Search Results (299)

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

In recent years, advances in organ transplantation medicine have led to an increase in pregnancies and births following transplantation. Pregnancy after organ transplantation is considered high-risk, and its impact on both the recipient and the child must be carefully evaluated. In this review, we summarize the current landscape of pregnancy and childbirth after organ transplantation, with a particular focus on uterus transplantation (UTx). Traditionally, organ transplants have involved vital organs; however, UTx, developed for women with absolute uterine factor infertility, represents a novel approach. Although the number of births following UTx remains limited, it is expected to grow due to the international expansion of this procedure. Importantly, the concept of pregnancy and delivery following UTx is fundamentally different from that of other organ transplants. UTx is a life-enhancing, non-vital, and temporary transplant uniquely intended to enable the creation of new life. Pregnancy after UTx carries specific risks such as a higher incidence of miscarriage, preterm birth, hypertensive disorders of pregnancy, and gestational diabetes. All deliveries are performed via cesarean section, and conception is typically allowed after a relatively short period following transplantation, given the temporary nature of the graft and the goal to minimize recipient burden, with generally good neonatal outcomes. As pregnancies after both solid organ transplantation and UTx continue to rise worldwide, the development of standardized, organ-specific perinatal management strategies, particularly for UTx, is essential. Multidisciplinary collaboration will be critical to supporting these high-risk pregnancies and ensuring the best possible maternal and neonatal outcomes. Full article

Improved antiretroviral therapy (ART) has significantly increased the life expectancy of people living with HIV (PLWH). At the same time, other complications like metabolic syndrome (MetS) are coming up as new challenges to handle. This review aims to explore the emerging evidence of gut microbiome and virome alterations in human immunodeficiency virus-1 (HIV-1) infection and associated metabolic disorders, such as type-2 diabetes (T2DM) and cardiovascular disease (CVD), with a focus on their interplay, contribution to immune dysfunction, and potential as therapeutic targets. We conducted a comprehensive review of the current literature on gut bacteriome and virome changes in HIV-1-infected individuals and those with metabolic comorbidities emphasizing their complex interplay and potential as biomarkers or therapeutic targets. HIV-1 infection disrupts gut microbial homeostasis, promoting bacterial translocation, systemic inflammation, and metabolic dysregulation. Similarly, metabolic disorders are marked by reduced beneficial short-chain fatty acid-producing bacteria and an increase in pro-inflammatory taxa. Alterations in the gut virome, particularly involving bacteriophages, may exacerbate bacterial dysbiosis and immune dysfunction. Conversely, some viral populations have been associated with immune restoration post-ART. These findings point toward a dynamic and bidirectional relationship between the gut virome, bacteriome, and host immunity. Targeted interventions such as microbiome modulation and fecal virome transplantation (FVT) offer promising avenues for restoring gut homeostasis and improving long-term outcomes in PLWH. Full article

Central nervous system diseases are highly complex in terms of etiology and pathogenesis, making their treatment and interventions for them a major focus and challenge in neuroscience research. Anthocyanins, natural water-soluble pigments widely present in plants, belong to the class of flavonoid compounds. As natural antioxidants, anthocyanins have attracted extensive attention due to their significant functions in scavenging free radicals, antioxidation, anti-inflammation, and anti-apoptosis. The application of anthocyanins in the field of central nervous system injury, particularly in neurodegenerative diseases, neurotoxicity induced by chemical drugs, stress-related nerve damage, and cerebrovascular diseases, has achieved remarkable research outcomes. However, anthocyanins often exhibit low chemical stability, a short half-life, and relatively low bioavailability, which limit their clinical application. Recent studies have found that the stability and bioavailability of anthocyanins can be significantly improved through nanoencapsulation, acylation, and copigmentation, as well as the preparation of nanogels, nanoemulsions, and liposomes. These advancements offer the potential for the development of anthocyanins as a new type of neuroprotective agent. Future research will focus on the innovative design of nano-delivery systems and structural modification based on artificial intelligence. Such research is expected to break through the bottleneck of anthocyanin application and enable it to become a core component of next-generation intelligent neuroprotective agents. Full article

