The identification of fetal cells in the blood and tissues of healthy mothers raised questions about the potential alloreactive origins of various diseases, such as autoimmunity, diabetes, arteriosclerosis, and cancer. However, the extent to which alloreactivity contributes to these diseases remains unverified. This study presents a basic mathematical disease model based on the genes’ origin and immunological interactions. This model, grounded in set theory, classifies these immunological interactions based on their intrinsic, extrinsic, and allogeneic nature. Therefore, this model offers an unexpected common theoretical foundation for understanding alloreactivity, genetic diseases, and infections. Furthermore, this model provides a valuable framework for scrutinizing the role of alloreactivity in health and disease.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

Globally, noncommunicable diseases (NCDs) were responsible for 41 million deaths in 2016, with the majority of these occurring in low and middle-income countries. These diseases were on the rise as a result of unhealthy, low-quality, and unbalanced diets, which resulted in overweight and obesity. The National School Nutrition Programme (NSNP) was created to regulate the foods sold to schoolchildren. To ascertain school management teams' perspectives on the relationship between the NSNP and the development of lifestyle diseases. A phenomenological qualitative study using Focus Group Discussions among 16 purposively selected members of the School Management Teams were conducted in Mt Frere, Eastern Cape in 2016. The narrative data was analyzed using Tesch's eight-phase thematic analysis approach. The data analysis revealed two themes (NSNP and the vendor system) and six sub-themes. The NSNP was viewed as making a significant contribution to children's food security, thereby improving academic output. However, reengineering of the NSNP was need through improved budgeting and inclusion of breakfast in the menu to control NCDs risk factors. The current implementation of the vendor system did not support reduction of NCDs risk factors. Improved implementation of the guide to vendor system is needed.

The prevalence of overweight/obesity in the adult population in the Philippines has doubled in the past 20 years. Zumba exercise has recently been implemented throughout the Philippines. However, there is scarce information on the effects of Zumba on obesity and Zumba participants’ characteristics in the Philippines. This study described the current practice of Zumba in the Philippines, along with the practitioners’ characteristics, and identified factors associated with Zumba participation. In this observational, cross-sectional study, a structured questionnaire was used to survey 10 Zumba locations in September 2019. Anthropometric measurements of participants were assessed. Respondents included 171 women (88.6%) and 22 men (11.4%), with a mean (±SD) age of 44.1 (± 8.9) years. All respondents answered that Zumba was enjoyable, and some answered “very enjoyable.” Determinants of frequent participation were as follows: being older than the mean age of participants, starting Zumba to enjoy dancing, starting Zumba not to lose weight, shopping mall location, and participation fee required. “To enjoy dance” being a motivation for Zumba practice was identified as a determinant of frequent participation, rather than “to lose weight.” The element of “enjoyable” may strongly influence continuation and frequent participation of Zumba exercise in the Philippines.

Past public health crises (e.g. tobacco, alcohol, opioids, cholera, HIV, lead, pollution, venereal disease, even COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCD’s) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation — addiction, toxicity, ubiquity, and externalities (how does your consumption affect me?). To its credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCD’s within their borders. This article also supplies scientific counters to food industry talking points, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

In the world, migraine is one of the most common cause of disability in adults. To date, there is no a single cause for this disorder, but rather a set of physio-pathogenic triggers, in combination with a genetic predisposition. Among factors related to the migraine onset, a crucial role seems to be played by gut dysbiosis. In fact, it has been demonstrated how the intestine is able to modulate the central nervous system activities, through the gut-brain axis, and how gut dysbiosis can influence neurological pathologies, including migraine attacks. In this contest, in addition to migraine conventional pharmacological treatments, attention has been paid to an adjuvant therapeutic strategy based on different nutritional approaches and lifestyle changes able to positively modulate the gut microbiota composition. In fact, the restoration of the balance between the different gut bacterial species, the reconstruction of the gut barrier integrity and the control of the release of gut-derived inflammatory neuropeptides, obtained through specific nutritional patterns and lifestyle changes, represent a possible beneficial additive therapy for many migraine subtypes. Herein, this review explores the bi-directional correlation between migraine and the main chronic non-communicable diseases, like diabetes mellitus, arterial hypertension, obesity, cancer and chronic kidney diseases, whose link is represented by gut dysbiosis.

A recent review of global vitamin C status indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here we provide a narrative of potential factors influencing vitamin C status. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use. Dietary intake can be influenced by cultural aspects such as staple foods and traditional cooking practices. Environmental factors can also affect vitamin C intake and status; these include geographic region, season and climate, as well as pollution. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various non-communicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time, therefore we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global recommended dietary intakes for vitamin C.

Climate change, recognized as a global crisis, is not only altering our environment but also significantly impacting human health. Particularly, its influence on non-communicable diseases (NCDs), a leading cause of global mortality, is becoming increasingly evident yet underexplored. This review aims to synthesize current research on the impact of climate change on NCDs, addressing a critical gap in our understanding of how environmental changes affect human health. We examine the complex interplay between climate change and NCDs, drawing insights from recent studies that highlight the adverse effects of climate variables on chronic diseases, such as cardiovascular and kidney diseases, and the role of food and nutrition security in this nexus. Furthermore, the review explores the disproportionate impact on vulnerable regions and populations, particularly in Pacific Island countries and territories, underscoring the urgent need for context-specific solutions and a cross-sectoral approach. By integrating findings from various disciplines, this review aims to inform policy and public health interventions, highlighting the necessity of collaborative efforts to mitigate the burgeoning burden of NCDs in a rapidly changing climate.

Laws and regulations make powerful contribution in addressing multitudes of public health concerns. We examined the Public Health Act (PHA) in Malawi to understand its relevance to the ever-growing and changing threats posed by infectious and non-infectious diseases. The current Public Health Act of Malawi came into effect in 1948 to protect and preserve public health. The Act has undergone several amendments, the last one being in 1975. It draws much of its inspiration and standards from the 19th century British laws on insanitary housing, poor ventilation, and drainage. Such laws are silent on emerging major public health concerns including non-communicable diseases (NCDs) such as cardiovascular diseases and diabetes as well as road traffic injuries. This makes the Act outdated and ill equipped to address the 21st century public health concerns. Although supplementary legislation such as the HIV/AIDS Act and Mental Treatment Act have recently been enacted, they are yet to be consolidated into the Public Health Act. Consequently, existing policies and strategic plans that are meant to address gaps in public health and ensure coordinated effort lack support of laws and regulations. The Act also places great emphasis on mandatory vaccinations, quarantine and isolation against smallpox, a disease that has long been eradicated. Furthermore, although the Public Health Act outlines powers, duties and penalties, it fails to reinforce acceptable behaviour due to the insignificant penalties for noncompliance. There is a need for immediate and prompt revision and restructuring of the Public Health Act based on scientific evidence. Such laws require adequate consultation and interaction with key experts and stakeholders from a wide range of disciplines.

Vitamin C is an essential nutrient that must be obtained through the diet in adequate amounts to prevent hypovitaminosis C and the potentially fatal deficiency disease scurvy. Global vitamin C status and prevalence of deficiency has not previously been reported, despite vitamin C’s pleiotropic roles in both non-communicable and communicable disease. This review highlights the global literature on vitamin C status and the prevalence of hypovitaminosis C and deficiency. Related dietary intake is reported if assessed in the studies. We also explore if global vitamin C status has changed over time. Overall, the review illustrates the shortage of high quality epidemiological studies of vitamin C status in many countries, particularly low- and middle-income countries. The available evidence indicates that vitamin C deficiency is common in low- and middle-income countries and not uncommon in high income settings. Further high quality studies are required to confirm these findings, including in the countries not yet represented, and to fully understand associations with a range of disease processes. Our findings suggest a need for interventions to prevent deficiency in a range of at risk groups and regions of the world.

The prevalence of Noncommunicable Diseases (NCDs) in South Africa is increasing annually, with the burden projected to escalate by 2030. Devastatingly, factors such as lifestyle changes, urbani- sation, and an aging population significantly contribute to a rising burden of Cardiovascular disease (CVDs), diabetes, and cancer which directly impact the mortality and morbidity rates seen in South Africa. Recognising this, the South African government has seen the need for emphasis on developing policies and interventions tar- geting physical inactivity to prevent and manage NCD, particularly cost-free and easy to administer training protocols. However, phys- ical inactivity remains a significant issue, leading to various health concerns in rural communities, including injuries and Fetal Alcohol Spectrum Disorders (FASD). Despite effort to promote physical ac- tivity, the prevalence of NCDs continues to rise, necessitating target- ed interventions to ensure equitable healthcare among South African citizens. On the Contrast, preservation and promotion of traditional games is vital as they offer indigenous populations accessible and culturally relevant means to maintain health and wellness. In this regard, it is important to recognize the importance of preserving and promoting traditional games as they potentially serve as a method for indigenous people to maintain their health and wellness in a way that is accessible and culturally relevant to them. These games have gained popularity in South Africa, with initiatives underway to show- case them globally fostering cultural exchange. Further, revitalizing and conserving these games can cultivate a culture of health and wellbeing in South Africa.

Aim: This study aimed to evaluate the sociodemographic, behavioral, and biological profile and its relationship with the emergence of chronic non-communicable diseases in riverside populations in the Xingu region, Pará, Brazil. Methods: Characteristics related to health indicators and which risk factors are considered most important were also analyzed. This is a cross-sectional, exploratory, and descriptive study. The sample consisted of riverside people over 18 years of both sexes. The sample size (n.86) was calculated with a confidence level of 95% and a sample error of 5%. To divide the groups, the K-means clustering algorithm was adopted through an unsupervised method and the values were expressed as median. For continuous and categorical data, the Mann-Whitney and Chi-square tests were used, respectively, and the significance level was set at p<5%. To classify the degree of importance of each variable, the multi-layer perceptron algorithm was applied. Results: Based on this information, the sample was divided into two groups: the group with low or no education, with bad habits and worse health conditions, and the group with opposite characteristics. The risk factors considered for cardiovascular diseases and diabetes in the groups were low education (p < 0.001), sedentary lifestyle (p < 0.01), smoking, alcoholism, body mass index (p < 0.05) and the waist-hip ratio, with values above the expected, in both groups. Conclusions: The factors considered important to have a good health condition or not were the educational and social conditions of these communities and a part of the riverside population was considered healthier than the other.

