significant degree of coupling exists because ASR induced expansions are relaxed by meso-scale creep driven by self-equilibriated stresses at the meso-scale. This explains and highlights the importance of considering ASR and other time dependent aging and deterioration phenomena at an appropriate length scale in coupled modeling approaches.

The disproportionate incidences of COVID-19-related hospitalization and mortality for different age groups and various underlying health conditions is a result of a complex social predisposition to the exposure, resistance, and tolerance for the infection. Based on the observed data as well as the molecular mechanisms for viral entry and replication, cellular senescence related to aging, obesity, hypertension, and diabetes appears to be strongly correlated with the SARS-CoV-2 infections resulting in higher COVID-19 related complications and mortality. Establishing such a correlation may allow us to better explain the pathobiology as well as the differential nature of the SARS-CoV-2 infections and consider targeted control and therapeutic strategies to combat the disease.

The Galvanic Skin Response (GSR, also widely known as electrodermal activity EDA) is one of the signals related to this emotional reaction. Given the sparsity of studies related to and the variety of devices, we experimented at the Human Health Activity Laboratory with 17 healthy subjects. The goal is to know the variability of detection changes in the electrodermal activity among a test group with heterogeneous respondents in response to valence and arousal stimuli, correlating GSR biosignals measured from different body sites. We experiment with the right and left wrist, left fingers, the right foot's inner side using Shimmer3GSR, and Empatica E4 sensors. Results indicate as the most promising homogeneous GSR measure place the left fingers and right foot. Results suggest that due to a significantly strong correlation among the inner side of the right foot and left fingers and moderate correlations with the right and left wrist, the foot is a good place to measure EDA. This paper also contributes knowledge about some wearable sensor technologies available in the market. Shimmer3GSR sensor may be better reliable to homogenous detecting electrodermal activity changes, as these have fewer anomalies among the respondents. However, we found some anomalies in signals from the Empatica E4 sensor, which we discuss in this work.

This paper investigates the evolution of microstructures and precipitations of an ultra-low iron alloy 625 subjected to long term aging treatment by scanning electron microscope (SEM) and X-ray diffraction(XRD). Use ASTM G28A acid Fe3(SO4)2 erosion to represent intergranular corrosion weightlessness and corrosive morphology. The result shows that alloy at 750C by aging treatment for 40h, precipitated γ'' phase in the grain boundary. In high density area of γ'' phase, occurs γ'' phase to δ phase degeneration transformation by aging treatment for 200h and the needle-like δ phase becomes more with time prolonged. And γ'' phase degenerated to δ phase completely until treated for 1000h. The sample which has aging treatment tends to have intergranular corrosion and mainly because alloy element spreading leads to dilution area and grain boundary precipitated phase, plus interlaced δ phase’s dissolving, which makes sample grain particle fall off and this results in apparent weightlessness. The weightlessness rate(WLR) is related with precipitated volume score. With aging sensitization time change, can be described by Johnson-Mehl-Avrami equation, i.e.: $WLR=44.32\left[1-\text{exp}\left(-\frac{t}{10.99}\right)\right]+44.62\left[1-\text{exp}\left(-\frac{t}{327.8}\right)\right]+1.267\left(mm/a\right)$

Psoriasis is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn’s disease, allergy, obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease as well as gives immune system role in the given condition. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting role of bacteria in the chronic disease and future studies in this field.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify. This arises particularly because the functionally interconnected nature of biological systems constrains the simultaneous optimization of coupled traits (interconnection constraints), or because individual traits cannot evolve (impossibility constraints). We present an account of aging that integrates AP and biological constraint with recent programmatic aging concepts, including costly programs, quasi-programs, hyperfunction and hypofunction. We argue that AP mechanisms of costly programs and triggered quasi-programs are consequences of constraint, in which costs resulting from hyperfunction or hypofunction cause senescent pathology. Impossibility constraint can also cause hypofunction independently of AP. We also describe how AP corresponds to Stephen Jay Gould’s constraint-based concept of evolutionary spandrels, and argue that pathologies arising from AP are bad spandrels. Biological constraint is a missing link between ultimate and proximate causes of senescence, including diseases of aging. That this was not realized previously may reflect a combination of hyperadaptationism among evolutionary biologists, and the erroneous assumption by biogerontologists that molecular damage accumulation is the principal primary cause of aging.

Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

Background: Skincare products are used daily to maintain a healthy skin (cleansing, moisturizing, protecting…), but their impact on this first layer, which corresponds to the skin microbiome, is still poorly understood. Preserving natural resources and mechanisms of the skin ecosystem is essential; an original approach based on these premises, called ecobiology, has recently emerged in skincare. Ecobiology considers the skin as an ever-evolving ecosystem which hosts human and microbial cells that interact together with their environment. In this context, we evaluated the impact on the skin microbiome of three types of leave-on face skincare products: a hydrophilic sterile solution, a micellar solution, and an oil-in-water emulsion. Materials and Methods: The individual microbial profiles of 20 Caucasian females were investigated. Samples were obtained twenty-four hours and four days following a daily application of the skincare products versus control area where no product was applied. To analyze the bacterial diversity and abundance of skin microbiome, a 16SrRNA gene sequencing was performed using the Illumina MiSeq platform. Results: Our results confirm the overall diversity of skin microbiome as previously observed and notably reveal the prevalence of Cutibacterium spp. and Staphylococcus spp. on sebaceous site (the back). Bacterial diversity and abundance were not affected by the products either twenty-four hours or four days after application, as indicated by comparison with the control. Moreover, no dissimilarity was observed between the three products versus their control, neither between each product. Conclusions: These preliminary results demonstrated for the first time that three different types of leave-on face skincare products such as a hydrophilic sterile solution, a micellar solution, and an emulsion have no impact on skin microbiome and can be considered as “microbiome friendly”.

Polyunsaturated fatty acids (PUFAs) and antioxidants are important mediators in the central nervous system (CNS). Lipid derivatives may be used to generate endocannabinoids or prostanoids derived from arachidonic acid, which attenuates excitotoxicity in quadripartite synapses with a focus in astrocytes and microglia; on the other hand, antioxidants, such as glutathione (GSH) and ascorbate, have been shown to signal through transmitter receptors and protect against acute and chronic oxidative stress, modulating the activity of different signaling pathways. Several authors have investigated the role of these nutrients in young and senescent brain, as well as in degenerative conditions such as Alzheimer’s and Parkinson's diseases. Through literature review, we aimed to highlight recent data on the role of fatty acids, antioxidants and physical activity in physiology and in molecular mechanisms of brain senescence. Data indicate the complexity and essentiality of endogenous/dietary antioxidants for maintenance of the redox status and control of neuroglial signaling under stress. Recent studies also indicate that omega-3 and -6 fatty acids act in a competitive manner to generate mediators for energy metabolism, feeding behavior, plasticity and memory mechanisms throughout aging. Finding pharmacological or dietary resources that mitigate or prevent neurodegenerative affections continues to be a great challenge and require additional efforts from researchers, clinicians and nutritionists in the field.

