According to known laws of physics, chronic positive mass balance is the actual etiology of obesity, not positive energy balance. The relevant physical law in terms of body mass regulation is the Law of Conservation of Mass, not the Law of Conservation of Energy. A recently proposed mass balance model (MBM) describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments, and it seems to provide a highly accurate description of the very best experimental human feeding data. By shifting to a mass balance paradigm of obesity, a deeper understanding of this disease may follow in the near future. The purpose of this living review is to present the core issues of the upcoming paradigm shift as well as some practical applications related to the topic.

People often say that beer tastes better from a bottle than from a can. However, one can ask whether this perceived difference is reliable across consumers; And, if so, whether it is purely a psychological phenomenon (associated with the influence of packaging on taste perception), or whether instead it reflects some more mundane physico-chemical interaction between the packaging material (or packing procedure/process) and the contents. We conducted two experiments in order to address these important questions. In the main experiment, 151 participants at the 2016 Edinburgh Science Festival were served a beer in a plastic cup. The beer was either poured from a bottle or can (i.e., a between-participants experimental design was used) and the participants were encouraged to pick up the packaging in order to inspect the label before tasting the beer. The participants rated the perceived taste, quality, and freshness of the beer, as well as their likelihood of purchase, and their estimate of the price. All of the beer came from the same batch (from Barney’s Brewery in Edinburgh). Nevertheless, those who evaluated the bottled beer rated it as tasting better than those who rated the beer that had been served from a can. Having demonstrated such a perceptual difference in terms of taste, we then went on to investigate whether people would prefer one packaging format over the other when the beer from bottle and can was served to a new group of participants blind (i.e., when the participants did not know the packaging material). The participants in this control study (N = 29) were asked which beer they preferred or else could state that the two samples tasted the same. No sign of preference was obtained under such conditions. Explanations for the psychological impact of the packaging format, in terms of differences in packaging weight (between tin and glass), and/or prior associations of quality with specific packaging materials/formats (what some have chosen to call ‘image molds’) are discussed.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

Sensitive and precise nucleic acid detection is critical for clinical diagnostics and biotechnological advancements. Diagnostic in infectious disease field is very unique from diagnosing any other disease, that is time is of the essence; in outbreaks people die even with each passing hour in some cases, if the correct diagnosis wasn't make; for example Zika in particularly is a very challenging virus to diagnose, because it's in very few numbers of copies in the infected person, so it need high sensitive diagnostic approach to spot it, In particular, the advanced tools SHERLOCKv2 and DETECTR, give almost an immediate detection of attomolar amounts of pathogenic nucleic acids with specificity similar to that of PCR but with slight technical settings and that will guide the correct intervention for the patient. SHERLOCKv2 and DETECTR technologies are game changers for our ability to identify infectious disease and rapid detection of tumor DNA or cancer-related viruses with ultra-sensitive tests that don’t require a lot of complicated processing to go through. In this paper, we will review cutting-edge infectious disease diagnosis by CRISPR-Cas systems.

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.

This work investigated the isothermal holding time dependence of the densification, microstructure, weight loss and tensile properties of Fe-Mn-Si powder compacts. Elemental Fe, Mn and Si powder mixtures with a nominal composition of Fe-28Mn-3Si (in weight percent) were ball milled for 5h and subsequently pressed under a uniaxial pressure of 400 MPa. The compacted Fe-Mn-Si powder mixtures were sintered at 1200 ℃ for 0, 1, 2 and 3 h, respectively. In general, the density, weight loss and tensile properties increased with the increase of isothermal holding time. A significant increase in density, weight loss and tensile properties occurred in the compacts isothermally holding for 1 h, as compared to those with no isothermal holding. However, further extension of isothermal holding time (2 and 3 h) only played a limited role in promoting the density and tensile properties. The weight loss of the sintered compacts was mianly caused by the sublimation of Mn in Mn depletion region on the surface layer of the sintered Fe-Mn-Si compacts. The length of the Mn depletion region increased as isothermal holding time increased. A single α-Fe phase was detected on the surface of all the sintered compacts, and the locations beyond the Mn depletion region were comprised of a dual dominant γ-austenite and minor ε-martensite.

We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree's utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to her full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA) utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

We take what we see, hear, smell and feel for the reality. However, as neuroscientists, we know that this reality, that is, our perceptual world, is in fact made up by the brain from the processing of the nerve impulses coming from receptors. Ancient Greeks used to think that this perceptual world, sometimes called our 3D movie (Chalmers), is emitted and has its own physical nature. Given how real the 3D movie looks to us, it is still difficult today to consider that all we would be dealing with would be patterns of brain activity The present study thus aimed at testing whether the perceptual world could have some physical existence in addition to that of the neural patterns responsible for it. To achieve that goal, we tried to see whether brains could be sensitive to the 3D movie of others. This, admittedly unusual, operational hypothesis was based on two assumptions. First, brains are sensitive to the 3D movie, as our experience includes reactions to our perceptual world. Second, the physicality at stake does not differ across individuals. We recorded the event-related brain potentials (ERPs) evoked by stimuli of the international affective picture system in pairs of closely-related participants. Most importantly, they could neither see the stimuli simultaneously presented to their partners nor their reactions to them. As in Bouten et al. (2015), around 400 ms after the onset of the stimuli, ERPs started being more positive in inconsistent conditions. Namely, when the two subjects of each pair were presented with the same stimulus whereas they were told it would be a different one and vice-versa (i.e., different-stimuli expected to be same). ERPs were less positive when the two subjects of a pair were presented with the same stimuli and were told they were the same and conversely (i.e., different-stimuli expected to be different). The same experiment was then run in pairs of strangers. No significant effect of consistency on ERPs was observed even though participants could, this time, see, in the very periphery of their visual field, the reactions of their partner to the stimuli. We thus use the results of both studies to support a new version of the emission theory of consciousness and to suggest that the sensitivity to the perceptual world of others may depend on their prior familiarity with it.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.

In this brief paper a quantum algorithm to calculate the Hamming distance of two binary strings of equal length (or messages in theory information) is presented. The algorithm calculates the Hamming weight of two binary strings in one query of an oracle. To calculate the hamming distance of these two strings we only have to calculate the Hamming weight of the xor operation of both strings. To test the algorithms the quantum computer prototype that IBM has given open access to on the cloud has been used to test the results.

Agavins consumption has lead to accelerate body weight loss in mice. We investigated the changes on cecal microbiota and short chain fatty acids (SCFA) associated to body weight loss in overweight mice. Firstly, mice were fed with standard (ST5) or high fat (HF5) diet for 5 weeks. Secondly, overweight mice were shifted to standard diet alone (HF-ST10) or supplemented with agavins (HF-ST+A10) or oligofructose (HF-ST+O10), five more weeks. Cecal contents were collected before and after supplementation to determine microbiota and SCFA concentrations. At the end of first phase, HF5 mice showed a significant increase of body weight, which was associated with reduction of cecal microbiota diversity (PD whole tree; non-parametric t-test, P < 0.05), increased Firmicutes/Bacteroidetes ratio and reduced SCFA concentrations (t-test, P < 0.05). After diet shifted, HF-ST10 normalized its microbiota, increase its diversity and SCFA levels, whereas agavins (HF-ST+A10) or oligofructose (HF-ST+O10) led to partial microbiota restoration, with normalization of the Firmicutes/Bacteroides ratio as well as higher SCFA levels (P < 0.1). Moreover, agavins noticeably enriched Klebsiella and Citrobacter (LDA > 3.0); this enrichment has not been reported previously under a prebiotic treatment. In conclusion, agavins or oligofructose modulated cecal microbiota composition, reduced extent of diversity and increased SCFA. Furthermore, identification of bacteria enriched by agavins, opens opportunities to explore new probiotics.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

This study presents an in–depth analysis and strategic planning techniques for approaching a situation or achieving progress related to information technology services of Nueva Ecija University of Science and Technology, particularly the San Isidro Campus. As an educational organization and one in the region excellence providers in education, the University has so much vital information to manage and services to offer to provide the student's needs through the Management Information System department, application of IT services as a competing instrument to combat tedious tasks such as online admission, grade release, enrollment information, and online learning, university announcement, and possible students’ internship. The objective of this study is to determine the influence of information technology in day–to–day activities of the organization and strategy applied to streamline processes more conveniently. The researchers develop a conceptual model that would analyze the IT services' impact by identifying its strengths, weaknesses, opportunities, and threats and cleverly act on it using the TOWS Matrix in generating strategic decisions. The overall results were beneficial to the University and MIS as a basis for formulating competitive strategies and integrating it in an extended development plan.

In this paper we show that the Schwarzschild radius can be extracted easily from any gravitationally-linked phenomena without having knowledge of the Newton gravitational constant or the mass size of the gravitational object. Further, the Schwarzschild radius can be used to predict any gravity phenomena accurately, again without knowledge of the Newton gravitational constant and also without knowledge of the size of the mass, although this may seem surprising at first. Hidden within the Schwarzschild radius are the mass of the gravitational object, the Planck mass (their relative mass), and the Planck length. We do not claim to have all the answers, but this seems to indicate that gravity is quantized, even at a cosmological scale, and this quantization is directly linked to the Planck units. This also supports our view that the Newton gravitational constant is a universal composite constant of the form $G=\frac{l_p^2{c}^3}{\hslash }$ , rather than relying on the Planck units as a function of G. This does not mean that Newton’s gravitational constant is not a universal constant, but that it is instead a composite universal constant that depends on the Planck length, the speed of light, and the Planck constant. Further, $\frac{G\times 1\hspace{0.17em}\mathrm{weight}\hspace{0.17em}\mathrm{unit}}{c^2}=\frac{G}{c^2}$ is the Schwarzschild radius off one weight unit. So G is only needed when we want to use gravity to find the weight of an object, such as weighing the Earth. This is, to our knowledge, the first paper that shows how a long series of major gravity predictions and measurements can be completed without any knowledge of the mass size of the object, or Newton’s gravitational constant. As a minimum we think it provides an interesting new angle for evaluating existing gravity theories, and it may even give us a small hint on how to combine quantum gravity with Newton and Einstein gravity.