Objectives: Low and Middle Income Countries (LMICs) are experiencing a fast-paced epidemiological rise in clusters of non-communicable diseases (NCDs) such as diabetes and cardiovascular disease, forming an imminent rise in multimorbidity (MMD). However, preventing MMD has received little attention in LMICs, especially in Sub-Saharan African Countries. Design: Narrative review which scoped the most recent evidence in LMICs about MMD determinants and appropriated them for potential MMD prevention strategies. Methods: MMD in LMICs is affected by several determinants including increased age, female gender, environment, lower socio-economic status, obesity, and lifestyle behavious, especially poor nutrition and physical inactivity. Results: MMD public health interventions in LMICs, especially Sub-Saharan are currently impeded by local and regional economic disparity, underdeveloped healthcare systems, and concurrent prevalence of communicable diseases. However, lifestyle interventions that are targeted towards preventing highly prevalent MMD clusters, especially hypertension, diabetes and cardiovascular disease, can provide an early prevention of MMD, especially within Sub-Saharan African countries with emerging economies and socio-economic disparity. Conclusion: Future public health initiatives should consider targeted lifestyle interventions and appropriate policies and guidelines in preventing MMD in LMICs.

Respiratory viral infections (RVI) are common reasons for healthcare consultations. The inpatient management of RVI consumes significant resources. From 2009-2014, we assessed the costs of RVI management in 4776 hospitalized chil-dren aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by de-tailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU (“non-ICU”) versus management requiring ICU-care (“ICU”) added up to 2,767.14€ (non-ICU) vs. 29,941.71€ (ICU) for Influenza, 2,713.14€ (non-ICU) vs. 16,951.06€ (ICU) for RSV infections, and 2,767.33€ (non-ICU) vs. 14,394.02€ (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all 8 RVI studied: Influenza, RSV, hRV, ade-novirus (hAdV), metapneumovirus (hMPV), parainfluenzavirus (hPIV), bocavirus (hBoV) and seasonal coronavirus (hCoV) infections. ICU-costs for Influenza however, ex-ceeded all other RVI. At the time of the study, Influenza was the only RVI with antivi-ral treatment options available for children, but only 9.8% of Influenza patients (non-ICU) and 1.5% of ICU-patients with Influenza received antivirals; only 2.9% were vac-cinated. Future studies should investigate the economic impact of treatment and pre-vention of Influenza-, COVID-19-, and RSV post vaccine introduction.

Policies to require front-of-package labels (FOPLs) on foods may help Indian consumers better identify foods high in nutrients of concern including sugar, saturated fat, and sodium, and discourage their consumption, outcomes critical for preventing rises in diet-related non-communicable disease. The objective was to test whether FOPLs helped Indian consumers identify ‘high-in’ foods and reduce intentions to purchase them. We conducted an in-person randomized experiment (n=2,869 adults between ages 18 and 60 years old) in six states of India in 2022. Participants were randomized to one of five FOPLs: a control label (barcode), warning label (octagon with “High in [nutrient]”), Health Star Warning (HSR), Guideline Daily Amount (GDA), or traffic light label. Participants then viewed a series of foods high in sugar, saturated fat, or sodium with the assigned FOPL, and rated product perceptions and label reactions. Fewer than half of participants in the control group (39.1%) correctly identified all products high in nutrient(s) of concern. All FOPLs led to an increase in this outcome, with the biggest differences observed for the warning label (60.8%, p<0.001) followed by the traffic light label (54.8%, p<0.001), GDA (55.0%, p<0.001), and HSR (45.0%, p<0.01). Relative to the control, only the warning label led to a reduction in intentions to purchase the products. The results suggest that warning labels are the most effective FOPL to help Indian consumers identify and avoid unhealthy foods.

Despite the well-documented health benefits of recreational sports, few opportunities exist in lower- and middle-income countries for adult women to participate in recreational physical activities. An explanatory sequential mixed methods approach was used to explore associations between an innovative soccer program for adult women and self-reported health status. Cross-sectional survey data were collected in 2018-2019 from 702 women in the Nikumbuke Project, a health and literacy program in southeastern rural Kenya, followed by focus group discussions with 225 women who also participated in the Project's soccer program. Quantitative findings suggest that women who participated in soccer had 67% greater odds of reporting good or excellent health than their non-soccer playing peers. Thematic analysis of qualitative data indicated that women credited soccer with less pain, fatigue, and stress, as well as weight loss and reduced dependence on medicine for hypertension, pain, and sleep problems. Women equated health benefits with greater ease and efficiency in completing chores, reduced worries, youthful energy, male-like strength, and pleased husbands. Soccer programs for adult women may be particularly effective interventions in settings where access to health care is limited and where lack of opportunity to engage in physical aerobic activity increases women's risks for poor health outcomes. .

Covid-19 has given a halt to all the activities in the world. Europe was most affected followed by the United States of America. In this study we have assessed the severity of Covid-19 by analyzing the mortality rate in Covid-19 and other diseases. The Covid-19 data and “death rate” data caused by other diseases (cardiovascular diseases, cancer, non-communicable respiratory diseases, respiratory infectious diseases, diabetes mellitus, and kidney diseases) were downloaded from the world health organization (WHO) website. A normalized period based method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths occurred by cardiovascular diseases, cancer, and respiratory diseases were more in number than the Covid-19 caused deaths in the 45 days period where most of the Covid-19 deaths had taken place. The mortality rate of Covid-19 was highest in France followed by Belgium and the lowest in Russia while the share of Covid-19 caused deaths in total deaths by all causes was the highest in Belgium followed by Spain and the lowest in Japan. The severity of Covid-19 in the USA was moderate. The severity of Covid-19 in Asian countries was found to be moderate to low. The severity of Covid-19 was diverse in the world. Europe showed the highest diversity in the mortality rate of Covid-19. Cardiovascular diseases, cancer, and non-communicable diseases were still more lethal and caused more deaths than Covid-19.

During the COVID-19 pandemic, the circulation of non–SARS-CoV-2 respiratory viruses changed throughout the world. This study aimed to analyze the effect of respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus (RV), and parainfluenza (PIV)-3 single infection, dual co-infection, and viral load on cytokine and chemokine expression in 300 Mexican patients with ARIs negative for SARS-CoV-2. Molecular detection and viral load were performed by RT-qPCR. Cytokine and chemokine expression was determined in samples positive for single RSV, MPV, RV, or PIV-3 infection, and in the most frequent dual co-infections, by a cytokine panel using a magnetic-bead-based multiplex immunoassay. Of the patients positive for viral infection, 91.7% had a single infection and 8.3% had dual co-infections. In this study, RSV was the respiratory virus with the highest prevalence, and the most common dual co-infection was RV+RSV. On the other hand, RV infections had the highest viral loads compared to the other viruses detected. FGF basic, MIP-1α IL-8, IP-10, MCP-1, IFN-γ, and RANTES showed differential expression between single infections and dual co-infections compared to healthy patients. We report, for the first time, the circulation of non-SARS-CoV-2 viruses in the south of Mexico and the cytokine and chemokine profiles associated with these viruses.

Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.

Background and Objectives: Elders’ needs are rarely examined beforehand, and thus, although technology-based tools can enhance self-management, acceptability rates are still low. This study aimed to examine and compare self-reported needs, priorities, and preferences of elders with heart failure (HF), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD) toward technology use to enhance self-management. Materials and Methods: A convenience sample of 473 participants over 60s (60.5% females), diagnosed with HF (N=156), DM (N=164), or COPD (N=153) was recruited. They were administered a questionnaire about the usefulness of technology in general and in specific areas of disease management. Results: Most participants (84.7%) admitted that technology is needed for better disease management. This was equally recognized across the three groups both for the overall and specific areas of disease management (in order of priority: ‘Information’, ‘Communication with Physicians &amp; Caregivers’, and ‘Quality of Life &amp; Wellbeing’). Sociodemographic differences were found. Cell phones and PCs were the devices of preference. The four common features prioritized by all three groups were related to ‘information about disease management’ (i.e., monitoring symptoms, reminders for medication intake, management and prevention of complications), whereas the fifth one was related to ‘communication with physicians and caregivers (i.e., in case of abnormal or critical signs). The top disease-specific feature was also monitoring systems (of respiratory rate or blood sugar or blood pressure, oxygen), whereas other disease-specific features followed (i.e., maintaining normal weight for HF patients, adjusting insulin dose for DM patients, and training on breathing exercises for COPD patients). Conclusions: Elders in these three samples seem receptive to technology in disease management. mHealth tools, incorporating both common and disease-specific features and addressing different chronic patients, and being personalized at the same time, could be cost-saving and useful adjuncts in routine clinical care to improve self-management.

Background Community health workers (CHWs) drawn from the general population are an important human resource in health care systems, preventing non-communicable diseases (NCDs) and contributing to an increase in healthy life expectancy in Japan. Thus, we have developed the COmmunity health workers perceptual and behavioral Competency Scale for preventing Non-communicable diseases (COCS-N) to measure CHWs’ competence in preventing NCDs. The purpose of this study is to examine individual and community factors affecting CHWs’ COCS-N scores. Methods Municipal public health nurses and other public health professionals are responsible for training and supporting CHWs in Japan. Therefore, the existence of CHWs and their willingness to participate in the study were confirmed with the municipalities, who were asked to distribute the self-administered questionnaire to CHWs where consent was obtained (N = 6,480). Variables used included demographic characteristics, COCS-N scores, and individual- and community-related factors. Logistic regression analysis was used to assess associations between variables. Results A total of 3,120 people completed the questionnaire, a valid response rate of 48.1%. The respondents’ mean age was 67.0 years (standard deviation = 9.0), and 88.0% were female. Comparison of the high- and low- competence groups in terms of NCD prevention based on COCS-N scores identified 13 factors associated with significant differences, including years spent working as a CHW (p < 0.001), subjective sense of health (p = 0.005), European Health Literacy Survey Questionnaire (HLS-EU-Q47) scores (p < 0.001), and community commitment scale (CCS) scores (p < 0.001). Logistic regression analysis revealed that HLS-EU-Q47 scores (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.02–1.03) were a significant individual factor, while CCS scores (OR: 1.14, 95% CI: 1.11–1.16) were a significant community factor. Conclusions We found that the COCS-N score was associated with the individual factors overall health literacy (HL), perceptions of HL, and subjective sense of health, and with the community factor CCS scores. These results suggest that strengthening individual factors such as HL and subjective sense of health, and community factors such as sense of community is an effective strategy for increasing CHWs’ competence in preventing NCDs.

This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.