The high demand for liquefied natural gas (LNG) requires more LNG carriers (LNGCs) to be in operation. During transportation, there is a high risk due to the required extremely low temperatures and the explosive nature of LNG cargo. Moreover, when there is a lack of experience in operating old LNGCs, there is a serious concern regarding operational accidents. A systematic maintenance strategy, especially for LNG cargo containment systems, is crucial for maintaining safe LNG transportation at sea. The purpose of this study is to develop preventive LNG cargo containment system maintenance models by using LNGC dock specifications from LNGCs of various ages. The dock specifications from a conventional LNGC repairing dock were analyzed using natural language processing techniques in order to develop preventive maintenance models of the LNG cargo containment system. From these results, and by considering the ship’s age, it was found that for young LNGCs the priority for repair should focus on checking routine consumable spare parts by tank inspections, whereas for older LNGCs the focus should be on tank condition maintenance rather than on other facilities. These results are expected to be useful in the development of a maintenance strategy of preventive LNG cargo containment systems in maritime LNG transportation.

More than 1,000,000 confirmed cases of COVID-19 have been registered worldwide since the beginning of the pandemic in Wuhan on December 2019. The high mortality rate of COVID-19 is associated with age, gender and the presence of comorbidities. Biochemical data have shown that COVID-19 patients develop a local and systemic hyper-inflammatory response associated with poor outcome. Therefore, the understanding of the biological mechanisms underlying SARS-CoV-2-induced inflammation is a compelling need. Following this reasoning, here we will focus on the importance of the progressive age-related development of a pro-inflammatory state (aka inflamm-aging) in the understanding of the unbalanced inflammatory response against SARS-CoV-2 in aged people. In particular, we underpin the role of mitochondrial DNA and genomic DNA telomeric sequences in local and systemic mechanisms of inflammation. Indeed, the leakage of mtDNA out of its natural compartment (i.e. the mitochondrion), into the cytoplasm and in the extracellular environment is a powerful trigger of innate immunity and inflammation, as part of an evolutionary-conserved signaling mechanism of cellular damage (e.g. viral infection). High levels of circulating mtDNA are increased in aged people and set up as inflammatory markers of poor prognosis in intensive care unit patients. In turn, telomeric DNA, which can be released into the cytoplasm and in the extracellular environment upon cell damage, has been proven to exert potent anti-inflammatory activity. Since that aged people (particularly those affected by co-morbidity) are equipped with shortened telomeres, we posit that, in aged people affected by COVID-19 the release of mtDNA, coupled with insufficient telomeric DNA favors the onset of a detrimental inflammatory response. In this regard, we highlight that the mechanism of action of some currently used drugs, as well as potential new ones may be better understood under the light of the above-depicted theoretical framework thus explaining how studies on inflamm-aging may help to understand and combat COVID-19 pandemic.

Abstract: Radiation-induced skin injury can be a serious cutaneous damage and have specific characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a critical role in the modulation of skin permeability and hydration and protects the body against a harsh external environment. However, an analysis on the skin barrier dysfunction against radiation exposure in the latent stage has not been conducted. Thus, we investigated whether skin barrier is impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier dysfunction. We analyzed skin barrier function and its components in SKH-1 mice that received 20 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an intervention target for skin barrier impairment.

For older adults, approaching end-of-life (EOL) brings unique transitions related to family relationships. Unfortunately, most families greatly underestimate the need to discuss these difficult issues. For example, parents approaching EOL issues often struggle with receiving assistance from others, avoiding family conflict, and maintaining their sense of personhood. In addition, discussions of EOL issues force family members to face their parents’ mortality, which can be particularly difficult for the adult children to process emotionally. This study explored aging issues identified by aging parents and their families as they traverse these impending EOL changes. Ten focus groups of seniors (n = 65) were conducted. Focus groups were organized according to race (African American/Caucasian), gender, and whether the older adult was living independently or in an assisted care facility. When asked open-ended questions about discussing aging and EOL issues with family members, participants revealed tensions that led us to consider Relational Dialectics Theory as a framework for analysis. The predominant tension highlighted in this report was certainty versus uncertainty, with the two sub-themes of sustained life versus sustained personhood and confronting versus avoiding EOL issues. For these data, there were more similarities than differences as a result of gender, race, or living situation than one might expect, although culture and financial status were found to be influential in the avoidance of EOL discussions. The results of this study help to provide additional insight into relational dialectics related to aging, EOL, and the importance of communication in facilitating family coping.

Butyl rubber-based composite (BRC) is one of the most popular materials for the fabrication of protective glove against chemical and mechanical risks. However, in many working places such as metal manufacturing or automotive mechanical services, its mechanical hazards usually appear together with metalworking fluids (MWFs). The presence of these contaminants, particularly at high temperature, could modify its properties due to the scission, the plasticization, the crosslinking of polymer network and thus led to severe modification of mechanical and physicochemical properties of material. This work aims to determine the effect of temperature and a metalworking fluid on mechanical behavior of butyl rubber composite dealing with crosslinking density, cohesion forces and elastic constant of BRC on the based on Mooney-Rivlin’s theory. The effect of temperature with and without MWFs on thermo dynamical properties and morphology of butyl membranes is also investigated. The prediction of service lifetime is then evaluated from extrapolation of Arrhenius plot at different temperatures.

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

An intricate relationship between impaired immune functions and the age-related accumulation of tissue senescent cells (SC) is rapidly emerging. The immune system is unique as it undergoes mutually inclusive and deleterious processes of immunosenescence and cellular senescence with advancing age. While factors inducing immunosenescence and cellular senescence may be shared, however, both these processes are fundamentally different which holistically influence the aging immune system. Immunosenescence is a well-characterized phenomenon, but our understanding and biological impact of cellular senescence in immune cells, especially in the innate immune cells such as macrophages, is only beginning to be understood. Tissue-resident macrophages are long-lived, and while functioning in tissue-specific and niche-specific microenvironments, senescence in macrophages can be directly influenced by senescent host cells which may impact organismal aging. In addition, evidence of age-associated immunometabolic changes as drivers of altered macrophage phenotype and functions such as inflamm-aging is also emerging. The present review describes the emerging impact of cellular senescence vis-à-vis immunosenescence in aging macrophages, its biological relevance with other senescent non-immune cells, and known immunometabolic regulators. Gaps in our present knowledge, as well as strategies aimed at understanding cellular senescence and its therapeutics in the context of macrophages, have been reviewed.

Marine algae have been considered as abundant source of bioactive compounds with cosmeceutical potential. Recently, a great deal of interest has focused on the health-promoting effects of marine bioactive compounds. Carbohydrate is a major and abundant constitute of marine algae that have been utilized in cosmetic formulations, such as moisturizing and thickening agents. In addition, marine carbohydrates have been suggested as promising bioactive biomaterials for various skin beneficial properties, such as anti-oxidant, anti-melanogenic and anti-skin aging. Therefore, marine algae carbohydrates have potential of skin health benefits for value-added cosmeceutical application. The present review focused on the various biological capacities and potential skin health benefits of bioactive marine carbohydrates.

Background: The efficacy of sunscreen is evaluated by SPF values, which are quantitatively determined in laboratories on the backs of human subjects according to a standardized procedure. However, SPF cannot be directly translated to sunburn protection under real-life situations because actual efficacy depends on various factors related to human behaviors and environmental conditions. This study clinically evaluated the efficacy of two sunscreen sprays (SPF 30 and SPF 70) under natural sunlight exposure on healthy subjects at the beach. Methods: Twenty subjects were divided into two cells for the two sunscreen sprays (SPF 70 and SPF 30) in a single-center, actual usage test. The primary endpoint of the study was sunburn protection on the dorsal arms and the secondary endpoint was protection on the face and neck. Subjects stayed at the beach for 4 h after application of the sunscreens with normal beach activities. Subjects’ behavior at the beach, the amounts of sunscreen applied and reapplied, and environmental conditions were all recorded. Results: There was no significant sunburn for a majority of the subjects in either cell. However, neither sunscreen completely blocked the sunburn, especially for the face/neck area. We found that the SPF 70 sunscreen was more effective than the SPF 30 sunscreen. Conclusion: Modern sunscreen sprays, applied liberally, are effective in providing sunburn protection for the body in a beach setting.