During the conceptual and preliminary design stage of a ship, designers need to ensure that the selected principal dimensions and parameters are good enough to deliver a stable ship (statically and dynamically) besides deadweight and speed. To support this, the initial intact stability of the proposed ship is required to be calculated, and in doing so, the lightship weight and its detailed breakdown are necessary to be known. After hull steel weight, machinery weight, mainly, marine propulsion and power generation machinery, play a vital role in the lightship weight estimate of a ship due to its robustness. The correct estimation of respective weights improves the accuracy of calculating a ship's initial stability typically to be designed and built. Hence, it would be advantageous for the designer to convince the ship owner. A total of 3006 marine propulsion (main marine diesel) engines and 348 power generation (auxiliary marine diesel) engines/generators of various power output (generators output for auxiliary engines), engine RPM and cylinder number of different engine makers are collected. These are analyzed and presented in both tabular and graphical forms to demonstrate the possible relationship between marine propulsion engine weight and power generation engine weight, and their respective power output, RPM, cylinder number, power-RPM ratio and power-RPM ratio per cylinder.In this article, the authors have attempted to investigate the behavior of marine propulsion engine weight and power generation engine/generator weight regarding engine power output, generator power output, engine RPM and cylinder number (independent variables). Further attempts have been made to identify those independent variables that influence the weight of the marine propulsion engine and power generation engine/generator (dependent variables), and their interrelationships. A mathematical model has thus been developed and proposed, as a guiding tool, for the designer to estimate the weight of main and auxiliary engines more accurately during the conceptual and preliminary design stage.

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

Cellular oxidation is responsive to external and internal stimulation and is generated via signal molecules in defense mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Oxidative stress is not necessarily harmful per se; it depends on the balance between oxidation and antioxidation cascades, which are induced according to stimuli and can maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and ROS production, using IV as an example. We introduce the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS production and various effects of IV infection. We also summarize the potential anti-IV agents that act by targeting oxidative stress.

The global polyvinyldene flouride market is estimated to reach $937,278.5 thousand by 2019, therefore to develop new membranes and gain pioneering ideas, which could create innovative business opportunities, a fundamental knowledge about membrane properties fabricated from recent commercially available PVDF polymers is highly mandatory. In this study, we successfully prepared nine non-woven supported PVDF membranes using a phase inversion precipitation method starting from a 15 wt% PVDF solution in N-methyl-2-pyrrolidone. Various membrane morphologies were obtained by using (1) PVDF polymers with diverse molecular weight in a range from 300.000 Da to 700.000 Da and (2) different temperatures of the coagulation bath (20, 40, and 60 ±2°C) used for the films precipitation. Environmental Scanning Electron Microscope (ESEM) was used for surface and cross-section morphologies characterization. Atomic Force Microscope (AFM) was employed to investigate surface roughness, while Contact Angle (CA) instrument was used for membranes wettability studies. Fourier Transform Infrared Spectroscopy (FTIR) results show that the fabricated membranes are formed by a mixture of TGTG’ chains in α phase crystalline domains and all-TTTT trans planar zigzag chains characteristic to β phase. Moreover, generated results indicate that the phases content and membrane morphologies depend on the polymer molecular weight and conditions used for the membranes preparation. The diversity of fabricated membranes could be applied by the End User Industries for different applications.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

Garment sector has crucial working field in Turkey.It has also very high risky occupational health conditions and safety.The objective of this study is to define level of job level, work-related stress’ symptoms, social support and coping mechanisms of garment workers and to determine any related factors.This study is descriptive and cross-sectional. The study population comprised garment workers in the 16-65 age range. The data was collected by Assessment Form, The Brief Stress Coping Profile and Brief Job Stress Questionnaire. The level of work-related stress was statistically higher among the workers who had chronic disease, low economic, education status and poor quality of sleep. Psychological and physical physiological reactions to stress were found higher among women workers and those with chronic disease.It also was seen that job stress scores had a meaningful relationship with “emotional expression involving others” (r =.20) and “Avoidance and suppression” coping profile (r =.16; p <.01).Psychological symptom scores were found to have a low level of meaningful relationship with “Seeking help for solution” (r =-.08), “changing point of view” (r=.13) and “emotional expression involving others” coping profiles (r=.21). Work-related stress causes many health and behavioral problems. Work related reasons and coping profiles have powerful effects on stress.

A practical method is presented to estimate rare earth elements (REE) concentrations in magmatic vapour phase (MVP) in equilibrium with water-saturated granitic melts based on empirical fluid-melt partition coefficients of REE (k_P^REE). The values of k_P^REEcan be calculated from a set of new polynomial equations linking to the chlorine molality (m_Cl^v) of the MVP associated with granitic melts, which are established via a statistical analysis on the existing experimental dataset. These equations may be applied to the entire pressure range (0.1 to 10.0 kb) within the continental crust, suggesting that light REEs behave differently in magmatic fluids, i.e. either being fluid compatible with higher m_Cl^v or fluid incompatible with lower m_Cl^v values. In contrast, heavy REEs are exclusively fluid incompatible and partition favourably into granitic melts. Consequently, magmatic fluids tend to be rich in LREE relative to HREE, leading to REE fractionation during the evolution of magmatic hydrothermal systems. Maximum k_P^REEvalue for each element is predicted and presented in a REE distribution diagram constrained by the threshold of m_Cl^v. REE contents of the granitic melt is approximated by whole-rock analysis, so that REE concentrations in the associated MVP would be estimated from the value of k_P^REE given chemical equilibrium retains. Two examples are provided respectively, to show the use of this method as a REE tracer to fingerprint the source of ore-fluids responsible for the Lake George intrusion-related Au-Sb deposit in New Brunswick (Canada), and for the Bakircay Cu-Au (-Mo) porphyry systems in northern Turkey.

The link between language processing and motor systems has been the focus of increasing interest to Cognitive Neuroscience. Some classical papers studying Event Related Potentials (ERPs) induced by linguistic stimuli have found differences in electrophysiological activity when comparing action and non-action words; more specifically, a bigger p200 for action words. On the other hand, a series of studies have validated the use of a grip force sensor (GFS) to measure language-induced motor activity during both isolated words and sentence listening, finding that action words induce an augmentation in the grip force around 250-300 ms after the onset of the stimulus. The purpose of the present study is to combine both techniques to assess if the p200 is related to the augmentation of the grip force measured by a GFS. We measured ERP and GFS changes elicited by listening to action and non-action words while maintaining an active grasping task in 10 healthy subjects. Our results show that the amplitude of the p200 in central electrodes is correlated to the augmentation in the GFS around 300 ms induced by linguistic stimuli. To our knowledge, this is the first study where the electrophysiological activity and the changes in the grip force induced by auditory language processing are put together, opening new venues of interpretation for the sensorimotor interaction in language processing.

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.

The incidence of obesity which leads to insulin resistance (IR) and metabolic disorder increases in developing countries including Indonesia. Male adult has higher risk to have abdominal obesity than female which is associated with cardiometabolic disorders. Several anthropometric measurements have been proposed to predict IR. The aim of this study was to investigate whether body mass, body mass index (BMI), waist circumference (WC), body fat percentage (BF) or visceral fat percentage (VF) could become a better predictor of IR in healthy young male adult. Total of 140 healthy young male adults ranging from 18-25 years were recruited in the study. Insulin resistance was measured by calculating Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Subjects with HOMA-IR value >75th percentile with cut off 3.75 were defined as IR. Anthropometric measurements included body weight, BMI, WC were performed whereas BF and VC were measured by bioelectrical impedance analysis (BIA). IR had significant strong correlation with body weight, BMI, WC, BF and VF. The area under curve of body mass, BF, VF were greater than WC and BMI. Anthropometric measurements correlated strongly with IR but body weight, BF, VF have stronger correlation than WC and BMI in healthy young male adult.

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

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex and habitual physical activity modulate exercise-induced appetite, energy intake and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain potential mediators of appetite responses to exercise.

Background: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the unknown risk of severity and mortality in COVID-19 patients with underlying kidney and liver diseases. Method: We retrieved data on the clinical features and primary composite end point of COVID-19 patients released from inception till 16^th of April 2020 from Medline and Embase. The data on two comorbidities, liver diseases and chronic kidney disease, present in COVID-19 were pooled and statistically analysed to explain the associated severity and mortality rate. Results: 142 abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and CKD were 3% (95%CI; 2%-3%) and 1% (95%CI; 1%-2%) respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) cases were severe with 17.65% mortality. While in CKD patients with COVID-19, 83.93% (47/56) severity and 53.33% (8/15) mortality were reported. Conclusion: This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases and CKD. This will allow for better clinical management and inform more stringent preventative measures for this group of patients.