Older adults in low-and middle-income countries experience a disproportionate burden of non-communicable diseases (NCDs). Unintentional injuries are among the major NCDs, and falls are the second leading cause of these injuries and deaths worldwide, including in Thailand. We aimed to culturally adapt the CDC’s Stopping Elderly Accidents, Deaths, and Injuries (STEADI) for Thai older adults and explore the feasibility, appropriateness, and acceptability of using STEADI in primary care via trained community health workers (CHWs) and care managers (CMs). STEADI takes a coordinated care approach that consists of three steps: screening, assessing, and intervening. In Step a, CHWs screened fall risk in 20 community-dwelling older adults using three key questions and found that all of them had fall risk, then CHWs screened with a Stay Independent questionnaire (range 0-14) and found that 100% have high fall risk (total scores 9.7± 2.4). In Step b, CMs assessed balance, vision, footwear, postural hypotension, medications, and CHWs assessed home hazards. They found that 50% had poor balance, 70% took 4+ medications,75% fell on the walkway, and 70% had no bathroom modifications. In Step c, individual participants received fall prevention interventions to mitigate their specific fall risk factors. CHWs and CMs indicated high acceptability (19.20±.1.31 of 20 total), appropriateness (18.80± 1.79 of 20 total), and feasibility (18.60±1.67 of 20 total) of the Thai-STEADI intervention. Our study showed that the community-based multifactorial Thai-STEADI delivered by CHWs and CMs is feasible and acceptable to prevent falls in older adults with limited access to health care.

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Abstract: The objective of this meta-analysis was to evaluate the factors associated with mortality of elderly Italians diagnosed with the new coronavirus who resided in institutions or who were hospitalized as a result of the disease. Methods: A systematic review following the recommenda-tions of The Joanna Briggs Institute (JBI), where the PEO strategy was utilized - Population, Exposure and Outcome. P, being the elderly over 65 years old. E, the SARS-CoV_2 pandemic. O, mortality. The NCBI / PubMed, LILACS, EMBASE and CINAHL databases were used until July 31, 2020.; Results: Five Italian studies were included in the meta-analysis, with the number of elderly people varying between 18 and 1591 patients. The main morbidities presented by the elderly in the studies were: dementia, diabetes, chronic kidney disease and hypertension. Conclusions: The factors as-sociated with the mortality of elderly Italian people diagnosed with SARS-CoV-2 who lived in in-stitutions or who were hospitalized because of the disease were evaluated. It was found that de-mentia, diabetes, chronic kidney disease and hypertension are the main the main diagnosed dis-eases for mortality in elderly people with Covid-19.

Egypt faces numerous challenges in achieving food and nutritional security, due largely to its unique geography, water stress, and population growth. However, nontraditional crops and pseudo cereals such as buckwheat, quinoa, sorghum, teff, and millet offer promising avenues for sustainable agricultural development and improved nutrition. These crops exhibit high tolerance to adverse environmental conditions such as soil salinity and drought and are rich in essential nutrients like protein, amino acids, and vitamins. They also present an economic advantage due to their short growing seasons and adaptability to marginal lands. Recent advancements in remote sensing and Geographic Information Systems (GIS) technology, along with crop simulation models, provide further opportunities for optimizing land and water resources for these nontraditional crops. Their exceptional nutritional values, including low glycemic indices and gluten-free properties, make them well-suited to address current health challenges, such as malnutrition and the increasing prevalence of non-communicable diseases. The study emphasizes the need for further research to investigate land suitability, water management, and economic viability for the cultivation and commercialization of these crops. By leveraging these opportunities, Egypt has the potential to not only close its food gap but also improve overall nutritional well-being, contributing to both food security and sustainable agriculture.

Respiratory therapist(RT)internet-supervised At-Home Telespirometry(AHT)was validated in pilot 22/95=23% ALS Clinic population. Erect, supine Vital Capacity(eFVC, sFVC)were measured longitudinally using ZephyRx smartphone interface and database recording in-clinic-conventional(Viaire-Vyasis-)and at-home-portable(MIR-Spirobank-Smart-)spirometers. Bland-Altman(BA)analysis supported content validity-precision and 7-day-test-re-test-validity [mean difference=0.15L(conventional–portable;95%CI -0.40L, 0.70L); = 2.7% predicted (conventional-portable;95%CI -12.1%, 17.5%) ]meeting ATS-ERS performance standards. RT Internet-supervised AHT measured sFVC was more frequently obtained[35/52=67.3 %]in-home-vs-in-clinic sFVC[9/21=42.9 %](Chi-Square;P=0.0533). Monthly mean eFVC slope decline for the eFVC > 60 % predicted baseline cohort was – 1.24% predicted per month[95% CI -2.15 ,-0.33% predicted]statistically significantly(P=0.015)less compared with the – 5.86% predicted per month[95% CI -9.44, -2.29 % predicted]decline for the eFVC < 60 % predicted baseline cohort and in this cohort was associated with statistically significant decreased survival(P=0.0219). RT Internet-supervised AHT facilitated initiation of non-invasive ventilation(NIV)in 5/22[23%]patients including 3/4[75%] homebound subjects. RT Internet-supervised AHT can be deployed for ALS patients stratified according to baseline eFVC for earlier detection of eFVC and sFVC decreases between clinic visits. A prospective research study[NCT05106569]is ongoing to further define the capability of online deployment of Respiratory therapist(RT)internet-supervised AHT in the timely initiation of NIV use to improve ALS respiratory care in larger numbers of ALS subjects.

(1) Background: Prevention of acute cardiovascular events in patients with cardiovascular diseases (CVDs) requires promoting health-protective behaviors (e.g., physical activity) and preventing health-compromising behaviors (sitting). Digital health interventions provide much potential. Based on multiple behavioral change theory, an intervention (reCardial app) was evaluated, and the following hypotheses were tested: H1: Health behaviors (physical activity, sitting) and disease self-management (self-care maintenance, self-care confidence) are closely interrelated. H2: Change in health behaviors and disease self-management indicators over time is more pronounced in reCardial app-users. H3: In the intervention group, changes in systolic and diastolic blood pressure indicate a positive trajectory. (2) Methods: A study with the design of a randomized controlled trial over 12 weeks was conducted. 40 CVD-patients were randomized equally to the Intervention Group (35% women; Mage=60.6years) and Control Group (45% women; Mage=61.5years). (3) Results: Findings support H1 with significant correlations between health behaviors (r=0.45-0.63**), and disease self-management (r=-0.32-0.54**), H2 with Eta²=0.21 (not statistically significant) and H3 partially with d=0.101 for systolic blood pressure but not regarding diastolic blood pressure. (4) Conclusions: Replications are needed with larger samples and more objective measures. The app can help prevent and manage CVD by means of promoting health-protective behaviors and preventing health-compromising behaviors. Taking different behaviors into account can increase intervention effects and with that support of users.

Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.

As Chronic Non-Communicable Diseases (CNCD) increase, preventive approaches become more crucial. In this review, Calorie Restriction (CR) effects on human beings were evaluated, comparing benefits and risks of different CR diets: classic CR vs ketosis-inducing diets, including Intermittent Fasting (IF), Classic Ketogenic Diet (CKD), Fasting Mimicking Diet (FMD), Very-Low-Calorie Ketogenic Diet (VLCKD) and Spanish Ketogenic Mediterranean Diet (SKMD). Special emphasis on Insulin Resistance (IR) was placed, as it mediates Metabolic Syndrome (MS), a risk factor for CNCD, and predicts MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.

Alzheimer´s Disease (AD) has currently no effective treatment; however, preventive measures can significantly delay the progress/onset of the disease. Thus, accurate and early prediction of risk is an important strategy to alleviate the AD burden. Neuroinflammation is a major factor prompting the onset of the disease. Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, it is affecting gene expression via modulation of non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation can also affect long non-coding RNAs (lncRNAs) expression. While the association between miRNAs and inflammation in AD has been extensively studied, the role of lncRNAs in neurodegenerative diseases has been less explored. In this review, we focus on lncRNAs and inflammation in the context of AD. Furthermore, since plasma-isolated extracellular vesicles (EVs) are increasingly recognized as an effective monitoring strategy of brain pathologies, we have focused on the studies reporting dysregulated lncRNAs in EVs isolated from AD patients and controls. The revised literature shows a positive association between pro-inflammatory lncRNAs and AD. However, the reports evaluating lncRNAs alterations in EVs isolated from plasma of patients and controls, although still limited confirm the value of specific lncRNAs associated with AD as reliable biomarkers. This is an emerging field that will open new avenues to improve risk prediction, patients’ stratification and may lead to the discovery of potential novel therapeutic targets for AD

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

Physical activity (PA) is a factor that may have an influence on the symptoms of Parkinson’s disease (PD). The aim of this study was to identify the potential determinants of spontaneous PA in the PD patient group. 134 PD patients aged 65.2±9.2 years, Hoehn-Yahr scale ≤ 4, Mini Mental State Examinaton (MMSE) ≥ 24 were examined. For the study purposes, the authors analyzed: age, sex, education, history of PD, dopaminergic treatment, the severity of PD symptoms using Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr scale. Additionally all participants were evaluated through a set of scales for specific neuropsychiatric symptoms including: depression, anxiety, apathy, fatigue and sleep disorders. An analysis of linear regression was used with backward elimination. In the total explanatory model, 12% of the variability in activity (R2=0.125; F(16.133)=2.185; p<0.01), the significant predictor was starting therapy with the dopamine agonist (DA) (β= 0.420; t= 4.068; p=0.000), which was associated with a longer duration of moderate PA. In the total explanatory model, for more than 13% of the variance in time spent sitting (R2=0.135; F(16.130)=2.267; p<0.01), the significant predictors were secondary education and the results of the UPDRS. The patients with secondary and vocational education, those starting treatment with DA and those with a less severe degree of Parkinson’s symptoms (UPDRS) spent less time sitting in a day. It is possible to identify determinants of spontaneous PA. It may elucidate consequences in terms of influence on modifiable conditions of PA and the proper approach to patients with unmodifiable PA factors.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated bidirectional relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass &lt;0.789 in men and &lt;0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs=1.213, 95% CIs=1.050–1.402). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs=1.564, 95% CIs=1.378–1.775). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a bidirectional relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder that has become a global health concern due to its increasing prevalence. Currently, there is a need for reliable biomarkers to aid in the diagnosis and prognosis of NAFLD. Extracellular vesicles (EVs) are promising candidates in biomarker discovery, as they carry proteins that reflect the pathophysiological state of the liver. In this review, we developed a list of EV proteins that could be used as diagnostic biomarkers for NAFLD. We employed a multi-step strategy that involved reviewing and comparing various sources of information. Firstly, we reviewed papers that have studied EVs proteins as biomarkers in NAFLD, as well as papers that have studied circulating proteins as biomarkers in NAFLD. To further identify potential candidates, we utilized the EV database Vesiclepedia.org to qualify each protein. Finally, we consulted the Human Protein Atlas to search for candidates' localization, focusing on membrane proteins. By integrating these sources of information, we developed a comprehensive list of potential EVs membrane protein biomarkers that could aid in the diagnosis and monitoring of NAFLD. In conclusion, our multi-step strategy for identifying EV-based protein biomarkers for NAFLD provides a comprehensive approach that can also be applied for other diseases. The protein candidates identified through this approach could have significant implications for the development of non-invasive diagnostic tests for NAFLD and improve the management and treatment of this prevalent liver disorder.