Recently scientific research began to shift their focus on looking at both the gut and the skin microbiota as having a reciprocal and integral relationship with one another, rather than assessing them as separate and unrelated fields. In the past five years, the field of microbial endocrinology emerged, which examines how our gut microbiota influences and modulates hormones. We’ve known for decades that hormones greatly affect the condition of the skin, and many skin conditions are often treated with oral hormonal therapy as means to internally treat skin conditions visible on the dermis. Now, a growing body research and discourse examining this triad of biological spheres – gut microbiota, skin microbiota, and the endocrine system – as interconnected rather than binary and unrelated. While there is ample research established and being conducted examining the gut-skin axis, the gut-brain axis, and the gut-hormone axis, through this paper I will review and synthesize some of the significant advancements in this emerging and inclusive field of science to suggest that the fields need to expand the axis and their modality for researching these fields as a connected whole in order to better understand the role of the microbiota in disease prevention as a whole.

The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.

This paper studies the combined effect of corrosion and fatigue on the growth of cracks in aircraft and on the effect of skin corrosion and stress corrosion cracking on the load bearing capacity of rib stiffened aircraft wings. In this context it is shown that the growth of cracks from surface pitting, and also from intergranular cracking at a fastener hole, can be accurately computed using the Hartman-Schijve variant of the NASGRO crack growth equation. The examples studied support the lead crack approach, that has been independently developed by the USAF and the Australian Defence Science Technology Group, in which the growth of lead cracks is often exponential. In the case of skin corrosion it is shown that to be consistent with the US Joint Service Structural Guidelines (JSSG2006) assessment of its effect on the load bearing capacity of the wing should involve an assessment of whether at 115% DLL the remaining material exceeds the yield stress of the material.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

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

Skin cancer is an exquisite disease globally nowadays. Because of the poor contrast and apparent resemblance between skin and lesions, automatic identification of skin cancer is complicated. The rate of human death can be massively reduced if melanoma skin cancer can be detected quickly using dermoscopy images. In this research, an anisotropic diffusion filtering method is used on dermoscopy images to remove multiplicative speckle noise and the fast-bounding box (FBB) method is applied to segment the skin cancer region. Furthermore, the paper consists of two feature extractor parts. One of the two features extractor parts is the hybrid feature extractor (HFE) part and another is the convolutional neural network VGG19 based CNN feature extractor part. The HFE portion combines three feature extraction approaches into a single fused feature vector: Histogram-Oriented Gradient (HOG), Local Binary Pattern (LBP), and Speed Up Robust Feature (SURF). The CNN method also is used to extract additional features from test and training datasets. This two-feature vector is fused to design the classification model. This classifier performs the classification of dermoscopy images whether it is melanoma or non-melanoma skin cancer. The proposed methodology is performed on two ordinary datasets and achieved the accuracy 99.85%, sensitivity 91.65%, and specificity 95.70%, which makes it more successful than previous machine learning algorithms.

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

Chronological age represents the greatest risk factor for many life-threatening diseases including neurodegeneration, cancer and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current therapies that effectively tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing. Cellular senescence is an essentially irreversible proliferation arrest mechanism that has important roles in development, wound healing and preventing cancer, but it may limit tissue function and cause widespread inflammation with age. The serine/threonine kinase mTOR is a regulatory nexus heavily implicated in both ageing and senescence. Excitingly, a growing body of research has highlighted rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum of age-related pathologies, including neurodegeneration, cancer, immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness, diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this review, we assess the use of mTOR inhibitors to treat age-related pathologies, discuss possible molecular mechanisms of action where evidence is available, and consider strategies to minimize undesirable side effects. We also emphasize the urgent need for reliable, non-invasive biomarkers of senescence and biological ageing to better monitor the efficacy of any healthy ageing therapy.

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

The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g. sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms and protochordates. These organisms illustrate a kaleidoscope of MISC-types that participate in the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and scarce ties were established with biomedical industries in attempts to harness MISCs for human welfare. Thus, it is important to: i) consolidate the fragmented European community working on MISCs; ii) promote and coordinate European research on MISC biology; iii) stimulate young researchers to embark on research in MISC-biology; iv) develop, validate, and network novel MISC tools and methodologies; v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognised gaps, the EC-COST Action 16203 “MARISTEM”, has recently been launched. At its initial stage the consortium unites 26 scientists from EC countries, Cooperating countries and Near Neighbor Countries.

Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.

Pain is a major problem in sick newborn infants, especially for those needing intensive care. Pharmacological pain relief is the most commonly used but may be ineffective, have side effects, including long-term neurodevelopmental sequelae. The effectiveness and safety of alternative analgesic methods are ambiguous. The objective is to review the effectiveness and safety of non-pharmacological methods of pain relief in newborn infants and to identify those that are the most effective. PubMed and Google Scholar were searched using the terms: ‘infant’, ‘premature’, ‘pain’, ‘acupuncture’, ‘skin to skin contact’, ‘sucrose’ ‘massage’, ‘musical therapy’ and ‘breastfeeding’. We included 24 studies assessing different methods of non-pharmacological analgesic techniques. Most resulted in some degree of analgesia but many were ineffective and some were even detrimental. Sucrose, for example, was often ineffective but more effective than music therapy, massage, breast milk (for extremely premature infants) or non-invasive electrical stimulation acupuncture. There were also conflicting results for acupuncture, skin to skin care and musical therapy. Most non-pharmacological methods of analgesia provide some modicum of relief for preterm infants but none are completely effective and there is no clearly superior method. Study is also required to assess potential long-term consequences of any of these methods.

In this paper we aim to help topical probiotics research and development achieve its potential as an incredible future solution for skin problems by investigating whether the current products on the market satisfy criteria for safe and effective use on the skin microbiome. As previously defined, this includes whether they use microbes known to be part of a healthy skin microbiome and in healthy amounts. In addition, we evaluate whether they contain live microbes, and therefore can be classified as probiotics according to the WHO’s definition. Using recent market analysis at least 84% of products do not contain live microbes. Of the products that appeared to use live microbes, they contained those used in research and development of probiotics for the gut. Due to the varying composition of each person’s microbiome, there is not a one size fits all probiotic solution. Personalisation of probiotics products is essential to satisfy the criteria for safe and effective use, but none of the products on the market, understandably, offer this. Upsetting the delicate ecosystem balance of the skin microbiome could have damaging effects and regulation could help to stop a loss of trust between consumers and cosmetics industry. Future work will perform an in-depth evaluation of the topical probiotics on the market in the EU, USA, and Canada. We will also investigate how to move the topic closer to achieving its potential by updating the criteria, including by discussing how to measure the success of a probiotic solution.

Although man is still rapidly evolving, he has not co-evolved with all of the modern chemicals made by man, including those in cosmetic products. Care must be taken when formulating products so that commonly used ingredients, such as polyethylene glycol, can be substituted with safer ingredients to which man has adapted and that will not cause irritation and inflammation. This is especially important given that induction of skin inflammation will cause systemic inflammation. A review of the literature and of commercially available products was made to highlight techniques and products that remediate inflammation or induce inflammation. Many skin care products contain chemicals that induce irritation and inflammation that may lead to chronic, systemic inflammation. Well studied natural products, especially skin identical chemicals, may offer an advantage compared to recent man-made chemicals in cosmetic and topical formulations and help to reduce skin inflammation as well as skin derived systemic chronic inflammation.