Poor understanding of malnutrition burden is a common reason for not prioritizing the care of small and nutritionally at-risk infants aged under-six months (infants u6m). We aimed to estimate the anthropometric deficit prevalence in infants u6m attending health centres, using the Composite Index of Anthropometric Failure (CIAF); and to assess the overlap of different individual indicators. We undertook a two-week survey of all infants u6m visiting each of 18 health centres in two zones of the Oromia region, Ethiopia. We measured weight, length, and MUAC (Mid upper arm circumference); and calculated weight-for-length (WLZ), length-for-age (LAZ), and weight-for-age z-scores (WAZ). Overall, 21.7% (95% CI: 19.2; 24.3) of infants u6m presented CIAF and of these, 10.7% (95% CI: 8.93; 12.7) had multiple anthropometric deficits. Low MUAC overlapped with 47.5% (95% CI: 38.0; 57.3), 43.8% (95% CI: 34.9; 53.1), and 42.6% (95% CI: 36.3; 49.2) of the stunted, wasted and CIAF prevalence, respectively. Underweight overlapped with 63.4% (95% CI: 53.6; 72.2), 52.7% (95% CI: 43.4; 61.7), and 59.6% (95% CI: 53.1; 65.9) of the stunted, wasted and CIAF prevalence, respectively. Anthropometric deficits, single and multiple, are prevalent in infants attending health centres. WAZ overlaps more with other forms of anthropometric deficits than MUAC.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

The inhibition impacts of 1,10-Phenanthroline-5,6-diamine (PTDA) on mild steel in 1 M HCl solution were investigated through weight loss method. The inhibition efficiencies of PTDA increase with increase in PTDA concentration at the temperature 303. Weight loss method indicate that PTDA is an excellent inhibitor the inhibition efficiency of 81.5% at the maximum PTDA concentration of 0.5 g/L at the temperature 303K.

The passion of bodybuilding athletes for a symmetric, lean, heavily muscled body leads them to carry out exhausting exercise programs and restrictive eating regimens, sometimes resulting in disordered eating behaviors. This study investigates potential exacerbators on the development of disordered eating in bodybuilding and strength athletes. The study involved 103 Cypriot bodybuilding athletes of both sexes, performing at three levels: professional, recreational and strength athletes. The Eating Attitude Test 26 (EAT-26) and The Three Factor Eating Questionnaire (TFEQ-R21) were used to evaluate disordered eating and eating behaviors respectively. The current study was performed under the auspices of the Hellenic Center of Education & Treatment of Eating Disorders (KEADD). The degree of deviation between the perceived ideal body weight and the actual body weight was associated with increased risk of eating disorder. Athletes who desired a lower body weight recorded higher scores on EAT-26 overall, and the subscales of dieting and bulimia. Cognitive restraint and emotional eating scales of TFEQ-R21 were more pronounced in the non-professional athletes. The emotional eating score was higher in women. There is a need for appropriate sport-specific, gender-specific preventive intervention to deescalate the risk of eating disorder, in both professional and non-professional bodybuilding athletes.

Music and language are hypothesized to share neural resources, particularly at the level of syntax processing. Recent reports suggest that attention modulates this sharing of neural resources, but the time-course of the effects of attention, and the degree to which attention operates similarly on music and language, are yet unclear. In this EEG study we manipulate the syntactic structure of simultaneously presented musical chord progressions and garden-path sentences in a modified rapid serial visual presentation paradigm, while varying top-down attentional demands to the two modalities. The Early Right Anterior Negativity (ERAN) was observed in response to both attended and unattended musical syntax violations. In contrast, an N400 was only observed in response to attended linguistic syntax violations, and a P3 only in response to attended musical syntax violations. Results show that top-down allocation of attention indeed affects the processing of syntax in both music and language, with different neural resources acting upon the two modalities particularly at later stages of cognitive processing. However, the processing of musical syntax at an earlier stage of the perceptual-cognitive pathway, as indexed by the ERAN, is partially automatic, and is strongly indicative of separate neural resources for music and language.

The present study was conducted to evaluate the effects of dietary supplementation of tea polyphenol （TP） on serum hormone, serum enzyme activity, antioxidant-related and immune-related gene expression of laying hens under heat stress. A total of 288 Chinese yellow chicken (186 days old) were randomly distributed among two treatments, each of which included 6 replicates of 24 hens. Dietary treatments were that the basal diet was supplemented with 200 mg / kg tea polyphenol. The study lasted for 7 weeks, including 1 week of adaptation and 6 weeks of the formal test. The content of high-density lipoprotein cholesterol (HDL-C) and total protein (TP) in serum significantly decreased by dietary supplementation with tea polyphenol. Dietary tea polyphenol supplementation improved serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activity and decreased serum malondialdehyde (MDA) content in treatments compared to the control. However, supplementation of tea polyphenol did not affect the activity of serum catalase (CAT). The results indicated that long-term feeding of tea polyphenols help to increase the amount of hormones (FSH, E2) associated with reproduction in laying hens and thus improve egg production. It also improved the immune function of laying hens in high temperature environments. Adding tea polyphenols to the diet can significantly increase the serum IgG, IgM content of the laying hens and can upregulate the IgA content. Dietary supplementation of tea polyphenols in the laying hens significantly increased the expression of antioxidant enzyme-related genes (SOD, CAT and GPX1) in the liver. Moreover, the addition of tea polyphenols significantly increased the expression of immune-related genes (Interferon-γ (INF-γ), Interleukin 2 (IL-2) and Interleukin 4 (IL-4)) in the spleen. It is concluded that addition of tea polyphenols has a positive effect on antioxidant activity and immune function of laying hens.

The aim of this cross-sectional study was to assess the perceived medication-related burden among patients with multiple non-communicable diseases (NCDs), and to investigate the association between perceived burden and adherence to medication therapy. Medication-related burden was measured in three primary care clinics in Qatar using the Living with Medicines Questionnaire (LMQ) among adults with diabetes, with or without other comorbidities. Adherence was measured using the Adherence to Refills and Medications Scale (ARMS). Two hundred ninety-three eligible patients participated in the study. Majority of participants reported experiencing minimum (66.6%) to moderate (24.1%) medication-related burden. There was a significant positive correlation between the medication-related burden (measured by the LWQ) and medication adherence (measured by ARMS) (rs (253) = 0.317, p <0.0005). The duration of diabetes diagnosis, adherence score, marital status, employment status, and presence diagnosis of hypertension were significant predictors of medication burden. A considerable proportion of the patients in this study have reported experiencing medication-related burden. Healthcare providers should seek strategies to address this burden especially among patients with risk factors of cardiovascular diseases, non-adherent to their medication therapy, living alone, or non-employed.

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-5-FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both c-mesenchymal–epithelial transition (MET)/ Kirsten Rat Sarcoma virus (KRAS)/ extracellular signal-regulated kinase (ERK) and c-MET/ phosphatidyl-inositol 3-kinases (PI3K)/ protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/ matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required to validate the results of the present study.

This study was designed to assess variation of possible phytochemical compounds in the ethanolic extracts of Gigantochloa scortechinii rhizome. Destructive sampling was done by using selective random sampling method on four consecutive rhizomes from healthy clumps and was conducted at two natural forests and one secondary forest (planted). Homogenized sample were extracted using solvent extraction (70% ethanol) method. Ethanolic extracts of G. scortechinii rhizome were qualitatively analyzed using GC/MS GC2010 Plus, Shimadzu to determine the composition of phytochemical compounds and identified using FFNSC 1.3, NIST11, PMW_tox2, and Wiley229 spectral library. A qualitative variation was observed with a total of 56 compounds were identified and differentiated between study site and rhizome age. Results revealed that G. scortechinii rhizome contains various phytochemical compounds with potential as a plant of phytopharmaceutical importance. This is the first finding on the spatial and age-related effects of phytochemical compounds in a consecutive rhizome and of G. scortechinii rhizome specifically.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

Objective: To assess the effects of chronic walnut consumption on body weight and adiposity in elderly individuals. Methods: The Walnuts And Healthy Aging study is a dual-center (Barcelona, Spain and Loma Linda University [LLU]), 2-year randomized parallel trial. This report concerns only the LLU cohort. Healthy elders (mean age 69 y, 67% women) were randomly assigned to walnut (n = 183) or control diets (n = 173). Subjects in the walnut group received packaged walnuts (28–56 g/d), equivalent to ≈15% of daily energy requirements, to incorporate into their habitual diet, while those in the control group abstained from walnuts. Adiposity was measured periodically, and data were adjusted for in-trial changes in self-reported physical activity. Results: After 2 years, body weight significantly decreased (P = 0.031), while body fat significantly increased (P = 0.0001). However, no significant differences were observed between the control and walnut groups regarding body weight (−0.6 kg and −0.4 kg, respectively, P = 0.67) or body fat (+0.9% and +1.3%, respectively, P = 0.53). Lean body mass, waist circumference and waist-to-hip ratio remained essentially unchanged. Sensitivity analyses were consistent with the findings of primary analysis. Conclusion: Our findings indicate that walnuts can be incorporated into the daily diet of healthy elders without concern for adverse effects on body weight or body composition.

The use of pain relief during castration and dehorning of calves on commercial beef operations can be limited by constraints associated with the delivery of analgesic agents. As topical anaesthetic (TA) and buccal meloxicam (MEL) are now available in Australia, offering practical analgesic treatments for concurrent castration and dehorning of beef calves, a study was conducted to determine their efficacy in providing pain relief when applied alone or in combination. Weaner calves were randomly allocated to; (1) no castration and dehorning / positive control (CONP); (2) castration and dehorning / negative control (CONN); (3) castration and dehorning with buccal meloxicam (BM); (4) castration and dehorning with topical anaesthetic (TA); and (5) castration and dehorning with buccal meloxicam and topical anaesthetic (BMTA). Weight gain, paddock utilisation, lying activity and behaviour following treatment were measured. CONP and BMTA calves had significantly greater weight gain than CONN calves (P < 0.001). CONN calves spent less time lying compared to BMTA calves on all days (P < 0.001). All dehorned and castrated calves spent more time walking (P = 0.024) and less time eating (P < 0.001) compared to CONP calves. There was a trend for CONP calves to spend the most time standing and CONN calves to spend the least time standing (P = 0.059). There were also trends for the frequency of head turns to be lowest in CONP and BMTA calves (P = 0.098) and tail flicks to be highest in CONN and BM calves (P = 0.061). The findings of this study suggest that TA and MEL can improve welfare and production of calves following surgical castration and amputation dehorning.