Background and aim: To explore the discriminant accuracy of Cytokeratin 18 (CK18, including M65 and M30 forms) for an elevated fatty liver index (FLI) as a validated proxy of Non-Alcoholic Fatty Liver Disease (NAFLD), and cardiovascular disease (CVD) risk in the general population. Methods: Both serum CK18 forms were measured using a commercial immunoassay in randomly selected samples from 312 participants of the PREVEND general population cohort. FLI ≥60 was used to indicate NAFLD. Framingham Risk Score (FRS) and the SCORE2 were used to estimate the 10-year risk of CVD. Receiver Operating Characteristic (ROC) curve, linear/logistic regression models and Spearman's correlations were used. Results: Intricate associations were found between CK18, FLI and CVD risk scores. While M30 was the only independent predictor of FLI≥60, M65 discriminated best NAFLD individuals at very-high 10-years CVD risk according to SCORE2 (AUC:0.71; p=0.001). Values above the predefined manufacturer cut-off (400 U/l), were associated with an independent 5-fold increased risk (adjusted odds ratio: 5.44, p=0.01), with negative predictive value of 93%. Conclusions: Confirming that NAFLD is associated with an increased CVD risk, our results point to CK18 M65 as a candidate biomarker to identify NAFLD individuals at low CVD risk in European general population.

Non-alcoholic fatty liver disease (NAFLD) continues to rise and has become the most common cause of chronic liver disease among all ages and ethnicities. Metabolic disorders such as obesity and insulin resistance are closely associated with sarcopenia and NAFLD. Sarcopenic obesity is a clinical disorder characterized by the simultaneous loss of skeletal muscle and gain of adipose tissue. It is associated with worse outcomes in individuals with NAFLD. It is projected that NAFLD and sarcopenia will rise as the prevalence of obesity continues to increase at an unparallel rate. Recently, sarcopenia and sarcopenic obesity have gained considerable interest, but we still lack a well-defined definition and a management approach. Therefore, it is imperative to continue shining the light on this topic and better understand the underlying mechanism as well as treatment options. In this review article, we aimed to address the pathophysiology, impact, and outcomes of sarcopenic obesity on NAFLD.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and elderly individuals. DM may accelerate the aging process, and the age-related declines in the estimated Glomerular Filtration Rate (eGFR), can pose a challenge to diagnose diabetic kidney disease (DKD) using standard diagnostic criteria especially with absence of severe albuminuria among the elderly. In the presence of CKD and DM, elderly patients may need multidisciplinary care due to susceptibility to various health issues e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to the elderly. We review the evidence that the benefits from these newer therapies apply equally to elderly and non-elderly patients and propose a framework for the management of DKD by discussing the nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), Sodium Glucose Co-Transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and Glucagon Like Peptide 1 Receptor Agonists (GLP1-RAs).

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

.Celiac disease (CeD) is a chronic, autoimmune disorder triggered by the ingestion of gluten, affecting around 1% of the global population. It is a multifactorial disease involving both genetics and environ-mental factors. Nowadays, the only available treatment for CeD is a life-long gluten-free diet (GFD), which can cause a significant burden for patients, since symptoms and mucosal injury can persist de-spite apparent compliance with a GFD. That could also lead to psychological consequences and affect the quality of life of these patients. Thankfully, recent advances in understanding the pathogenesis of CeD and the availability of various targets have made it feasible to explore pharmaceutical treatments specific to CeD. Recently, the FDA has highlighted the unmet needs of adult patients on GFD who expe-rience ongoing symptoms attributed to CeD and also show persistent duodenal villous atrophy. This re-view will outline the limitations of a GFD, describe the targets of potential novel treatment of CeD and provide an overview of the primary clinical trials involving oral and injectable agents for a non-dietary treatment of CeD.

Mitochondria are classically termed as powerhouse of a mammalian cell. Most of the cellular chemical energy in the form of adenosine tri phosphate (ATP) is generated by mitochondria and dysregulation of mitochondrial functions thus can be potentially fatal of cellular homeostasis and health. Acute respiratory distress has been earlier linked to mitochondrial dysfunction. SARS-CoV-2 infection severity leads to acute respiratory distress syndrome (ARDS) and can be fatal. We tried to investigate possible connection between SARS-CoV-2, ARDS and mitochondria. Here, we report identification of SARS-CoV-2 non-structural proteins (particularly Nsp12 and 13) that have recognition sequence with respect to mitochondrial entry. We also report that these proteins can potentially shuttle between cytoplasm and mitochondria based on the localization signals and help in downstream maintenance of the virus. Their properties to use ATP for enzymatic activities may cause ATP scavenging allowing viral RNA functions in lieu of host cell health.

Non-alcoholic fatty liver disease (NAFLD) has gained attention in the last few years due to its increasing prevalence worldwide becoming a global epidemic. This review aims to discuss the latest recommendations regarding diagnosis and treatment of NAFLD-associated HCC and the remaining challenges. Thus, there is a high amount of data derived from basic and clinical studies that revealed the molecular pathways which drive NAFLD-associated hepatocellular carcinoma (HCC). Based on these findings, new prevention, surveillance and treatment strategies are emerging. However, current data on treatment modalities in NAFLD-associated HCC are still scarce, but based on subgroup analysis results from non-NAFLD HCC studies are promising and could provide a basis for future research agenda to address NAFLD/NASH patients. Conclusion: Due to the pandemic proportions that NAFLD gained in the last few years, there is a high amount of data derived from basic and clinical studies that revealed the molecular path-ways which drive NAFLD-associated HCC. Based on these findings, new prevention, surveillance and treatment strategies could be developed at an individual level.

Background: Dynapenia and non-alcoholic fatty liver disease (NAFLD) are common, especially in the middle and advanced-age diabetic male population. We aimed to examine the clinical features, NAFLD severity, and parameters associated with the presence of dynapenia in type 2 diabetes mellitus (T2DM) cases. Material and Methods: One hundred thirty-five male patients diagnosed with T2DM between 45 and 65 years of age were included. Patients were staged by ultrasonography according to NAFLD status. Results: There were significant differences in muscle strength, upper arm circumference, calf circumference, and up-and-go test scores between the NAFLD groups (p<0.001 for all). The frequency of dynapenia was lower, and arm and calf circumferences were higher in patients without NAFLD. The muscle strength, upper arm circumference, calf circumference, and up-and-go test scores were significantly lower in the dynapenic group compared to the non-dynapenic group (p<0.005 for all). The prevalence of dynapenia increased along with the increase in NAFLD stages (p<0.001). Conclusions: We detected a significant association between NAFLD and dynapenia in middle-aged men with T2DM. As muscle strength decreases, the amount of fat in the liver increases, and as the fat in the liver increases, muscle strength decreases.

Mycobacterium avium ssp paratuberculosis (MAP) is the causative agent of Johne’s disease (JD) in animals and a suspected cause of Crohn’s disease (CD) in humans. Crohn’s Disease is a progressive, detrimental granulomatous enteritis of which common therapies are targeted to suppressing certain components of the immune system. The efficacy of these treatments can be variable and temporary with no clear process of selection for the individual patient. However, diagnosis of MAP has been elusive in patients with Crohn’s Disease. In animals it can be detected by several different techniques, including bacterial cell culture, polymerase chain reaction (PCR), and immunological targets. To move to an understanding of the possible pathogenicity of MAP and the sup-posed cause of CD in humans, it is necessary to demonstrate the presence of cell wall deficient mycobacterial (CWDM) forms of MAP in blood and tissue cultures from patients with CD. From this, more tailored and accurate therapies can be implemented and be developed to eradicate this infectious organism from humans. Current anti-mycobacterial antibiotics have limited efficacy as MAP is subtly different from tuberculosis. Newer methods, such as vaccination and gut microbiome remediation will be essential as part of combination therapies.

It is unknown whether postprandial plasma glucose measured from blood taken between 4 and 7.9 h (PPG4-7.9h) is associated with mortality from hypertension, diabetes, or cardiovascular disease (CVD). This study aimed to investigate these associations in 4,896 US adults who attended the third National Health and Nutrition Examination Survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of PPG4-7.9h for mortality. This cohort was followed up for 106,300 person-years (mean follow-up, 21.7 years). A 1-natural-log-unit increase in PPG4-7.9h was associated with a higher risk of mortality from hypertension (HR, 3.50; 95% CI, 2.34-5.24), diabetes (HR, 11.7; 95% CI, 6.85-20.0), and CVD (HR, 2.76; 95% CI, 2.08-3.68) after adjustment for all the tested confounders except hemoglobin A1c (HbA1c). After further adjustment for HbA1c, PPG4-7.9h remained positively associated with mortality from hypertension (HR, 2.15; 95% CI, 1.13-4.08) and CVD (HR, 1.62; 95% CI, 1.05-2.51), but was no longer associated with diabetes mortality. Subgroup analyses showed that similar results were obtained in the sub-cohort of participants without a prior diagnosis of myocardial infarction or stroke. In conclusion, PPG4-7.9h predicts mortality from hypertension and CVD independent of HbA1c.

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of lipids in the form of lipid droplets in more than 5% of hepatocytes. It is regarded as a range of diverse pathologies, including simple steatosis and steatohepatitis. The structural characteristics of lipid droplets have been implicated in the etiology of the disease, along with their protein composition, mainly perilipins. These proteins have garnered increasing attention as a pivotal regulator, since their levels and distinct expression appear to be associated with the progression from simple steatosis to steatohepatitis. Perilipins are target proteins of chaperone-mediated autophagy, and their degradation is a prerequisite for lipolysis and lipophagy to access the lipid core. Both lipophagy and chaperone-mediated autophagy have significant implications in the development of the disease, as evidenced by their upregulation during the initial phases of simple steatosis, and their subsequent downregulation once steatosis is established. On the contrary, during steatohepatitis, the process of chaperone-mediated autophagy is enhanced, although lipophagy remains suppressed. Evidently, the reduced levels of autophagic pathways observed in simple steatosis serve as a defensive mechanism against lipotoxicity. Conversely, in steatohepatitis chaperone mediated autophagy fails to compensate for the continuous generation of small lipid droplets and thus cannot protect hepatocytes from lipotoxicity.

Sodium glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i act by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys.