The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing – including spectral, temporal, spatial hearing – and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Depending on human body conditions and environmental conditions, it is sometimes difficult to conduct subject experiments. In such cases, it is effective to use a thermal manikin. There are few studies that investigate the effect of the non-uniform and asymmetric outdoor thermal environment on the mean skin temperature. The purpose of this study is to clarify the influence of the non-uniform and asymmetric thermal radiation of short-wavelength solar radiation in an outdoor environment on the calculation of the mean skin temperature. The skin temperature of the front of the coronal surface, which was facing the sun and where the body received direct short-wavelength solar radiation, and the skin temperature of the rear of the coronal surface, which was in the shadow and did not receive direct short-wavelength solar radiation were respectively measured. The feet, upper arm, forearm, hand and lower leg, which are susceptible to short-wavelength solar radiation in a standing posture, had a noticeable difference in skin temperature between sites in the sun and in shade. The mean skin temperature of sites facing the sun was significantly higher than the mean skin temperature of those in the shade.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Electromagnetic eddy current sensors are commonly used to identify and quantify the surface notches of metals. However, the unintentional tilt of eddy current sensors affects results of size profiling, particularly for the depth profiling. In this paper, based on the eddy current thin-skin regime, a revised algorithm has been proposed for the analytical voltage or impedance of a tilted driver–pickup eddy current sensor scanning across a long ideal notch. Considering the resolution of the measurement, the bespoke driver–pickup, also termed as transmitter-receiver (T-R) sensor is designed with a small mean radius of 1 mm. Besides, the T-R sensor is connected to the electromagnetic instrument and controlled by a scanning stage with high spatial travel resolution , with a limit of 0.2 μm and selected as 0.25 mm. Experiments have been out on the voltage imaging of an aluminium sheet with 7 machined long notches of different depths using T-R sensor under different tilt angles. By fitting the measured voltage (both real and imaginary part) with proposed analytical algorithms, the depth profiling of notches is less affected by the tilt angle of sensors. From the results, the depth of notches can be retrieved within a deviation of 10 % for tilt angles up to 60 degrees.

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

Burns is a pervasive and oppressive basic care issue. In children, burn injuries are a major reason for bleakness and mortality. The quirks in the physiology of liquid and electrolyte taking care of, the vital necessity and the distinctions in the different body extends in children direct that the pediatric wounds administration ought to be brought with an alternate point of view than for adults. Notwithstanding, for the intensivist, challenges regularly exist that muddle quiet help and adjustment. Moreover, burn injuries are mind-boggling and can show exceptional challenges that require deep-rooted recovery. Investigation in burn wound care has yielded progressions that will keep on improving practical recuperation. What's more, pain management all through this period is essential. Managing these wounds requires escalated therapeutic treatment for multi-organ dysfunction, and forceful surgical treatment to forestall sepsis and other inconveniences. The biological therapeutic bilayered skin substitutes with a long shelf life that recapitulates the normal barrier function of the intact human skin and stimulate wound repair and skin regeneration. A definitive objective is to accomplish a perfect skin substitute that gives a successful and without scar wound recuperating. This review article features the headway in pediatric burn wounds with an emphasis on the pathophysiology and treatment of burn wounds.

Reusing the tactile knowledge of some previously explored objects helps us to easily recognize the tactual properties of new objects. In this paper, we enable a robotic arm equipped with multi-modal artificial skin, like humans, to actively transfer the prior tactile exploratory action experiences when it learns the detailed physical properties of new objects. These experiences, or prior tactile knowledge, are built by the feature observations that the robot perceives from multiple sensory modalities, when it applies the pressing, sliding, and static contact movements on objects with different action parameters. We call our method Active Prior Tactile Knowledge Transfer (APTKT), and systematically evaluated its performance by several experiments. Results show that the robot improved the discrimination accuracy by around 10% when it used only one training sample plus the feature observations of prior objects. By incorporating the auxiliary features, the transfer learning improved the discrimination accuracy by over 20%. The results also show that the proposed method is robust against transferring irrelevant prior tactile knowledge (negative knowledge transfer).

The lumpy skin disease virus (LSDV) is an animal virus and a member of the Poxviridae family, which causes lumpy skin disease (LSD) in livestock animals like cows and buffaloes. LSD is an important transboundary disease of economic importance that was first discovered in 1929 in Zambia. LSDV has been prevalent in African countries, where several outbreaks have been reported previously. However, the virus has spread rapidly across the Middle East in the past two decades, reaching Russia and, recently, the Asian subcontinent. With the unprecedented cluster outbreaks reported across Asian countries, LSDV is certainly undergoing an epidemiological shift and expanding its geographical footprint globally. The recent LSD outbreaks have gained attention from global regulatory authorities and raised serious concerns among epidemiologists and veterinary researchers. Although there is no dearth of knowledge about LSDV, the disease lacks networked global surveillance and management, consequently making the current statistics deficient, fragmented, and unreliable. Hence, recurrent LSD outbreaks seriously threaten the global livestock industry. This review provides recent insights into LSDV by augmenting latest literature associated with its epidemiology, pathogenesis, transmission, currently-available intervention strategies, and economic implications on the dairy industries. The review also critically examines the changing epidemiological footprint of LSD and speculates on the possible reasons contributing to the ongoing multi-country LSD outbreak.

INTRODUCTION: Superficial cutaneous bacterial infections have a high incidence in geriatric patients. The most implicated pathogens are gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes) while gram-negative germs are also implicated. Resistances to common topical antibiotics (mupirocin, fusidic acid) require alternatives to gram-positive and gram-negative microorganisms.Ozenoxacin cream for topical use (non-fluorinated bactericidal quinolone), in other countries and with other galenics, is indicated in children older than 6 months and in adults as a treatment of superficial bacterial infections, such as acne. In Spain, ozenoxacin cream is indicated only for non-bullous impetigo; scientific evidence show effectiveness also in other superficial skin bacterial infections.A cases series of clinical use of ozenoxacin in bacterial superficial skin infections in geriatric patients (institutionalized or community dwelling) is presented.METHODS: Multicenter case series (March-August 2022) of bacterial superficial skin infections treated with ozenoxacin cream (10mg/g every 12h, 5days); data from medical records (controls: 1-3-5 days), after obtaining informed consent (use of data and images).RESULTS: Series of 28 patients (mean age: 84,79) from nine nursing homes and one outpatient geriatric service, including acute and subacute/chronic cases.In all cases treatment was ozenoxacin 10mg/g topical cream applied every 12 hours for 5 days according to medical prescription (except for one case in which 3 days were enough for complete healing and another case treated for 10 days).Results showed complete healing in all 20 acute cases and significant clinical improvement in all subacute/chronic cases (with complete healing in one of them). Professionals scored the effectiveness in acute cases as a mean 4.5 points (maximum score: 5, p<.0001) and in subacute/chronic cases as 3.8 points (p=.010).There was no skin irritation or other adverse effects in anyone of the patients, and clinical improvement of pain, itching and other symptoms was observed, suggesting an anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: Our results seem to demonstrate the effectiveness and tolerability of ozenozacin cream in bacterial infections other than non-bullous impetigo. Ozenoxacin cream is indicated only for the treatment of non-bullous impetigo; however, it is also shown to be effective, both in the scientific evidence and in our case series, for other superficial bacterial skin infections, both acute and subacute/chronic, suggesting the opportunity for clinical studies with an experimental design to evaluate the findings of clinical practice and to be able to have a therapeutic alternative to compensate for the complications of the appearance of resistance.