The conventional method used for calculating pavement condition index (PCI) has two major drawbacks: safety problems during pavement inspection, and human error. This paper proposes a method for removing these problems. The proposed method uses surface deflection data in falling weight Deflectometer test to estimate PCI. The data used in this study were derived from 236 pavement segments taken from Tehran-Qom freeway in Iran. The data set was analyzed using multi layers perceptron (MLP) and radial basis function (RBF) neural networks. These neural networks were optimized by levenberg-marquardt (MLP-LM), scaled conjugate gradient (MLP-SCG), imperialist competitive (RBF-ICA), and genetic (RBF-GA) algorithms. After initial modeling with four neural networks mentioned, the committee machine intelligent systems (CMIS) method was adopted to combine the results and improve the accuracy of the modeling. The results of analysis have been verified by the four criteria of average percent relative error (APRE), average absolute percent relative error (AAPRE), root mean square error (RMSE) and standard error (SD). The best reported results belonged to CMIS, including APRE=2.3303, AAPRE=11.6768, RMSE=12.0056, and SD=0.0210.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

The COVID-19 pandemic starting in the first half of 2020 has changed the lives of everyone across the world. Reduced mobility was essential due to it being the largest impact possible against the spread of the little understood SARS-CoV-2 virus. To understand the spread, a comprehension of human mobility patterns is needed. The use of mobility data in modelling is thus essential to capture the intrinsic spread through the population. It is necessary to determine to what extent mobility data convey the same message of mobility within a region. This paper compares different mobility data sources by constructing spatial weight matrices and further compares the results through hierarchical clustering. This provides insight for the user into which data provides what type of information and in what situations a particular source is most useful.

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 hours, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which - through metabolic, cellular and circadian mechanisms - lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischaemic stroke, autism spectrum disorder and mood- and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Also, variations in fasting patterns, total caloric intake and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and Randomized Clinical Trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

Empirical equations representing, interpolating and smoothing groups of measurement results by regression methods are in widespread use in metrology and other fields of science and engineering. Standard equations for the propagation of measurement uncertainties to values computed from such equations are available but suffer from a lack of general acceptance and are only infrequently applied in practice. One reason for the slow uptake is the lack of clear methods to account for systematic error. In this paper, uncertainty propagation equations in terms of covariance matrices are generalized to allow for systematic errors in least-squares regression, and effects of the resulting uncertainties are investigated analytically. A stochastic ensemble model of systematic error is proposed for the computation of the non-diagonal elements of the weight matrix of the Generalized Least-Squares method (GLS) from the measurement uncertainty. A GLS projector formalism is described which separates the effects of measurement scatter on values calculated by the equation from those on the related “residuals”, i.e., the residual errors in the fitted data. The same projectors act similarly on the associated uncertainties and covariance matrices and permit the effects of systematic errors on the simulation covariance to be quantified. It is demonstrated that, in order to include systematic errors in the uncertainty estimates of GLS, covariance matrices may be substituted by novel, specifically defined dispersion matrices that are not specified yet by the GUM[1]. Systematic measurement errors may be estimated from various sources; a particularly easy way suggested here involves analyzing the structure in the regression residuals. It is demonstrated that GLS projectors exhibit inherent features of “error blindness” also with respect to systematic errors. [1] GUM: Guide to the Expression of Uncertainty in Measurement, http://www.bipm.org/en/publications/guides

Machine Learning (ML) approaches have been fruitfully applied to several classification problems of neurophysiological activity. Considering the relevance of emotion in human cognition and behaviour, ML found an important application field in emotion identification based on neurophysiological activity. Nonetheless, the literature results present a high variability depending on the neuronal activity measurement, the signal features and the classifier type. The present work aims to provide new methodological insight on ML applied to emotion identification based on electrophysiological brain activity. For this reason, we recorded EEG activity while emotional stimuli, high and low arousal (auditory and visual) were provided to a group of healthy participants. Our target signal to classify was the pre-stimulus onset brain activity. Classification performance of three different classifiers (LDA, SVM and kNN) was compared using both spectral and temporal features. Furthermore, we also contrasted the classifiers performance with static and dynamic (time evolving) features. The results show a clear increased in classification accuracy with temporal dynamic features. In particular, the SVM classifiers with temporal features showed the best accuracy (63.8 %) in classifying high vs. low arousal auditory stimuli.

This study explored intraindividual multidimensional profiles integrating psychosocial factors, namely, body image and satisfaction, weight-related self-stigma, positivity, and happiness, and behavioural-lifestyle factors, namely, adherence to a healthy diet, among Spanish adults with overweight or obesity. We further aimed to investigate the association of excess weight (i.e., measured body mass index, BMI) with the abovementioned multidimensional configurations. A convenience sample of adult individuals with excessive weight completed self-reports regarding the study variables, and their weight and height were measured. With a perspective centred on the individual, a cluster analysis established three distinct intraindividual psychosocial and diet-related profiles: a group of healthy individuals with excess weight; a group of individuals who were negatively affected by their excessive weight and showed the most distressed profile; and a group of dysfunctional individuals who seemed to be excessively unrealistic and optimistic regarding their excessive weight and unhealthy lifestyles. Furthermore, individuals in the affected cluster had higher obesity. The results showed that there are specific psychosocial and lifestyle profiles in the adult population with excess weight and that there are relationships among psychological, behavioural, and body-composition factors. For clinical application purposes, it is important to account for the heterogeneity within individuals who are obese.

The workplace is an ideal setting for health promotion. The regular medical examination of workers enables us to screen for numerous diseases, spread good practices and correct lifestyles, and obtain a favourable risk/benefit ratio. The continuous monitoring of the level of workers' wellbeing using a holistic approach that goes beyond the simple prevention of occupational risks enables us to promptly identify problems in work organization and the company climate. Problems of this kind can be adequately managed by using a participatory approach. In this study participatory ergonomics groups were used to improve occupational life in a small company. After intervention we observed a reduction in levels of perceived occupational stress measured with the effort / reward imbalance model, and an improvement in psychological wellbeing assessed by means of the Goldberg anxiety / depression scale. Although the limited size of the sample calls for a cautious evaluation of this study, the GEP© strategy proved to be a useful tool due to its cost-effectiveness.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

Fetal weight estimation before delivery is important in obstetrics, which assists doctors diagnose abnormal or diseased cases. Linear regression based on ultrasound measures such as bi-parietal diameter (bpd), head circumference (hc), abdominal circumference (ac), and fetal length (fl) is common statistical method for weight estimation but the regression model requires that time points of collecting such measures must not be too far from last ultrasound scans. Therefore this research proposes a method of early weight estimation based on expectation maximization (EM) algorithm so that ultrasound measures can be taken at any time points in gestational period. In other words, gestational sample can lack some or many fetus weights, which gives facilities to practitioners because practitioners need not concern fetus weights when taking ultrasound examinations. The proposed method is called dual regression expectation maximization (DREM) algorithm. Experimental results indicate that accuracy of DREM decreases insignificantly when completion of ultrasound sample decreases significantly. So it is proved that DREM withstands missing values in incomplete sample or sparse sample.

In this study was found that these cancers were attributable to risk factors such as cigarette smoking, second-hand smoke, alcohol intake, excess body weight, diet, and six cancer-associated infections. Several databases were reviewed including PUBMED, Google scholar, and Web of Science. The facts suggest that a number of individuals present risk factors for cancer, which can be modifiable.

By combing continuum topology optimization (TO) method and lattice structure technique, a sandwich aircraft spoiler with a high stiffness-to-weight is designed. TO method is served to produce the shell of the aircraft spoiler and the lattice structure, used as cores, is employed to support the shell. TO problem is established as maximizing the stiffness of the structure with limited material volume. Density-based method is utilized to achieve a 0/1 solution. We then empirically replace the core of the aircraft spoiler by using 3D kagome lattice structure. Two different materials, i.e., aluminum alloy and titanium alloy, are synthetically applied to further reduce the weight and simultaneously improve the strength of the aircraft spoiler. Numerical simulations are conducted to show that the designed aircraft spoiler can meet the service environment with a reduction of its weight by approximately 80% when compared with that of the initial design model. Finally, we have fabricated the designed model with photosensitive resin by using 3D printing technique.

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4⁺ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

This paper examines interlinkages and hedging opportunities between nine major cryptocurrencies for the period between 30 September 2015 and 4 June 2020, which notably includes the coronavirus disease 2019 (COVID-19) outbreak lasting from early 2020 through the end of the sample period. The results of dynamic conditional correlation (DCC) analysis using a minimum connectedness approach show a high degree of correlation between cryptocurrencies throughout the sample period. However, the correlations reach their minimum values during the COVID-19 pandemic, which indicates that cryptocurrencies acted as a hedge or safe haven during the stressful period of the COVID-19 pandemic. The weight of cryptocurrencies was significantly reduced and their hedging effectiveness varied greatly during the pandemic, which indicates that investors’ preferences changed during the COVID-19 period.