Exosomes, a subset of extracellular vesicles, have emerged as pivotal mediators of intercellular communication, revolutionizing our comprehension of cellular interactions. Their diverse cargo, comprising proteins, nucleic acids, and bioactive molecules, plays a crucial role in various physiological and pathological processes. In the intricate landscape of adult neurogenesis, exosomes wield significant influence, actively participating in the generation of new neurons within the adult mammalian brain. Originating predominantly from non-niche cells, these vesicles contribute substantially to the regulation of neuroinflammation, thereby impacting neurogenesis and offering therapeutic promise for neurological disorders. In the specific context of Parkinson's disease (PD), exosomes assume a multifaceted role, prominently implicated in the propagation of α-synuclein oligomers and the orchestration of neuroinflammation. Stem cell-derived exosomes present themselves as promising therapeutic agents, capable of reshaping the microenvironment, repairing neuronal damage, and mitigating apoptosis. The ongoing exploration of exosomes continues to unravel intricate biological processes, paving the way for innovative medical interventions and treatments, particularly within the challenging landscape of neurodegenerative diseases such as PD. The comprehensive understanding of exosomal functions holds the potential to advance our therapeutic approaches, offering new avenues for intervention and treatment strategies in the realm of neurodegenerative disorders.

Exercise can be hypothesized to play an important role in NAFLD treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n=49) or dietary restriction (n=21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

Healthcare visits were reduced during COVID-19 pandemic causing the disturbance of the sustainability in NAFLD monitoring. Telemedicine acts to maintain connectivity between patients and healthcare professionals. This review aimed to assess telemedicine helps to monitoring in NAFLD. The database was searched from The PubMedCentral and ScienceDirect from 2020 to 2023. We assessed the Cochrane Risk of Bias (RoB) for randomized controlled trial (RCT) and the Newcastle-Ottawa scale for non-RCTs systematic reviews. Meta-analyses with random-effects model to determine the pooled mean difference (MD) and p-value. There were three RCT and two non-RCT were included (n=239) with 56.9% males and the mean age was 51.3 years. Median intervention lasted 5.5 months. The parameter were body weight (BW), body mass index (BMI), waist circumference, liver function (AST/ALT), lipid profile and HbA1c. Metaanalysis showed telemedicine had a significant effect on improving outcomes for BW (MD -2.81: 95% CI, -4.11, -1.51, P 0.0001) and BMI (MD -1.01: 95% CI, -1.47, -0.55, P 0.0001) compared to standard care, while the AST/ALT were not significantly reduced. Other laboratory parameter were decreased from systematic reviews. Telemedicine through mobile-based applications could be an option for monitoring body weight and BMI in NAFLD patients facing the pandemic.

Background: This study explores the impact of a gluten-free diet (GFD) on regional gastrointestinal (GI) transit times in individuals with celiac disease (CD) and non-celiac gluten sensitivity (NGCS). While a GFD is established for managing CD and wheat allergy, its effects on NGCS remain controversial due to inconclusive evidence. Methods: Utilizing a wireless motility and pH capsule (WMC) to assess regional and whole gut transit, newly diagnosed CD (n=12) and NGCS (n=12) patients underwent baseline evaluations, including measurements of gastric, small bowel, and colonic transit times. Results: At baseline conditions, individuals diagnosed with CD exhibited prolonged colonic and intestinal transit times when compared to those with NGCS (p&lt;0.05). Following a 4-week GFD, CD patients experienced significant reductions in both intestinal and colonic transit times, along with enhanced small intestine contractility. NGCS individuals showed improvements in intestinal transit time and contractility with a GFD, although the colon exhibited no discernible effect. The GFD did not significantly impact intragastric, intestinal, or colonic pH. Conclusions: This study, employing WMC for the first time, provides novel insights into the positive effects of a GFD on intestinal and colonic transit, as well as contractility, in CD patients, and to a lesser extent, in those with NGCS.

We aimed to develop a non-linear regression model that could predict the fat fraction of the liver (USFF), similar to magnetic resonance imaging proton density fat fraction (MRI-PDFF), based on quantitative ultrasound (QUS) parameters. We measured and retrospectively collected the ultrasound attenuation coefficient (AC), backscatter-distribution coefficient (BSC-D), and liver stiffness (LS) using shear wave elastography (SWE) in 90 patients with clinically suspected non-alcoholic fatty liver disease (NAFLD) and 51 patients with clinically suspected metabolic-associated fatty liver disease (MAFLD). The MRI-PDFF was also measured in all patients within a month of the ultrasound scan. In the linear regression analysis, only AC and BSC-D showed a significant association with MRI-PDFF. Therefore, we developed prediction models using non-linear least-squares analysis to estimate MRI-PDFF based on the AC and BSC-D parameters. We fitted the models on the NAFLD dataset and evaluated their performance in 3-fold cross-validation repeated five times. We decided to use the model based on both parameters to estimate the ultrasound fat fraction (USFF). The correlation between USFF and MRI-PDFF was strong in NAFLD and very strong in MAFLD. According to a receiver operating characteristics (ROC) analysis, USFF could differentiate between <5% vs. ≥ 5% and < 10% vs. ≥ 10% MRI-PDFF steatosis with excellent, 0.97 and 0.91 area under the curve (AUC) accuracy in the NAFLD and with AUCs of 0.99 and 0.96 in the MAFLD groups. In conclusion, USFF calculated from QUS parameters is an accurate method to quantify liver fat fraction and to diagnose ≥ 5% and ≥ 10% steatosis in both NAFLD and MAFLD. Therefore, USFF can be an ideal non-invasive screening tool for patients with NAFLD and MAFLD risk factors.

Since certain Mycobacterium tuberculosis complex (MTBC) members, like M. bovis, are endemic in specific South African wildlife reserves and zoos, cases of clinically important nontuberculous mycobacteria (NTM) in wildlife may be neglected. Additionally, due to the inability of tests to differentiate between host responses to MTBC and NTM, the diagnosis of MTBC may be confounded by the presence of NTMs. This may hinder control efforts. These constraints highlight the need for enhanced rapid detection and differentiation methods for MTBC and NTM, especially in high MTBC burden areas. We evaluated the use of the GeneXpert MTB/RIF Ultra, the Hain CMdirect V1.0, and novel amplicon sequencing PCRs targeting the mycobacterial rpoB and ku gene targets, directly on antemortem respiratory samples from known MTBC-infected and NTM culture-positive African elephants (n=26 animals) and rhinoceros (n=23 animals). Our findings suggest that the Ultra is the most sensitive diagnostic test for MTBC DNA detection directly in raw antemortem respiratory specimens and that the rpoB PCR is ideal for Mycobacterium genus DNA detection and species identification through amplicon sequencing.

Non-alcoholic fatty liver disease (NAFLD), a frequent complication of metabolic syndrome and visceral obesity, is characterized by marked accumulation of lipids in hepatocytes, accompanied by oxidant stress. In a substantial minority of cases, this progresses to steatohepatitis, which in turn can lead to life-threatening hepatic fibrosis and/or hepatocarcinogenesis. This essay analyzes the molecular biology underlying fat accumulation and oxidant stress in NAFLD, and identifies targets that can be addressed by nutraceutical or dietary measures. Nutraceuticals with potential for prevention or control of NAFLD – as suggested on theoretical grounds, and borne out by experience in rodent studies and/or clinical trials - include ferulic acid, melatonin, methylnicotinamide, tetrahydrocurcumin, nicotinamide riboside, carnosic acid, urolithin A, quercetin, high-dose biotin, citrulline, astaxanthin, long-chain omega-3 fatty acids, berberine, lipoic acid, silibinin, N-acetylcysteine, taurine, capsaicin, spermidine, spirulina, and carnitine. Some of these agents can also address the NLRP3 inflammasome activation and transforming growth factor-β signaling that play a role in driving the transition to steatohepatitis and fibrosis. In addition, soy isoflavones, via estrogen receptor-beta agonism, have anti-fibrotic potential, and supplemental glycine may blunt the contribution of Kupffer cells to the progression of NAFLD. Whole-food plant-based diets of modest protein content, owing to their impact on hormones such as fibroblast growth factor 21 and adiponectin, as well as on the obesity and metabolic syndrome underlying NAFLD, may also be protective in this syndrome. There is considerable potential for complex medical foods or nutraceutical supplementation regimens of rational design to aid prevention and control of NAFLD.

Atherosclerosis (ATH) and Coronary Artery Disease (CAD) are chronic inflammatory diseases with an important genetic background which derive from the cumulative effect of multiple common risk alleles, most of them located in genomic non-coding regions. These complex diseases behave as non-linear dynamical systems that show a high dependence on their initial conditions, so that long-term predictions of disease progression are unreliable. One likely possibility is that the non-linear nature of ATH could be dependent on non-linear correlations in the structure of the human genome. In this review we show how Chaos theory analysis highlighted genomic regions that shared specific structural constraints that could have a role in ATH progression. These regions were shown to be enriched in repetitive sequences of the Alu family, genomic parasites which colonized the human genome, which show a particular secondary structure and have been involved in the regulation of gene expression. We also review the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms by which the Alu elements could alter the inflammatory homeostasis. We devise especial attention to their relationship with the lncRNA ANRIL, the strongest risk factor for ATH, their role as miRNA sponges, and their ability to interfere with the regulatory circuitry of the NF-kB response. We aim to characterize ATH as a non-linear dynamic system in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

As non-operative management (NOM) of esophageal and rectal cancer is becoming more prevalent, blood-biomarkers such as circulating tumor DNA (ctDNA) may provide clinical information in addition to endoscopy and imaging to aid in treatment decisions following chemotherapy and radiation therapy. In this feasibility study, we prospectively collected plasma samples from locally advanced esophageal (n=3) and rectal cancer (n=2) patients undergoing multimodal neoadjuvant therapy to assess the feasibility of serial ctDNA monitoring throughout neoadjuvant therapy. Using the DIDA-Seq error-correction method, we serially interrogated plasma cell-free DNA at 28-41 tumor-specific genomic loci throughout therapy and in surveillance with an average limit of detection of 0.016% mutant allele frequency. In both rectal cancer patients, ctDNA levels were persistently elevated following total neoadjuvant therapy with eventual detection of clinical recurrence prior to salvage surgery. Among the esophageal cancer patients, ctDNA levels closely correlated with tumor burden throughout and following neoadjuvant therapy, which was associated with a pathologic complete response in one patient. In this feasibility study, patient and tumor-specific ctDNA levels correlated with clinical outcomes throughout multi-modality therapy suggesting that serial monitoring of patient ctDNA has the potential to serve as a highly sensitive and specific biomarker to risk-stratify esophageal and rectal cancer patients eligible for NOM. Further prospective investigation is warranted.