Intradermal injection of botulinum neurotoxin is a frequently performed procedure in aesthetic dermatology to improve facial skin tone, texture, fine wrinkles, and enlarged pores. In practice, botulinum neurotoxin type A is also used to reduce skin oiliness of the face. There is increasing evidence that acetylcholine plays specific roles in sebum production, suggesting that botulinum neurotoxin type A may reduce sebum production by interfering with cholinergic transmission between sebaceous glands and autonomic nerve terminals. Botulinum neurotoxins can also inhibit several pathogenetic components of acne development, suggesting that botulinum neurotoxins can be used as a safe and effective treatment modality for acne and other skin disorders related to the overactivity of sebaceous glands. This review aims to explore the current evidence behind the treatment of oily skin and acne with botulinum neurotoxin type A.

Onchocerciasis causes debilitating pruritus and rashes as well as visual impairment and blindness . Prior to control measures, eye disease was particularly prominent in savanna areas of sub-Saharan Africa whilst skin disease was more common across rainforest regions of tropical Africa. Mass drug distribution with ivermectin is changing the global scene of onchocerciasis. There has been successful progressive elimination in Central and Southern American countries and the World Health Organization has set a target for elimination in Africa of 2025. This literature review was conducted to examine progress regarding onchocercal skin disease. PubMed searches were performed using keywords "onchocerciasis", "onchodermatitis" and "onchocercal skin disease" over the past eight years. Articles in English, or with an English abstract, were assessed for relevance, including any pertinent references within the articles. Recent progress in awareness of, understanding and treatment of onchocercal skin disease is reviewed with particular emphasis on publications within the past 5 years. The global burden of onchodermatitis is progressively reducing and is no longer seen in children in many formerly endemic foci.

In the era of nanotechnology, researchers are implementing point to care service to cancer patients to detect malignancy beforehand and to reduce the mortality rate of cancers. Cancer is known to be the most fatal disease among all other diseases and the survivability from cancer is quite impossible if the stage of the cancer is an advanced level. Though the early detection of cancer can increase the chances of survival with a double fold. Biosensor is a part of nanotechnology which is capable to provide point to care service in the field of medicine. With the rising number of cancer occurrences being identified around the world and the increasing number of deaths because of the identification of advanced cancer, biosensors can play a significant part in the early detection of cancer. New molecular methods, including as genomic and proteomic approaches, are increasingly being used to study patient molecular profiles. When such diagnosis method is paired with bioinformatics tools, they generate new data that can be used to discover new disease biomarkers. Finding precise and sensitive indicators that are corelated to a specific disease, as with many other diseases, can be challenging. Furthermore, the concentration of biomarkers in biological fluids varies according to illness states and phases. Peptides, proteins, up or down regulated expression of gene markers, and gene alternation are all examples of molecular markers that are commonly used to diagnose cancer. In this article, we have highlighted six different deadliest cancers such as Ovarian, Breast, Prostrate, Lung, Colorectal and Liver cancer. The article contains distinct types of biomarkers which are normally found in these kinds of cancer and generally used as a potential diagnostic target in the medicine field. The article mainly summarized the application of different types of biosensors devices in the detection of the mostly found biomarkers in the above cancer types.

Lumpy skin disease (LSD) is an emerging transboundary viral disease of cattle originating from the African continent. Here we describe the first LSD outbreak reported in the Republic of Kazakhstan, in July 2016. Initially, LSD was reported in a cattle farm located 49 km from Kazakh –Russian border in, Atyrau Oblast in West Kazakhstan. Subsequently, the disease spread to neighbouring farms situated within the same district. Following a preliminary investigation, the local State Veterinary Service declared a strict quarantine according to the State Contingency Plan, along with immediate total stamping out and cattle movement restrictions. During the outbreak, the number of affected cattle within an epidemiological unit reached 459 cattle out of registered 3557 susceptible cattle with 12.90% morbidity and 0.96%, mortality. This manuscript presents the epidemiological situation, the diagnosis, the control measures including mass vaccination and the stamping out campaign.s

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

Skin involvement is an overlooked aspect in the management of paediatric patients with type 1 diabetes. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: “children”, “pediatric/paediatric patients”, “skin”, “skin disorders”, “type 1 diabetes”. Dermatological side effects are frequently observed among diabetic children and adolescents. Insulin-induced lipodystrophies and allergic contact dermatitis caused by insulin pumps or glycaemic sensors are the most common skin reactions in these patients. Furthermore, several diabetes-associated skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum may already be present in paediatric age. Paediatric diabetes specialists should pay attention to their patients’ skin so as to recognize these disorders, identify the potential causes, and choose the most suitable treatment. Finally, the evaluation of skin concentrations of advanced glycation end-products using non-invasive diagnostic techniques may be used to assess the risk of chronic complications of diabetes as early as adolescence.

Sphingomonas paucimobilis is an opportunist pathogen bacillus gram-negative aerobic with a rare occurrence. We present a case in an immunocompetent man successfully treated by surgical debridement, purulent drainage and with an associated course of antibiotics. A large necrotic infection, approximately 5 cm x 3 cm, in a 74-year-old man was identified. Empirical antibiotic therapy with ciprofloxacin 400mg EV 12/12 hours, associated with clindamycin 600mg EV 6/6 hours and pain control was done through dipyrone 1gr, tramadol 400 mg. Deep venous thrombosis was prevented through the prescription of enoxaparin 40mg subcutaneous once a day during hospitalization. The case was well illustrated with pictures throughout treatment. Complete healing was achieved after 90 days. Herein, we present a case of cutaneous contamination. The presented case is the third cutaneous contamination case reported in the literature and the first reported case in the Amazonia region in Brazil.

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

Currently, old-style personal medicare techniques rely mostly on traditional methods, such as cumbersome tools and complicated processes, which can be time-consuming and inconvenient in some circumstances. Furthermore, such old methods need the use of heavy equipment, blood draws, and traditional bench-top testing procedures. Invasive ways of acquiring test samples can potentially cause patients discomfort and anguish. Wearable sensors, on the other hand, may be attached to numerous body areas to capture diverse biochemical and physiological characteristics as a developing analytical tool. Physical, chemical, and biological data transferred via the skin is used to monitor health in various circumstances. Wearable sensors can assess the aberrant conditions of the physical or chemical components of the human body in real-time, exposing the body state in time, thanks to unintrusive sampling and high accuracy. Most commercially available wearable gadgets are mechanically hard components attached to bands and worn on the wrist, with form factors ultimately constrained by the size and weight of the batteries required for the power supply. Wearable gadgets with “skin-like” qualities are a new type of automation that is only starting to make its way out of research labs and into pre-commercial prototypes. In this paper, we studied the recent advancement in battery-powered wearable sensors established on optical phenomena and skin-like battery-free sensors which brings a breakthrough in wearable sensing automation.

Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.

In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

Multicellular life evolved from simple unicellular organisms that could replicate indefinitely being essentially ageless. At this point, life split into 2 fundamentally different cell types: the immortal germline representing an unbroken lineage of cell division with no intrinsic endpoint and the mortal soma which ages and dies. In this review, we describe the germline as clock-free and the soma as clock-bound and discuss aging with respect to 3 DNA-based cellular clocks (telomeric, DNA methylation, and transposable element). The ticking of these clocks corresponds to the stepwise progressive limitation of growth and regeneration of somatic cells that we term, somatic restriction. Somatic restriction acts in opposition to strategies that ensure continued germline replication and regeneration. We thus consider the plasticity of aging as a process not fixed to the pace of chronological time but one that can speed up or slow down depending on the rate of intrinsic cellular clocks. We further describe how germline factor reprogramming might be used to slow the rate of aging and potentially reverse it by causing the clocks to tick backwards. Therefore, reprogramming may eventually lead to therapeutic strategies to treat degenerative diseases by altering aging itself, the one condition common to us all.