As a result of the cancer immunotherapy revolution hundreds of clinical trials of the newly approved immunotherapies are now under way to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by blockade of co-inhibitory signals. While success stories of terminal cancer patients achieving complete remissions are accumulating, not enough research has been done into the risks of the new therapies. Since the use of immunotherapy is becoming more common, and is expected to develop into first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the nemesis of immunotherapy. Immune-related adverse events (IrAEs) could affect any tissue, their incidence may reach up to 90% of patients and toxicity is dose-dependent. While the combination of two immune checkpoint inhibitors (ICIs) increased efficacy, the incidence of severe adverse events was also increased. Apparently, ICIs cannot be restricted to the targeted anti-tumor T cell population. The long lasting objective of cancer regression can only be achieved by paying a price: tolerance to healthy self tissues is compromised. In the face of an ipilimumab induced pan-lymphocytic activation, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune suppressive treatments, but instead harnessing the autoimmune forces by an off label low-dose combined anti-CTLA-4 and anti-PD1 antibody blockade, which is supplemented with conventional interleukin-2 stimulation and hyperthermia. The proof-of-principle of the low-dose-combination therapy was demonstrated in a heavily pre-treated triple negative breast cancer (TNBC) patient with far advanced pulmonary metastases and severe shortness of breath, who had exhausted all conventional treatment. Her pulmonary metastases went into complete remission with transient WHO I-II diarrhea and skin rash. She lived for 27 months after starting the low-dose-combination therapy. She had recurrence as a sternal mass and pleural metastases up to 3 cm. Since the low-dose-combination protocol consists only of approved drugs and treatments, this exceptional response should instigate further research efforts.

High temperature (HT) significantly affects the crop physiological traits and reduces the 12 productivity in plants. To increase yields as well as survival of crops under HT, developing heat13 tolerant plants is one of the main targets in crop breeding programs. The present study attempted 14 to investigate the linkage of the heat tolerance between the seedling and the reproductive growth 15 stages of tomato cultivars ’Dafnis‘ and ’Minichal’. This research was undertaken to evaluate heat 16 tolerance under two experimental designs such as screening at seedling stage and screening from 17 reproductive traits in greenhouses. Survival rate and physiological responses in seedlings of 18 tomatoes with 4-5 true leaf were estimated under HT (40 °C, RH 70%, day/night, respectively) and 19 under two control and HT greenhouse conditions (day time 28 °C and 40 °C, respectively). Heat 20 stress significantly affected physiological-chemical (photosynthesis, electrolyte conductivity, 21 proline) and vegetative parameters (plant height, shoot fresh weight, root fresh weight) in all 22 tomatoes seedlings. The finding revealed that regardless of tomato cultivars the photosynthesis, 23 chlorophyll, total proline and electrical conductivity parameters were varied in seedlings during the 24 heat stress period. The heat tolerance rate of tomatoes in the seedling stage might not be associated 25 always with reproductive parameters. HT reduced the fruit parameters likeas fruit weight (31.9%), 26 fruit length (14.1%), fruit diameter (19.1%) and fruit hardness (9.1%) in compared to NT under HT 27 in heat susceptible tomato cultivar ‘Dafnis’, while in heat tolerant cultivar ‘Minichal’ fruit length 28 (7.1%) and fruit diameter (12.1%) was decreased by the affect of HT but on the contrary fruit weight 29 (3.6%) and fruit hardness (8.3%) were increased. In conclusion, screening and selection for tomatoes 30 should be evaluated at the vegetative and reproductive stages with consideration of reproductive 31 parameters.

Apathy is a fundamental neuropsychiatric symptom of Korsakoff’s syndrome (KS) and has also been reported in patients with alcohol use disorder with no (AUD) or less severe cognitive disorders (ALC). However, research on the nature of apathy is limited in these groups. Aim of this study was to examine the multidimensional nature of apathy in patients with KS, ALC and AUD. Moreover, we examined differences between apathy ratings by patients and their professional caregivers, and related apathy to everyday functioning and overall cognition. Twenty-four patients with KS, 24 patients with ALC and 21 patients with AUD participated in this study. Apathy was measured using the Apathy Motivation Index (AMI), which distinguishes behavioral, emotional and social apathy. Both patients and professional caregivers reported social apathy as most prominent symptom, compared to behavioral and emotional apathy. Apathy ratings did not differ across the three patient groups. Discrepancies between patient and caregiver ratings were observed in patients with KS and ALC, with more severe apathy reported by caregivers. Caregiver-reported behavioral and social, but not emotional, apathy was related to everyday functioning. These results show that apathy is present in a substantial proportion of patients with alcohol addiction with or without cognitive impairments.

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.

Recent evidence suggests that among behavioral-lifestyle factors, adherence to a healthy dietary pattern such as the Mediterranean Diet (MedDiet) is linked not only to better psychological health and mental positive status but also to increased subjective well-being (SWB). Nevertheless, this association has been unexplored among individuals with excessive weight. This study explored whether adherence to the MedDiet and the intake of healthy foods such as fruits and vegetables (FV) are associated with increased happiness and life satisfaction among Spanish adults with overweight or obesity when weight, body image, and body satisfaction are also considered. A convenience sample of adult individuals with excessive weight completed self-reports on the study variables, and weight and BMI were measured by bioimpedance. No evidence of a relationship with SWB indicators was obtained for MedDiet global indicators, probably due to the low adherence to a healthy diet by these individuals. In contrast, FV intake, as a powerful indicator of healthy eating, was associated with life satisfaction when BMI and body image dimensions were considered, among which body satisfaction also had a key role. Moreover, life satisfaction fully mediated the relationship between FV consumption and happiness. Our findings are expected to make a relevant contribution to knowledge on the positive correlates or protective factors for overall well-being in obesity, including dietary habits and body appreciation. Our results may inform obesity management actions focused on inclusive, positive aesthetic models and promoting a healthy lifestyle for happiness in obesity.

Levan is a fructan-type exopolysaccharide, which is produced by many microbes from sucrose via extracellular levansucrases. The hydrocolloid properties of levan depend on its molecular weight, while it is unknown why and to which extent levan is functionally diverse in dependence of its size. The aim of our study was to get deeper insights into the size-dependent, functional variability of levan. For this purpose, levans of different sizes were produced using the water kefir isolate Gluconobacter albidus TMW 2.1191 and subsequently rheologically characterized. Three levan types could be identified, which are similarly branched, but significantly differ in their molecular size and rheological properties among each other. The smallest levan (< 107 Da) produced without adjustment of the pH exhibited Newton-like flow behavior up to a specific concentration of 25% (w/v). On the contrary, larger levans (> 108 Da) produced at pH ≥ 4.5 were shear-thinning and showed a gel like behavior at ≥ 5% (w/v). A third (intermediate) levan variant was obtained via production in buffers at pH 4.0 and exhibited the properties of a viscoelastic fluid at ≥ 5% (w/v). Our study reveals that the variable size and composition of levan are controllable and more decisive for its functionality than the amount of exerted levan.

Dietary approach is essential to obesity control, but the effectiveness of changes in meal frequency (MF) as strategies for loss and maintenance of body mass remain unclear. This study aimed to evaluate the influence of MF on a hypocaloric diet on weight loss, active ghrelin levels and metabolic indicators of women with obesity. This is a randomized, parallel clinical trial, including forty women, randomized in two groups, both following a hypocaloric diet, according to MF (G1 – six meals/day; G2 – three meals/day). Dietary, laboratory, anthropometric and body composition indicators were assessed, as well as energy expenditure (EE), before and after the 90 days of intervention. After intervention, both groups decreased body weight, body mass index (BMI), waist circumference, fat mass (FM), insulin and HOMA-IR. G1 increased insulin sensitivity and G2 reduced triglyceride and FM and increased fat-free mass (FFM). MF increased ghrelin levels. There were no differences in EE variables. Hypocaloric diet with different MF promoted a reduction in total weight, BMI, WC and FM and an improvement in glycidic metabolism. However, the accomplishment of the three meals/day increased the FFM and active ghrelin and reduced triglyceride, while six meals/day was more beneficial in increasing insulin sensitivity.

This study explored intraindividual multidimensional profiles integrating psychosocial factors, namely, body image and satisfaction, weight-related self-stigma, positivity, and happiness, and behavioural-lifestyle factors, namely, adherence to a healthy diet, among Spanish adults with overweight or obesity. We further aimed to investigate the association of excess weight (i.e., measured body mass index, BMI) with the abovementioned multidimensional configurations. A convenience sample of adult individuals with excessive weight completed self-reports regarding the study variables, and their weight and height were measured. With a perspective centered on the individual, a cluster analysis established three distinct intraindividual psychosocial and diet-related profiles: a group of healthy individuals with excess weight; a group of individuals who were negatively affected by their excessive weight and showed the most distressed profile; and a group of dysfunctional individuals who seemed to be excessively unrealistic and optimistic regarding their excessive weight and unhealthy lifestyles. Furthermore, individuals in the affected cluster had higher obesity. The results showed that there are specific psychosocial and lifestyle profiles in the adult population with excess weight and that there are relationships among psychological, behavioural, and body-composition factors. For clinical application purposes, it is important to account for the heterogeneity within individuals who are obese and to individualize the interventions, with a focus from weight change to individual's overall well-being.

Failure of various weight-loss programs and long-term maintenance of favorable body composition in all kinds of people is high, since the majority go back to old dietary patterns. Many studies have documented the efficacy of a plant-based diet (PBD) for body mass management, but there are opinions that maintaining a PBD is difficult. We aimed to evaluate the long-term success of a whole-food plant-based (WFPB) lifestyle program. We investigated the differences in the obesity indices and lifestyle of 151 adults (39.6 ± SD 12.5 years), who were on our program for short (0.5–<2 years), medium (2–<5 years), or long term (5–10 years). Body-composition changes were favourable for all three groups, both genders and all participants. There were no differences in relative body-composition changes (BMI, body fat percentage and muscle mass index (MMI)) between the three groups. All participants improved their BMI (baseline mean pre-obesity BMI range (kg/m²): 26.4 ± 5.6 to normal 23.9 ± 3.8, p < 0.001), decreased body mass (–7.1 ± 8.3 kg, p < 0.001) and body fat percentage (–6.4 ± 5.6 % points, p < 0.001). Those with the highest BMI at baseline lost the most of: a) BMI units, b) total body mass and c) body fat (a) (kg/m²) (–5.6 ± SD 2.9, –2.4 ± 1.8 and –0.9 ± 1.5), b) (kg) (–16.1 ± SD 8.8, –7.1 ± 5.4 and –2.5 ± 4.5) and c) (% points) (–9.5 ± SD 5.7, –6.6 ± 4.6 and –4.7 ± 5.3) for participants who had baseline BMI in obese, overweight and normal range, respectively; p_{baseline vs. current} < 0.001 for all). 85.6% (101 out of 118) of parents of underage children (< 18 years), introduced WFPB lifestyle to their children. WFPB lifestyle program provides long-term lifestyle changes for reversal of obesity and is effective transferred to the next generation.

Healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence on the benefits of physical activity and other health-related behaviors in the early-stage CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from January 1st, 2009 to December 31st, 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan-Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64-0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06-1.95; p < 0.02) and 1.61 (95% CI: 1.44-1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD.

This study aimed to evaluate the impact of selected pregnancy pathologies statistically depending on overweight/obesity and excessive maternal weight gain during pregnancy on women who gave birth in the years 2013–2015 at the Second Department of Gynecology and Obstetrics at the University Hospital in Bratislava, Slovakia. In a retrospective study, we analyzed data gathered from the sample, which consisted of 7,122 women. Our results indicate a positive statistical dependency of the groups of women with overweight and obesity and gestational hypertension (adjusted odds ratio [AOR]=15.3; 95% CI 9.0−25.8 for obesity), preeclampsia (AOR=3.4; 95% CI 1.9−6.0 for overweight and AOR=13.2; 95% CI 7.7−22.5 for obesity), and gestational diabetes mellitus (AOR=1.9; 95% CI 1.2−2.9 for overweight and AOR=2.4; 95% CI 1.4−4.0 for obesity). A higher incidence of pregnancies terminated by cesarean section was observed in the group of obese women. Gestational weight gain above the IOM (the Institute of Medicine) recommendations was associated with a higher risk of pregnancy terminated by C-section (AOR=1.2; 95% CI 1.0−1.3), gestational hypertension (AOR=1.7; 95% CI 1.0−2.7), and infant macrosomia (AOR=1.7; 95% CI 1.3−2.1). Overweight and obesity during pregnancy significantly contribute to the development of pregnancy pathologies and increased incidence of cesarean section. Systematic efforts to reduce weight before pregnancy through pre-pregnancy dietary counseling, regular physical activity, and healthy lifestyle should be the primary goal.

Mastocytosis is characterized by pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. Yet, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we assessed N200 (conflict monitoring) and P300 (response inhibition, performance evaluation) event-related potentials (ERPs) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally interrogated the continuous spatio-temporal dynamics of N200- and P300-related activation within each group. Young adults had left hemisphere dominant N200, while older adults had overall larger amplitudes and right hemisphere dominance. N200 activation was biphasic in both groups but differed in scalp topography. P300 also differed, with larger right amplitudes in young, but bilateral amplitudes in old, with old larger than young in the left hemisphere. P300 was characterized by an early parieto-occipital peak in both groups, followed by a parietal slow wave only in older adults. A temporally similar but topographically different final wave followed in both groups that showed anterior recruitment in older adults. These findings illuminate differential age-related spatio-temporal recruitment patterns for conflict monitoring and response inhibition that are critically important for understanding age-related compensatory activation.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anticancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50kDa), medium (MMW, 50-100kDa) and high (HMW, >100kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had highest the levels of sugars, acids and sulphation among molecular weight fractions. There was a dose dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in sub G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress induced apoptosis-like cell death for F. vesiculosus fucoidan but features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Accumulating evidences demonstrate that the host genome's epigenetic modificationsare essential for living organisms to adapt extreme conditions.DNA methylation, covalent modifications of histone, andinter-association of non-coding RNAs facilitate the cellular manifestation ofepigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, miRNA (microRNA) and LncRNA (Long non-coding RNA) are new generationnon-coding molecules that influence a variety of cellular processes like immunity, cellular differentiation, and tumor development. During tumor development, temporal changes in miRNA/LncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signalling in the host. At the cellular level, this is manifested by the up-regulation of Inflammasome and inflammatory pathways, which promotes cancer-related inflammation. In view of this, we discuss the potential of lncRNA and miRNA directed interventions in regulating inflammation and tumor development in the host.

This study aims to develop a performance evaluation system that can facilitate performance evaluation at region, hospital, and department levels to enable better cost management for sustainable development. A multi-level system of performance evaluation informs a hierarchical assessment of cost management from regions to hospitals to departments using diagnosis-related group (DRGs). Various metrics are developed employing the variances between targets and actuals where targets are determined from two perspectives: benchmarking using external regional prices and change management using internal data. Targets for the latter are statistically based and specifically incorporate variability. The model is applied to two hospitals, twenty departments, nine DRGs and 1071 inpatients. The analyses indicate that the approach can provide a practical evaluation tool that allows for particular characteristics at multiple levels. The system provides macro-micro and external-internal perspectives in performance, enabling high-level variances to be decomposed thereby identifying sources of performance variability and financial impact.

As Automated Driving Systems (ADS) technology gets assimilated into the market, the driver’s obligation will be changed to a supervisory role. A key point to consider is the driver’s engagement in the secondary task to maintain the driver/user in the control loop. The paper’s objective is to monitor driver engagement with a game and identify any impacts the task has on hazard recognition. We designed a driving simulation using Unity3D and incorporated three tasks: No-task, AR-Video, and AR-Game tasks. The driver engaged in an AR object interception game while monitoring the road for threatening road scenarios. From the results, there was less than 1 second difference between the means of gaming task (mean = 2.55s, std = 0.1002s) to no-task (mean = 2.55s, std = 0.1002s). Game scoring followed three profiles/phases: learning, saturation, and decline profile. From the profiles, it is possible to quantify/infer drivers’ engagement with the game task. The paper proposes alternative monitoring that has utility, i.e., entertaining the user. Further experiments AR-Game focusing on real-world car environment will be performed to confirm the performance following the recommendations derived from the current test.

Introduction: In general, everyone believes that the smallest preterm infants should achieve normal intrauterine growth rates, but many thinks that this is not possible with current nutrition guidelines. There is resistance to giving enough nutrition for fear of "toxicity". The difference in weight Z-score between birth and a corrected gestational age (CGA) at discharge is assess in postnatal growth in our unit. Material and methods: An observational study was done between January 2018 and December 2020 where all cases that had ≤ 29 weeks of GA at birth and survived to 36 weeks corrected GA or that were discharged home. An aggressive nutrition protocol including parenteral as well as enteral nutrition was followed. Patients and their weight trajectory was plotted on the Fenton 2013 growth curve. The patients who had had a smaller WZP difference were also plotted. Results: A total of 32 cases were found. The median change in Z-score between birth and discharge of the whole group was -0.52 (IQR 0.53). Six of 32 (19%) had a more than one WZP, all of whom had severe pathologies. The median decline in Z score for this group with poor growth was 1.24 (IQR 0.22). There were 26 cases with a < 1 WZP (81%) and a median Z score fall of 0.39 (IQR 0.55). No important complications secondary to the ingested volumes or parenteral nutrition were reported. Conclusion: The group of cases with a > 1 WZP drop had severe pathologies. All the other cases had adequate growth parallel to normal weight growth charts and a few cases had some catch-up growth. The study showed that it is possible for many preterm infants to achieve normal intrauterine growth rates if they are given enough nutrition, but bigger multicenter studies are needed to confirm these findings.

The use of New-age (Nano) Modified Emulsions (NME) for the stabilisation of marginal materials for use in the upper-pavement layers of roads have been proven in laboratories, through Accelerated Pavement Tests (APT) and in practice. In addition, material design methods have been developed based on the scientific analysis of granular material mineralogy and the chemical interaction with the binder to design a material compatible NME stabilising agent for naturally available (often marginal) materials. However, the introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology enables the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In practice, few road construction projects are without any problems. The introduction of new-technologies obviously makes it an easy target to blame for any non-related problem that may arise during construction. This article aims to assist in pre-empting, recognising, preventing and resolving material or non-material related construction problems through the correct identification of the cause of the problem and recommending the best, most cost-effective way to correct any deficiencies on site.

Background: Identification of cancer biomarkers that are differentially expressed (DE) under two biological conditions is an important task in many microarray studies. There exist several methods in the literature in this regards and most of these methods designed especially for unpaired samples, which does not satisfy the requirements of paired samples where the gene expressions are taken from the same patients before and after treatment. Furthermore, the traditional biomarker identification methods based on either p-values or fold change (FC) values. However, sometimes, p-value based results do not comply with FC based results due to the smaller variance of gene expressions. There are some methods that combine both p-values and FC values to solve this problem. But, these methods also show weak performance for small-sample case in presence of outlying expressions. To overcome this problem, in this paper an attempt is made to develop a hybrid robust SAM-FC approach by combining rank of FC values and rank of p-values based on SAM statistic using minimum β-divergence method, which is designed for paired samples. This method introduces a weight function known as β-weight function. This weight function produces larger weights corresponding to usual/normal expressions and smaller weights for unusual/outlying expressions. The β-weight function plays the significant role on the performance of the proposed method. Results: The proposed method uses β-weight function as a measure of outlier detection by setting β=0.2. We unify both classical and robust estimates using β-weight function such that maximum likelihood estimators (MLEs) are used in absence of outliers and minimum β-divergence estimators are used in presence of outliers to obtain reasonable p-values and FC values in the proposed method. We examined the performance of proposed method in a comparison of some popular methods (t-test, SAM, LIMMA, Wilcoxon, WAD, RP and FCROS) using both simulated and real gene expression profiles for both small-and large-sample cases. From the simulation and a real spike in data analysis results we observed that the proposed method outperforms other methods for small-sample case in presence of outliers and it keeps almost equal performance with other robust methods (Wilcoxon, RP and FCROS) otherwise. From a head-and-neck cancer (HNC) dataset the proposed method identified 2 genes (CYP3A4, NOVA1) that are significantly enriched in linoleic acid metabolism, drug metabolism, steroid hormone biosynthesis and metabolic pathways. The survival analysis through Kaplan-Meier curve revealed that combined effect of these 2 genes has prognostic capability and they might be promising biomarker of HNC. Moreover, we retrieved the 12 candidate drugs based on gene interaction from glad4u and drug bank databases. Conclusion The identified drugs showed statistical significance and critical role of the proteins indicate that these proteins might be therapeutic target in cancer. Thus, elucidating the associations between the drugs identified in the present study require further investigations.