Gradual disability worsening in Multiple Sclerosis (MS) is indicative of confirmed progression that mostly involves progression independent of relapse activity (PIRA) and is associated with neurodegeneration. Insights from pathology reveal grey matter involvement (neocortex, hippocampus, spinal cord, and deep grey matter structures) and microglia activation in early stages of MS. Cortical lesions result in thinning and atrophy and are considered accurate predictors of disability progression and cognitive decline.Neuroimaging biomarkers, such as high-resolution 7T MR images and TSPO-PET, have been examined for the detection of cortical pathology linked to cognitive deficits and thus progression, but are limited in clinical practice due to availability, time constraints, and cost.Electroencephalography (EEG) emerges as a non-invasive, cost-effective tool that reflects cortical activity in MS. Its potential in monitoring cognitive impairment is explored by focusing on nonlinear EEG analysis. The MuST PREDICT^TM project aims to extract linear and nonlinear EEG features, investigating their role in predicting disease progression and optimizing treatment. The study employs retrospective, cross-sectional, and prospective designs, utilizing EEGs from various MS forms, cognitive assessments, serum/cerebrospinal fluid biomarkers and neuroimaging. The methodology involves time-based and spectral feature extraction, employing artificial intelligence classifiers and brain criticality-based approaches.The conceptual framework of an innovative modality is herein presented, that would EEG for early MS progression detection. Standardization of the methodology could lead to the creation of a digital tool for better prognostication and treatment strategy optimization.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

Reporting on CSR activities has become the essence of reporting for modern business entities. In this regard, particular attention is paid to public interest companies. Therefore, the following paper aims to answer the question of whether there are differences in the linguistic structure of the studied CSR reports in three selected industry indices on the Warsaw Stock Exchange (WSE) in Poland, i.e. WIG-energy index, WIG-fuel index, WIG-mining index and their relationship with the performance of selected companies. The study was conducted on a purposely selected sample of companies between 2013 and 2018. A total of 138 CSR reports and 138 annual separate financial statements prepared in accordance with international balance sheet law were collected. The study was carried out based on a panel regression model. It was found that CSR reports contained similar average percentages of parts of speech such as nouns and adjectives. When linking the economic performance of companies, expressed with selected indices, to the information on the implementation of CSR concepts, it was revealed that the results are more likely to describe business performance when it is satisfactory.

In a single-center, retrospective study, 22 cases were enrolled and divided into two groups: those who underwent surgical wide excision (group A) and those who did not (group B). The study included 13 cases in group A and 9 cases in group B. In group A, 6 cases solely underwent surgical wide excision, while 7 cases received additional treatments like radiotherapy or chemotherapy. Conversely, in group B, 4 cases received chemotherapy, 4 cases received radiotherapy, and 1 case was managed through observation alone. The mean follow-up time was 60.15 months in group A and 43.44 months in group B, with no significant difference observed. In group A, 9 cases resulted in mortality, whereas 6 cases died within the follow-up period in group B. Lesion-free intervals post-operation were observed predominantly in group A, while 7 cases in group B never experienced freedom from skin lesions. Kaplan-Meier survival curve analysis demonstrated a significant difference between the survival curves of the two groups (P = 0.046). Among non-HIV Kaposi’s sarcoma patients, surgical wide excision appears to have a role in treatment. Patients in group A exhibit a more favorable outcome in the survival curve analysis.

The most common liver disorder nowadays is non-alcoholic fatty liver disease(NAFLD) and it is a progressive disease that rises in severity from steatosis to nonalcoholic steatohepatitis(NASH), fibrosis and cirrhosis to increase risk of developing hepatocellular carcinoma. It is a cause of great concern as there is an estimated seventy million Americans who are currently affected by NAFLD, and this is expected to only increase because of its association with obesity and diabetes and also a lack of therapies to keep its development and progression in check. In this particular study we performed a gene set enrichment analysis(GSEA) of differentially expressed genes in a green tea against methionine-choline deficient diet in high-fat patients in the development of non-alcoholic fatty liver disease(NAFLD). The downregulated genes were used to perform an enrichment analysis and in the ARCHS4 TFs Coexpression database the most significant gene was found to be KLF5_human_tf_ARCHS4_coexpression. In the ARCHS4 Kinases Coexpression pathway database STYK1_human_kinase_ARCHS4 Coexpression was found to be the most significant gene. And finally for the upregulated genes a similar enrichment analysis was performed and in the humancy database γ-linolenate biosynthesis_Homo sapiens_PWY-6000 gene was discovered to be the most significant one. This study has used bioinformatics tools and the Enrichr software to perform a comparative analysis of differentially expressed gene sets for high-fat patients having a diet consisting of green tea against a methionine-choline deficient diet. Green tea is known to contain several antioxidants and polyphenols which provide protection against many liver diseases such as non-alcoholic fatty liver disease(NAFLD). The present study simply tries to build awareness of this to the general public and allow them to learn more about certain diets which have protective effects against liver diseases. Hopefully by implementing these in their daily lifestyles the public can gain some form of protection against these types of liver disorders.

Objective: To investigate whether impaired plantar cutaneous vibration perception contributes to axial motor symptoms in Parkinson’s disease (PD) and whether anti-parkinsonian medication and subthalamic nucleus deep brain stimulation (STN-DBS), show different effects. Methods: Three groups were tested: PD patients on medication (PD-MED), PD patients on medication and additional STN-DBS (PD-MED–DBS), and healthy subjects (HS) as reference. Motor performance was analyzed using a pressure distribution platform. Plantar cutaneous vibration perception thresholds (VPT) were investigated using a customized vibration exciter at 30 Hz. Results: Motor performance of PD-MED and PD-MED–DBS was characterized by greater postural sway, smaller limits of stability ranges, and slower gait, due to shorter strides, fewer steps per minute, and broader stride widths compared to HS. Comparing patient groups, PD-MED–DBS showed better overall motor performance than PD-MED, particularly for the functional limits of stability and gait. VPTs were significantly higher for PD-MED compared to HS, which suggests impaired plantar cutaneous vibration perception in PD. However, PD-MED–DBS showed less impaired cutaneous vibration perception than PD-MED. Conclusion: PD patients suffer from poor motor performance compared to healthy subjects. Anti-parkinsonian medication in conjunction with STN-DBS seems to be superior for normalizing axial motor symptoms compared to medication alone. Plantar cutaneous vibration perception is impaired in PD patients, whereas anti-parkinsonian medication together with STN-DBS is superior for normalizing tactile cutaneous perception compared to medication alone. Consequently, based on our results and the findings of the literature impaired plantar cutaneous vibration perception might contribute to axial motor symptoms in PD.

For the treatment of cancer and other diseases, therapeutic targeting of non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) is an attractive approach. RNA-based therapeutics have been extensively researched over the past decade, with antisense oligonucleotides and small interfering RNAs being the most commonly used. Some of these have even gained FDA approval. However, the results of trials have been mixed, with some studies reporting strong effects while others have shown limited effectiveness or toxicity. Alternative treatments, such as antimiRNAs, are currently in clinical trials. There is growing interest in the use of lncRNA-based therapies. This Perspective discusses the main challenges of ncRNA therapeutics, including specificity, delivery and tolerability. It also highlights emerging approaches that aim to improve their success.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

Non-compliant (NC) structures are often encountered in building construction in developing countries. This is a condition whereby erected buildings do not follow regulatory standards, especially in the provision of reinforcements. Therefore, under an earthquake load, the structures do not have sufficient resistance against such load. The structural elements of the building, which often have NC conditions, are the beam-column joints because they do not contain adequate shear reinforcements due to installation difficulty. This study aims to determine the structural performance of the reinforced concrete (RC) frame, which has a reinforcement deficiency in the beam-column joints. Numerical simulation was conducted on the Kakaletsis structure model by modifying the reinforcement details at the joints to represent the NC conditions. The non-linear modeling and analysis of the structural model were carried out using ATENA software. The analysis showed that the reduction in shear reinforcements in the NC model joint caused a decrease in load-carrying capacity by about 26.04%. A shift was also observed in the collapse pattern, i.e., from the beam to the end of the column, causing global failure and reducing the undamaged but increasing more severely damaged condition. This showed that the NC structure, due to the non-conformance of reinforcement, significantly reduced the structure's performance.

An exhaustive list of thirteen instances of reports confirming experimentally the relativistic Doppler relation, are examined. For those involving longitudinal Doppler, the non-relativistic relation is seen to be confirmed, within the reported experimental accuracies, to the same degree as the standard relativistic relation. Higher values of the speed of the emitter would be required to examine further the claimed confirmations. For those reports involving saturation spectroscopy, there is much confusion over the appropriate Doppler relation to be used, together with some serious analytical flaws. For the two cases that involve transverse Doppler, there are seen to be either serious faults in the theoretical part, or intrusion from the first order effect. Therefore, the reported conclusions - that the results for the experiments confirm the relativistic SR relation - cannot be justified by any of the experimental works.

We introduce a novel key exchange protocol based on non-commutative matrix multiplication defined in $\mathbb{F}_p^{n \times n}$. The security of our method does not rely on computational problems as integer factorization or discrete logarithm whose difficulty is conjectured. We show that the public, secret and channel keys become indistinguishable to the eavesdropper under matrix multiplication. Remarkably, for achieving a 512-bit security level, the public key is 1024 bits and the private key is 768 bits, making them the smallest keys among post-quantum key exchange algorithms. Also, we discuss how to achieve key authentication, interdomain certification and Perfect Forward Secrecy (PFS). Therefore, Lizama's algorithm becomes a promising candidate to establish shared keys and secret communication between (IoT) devices in the quantum era.

We introduce a novel key exchange protocol based on non-commutative matrix multiplication defined in $\mathbb{Z}_p^{n \times n}$. The security of our method does not rely on computational problems as integer factorization or discrete logarithm whose difficulty is conjectured. We claim that the unique eavesdropper's opportunity to get the secret/private key is by means of an exhaustive search which is equivalent to the unsorted database search problem. Furthermore, we show that the secret/private keys become indistinguishable to the eavesdropper. Remarkably, to achieve a 512-bit security level, the keys (public/private) are of the same size when matrix multiplication is done over a reduced 8-bit size modulo. Also, we discuss how to achieve key certification and Perfect Forward Secrecy (PFS). Therefore, Lizama's algorithm becomes a promising candidate to establish shared keys and secret communication between (IoT) devices in the quantum era.

This article develops duality principles and numerical results for a large class of non-convex variational models. The main results are based on fundamental tools of convex analysis, duality theory and calculus of variations. More specifically the approach is established for a class of non-convex functionals similar as those found in some models in phase transition. Finally, in the last section we present a concerning numerical example and the respective software.

Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying \begin{align*} \left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2, \quad \forall \lambda_j \in \mathbb{K}, 1\leq j \leq n, \forall n \in \mathbb{N}. \end{align*} For $d\in \mathbb{N}$, let $\mathbb{K}^d$ be the standard $d$-dimensional non-Archimedean Hilbert space. Let $m \in \mathbb{N}$ and $\text{Sym}^m(\mathbb{K}^d)$ be the non-Archimedean Hilbert space of symmetric m-tensors. We prove the following result. If $\{\tau_j\}_{j=1}^n$ is a collection in $\mathbb{K}^d$ satisfying $\langle \tau_j, \tau_j\rangle =1$ for all $1\leq j \leq n$ and the operator $\text{Sym}^m(\mathbb{K}^d)\ni x \mapsto \sum_{j=1}^n\langle x, \tau_j^{\otimes m}\rangle \tau_j^{\otimes m} \in \text{Sym}^m(\mathbb{K}^d)$ is diagonalizable, then \begin{align}\label{WELCHNONABSTRACT} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |\langle \tau_j, \tau_k\rangle|^{2m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{WELCHNONABSTRACT}) as the non-Archimedean version of Welch bounds obtained by Welch [\textit{IEEE Transactions on Information Theory, 1974}]. We formulate non-Archimedean Zauner conjecture.

Nonionizing millimeter-waves (MMW) interact with cells in a variety of ways. Here the inhibited cell division effect was investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm2 safety standards. Irradiation using a power density of about 1.0 mW/cm2 , SAR over 5-6 hours on 50 cells/μl samples of Saccharomyces cerevisiae model organism resulted in 62% growth rate reduction compared to the control (sham). The effect was specific for 85-105 GHz range, and was energy and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deleted cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause permanent genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm2) and compared to that of a compact waveguide (17.17 mW/cm2) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. We have shown that non-thermal MMW radiation has potential for future use in treatment of yeast related diseases and other targeted biomedical outcomes.

Nonionizing millimeter-waves (MMW) are reported to interact with cells in a variety of ways. Possible mechanisms of the inhibited cell division effect were investigated using 85-105 GHz MMW irradiation within the ICNIRP (International Commission on Non-Ionizing Radiation Protection) non-thermal 20 mW/cm² safety standards. ~1.0 mW/cm² exposure over 5-6 hours treatment on 50 cells/μl samples of Saccharomyces cerevisiae model organism, resulted in 62% growth rate reduction compared to control (sham). The effect was specific for 85-105 GHz range and energy dose and cell density dependent. Irradiation of wild type and Δrad52 (DNA damage repair gene) deletion cells presented no differences of colony growth profiles indicating non-thermal MMW treatment does not cause genetic alterations. Dose versus response relations studied using a standard horn antenna (~1.0 mW/cm²) and compared to that of a compact waveguide (17.17 mW/cm²) for increased power delivery resulted in complete termination of cell division via non-thermal processes supported by temperature rise measurements. Combinations of MMW mediated Structure Resonant Energy Transfer (SRET), membrane modulations eliciting signaling effects, and energetic resonance with biomolecules were indicated to be responsible for the observations reported. Our results provide novel mechanistic insights enabling innovative applications of nonionizing radiation procedures for eliciting targeted biomedical outcomes.

Non-isocyanate polyurethane synthesis by non-Sn catalysis is an essential challenge toward green polyurethane synthesis. Bismuth compounds are attractive candidates due to their low cost, low toxicity, and availability to urethane chemistry. We applied various Bi catalysts to the self-polycondensation of a bishydroxyurethane monomer and found BiCl3 to be an excellent catalyst through optimization. The catalytic activity and price of BiCl3 are comparable to those of Bu2SnO, while its toxicity is significantly low. BiCl3 is, therefore, a promising alternative to Sn-based catalysts in non-isocyanate polyurethane synthesis.

Wine is a processed beverage that offers high nutritional and health benefits. It is produced from grape must, which undergoes fermentation by yeasts (and sometimes lactic acid bacteria) to create a product that is highly appreciated by consumers worldwide. However, if only one type of yeast, specifically Saccharomyces cerevisiae, were used in the fermentation process, the resulting wine would lack aroma and flavor and may be rejected by consumers. To produce wine with a desirable taste and aroma, non-Saccharomyces yeasts are necessary. These yeasts contribute volatile aromatic compounds that significantly impact the wine’s final taste. They promote the release of primary aromatic compounds through a sequential hydrolysis mechanism involving several glycosidases unique to these yeasts. This review will discuss the unique characteristics of these yeasts (Schizosaccharomyces pombe, Pichia kluyveri, Torulaspora delbrueckii, Wickerhamomyces anomalus, Metschnikowia pulcherrima, Hanseniaspora vineae, Lachancea thermotolerans, Candida stellata, and others) and their impact on wine fermentations and co-fermentations. Their existence and the metabolites they produce enhance the complexity of wine flavor, resulting in a more enjoyable drinking experience.

Post-quantum public cryptosystems introduced so far do not define an scalable public key infrastructure for the quantum era. We demonstrate here a public certification system based in Lizama’s non-invertible Key Exchange Protocol which can be used to implement a public key infrastructure (PKI), secure, scalable, interoperable and efficient. We show functionality of certificates across different certification domains. Finally, we discuss that non-invertible certificates can exhibit Perfect Forward Secrecy (PFS).

It is well established in literature that the public debt and economic growth bear positive and non-linear relationship. However, in recent literature, evidence of no causal relationship is found when accounted for endogeneity in case of advanced economies (Panizza & Presbitero, 2014). Chudik, Mohaddes, Pesaran, & Raissi, (2017) analyse the data on forty countries and find no evidence of universally applicable threshold effect in the relationship between debt and growth. These advancements in the debt-growth literature provides the motivation to re-explore the relationship between public debt and economic growth under non-linearity and endogeneity in context of developing economies of South Asia including Pakistan, India, Bangladesh and Sri-Lanka for the period 1980-2014. There exists a significant, positive but nonlinear relationship between the public debt and economic growth for the selected set of developing countries when accounted for endogeneity and non-linearity. The negative association between the public debt and economic growth for SAARC region is found when the debt level is higher than 61% of GDP which is quite lower than developed economies (90% of GDP). Individual threshold levels for debt-to-GDP ratio divulge that Sri Lanka, Pakistan and India need to control their public borrowings as their current debt levels are higher and/or around the respective threshold levels.

Coronavirus disease 2019 (COVID-19) has detrimental multi-system consequences. Symptoms may appear during the acute phase of infection, but literature on long-term recovery of young adults after mild-to-moderate infection is lacking. Heart rate variability (HRV) allows observation of autonomic nervous system (ANS) modulation post SARS-CoV-2 infection. Additionally, physical activity (PA) helps improve ANS modulation, where investigation of PA influence on ANS recovery is vital to reduce risk and severity of symptoms. Clinicians may use this research to aid development of non-medication interventions. At baseline, 18 control (CT) and 20 post-COVID-19 (PCOV) participants were observed where general amnamnesis was performed, followed by HRV and PA assessment. 10 CT and 7 PCOV subjects returned for follow-up (FU) evaluation 6 weeks after complete immunization (2 doses) and assessments were repeated. Over the follow-up period, decrease in sympathetic (SNS) activity (mean heart rate: p=0.0024, CI=-24.67- -3.26; SNS index: p=0.0068, CI=-2.50- -0.32) and increase in parasympathetic (PNS) activity (mean RR:p=0.0097, CI=33.72-225.51; PNS index: p=0.0091, CI=-0.20-1.47) were observed. At follow-up, HRV was not different between groups (p>0.05). Additionally, no differences were observed in PA between moments and groups. This study provides evidence of ANS recovery after SARS-CoV-2 insult in young adults over a follow-up period, independent of changes in PA.

We establish a new Gagliardo-Nirenberg inequality characterized by radial symmetry and involving potentials exhibiting pure power polynomial behaviour. As an application of our result, we investigate the existence of extremals for this inequality, which also correspond to stationary solutions for the nonlinear Schrödinger equation with inhomogeneous nonlinearity, competing with Hs-subcritical nonlinearities, either of local or non-local nature.

Non-alcoholic steatohepatitis (NASH), which is the most severe manifestation of non-alcoholic fatty liver disease (NAFLD), has been recognized as a major hepatocellular carcinoma (HCC) catalyst. However, the molecular mechanism of NAFLD-NASH-HCC sequence remains unclear and a specific and effective treatment for NASH has not yet been established. The progress in this field depends on the availability of reliable preclinical models which show the steady progress to NASH, liver cirrhosis, and HCC. However, most of NASH mouse models that have been described to date develop NASH generally for more than 24 weeks and there is an uncertainty of HCC development. To overcome such shortcomings of experimental NASH studies, we established a novel NASH-HCC mouse model with very high reproducibility, generality, and convenience. We treated male C57BL/6J mice with a newly developed choline-deficient and methionine-restricted high-fat diet (CDMRHFD) for 60 weeks. Treatment of CDMRHFD for 3 weeks revealed marked steatosis, lobular inflammation, and fibrosis, histologically diagnosed as NASH. Liver cirrhosis was observed in all mice with 36-week treatment. Liver nodule emerged at 12 weeks of the treatment, and diameter >2 mm liver tumors developed in all mice at 24 weeks of the treatment. In conclusion, our rapidly progressive and highly reproducible NASH-liver cirrhosis-HCC model is helpful for preclinical development and research on the pathogenesis of human NAFLD-NASH-HCC. Our mouse model would be useful for the development of novel chemistry for NASH-HCC-targeted therapies or HCC prevention strategies.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

This article develops a duality principle and a related convex dual formulation suitable for a large class of models in physics and engineering. The results are based on standard tools of functional analysis, calculus of variations and duality theory. In particular, we develop applications to a model in non-linear elasticity.

The connection of two phenomena - non-conservative friction forces and dissipation-induced instability can lead to many interesting engineering problems. The paper studies general material-dependent damping influence on dynamical instability of disc brake systems leading to brake squeal. The effect of general damping is demonstrated on a minimal and complex model of a disc brake. A complex system including material-dependent damping is defined in the commercial finite element software. The finite element model validated by experimental data on the brake-disc test bench is used to compute the influence of a pad and a disc damping variations on system stability by complex eigenvalue analysis. Analyzes show a significant sensitivity of the experimentally verified unstable mode of the system to the ratio of the damping between the disc and the friction material components.