As described in previous work, the use of synthetic chemical ingredients in modern cosmetics is postulated to be a cause of damage to the skin microbiome. The discovery that biodiversity on the human skin is currently the only reliable indicator of skin health, meant that for the first time, a mechanism to test for healthy skin was possible. Using this mechanism and in collaboration with The Medical University of Graz, who carried out the independent study, this work aimed to help answer whether modern day synthetic cosmetics are a main cause of long term damage to the skin microbiome. Thirty-two human participants tested three different face washes for their effect on the skin’s microbial diversity, along with skin pH, moisture and TEWL (trans-epidermal water loss), washing twice a day for four weeks. The upper volar forearm of the volunteers was swabbed at the beginning, two weeks in and end (four weeks). 16S rRNA sequencing was used. One leading ‘natural’ brand full of synthetic ingredients, a leading synthetic brand and a 100% natural face wash were used. Results give the first indications of a link between synthetic ingredients in a cosmetics product, and its effect on skin microbiome biodiversity. It paves the way for future studies on the topic with a larger sample group, longer test period and standardised methodology to create a universal standard for testing the health of skin using benchmark diversity values. This can be used in the future to test the effectiveness of cosmetics or ingredients on skin health, leading to the banning of products proven to harm the skin’s natural environment.

Osteosarcopenic obesity (OSO) is described by the simultaneous presence of osteopenia/osteoporosis, sarcopenia, and increased adiposity. Over time, older adults with OSO syndrome might be at greater risk for loss of physical function and bone fractures. Furthermore, a sedentary lifestyle, inadequate nutrition, pharmaceutical drugs and chronic conditions encompass the multifactorial nature of OSO syndrome. Physical activity and a healthy diet play a crucial role in management and treatment of OSO syndrome. Research has shown that even low-intensity physical activity or daily habitual activity can maintain bone mineral density, muscle strength and improve muscle quality, and reduce adiposity. However, older adults with high risk of fall and injuries require tailored exercise intensity. Also, balanced daily intake of vitamin D, calcium and protein is important in prevention and treatment of OSO syndrome in postmenopausal women. Effective measurement of bone mass, muscle mass and strength is required when detecting OSO syndrome and to evaluate the balance, strength and endurance of elder individuals and severity of the condition.

Although our emotional connection with the physical urban setting is often valued, it is rarely recognised or used as a resource to understand future actions in city planning. Yet, despite the importance of emotion, citizens’ emotions are typically seen as difficult to quantify and individualistic, even though knowledge about people’s response to space could help planners understand people’s behaviours and learn about how citizens use and live in the city. The study explores the relationship between the physical space and emotions through identifying the links between stress levels, and specific features of the urban environment. This study aims to show the potential of integrating the use of galvanic skin response (GSR) within urban spatial analysis and city planning, in order to address the relationship between emotions and urban spaces. This method involved participants using a (GSR) device linked to location data to measure participant’s emotional responses along a walking route in a city centre environment. Findings show correlations between characteristics of environment and stress levels, as well as how specific features of the city spaces such as road crossing create stress ‘hotspots’. We suggest that the data obtained could contribute to citizens creating their own information layer - an emotional layer- that could inform urban planning decision-making. The implications of this application of this method as an approach to public participation in urban planning are also discussed.

In recent years, the field of deep learning achieved considerable success in pattern recognition, image segmentation and may other classification fields. There are a lot of studies and practical applications of deep learning on images, video or text classification. In this study, we suggest a method for changing the architecture of the most performing CNN models with the aim of designing new models to be used as stand-alone networks or as a component of an ensemble. We propose to replace each activation layer of a CNN (usually a ReLu layer) by a different activation function stochastically drawn from a set of activation functions: in this way the resulting CNN has a different set of activation function layers.

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

Daily exposure of skin to environmental stressors leads to molecular and morphological changes ascribed as premature aging. These stressors include solar radiation, industrial pollution, fossil fuel and carbon emissions, which cause cellular damage that induces an inflammatory response in skin. Several inflammatory components are known to be involved in triggering the senescence-associated secretory phenotype (SASP) which is known to accelerate aging. It is hypothesized that preventing induction of inflammation by environmental stressors can prevent premature aging. Since it is known that nicotinamide (Nam) has anti-inflammatory properties, we tested whether Nam can inhibit environmental stressor-induced inflammation. Exposure of keratinocytes to UVB, urban dust, diesel exhaust, and cigarette smoke extract stimulated production of the inflammatory mediators PGE2, IL-6, and IL-8 and induced gene expression patterns associated with apoptosis, DNA repair, and cell cycle control. In all cases, Nam treatment significantly inhibited these stress-induced responses. Nam also reduced IL-8 levels stimulated by the combination of topically applied particulate matter (PM2.5) and UV exposure in 3D skin equivalents. Under 5% 02 conditions that more closely mimic physiological 02 levels, Nam had a heightened inhibitory effect on UVB-induced PGE2 levels in keratinocytes. In a UV-challenge study, treatment with Nam reduced skin surface IL-1RA/IL-1 inflammatory biomarkers and erythema that were induced by solar simulated radiation. These findings provide a body of evidence that Nam can mitigate in part the skin’s inflammatory response elicited by exposure to environmental stressors. This supports the potential that Nam can inhibit premature aging and help maintain skin’s functionality and appearance.

In the recent years, tissue engineering researchers have exploited a variety of biomaterials that can potentially mimic extracellular matrix (ECM) for tissue regeneration. Natural cellulose, mainly obtained from bacterial (BC) and plant-based (PC) sources, can serve as a high potential scaffold material for different regenerative purposes. Natural cellulose has drawn the attention of researchers due to its advantage over synthetic cellulose in terms of availability, cost-effectiveness, perfusablility, biocompatibility, negligible toxicity, mild immune response and due to imitating native tissues. In this article, we will review the recent in vivo and in vitro studies aimed to assess the potentials of natural cellulose for the purpose of soft (skin, heart, veins, nerve, among others) and hard (bone and tooth) tissue engineering.

The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

Steroidal anti-inflammatory drugs are widely used for treatment of chronic cutaneous inflammation, such as atopic dermatitis, although it remains unknown how they modulate cutaneous mast cell functions. Murine connective tissue-type mast cells, which were sensitive to mast cell secretagogues, such as compound 48/80 and substance P, were generated by co-culture of bone marrow-derived mast cells with Swiss 3T3 fibroblasts in the presence of stem cell factor. This process was accompanied by up-regulation of a subunit of a trimeric G protein, G_i1, and several Mas-related G protein-coupled receptor (Mrgpr) subtypes. Secretagogue-induced degranulation and up-regulation of these genes were suppressed when they were cultured in the presence of a synthetic glucocorticoid, dexamethasone. The profiles of granule constituents were drastically altered by dexamethasone. Several Mrgpr subtypes were found to be expressed in the cutaneous tissues and their expression levels were decreased in response to topical application of dexamethasone. The numbers of degranulated cutaneous mast cells in response to compound 48/80 were decreased in mice treated with dexamethasone. These results suggest that mast cell-mediated IgE-independent cutaneous inflammation could be suppressed by steroidal anti-inflammatory drugs through down-regulation of G_ai1 and several Mrgpr subtypes in mast cells.