Changes in food preferences after bariatric surgery may alter its effectiveness as a treatment for obesity. We aimed to compare food reward for a comprehensive variety of food categories between patients who received a sleeve gastrectomy (SG) or a Roux-en-Y gastric bypass (RYGB) and to explore whether food reward differs according to weight loss. In this cross-sectional exploratory study, food reward was assessed using the Leeds Food Preference Questionnaire (LFPQ). We assessed liking and wanting of eleven food categories. Comparisons were done regarding type of surgery and Total Weight Loss (TWL; based on tercile distribution). Fifty-six patients (30 SG and 26 RYGB) were included (women: 70%; age: 44.0 (11.1) y). Regarding the type of surgery, scores were not significantly different between SG and RYGB, except for ‘non-dairy products – without color’ explicit liking (p = 0.04). Regarding TWL outcomes, explicit liking, explicit wanting and implicit wanting, scores were significantly higher for Good responders than Low responders for ‘No meat – High fat’ (post-hoc corrected p-value: 0.04, 0.03 and 0.04, respectively). Together, our results failed to identify major differences in liking and wanting regarding the type of surgery and tended to indicate that higher weight loss might be related to a higher reward for high protein-content food. Rather to focus only on palatable foods, future studies should also consider a broader range of food items, including protein reward.

Dehydrolutein accumulates in substantial concentrations in the retina. The aim of this study was to compare antioxidant properties of dehydrolutein with other retinal carotenoids, lutein and zeaxanthin, and their effects on ARPE-19 cells. The time-resolved detection of characteristic singlet oxygen phosphorescence was used to compare the singlet oxygen quenching rate constants of dehydrolutein, lutein, and zeaxanthin. The effects of these carotenoids on photosensitized oxidation were tested in liposomes, where photooxidation was induced by light in the presence of photosensitizers, and monitored by oximetry. To compare the uptake of dehydrolutein, lutein, and zeaxanthin, ARPE-19 cells were incubated with carotenoids for up to 19 days, and carotenoid contents were determined by spectrophotometry in cell extracts. To investigate the effects of carotenoids on phototocytotoxicity, cells were exposed to light in the presence of rose bengal or all-trans-retinal. The results demonstrate that the rate constants for singlet oxygen quenching are 0.77x1010, 0.55x1010, and 1.23x1010 M-1s-1 for dehydrolutein, lutein and zeaxanthin, respectively. Overall, dehydrolutein is similar to lutein or zeaxanthin in protection of lipids against photosensitized oxidation. ARPE-19 cells accumulate substantial amounts of both zeaxanthin and lutein but no detectable amounts of dehydrolutein. Cells pre-incubated with carotenoids are equally susceptible to photosensitized damage as cells without carotenoids. Carotenoids provided to cells together with the extracellular photosensitizers offer partial protection against photodamage. In conclusion, the antioxidant properties of dehydrolutein are similar to lutein and zeaxanthin. The mechanism responsible for its lack of accumulation in ARPE-19 cells deserves further investigation.

TThe passion of bodybuilding athletes for a symmetric, lean, heavily muscled body leads them to carry out exhausting exercise programs and restrictive eating regimens, sometimes resulting in disordered eating behaviors. This study investigates potential exacerbators on the development of disordered eating in bodybuilding and strength athletes. The study involved 103 Cypriot bodybuilding athletes of both sexes, performing at three levels: professional, recreational and strength athletes. The Eating Attitude Test 26 (EAT-26) and The Three Factor Eating Question-naire (TFEQ-R21) were used to evaluate disordered eating and eating behaviors respectively. The current study was performed under the auspices of the Hellenic Center of Education & Treatment of Eating Disorders (KEADD). The degree of deviation between the perceived ideal body weight and the actual body weight was associated with increased risk of eating disorder. Athletes who desired a lower body weight recorded higher scores on EAT-26 overall, (p=0.001), and the subscales of dieting (p=0.01) and bulimia. (p=0.001). Cognitive restraint and emotional eating scales of TFEQ-R21 were more pronounced in the non-professional athletes. (p=0.01). The emotional eating score was higher in women. There is a need for appropriate sport-specific, gender-specific preventive intervention to deescalate the risk of eating disorder, in both profes-sional and non-professional bodybuilding athletes.

We do fuzzification the concept of domination in crisp graph by using membership values of nodes, $\alpha$-strong arcs and arcs. In this paper, we introduce a new variation on the domination theme which we call vertex domination. We determine the vertex domination number $\gamma_v$ for several classes of fuzzy graphs, specially complete fuzzy graph and complete bipartite fuzzy graphs. The bounds is obtained for the vertex domination number of fuzzy graphs. Also the relationship between $M$-strong arcs and $\alpha$-strong is obtained. In fuzzy graphs, monotone decreasing property and monotone increasing property is introduced. We prove the vizing's conjecture is monotone decreasing fuzzy graph property for vertex domination. we prove also the Grarier-Khelladi's conjecture is monotone decreasing fuzzy graph property for it. We obtain Nordhaus-Gaddum (NG) type results for these parameters. The relationship between several classes of operations on fuzzy graphs with the vertex domination number of them is studied.

In order to solve the labor-intensive and time-consuming problem in the process of measuring yak body ruler and weight in yak breeding industry in Qinghai Province, a non-contact method for measuring yak body ruler and weight was proposed in this experiment, and key technologies based on semantic segmentation, binocular ranging and neural network algorithm were studied to boost the development of yak breeding industry in Qinghai Province. Main conclusions: (1) Study yak foreground image extraction, and implement yak foreground image extraction model based on U-net algorithm; select 2263 yak images for experiment, and verify that the accuracy of the model in yak image extraction is over 97%. (2) Develop an algorithm for estimating yak body ruler based on binocular vision, and use the extraction algorithm of yak body ruler related measurement points combined with depth image to estimate yak body ruler. The final test shows that the average estimation error of body height and body oblique length is 2.6%, and the average estimation error of chest depth is 5.94%. (3) Study the yak weight prediction model; select the body height, body oblique length and chest depth obtained by binocular vision to estimate the yak weight; use two algorithms to establish the yak weight prediction model, and verify that the average estimation error of the model for yak weight is 10.7% and 13.01% respectively.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Waterbomb structures are origami-inspired deformable structural components used in new types of robots. They have a unique radially deployable ability that enables robots to better adapt to their environment. In this paper, we propose a series of new waterbomb structures with square, rectangle, and parallelogram base units. Through quasi-static axial and radial compression experiments and numerical simulations, we prove that the parallelogram waterbomb structure has a twist displacement mode along the axial direction. Compared with the square waterbomb structure, the proposed optimal design of the parallelogram waterbomb structure reduces the critical axial buckling load-to-weight ratio by 55.4% and increases the radial stiffness-to-weight ratio by 67.6%. The significant increase in the radial stiffness-to-weight ratio of the waterbomb structure and decrease in the critical axial buckling load-to-weight ratio make the proposed origami pattern attractive for practical robotics applications.

Tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC), but high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed grade 4 cholestasis during combined therapy with nivolumab and cabozantinib. After the exclusion of common disorders associated with choles-tasis and a failure of corticosteroids (CS), a liver biopsy was performed that demonstrated severe ductopenia. Consequently, a diagnosis of vanishing bile duct syndrome related to TKI and ICI administration was made, resulting in CS discontinuation and ursodeoxycholic acid administra-tion. After a 7-months follow-up, liver tests had returned to normal values. Immunological studies revealed that our patient had developed robust T-cells and macrophages infiltrates in his lung metastasis, as well as in skin and liver tissues at the onset of toxicities. At the same time, peripheral blood immunophenotyping revealed significant changes in T-cell subsets suggesting their potential role in the pathophysiology of the disease.

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53-/- cells are insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis is promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulting in endoplasmic reticulum (ER) stress-mediated DR5 expression, which is upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with TRAIL synergistically enhanced I3M-induced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53-/- cells were resistant to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells.

The use of whole-body vibration (WBV) for therapeutic purposes is far from being standardized and only very recently an empirical foundation for reporting guidelines for human WBV studies has been published. Controversies about safety and therapeutic dosage stll exist. The present study aimed to investigate the metabolic and mechanical effects of low-intensity WBV in according to the ISO 2631 norm on subjects with obesity. 41 obese subjects (BMI≥ 35 kg/mˆ2) were recruited to participate in a 3-week multidisciplinary inpatient rehabilitation program including fitness training and WBV training. During WBV the posture was monitored with an optoelectronic system with 6 infrared cameras (Vicon, Vicon Motion System, Oxford, UK). The primary endpoints were: variation in body composition, factors of the metabolic syndrome, functional activity (sit-to-stand and 6-min walking test), muscle strength, and quality of life. Secondary endpoints were: modification of irisin, testosterone, growth hormone, IGF1 levels. We observed significant changes in salivary irisin levels, Group 2 (p&lt;0.01) as compared to the control group, while muscle strength, function, and other metabolic and hormonal factors did not change after a 3-week low-intensity WBV training respect control group. Future studies are needed to deeper investigate the potential metabolic effect of low-intensity WBV in managing weight.

Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. This paper provides deep insight into immune related adverse events (irAEs) posing a major challenge and drawback to ICIT, and presents right management strategies for very complex complications. Moreover, for the first time in literature, a non-linear mathematical model is introduced to measure the ICIT success rate and to decide about the optimum ICIT duration. Furthermore, a strategy is presented to overcome or to delay the progression after initial good response in a subset of patients.

This paper introduces the spatial component in cross-section econometric estimations and specifically, the spatial dependence effect inherent in some of the variables involved in the modelling process. First, the spatial structure of the data from thematic maps is observed and Moran's spatial autocorrelation indicators are presented. Subsequently, the spatial weights matrix is built under different specifications. Finally, several modelling specification strategies are shown and the interpretation of the estimated coefficients. The theoretical concepts are illustrated with examples and their corresponding R software codes. This code and databases are available in a freely accessible repository in the BE2SHARE-EUDAT platform so that they can be easily reproduced.

ABSTRACT Two years after first patients approached the emergency rooms of hospitals in Wuhan becouse of respiratory distress,thousend of SARS-CoV-2 infected persons continue to die every day worldwide.SARS-CoV-2-infected patients undergo a process of dehydration and malnutrition before they develop respiratory problems and approach the emergency room of a hospital.This is,in many cases, the consequence of high fever which causes massive loss of fluids. In addition loss of appetite, is responsible for the deficit of protein intake.Most of the virus-infected patients admitted to the emergency room are therefore hypovolemic and hypoproteinemic and suffer of respiratory distress accompanied by ground grass opacities at CT-scan of the lungs.Critically ill patients are treated following the guidelines for treatment of septic shock but with „conservative“ fluid replacement and administration of diuretics to assure sufficient hourly urine production. The combination of conservative fluid administration with reduced protein content in the enterally administered diet, together with administration of diuretics, has severe hemodynamic consequenses in mostly aged,dehydrated,critically ill patients. Many of them will develop acute kidney injury in the next 24 hours.In most of the cases, patients continue to loose weight by loosing skeletal muscle mass. Ischemic damage in the lung capillaries is responsible for the acute respiratory distreass syndrome (ARDS) and for the hallmark of autoptic findings,diffuse alveolar damage (DAD) characterized by hyaline membrane formation,fluid invasion of the alveoli recruitment of some inflammatory cells and progressive arrest of blood flow in the pulmonary vessels.The consequence is progressive congestion , increase of lung weight and progressive hypoxia (progressive severity of ARDS).Sequestration of blood in the lungs worsen hypovolemia and ischemia in different organs.This is most probably responsible for recruitment of inflammatory cells and for persistance of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autoptic studies have been performed mostly in patients who died in the ICU after SARS-CoV-2-infection because of progessive ARDS.In those patients, tubulus epithelium necrosis in the kidney is a frequent finding as it has been the case in the first SARS-CoV-1 pandemic.In the death certification charts, many times weeks after first symptoms have started ,cardiac arrest is the cause of death after respitatory insufficiency.Replacement therapy with sufficient amount of fluid and albumin should be part of the early individualized life-saving supportive measures avoiding mechanical ventilation.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

Purposely slow velocity resistance exercise (i.e., 10 s concentric and eccentric phases) is a popular training method, but limits the loads that can be lifted (e.g., <50% 1 RM). This study compared the biomechanical properties of purposely slow velocity (SLOW) and traditional resistance exercise (TRAD) that uses maximal lifting velocities. Healthy resistance-trained men (n=5) performed two testing sessions (barbell squat and bench press) in random-order; a SLOW session (1 set x 10 repetitions at 28% 1 RM, 10 s concentric & eccentric), and a TRAD session (3 x 10 at 70% 1 RM, controlled eccentric and maximal concentric). A force plate and linear position transducer were used to collect kinetic and kinematic data for every repetition of both protocols (α = 0.05). For both exercises, both concentric and eccentric mean force (N) and power (W) for each repetition was greater for TRAD. When the entire training session (squat + bench press) was examined, SLOW exhibited greater time under tension, while TRAD produced greater work (J) and impulse (N·s). Contrary to suggestions in both the lay and scientific literature, purposely slow resistance exercise produced less force, power, and work than traditional velocity resistance exercise.

The COVID-19 pandemic has had a significant impact on all facets of life and has exacerbated many challenges faced by people living with tuberculosis (TB). This study aimed to assess the health-related quality of life (HRQoL) of TB patients in Guinea during the COVID-19 pandemic. A mixed-methods study was conducted using two validated psychometric tools to assess HRQoL and qualitative interviews among TB patients enrolled in treatment at three centers in Conakry, Guinea. Multinomial logistic regression was used to identify factors associated with the deterioration of HRQoL. We included 439 participants in the study, among whom 44% and 31% experienced pain and anxiety, respectively. We found that an increase in the number of household members and the distance from participants’ residence to the health centre were significantly associated with lower HRQoL. Qualitative interviews highlighted nutritional and financial concerns which were exacerbated during COVID-19 pandemic and beliefs that the Guinean Government’s assistance plan was insufficient. This study supports the implementation of specific relief plans for TB patients which includes nutritional and psychological support, especially those whose movements are limited by travel restrictions, impeding access to TB care, reducing work opportunities and exacerbating financial needs and stress.

: This paper presents a couple of meal monitoring systems for senile dementia patients by using electronic weight and temperature sensors. These monitoring systems enable to convey the information of the amount of meal taken by the patients in real-time via wireless communication networks onto the mobile phones of their families or nurses in charge. Thereby, the nurses can easily spot the most desperate patient to take care of while the families can have relief to see the crucial information for survival of their parents at least three times a day. Meanwhile, the senile dementia patients tend to suffer the burn of their tongues because they can hardly recognize the temperature of hot meals served and therefore avoid the burn of tongues. This phenomenon can be discarded by utilizing the meal temperature monitoring system which displays alarm to the patients when the meal temperature is above the reference. These meal monitoring systems can be easily implemented by utilizing low-cost sensor chips and Arduino UNO boards so that elder-care hospitals and nursing homes can afford to exploit them with no additional cost. Hence, we believe that the proposed monitoring systems would be a potential solution to provide a great help and relief not only for the professional nursing nurses working in elder-care hospitals and nursing homes, but also for the families of the dementia patients.

Objectives: The aim of this study was to compare the performance of the EQ-5D-Y-3L (Y-3L) and the expanded five level version, the EQ-5D-Y-5L (Y-5L). Methods: Children/adolescents with an acute or chronic health condition and from the general population completed the Y-5L and Y-3L self-report questionnaires. Performance of the Y-5L and Y-3L was determined by comparing feasibility, redistribution of dimension responses, discriminatory power, validity, and test-retest reliability. Results. Five hundred and fifty children/adolescents completed baseline measures and 173 completed repeat measures. The ceiling effect decreased by 15% from the Y-3L to Y-5L. Informativity of dimensions improved by 0.094 on the Y-5L. There was a range of 4-9% inconsistent responses moving from the Y-3L to Y-5L. Convergent validity of the Visual Analogue Scale (VAS) and Y-3L, Y-5L dimensions was similar, weak to moderate (r_s range: 0.18 – 0.38) but similar and strong on paired Y-3L and Y-5L dimensions: Kendall Tau B (range 0.69 – 0.80) and Gamma (range 0.92 – 0.98). The Y-5L and Y-3L showed moderate to substantial agreement for test-retest reliability across dimensions and VAS scores in stable chronic health conditions and fair agreement for the general population. Conclusion: The EQ-5D-Y-5L is a valid, reliable extension of the Y-3L for children/adolescents across health conditions and healthy children/adolescents. The expanded levels reduced the ceiling effect. The relative informativity of report across dimensions increased on the Y-5L compared to the Y-3L with retention of the evenness of reporting. The convergent validity and test-retest reliability of the Y-5L was comparable to the Y-3L.

Attackers are perpetually modifying their tactics to avoid detection and frequently leverage legitimate credentials with trusted tools already deployed in a network environment, making it difficult for organizations to proactively identify critical security risks. Network traffic analysis products have emerged in response to attackers’ relentless innovation, offering organizations a realistic path forward for combatting creative attackers. Additionally, thanks to the widespread adoption of cloud computing, Device Operators (DevOps) processes, and the Internet of Things (IoT), maintaining effective network visibility has become a highly complex and overwhelming process. What makes network traffic analysis technology particularly meaningful is its ability to combine its core capabilities to deliver malicious intent detection. In this paper, we propose a novel darknet traffic analysis and network management framework to real-time automating the malicious intent detection process, using a weight agnostic neural networks architecture. It is an effective and accurate computational intelligent forensics tool for network traffic analysis, the demystification of malware traffic, and encrypted traffic identification in real-time. Based on Weight Agnostic Neural Networks (WANNs) methodology, we propose an automated searching neural net architectures strategy that can perform various tasks such as identify zero-day attacks. By automating the malicious intent detection process from the darknet, the advanced proposed solution is reducing the skills and effort barrier that prevents many organizations from effectively protecting their most critical assets.

Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from LMICs is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/d algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 X 2= 400 mg/d) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n=478 and placebo; n=479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo group for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p=0.54), length (47.3 ± 2.0 vs. 47.5 ±2.0 cm, p=0.13) or head circumference (33.7 ± 1.4 vs 33.8 ± 1.4 cm, p=0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p= 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400mg/d DHA did not impact the offspring birthweight, length or head circumference.