Near-fault ground motions can cause severe damage to civil structures, including bridges. Safety assessment of these structures for near fault ground motion is usually performed through Non-Linear Dynamic Analyses, while faster methods are often used. IMPAb (Incremental Modal Pushover Analysis for Bridges) permits to investigate the seismic response of a bridge by considering the effects of higher modes, which are often relevant for bridges. In this work, IMPAb is applied to a bridge case study considering near-fault pulse-like ground motion records. The records were analyzed and selected from the European Strong Motion Database and the pulse parameters were evaluated. In the paper results from standard pushover procedures and IMPAb are compared with nonlinear Response-History Analysis (NRHA), considering also the vertical component of the motion, as benchmark solutions and incremental dynamic analysis (IDA). Results from the case study demonstrate that the vertical seismic action has a minor influence on the structural response of the bridge. Therefore IMPAb, which can be applied considering vertical motion, remains very effective conserving the original formulation of the procedure, and can be considered a well performing procedure also for near-fault events.

Abrasive Water Jet Machining (AWJM) is a non-conventional machining process that, unlike other methods, is deemed superior because of its applicability, versatility, and no heat-affected zones in the target material. The main objective of this paper was to develop a cheap, practical model for a low-pressure water jet cutting machine and provide some empirical test data for cutting delicate materials. Proper design calculations were performed and are included for both the water jet machine and the two-axis numerical control. Finite Element Analysis results validate the structural integrity of beams and columns in AWJM. Computational Fluid Dynamic analysis of the nozzle shows good agreement with the theoretical calculations regarding the pressure and velocity of the water-abrasive mixture exiting the nozzle. Modal analysis in ANSYS was done to mitigate potential failure due to resonance induced by vibrations. Limited testing on various thicknesses of polystyrene foam ranging from 1-5 mm thickness and rubber sheet of 1 mm thickness showed that even low pressure of 25-30 bar was sufficient to produce a kerf without any burr. However, extensive testing to report optimized parameters like nozzle transverse speed, standoff distance, abrasive flow rate, etc for working at low-pressure ranges is still a consideration for future investigation.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

Turbulent dissipation is a central issue in the star and galaxy formation process. Its fundamental property of space-time intermittency, well characterised in incompressible laboratory experiments, remains elusive in cosmic turbulence. Progress requires the combination of state-of-the-art modelling, numerical simulations and observations. The power of such a combination is illustrated here where the statistical method intended to locate extrema of velocity shears in a turbulent field is applied to numerical simulations of compressible magneto-hydrodynamical (MHD) turbulence dedicated to dissipation scales and to a nearby turbulent diffuse molecular cloud. We demonstrate that short-spacing increments of observables can detect strongly dissipative structures. In our simulations, we compute structure functions of various synthetic observables and show that they verify Extended Self-Similarity. This allows to compute their intermittency exponents and we show how they could help constraining some properties of the underlying three-dimensional turbulence. In observations of a turbulent cloud close to the Sun in our Galaxy, a remarkable coherent structure of velocity shear extremum is disclosed . At the location of the largest velocity shear, this coherent structure is found to foster 10 × more carbon monoxide molecules than standard diffuse molecular gas, an enrichment supported by models of non-equilibrium warm chemistry triggered by turbulent dissipation. The power of the combination between modelling and observations is also illustrated by observations of the CH+ cation that provide unique quantitative informations on the kinetic energy trail in the massive, multi-phase and turbulent circum-galactic medium of a galaxy group at redshift z = 2.8.

In this paper is presented the design and syntheis of a dynamic output feedback neural network controller for a non-holonomic mobile robot. First the dynamic model of a non-holonomic mobile robot is presented, in which these constraints are considered for the mathematical derivation of a feasable representation for this kind of robot. Then two control strategies are provided based on kinematic control for this kind of robot. The first control strategy is based on driftless control, this means, that considering that the velocity vector of the mobile robot is orthogonal to its restriction a dynamic output feedback and neural network controller is designed in order that the control action would be zero only when the velocity of the mobile robot is zero. The Lyapunov stability theorem is implemented in order to find a suitable control law. Then another control strategy is designed for trajectory tracking purposes, which similar to the driftless controller, a kinematic control scheme is provided but suitable to implement in more sophisticated hardware. In both control strategy a dynamic control law is provided along with a feedforward neural network controller, so in this way, by the Lyapunov theory the stability and convergence to the origin of the mobile robot position coordinates is ensured. Finally, two numerical experiment are presented in order to validate the theoretical results synthetized in this research study. Discussions and conclusions are provided in order to analyze the results found in this research study.

Non-vertebrate species represent about ~95% of known metazoan (animal) diversity. They remain to this day relatively unexplored genetically, but understanding their genome structure and function is pivotal for expanding our current knowledge of evolution, ecology and biodiversity. Following the continuous improvements and decreasing costs of sequencing technologies, many genome assembly tools have been released, leading to a significant amount of genome projects being completed in recent years. In this review, we examine the current state of genome projects of non-vertebrate animal species. We present an overview of available sequencing technologies, assembly approaches, as well as pre and post-processing steps, genome assembly evaluation methods, and their application to non-vertebrate animal genomes.

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1×10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

The quality and shelf-life of NCS (Non-centrifugal sugar) mainly depend on the moisture content present in it. NCS formed by the current practice of open sun drying contains moisture substantially greater than the acceptable level of 3%. This paper presents the work taken up to design a tunnel dryer to attain require moisture content in granular NCS for various load conditions. Initially, an experimental investigation had been carried out on a laboratory scale dryer to achieve required moisture content (< 3%) for various load conditions. This experimental data was used for validating two drying models and found that one of the models is best suitable for designing an industrial-scale dryer. For various load conditions on each tray and dryer exit temperature, nine different cases were arrived at. The number of trucks, trays, drying time and energy requirements were computed using the suitable theoretical model. Tunnel dryer with a length of 18 m, a height of 1.2 m, a width of 1 m, number of trucks of 18 and 24 number of trays on each truck was found to be the suitable dryer to dry 1 tone of NCS based on the minimum energy requirement of 176.49 MJ, and a minimum drying time of 68 minutes.

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3'UTR of tick-borne, insect-specific and no-known-vector flaviviruses in silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs xrRNAs within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3'UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs

The aim of the study was to identify factors associated with non-adherence to tuberculosis (TB) preventive treatment among contacts with latent TB infection of new cases of pulmonary TB cases reported in Catalonia in 2019-2021. All contacts aged 18 years or older with a latent TB infection who received a TB preventive treatment were included in the study. The Chi square test and the odds ratios (OR) were used to assess the association between non-adherence to TB preventive treatment and the study variables, considering a p < 0.05 as statistically significant. Multiple logistic regression analysis was used to detect the in-dependent factors associated with TB preventive treatment non-adherence, considering a p < 0.05 as statistically significant. The percentage of non-adherence to TB preventive treatment found in this study was 23.7%. A multivariable logistic regression analysis determined that the following factors were significantly associated with TB preventive treatment non-adherence among adult contacts: “exposure at school or workplace” (aOR = 3.34), “exposure to an index case without laboratory confirmation of TB” (aOR = 2.07), “immigrant contact” (aOR = 1.81), “male gender” (aOR = 1.75) and “exposure duration <6 hours per week or sporadic exposure” (aOR = 1.60). By contrast, the factor “short-term TB preventive treatment regimen” (aOR = 0.38) was significantly associated with a lower treatment non-adherence. Adherence to TB preventive treatment should be improved among adult contacts of TB pulmonary cases with latent TB infection by recommending short-term treatment regimens and by developing health education activities, with a greater focus on contacts with factors associated with treatment non-adherence.

Non-alcoholic beer (NAB) or low alcoholic beer (LAB) are taking over the market with a growing sale. Sus-tainable recycling and valorization of exhausted brewer’s spent grains (BSG) coming from craft beer is a relevant issue in brewing process. In this work, recycled BSG and BSG+GJ (supplemented with 10% grape juice) were used as wort-substrate to inoculate already selected non-conventional yeasts to produce NABLAB craft beer. Results showed that wort composed by only recycled BSG produced appreciate NAB beers (ethanol from 0.12% to 0.54 % v/v) while the addition of 10% of grape juice made LAB beers (ethanol from 0.82 to 1.66 % v/v). As expected, volatile compounds production was highest with the addition of grape juice. Lachancea thermotolerans confirmed the lactic acid production and, as Saccharomyces cerevisiae, is characterized by (in both worts) ethyl butyrate and isoamyl acetate, while Torulaspora delbrueckii produced relevant amounts of exanol, phenylethyl acetate and β-phenyl ethanol (wort added with grape juice). Wickeramhomyces anomalus and Pichia kluyvery showed consistent volatile production but only in wort with grape juice addition where a fermentation activity was exhibited. The overall results indicated that reused BSGs, non-conventional yeasts and grape juice is a suitable strategy for specialty NABLAB beer.

With increased vulnerabilities and vast technology landscapes, it is extremely critical to build systems which are highly resistant to cyber-attacks, to break into systems to exploit. It is almost impossible to build 100% secure authentication & authorization mechanisms merely through standard password / PIN (With all combinations of special characters, numbers & upper/lower case alphabets and by using any of the Graphical password mechanisms). The immense computing capacity and several hacking methods used, make almost every authentication method susceptible to cyber-attacks in one or the other way. Only proven / known system which is not vulnerable in spite of highly sophisticated computing power is, human brain. In this paper, we present a new method of authentication using a combination of computer’s computing ability in combination with human intelligence. In fact this human intelligence is personalized making the overall security method more secure. Text based passwords are easy to be cracked ^[6]. There is an increased need for an alternate and more complex authentication and authorization methods. Some of the Methods ^{[7] [8]} in the category of Graphical passwords could be susceptible, when Shoulder surfing/cameras/spy devices are used.

Previous studies demonstrate the critical importance of non-coding RNAs interfacing with chromatin-modifying machinery resulting in promoter-enhancer-based gene regulation and raise the possibility that many other enhancer-like RNAs may operate via similar mechanisms. Critically, more than 80% of the disease-linked variations identified in genome-wide studies are located in the non-coding regions of genomes, especially non-coding RNA, suggesting non-coding RNAs are relevant to disease. Thus, a critical path forward for understanding non-coding RNAs' role, especially long non-coding RNAs, is to understand the genomic regions' transcriptional regulation, especially non-coding regions. Here, we developed a user-friendly R package called SomaGene for studying and identifying enhancer-like non-coding RNAs with enriched somatic mutations in the cancer genome. SomaGene accepts different genomic variants (whole genome/exome somatic point mutations, structural variations, copy number variations) to identify those RNAs that significantly mutated in diseases (e.g., cancer). It then uses multiple publicly available genomics and epigenetics datasets including ENCODE epigenomics annotations, FANTOM5 tissue-specific expression profiles, disease-associated genome-wide association SNPs, and tissue-specific eQTL pairs to identify those RNAs with potentially enhancer function. SomaGene, as a powerful R package, can provide the opportunity to cancer scientists to study the roles of non-coding RNAs in different cancer genomes.