Marine macroalgae have garnered significant attention in the field of cosmeceutical research due to their rich abundance of bioactive compounds. These compounds offer remarkable skin benefits without inducing any adverse effects on human health, such as cytotoxicity, reproductive toxicity, genotoxicity, mutagenicity, or carcinogenicity. Among the various bioactive compounds found in brown algae, phenolic compounds exhibit diverse chemical structures and are present in high concentrations. In addition to phenolic compounds, brown algae also contain terpenoids, bro-mophenols, mycosporine amino acids (MAAs), and flavonoids, with the well-studied poly-phenol compound, phlorotannin, being particularly prominent. Marine macroalgae further possess an array of pigments derived from their natural pigmentation, including chlorophylls, carotenoids (such as fucoxanthin and β-carotene), phycobiliproteins (such as phycoerythrin and phycocyanin), and melanin. These pigments have been extensively investigated for their potential cos-meceutical applications. The phenolic compounds and pigments derived from marine macroalgae have been thoroughly studied for their beneficial effects on the skin, including skin whitening, moisturizing, photoprotection, anti-aging, anti-wrinkle, anti-melanogenic, and anti-oxidant properties. This comprehensive review aims to explore the extraction, characterization, and skin cosmetic effects of phenolic compounds and pigments derived from marine macroalgae, as documented in the existing literature, thereby enhancing our understanding of their therapeutic potential.

Automated skin lesion analysis is one of the trending fields that has gained attention among the dermatologists and healthcare practitioners. Skin lesion restoration is an essential preprocessing step for lesion enhancements for accurate automated analysis and diagnosis. Digital hair removal is a non-invasive method for image enhancement by solving the hair-occlusion artefact in previously captured images. Several hair removal methods were proposed for skin delineation and removal. However, manual annotation is one of the main challenges that hinder the validation of these proposed methods on a large number of images or using benchmarking datasets for comparison purposes. In the presented work, we propose a realistic hair simulator based on context-aware image synthesis using image-to-image translation techniques via conditional adversarial generative networks for generation of different hair occlusions in skin images, along with the ground-truth mask for hair location. Besides, we explored using three loss functions including L1-norm, L2-norm and structural similarity index (SSIM) to maximise the synthesis quality. For quantitatively evaluate the realism of image synthesis, the t-SNE feature mapping and Bland-Altman test are employed as objective metrics. Experimental results show the superior performance of our proposed method compared to previous methods for hair synthesis with plausible colours and preserving the integrity of the lesion texture.

NAD⁺ is known classically as a metabolite that participates in catabolic and anabolic pathways throughout the metabolism that is taught to students in introductory biochemistry courses. However, non-classical studies starting over a decade ago found that NAD⁺ is also involved in higher order functions, in part because of its involvement in the activation of SIRTs and the support of the mitochondrial unfolded protein response. Many studies since have suggested that NAD⁺ is involved in an extensive spectrum of human pathologies, including neurodegenerative disorders, cardiomyopathy, obesity, and diabetes, Further, healthy aging and longevity appear to be closely related to NAD⁺ and its related metabolites, including NAR and NMN. Together, these studies show that this system has value as a dietary supplement to improve general health overall, as well as mitigating specific disease conditions. Accordingly, many are now recommending the consumption of materials in this system as dietary supplements. Nicotinamide riboside (NAR) appears to have special value in this regard. It appears to be better tolerated than other molecules in this system, as well as better pharmacodynamics and greater potency. Unfortunately, NAR is a reactive molecule, often unstable during its manufacturing, transport, and storage. Indeed, HPLC analyses of many commercial samples of NAR shows that they contain substantial amounts of material that are not, in fact, NAR. In some of these commercial preparations, NAR is a minority component. Therefore, more stable derivatives of NAR that are easily converted upon consumption into NAR are therefore desired. Recently work related to prebiotic chemistry provided the borate derivative of NAR. NARB is considerably more stable than NAR itself. However, immediately upon consumption, the borate dissociates from NARB, and is lost in the body through dilution and binding to other species, notably carbohydrates such as fructose and glucose. The NAR left behind is expected to behave pharmacologically in ways identical to NAR itself. This review provides a comprehensive summary (through Q1 of 2023) of literature that makes the case for the consumption of NAR as a dietary supplement. It then summarizes the challenges of delivering quality NAR to consumers using standard synthesis, manufacture, shipping, and storage approaches. It concludes by outlining the advantages of NAR-borate in these processes.

For the past few decades, researchers have been intrigued with glassy polymers, which have applications ranging from gas separations to corrosion protection to drug delivery systems. The techniques employed to examine the sorption and diffusion of small molecules in glassy polymers are the subject of this review. Diffusion models in glassy polymers are regulated by Fickian and non-Fickian diffusion, with non-Fickian diffusion being more prevalent. The characteristics of glassy polymers are determined by sorption isotherms, and different models have been proposed in the literature to explain sorption in glassy polymers during the last few years. This review also includes the applications of glassy polymer. Despite having so many applications, current researchers still have difficulty in implementing coating challenges due to issues like as physical ageing, which is briefly discussed in the review.

The recent COVID-19 outbreak in China led to a worldwide pandemic associated with a severe acute respiratory illness. A higher incidence of COVID-19 infection was demonstrated in cancer patients, including patients with lung cancer. This study was conducted to get insights into the reasons for this enhanced frequency of COVID-19 infection. Methods: Using different bioinformatic tools, the expression and methylation pattern of ACE2 and TMPRSS2 gene were analyzed in healthy and malignant tissues with a focus on lung adenocarcinoma (LUAD) and correlated to clinical parameters and smoking history. Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression in digestive, urinary and reproductive organs, while their expression was significantly lower in 36 cancer tissues. In LUAD, ACE2, but not TMPRSS2 was overexpressed, which inversely correlated to the promoter methylation. An age-dependent upregulation of ACE2 expression was found in LUAD compared to normal lung tissues. In a healthy lung, TMPRSS2 expression was dependent on sex and smoking history and downregulated in LUAD of smokers. Cancer progression was associated with decreased TMPRSS2, but unaltered ACE2 expression, while ACE2 expression in lung metastases of different cancers was higher than in metastasis of other sites. TMPRSS2, but not ACE2 expression, was associated with LUAD patients’ survival. Conclusions: Comprehensive molecular analyses revealed a heterogeneous, distinct expression and methylation profile of ACE2 and TMPRSS2 in healthy lung vs LUAD tissues across sex, age and smoking history, which is associated with clinical parameters and might have implications for COVID-19 disease.

With the advent of modern technologies, the healthcare industry is moving towards a more Personalised smart care model. The enablers of such care models are the Internet of Things (IoT) and Artificial Intelligence. These technologies collect and analyse data from persons in care to alert relevant parties if any anomaly is detected in a patient’s regular pattern. However, such reliance on IoT devices to capture continuous data extends the attack surfaces and demands high-security measures. Both patients and devices need to be authenticated to mitigate a large number of attack vectors. The biometric authentication method has been seen as a promising technique in these scenarios. To this end, this paper proposes an AI-based multimodal biometric authentication model for single and group-based users’ device-level authentication that increases protection against the traditional single modal approach. To test the efficacy of the proposed model, a series of AI models are trained and tested using physiological biometric features such as ECG (Electrocardiogram) and PPG (Photoplethysmography) signals from five publicly available datasets from Physionet and Mendeley data repositories. The multimodal fusion authentication model shows promising results with 99.8% accuracy and an Equal Error Rate (EER) of 0.16.

Most hair relaxers or straighteners used for Afro-textured hair have a pH above 11. This pH, according to international occupational health and safety guidelines, is corrosive to the skin. Further, relaxers are associated with a 3-6 times increased risk of alopecia. The skin also gets into contact with these hair straightening products during application resulting in skin irritation. Using animals as test subjects to determine these products' potential risk and safety margin is standard practice; however, with the European Union (EU) ban on animal testing, the testing method needs to be replaced by newer in vitro laboratory technologies. This study used previously and newly established in vitro cell-based technologies and human-skin derived cells as laboratory models to evaluate relaxer-induced cytotoxicity. These technologies include endpoint (MTT, CCK-8 and flow cytometry) and real-time assays (real-time cell analysis (RTCA) and extracellular flux analysis). Cellular toxicity was evident following treatment of keratinocytes and fibroblasts with acceptable concentrations of thioglycolic acid (TGA, HSCH2COOH), ammonium bisulphite (NH4HSO3), lithium hydroxide (LiOH) and sodium hydroxide (NaOH) based relaxers. Real-time assays showed significant reductions (P<0.001) in cell index and ATP production following treatment of keratinocytes with as little as one-tenth of the acceptable concentrations. Increased apoptosis (47.9%, 58.0%, 76.7% and 80.3%) also occurred in cells after treatment with TGA, NH4HSO3, NaOH and LiOH, respectively. In conclusion, this study demonstrated that using skin cells in conjunction with advanced cell-based technologies could serve as alternatives to laboratory animals for accessing the toxicity margin of hair relaxers, straighteners and other cosmetics.

Advanced paternal age at fertilization has been suggested to be a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental factors that modify such changes. In this study, we characterize age-dependent changes in sperm DNA methylation profiles between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). Reduced representation bisulfite sequencing (RRBS) libraries were prepared from caudal epididymal sperm DNA and differentially methylated regions (DMRs; ≥ 10x coverage depth, ≥ 3 CpGs per cluster, ≥ 5% methylation change, q < 0.05) were identified via MethPipe package. In control animals, 5,319 age-dependent DMRs were identified, with 99.3% DMRs hypermethylated in mature animals compared to young pubertal rats. These age-related DMRs were enriched for functional categories essential for embryonic development, such as pattern specification, forebrain and sensory organ development, Hippo and Wnt pathways. Age-related changes in sncRNA, reported in different study, target similar list of genes and biological categories.In BDE-47 exposed rats, sperm DNA methylation was higher in young pubertal and lower in mature animals when compared to controls, which resulted in a significant attenuation in the number of age-dependent DMRs (N = 189) identified in the exposed group. In conclusion, our results indicate that the natural aging process has profound effects on sperm methylation levels and this effect may be modified by environmental exposures. Moreover, our results further support the role of epigenetic mechanisms as a likely link betwen paternal age and offspring health and development.

The majority of skin cancers are caused by over exposure to ultraviolet (UV) radiation. The effects of UV radiation on the expression of drug transporters expressed in human skin has never been studied. In this the effects of UVA and UVB irradiation on the expression of ATP-binding cassette (ABC) transporters and Solute carrier (SLC) transporters was evaluated in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) in primary culture. First experiments were intended to validate the inflammatory reaction in response to stimulation by lipopolysaccharide (LPS) in NHEK, NHDF and 3D-reconstructed human epidermis (3D-RHE) model. LPS treatment has shown to increase the expression of IL-8 and TNF-alpha in all three in vitro models. Expression of the most expressed ABC and SLC transporters was then measured in NHEK and NHDF after UVA (30 J/m²) and UVB (40 mJ/m²) irradiation. The most striking result was a significant 29-fold increase of the expression of SLCO4A1 in normal human dermal fibroblasts. In summary, this study shows for the first time a significant regulation of the expression of SLCO4A1 in human dermal fibroblasts induced by UVA irradiation. This finding is of particular interest as most of skin cancers are caused by over exposure to ultraviolet radiation and need to be considered in pharmacokinetic evaluation of topical drugs.

Capacitive contact imaging has shown potential in measuring skin properties including hydration, micro relief analysis, as well as solvent penetration measurements. Through calibration we can also measure the absolute permittivity of the skin, and from absolute permittivity we then work out the absolute solvent content in skin. In this paper, we present our latest study of capacitive contact imaging for skin characterizations and vivo skin solvent penetration. We will show how to use capacitive occlusion measurements to characterize skin damages, and how to calculate the absolute water content and solvent content in skin.

We have experimentally analyzed multi-azimuth degradation mechanisms that govern failures of commercially-available high-power (1 Watt) phosphor-coated white (hppc-W) light-emitting diodes (LEDs) covered with peanut-shaped lens under three current-stress aging (CSA) conditions. Comprehensive analyses focus on photometric, chromatic, electrical, thermal, and packaging characteristics. At the packaging level, (a) the decrease of the phosphor-conversion efficiency, (b) the yellow-browning of the optical lens, and (c) the darkening of the silver-coated reflective layer deposited with extraneous chemical elements (e.g., C, O, Si, Mg, and Cu, respectively) contribute collectively to the integral degradation of the optical power. By contrast, Ohmic contacts, thermal properties, and angles of maximum intensity remain unchanged after 3840 h aging in three cases. Particularly at the chip level, the formation of point defects increases the number of non-radiative recombination centers, and thus decreases the optical power during aging stages. Nevertheless, in view of the change of the ideality factor, the dopant activation and the annealing effect facilitate the increase of the optical power in two specific aging stages (192 h∼384 h and 768 h∼1536 h), respectively. This work offers a systematic guidance for the development of reliable LED-based light sources in general-lighting areas.

Biomedical aspects of tattooing have been extensively discussed in literature, however pathophysiological effects of tattoo inks in the human body are still unexplored. Oxidative stress is considered responsible for the adverse effects of tattooing, however no experimental evidence for tattoo ink-related oxidative stress in the human body currently exists. The aim was to examine the effect of a blue tattoo on skin redox regulatory network (RRN) parameters in a single human subject. Skin surface oxidation-reduction potential (ORP) was analyzed with a PH60F flat probe. Interstitial and intracellular fluid enriched capillary blood from the tattoo and the control area was extracted and analyzed with I₂/KI-stabilized microORP, nitrocellulose redox permanganometry (NRP), carbonato-cobaltate (III) formation-derived H₂O₂ dissociation rate assay, 1,2,3-trihydroxybenzene autoxidation assay, thiobarbituric reactive substances (TBARS) assay and 5,5,’-dithio-bis-(2-nitrobenzoic acid) (DTNB)-based determination of free thiol content in low molecular weight and protein precipitate fractions. Surface ORP analysis revealed a greater antioxidant capacity of tattooed skin in comparison with the control (CTR). Capillary blood analysis confirmed greater reductive capacity in the tattoo sample both by microORP (-4.33mV vs CTR) and NRP (+10.8%). Hydrogen peroxide dissociation rate (+11.8%), and protein sulfhydryl content (+8.5%) were increased, and lipid peroxidation (-15%) was reduced in the tattoo sample in comparison with the CTR. In this N-of-1 study, RRN of tattooed skin was shifted towards a more reductive state with all parameters indicating reduced levels of oxidative stress in comparison with nontattooed skin. The local antioxidant effect of copper(II) phthalocyanine provides one possible explanation of the observed effects.