Background/Objectives: Consuming comfort food is a common experience in daily life, but the underlying motives for engaging in comfort eating remain unclear. This study examined people’s expectations regarding their comfort food and investigated whether these expectations are associated with their frequency of comfort eating. As an exploratory aim, we also examined whether there are gender differences in preference for different categories of comfort food (i.e., sweet or savory) and the frequency of engaging in comfort eating. Methods: Through an online survey, participants (n = 214) reported their primary comfort food, the frequency of comfort eating in the short term (i.e., the past two weeks), and the general trend over the long term. They also rated statements related to their primary comfort food based on five expectation subscales (i.e., Manage Negative Affect; Pleasurable and Rewarding; Enhances Cognitive Competence; Alleviates Boredom; Positive Feelings). Results: Although Pleasurable and Rewarding and Positive Feelings received the strongest level of endorsement, their associations with the frequency-related variables were weak in both correlational and regression analyses. In contrast, Manage Negative Affect, Alleviates Boredom, and Enhances Cognitive Competence were positively associated with all frequency-related variables, with Alleviates Boredom showing the most consistent pattern. There were no significant gender differences in preferences for sweet or savory comfort food, and no significant gender differences in the frequency of eating comfort food. Conclusions: These findings suggest people believe they can gain a range of expected benefits from consuming comfort foods and perceive themselves as consuming comfort food primarily for rewarding themselves or gaining positive feelings. However, it is the expectations of managing negative affect, alleviating boredom, and enhancing cognitive competence that motivate them to engage in comfort eating. Full article

Prefabricated unidirectional carbon fiber reinforced polymer (CFRP) composite strips are extensively used as a means of infrastructure rehabilitation through adhesive bonding to the external surface of structural concrete elements. Most data to date are from laboratory tests ranging from a few months to 1–2 years providing an insufficient dataset for prediction of long-term durability. This investigation focuses on the assessment of the response of three different prefabricated CFRP systems exposed to water, seawater, and alkaline solutions for 5 years of immersion in deionized water conducted at three temperatures of 23, 37.8 and 60 °C, all well below the glass transition temperature levels. Overall response is characterized through tensile and short beam shear (SBS) testing at periodic intervals. It is noted that while the three systems are similar, with the dominant mechanisms of deterioration being related to matrix plasticization followed by fiber–matrix debonding with levels of matrix and interface deterioration being accelerated at elevated temperatures, their baseline characteristics and distributions are different emphasizing the need for greater standardization. While tensile modulus does not degrade appreciably over the 5-year period of exposure with final levels of deterioration being between 7.3 and 11.9%, both tensile strength and SBS strength degrade substantially with increasing levels based on temperature and time of immersion. Levels of tensile strength retention can be as low as 61.8–66.6% when immersed in deionized water at 60 °C, those for SBS strength can be 38.4–48.7% at the same immersion condition for the three FRP systems. Differences due to solution type are wider in the short-term and start approaching asymptotic levels within FRP systems at longer periods of exposure. The very high levels of deterioration in SBS strength indicate the breakdown of the materials at the fiber–matrix bond and interfacial levels. It is shown that the level of deterioration exceeds that presumed through design thresholds set by specific codes/standards and that new safety factors are warranted in addition to expanding the set of characteristics studied to include SBS or similar interface-level tests. Alkali solutions are also shown to have the highest deteriorative effects with deionized water having the least. Simple equations are developed to enable extrapolation of test data to predict long term durability and to develop design thresholds based on expectations of service life with an environmental factor of between 0.56 and 0.69 for a 50-year expected service life. Full article

Studies have indicated that there was a disease interaction of pandemic influenza with respiratory tuberculosis (TB) in Malta, which could explain the heightened mortality recorded in young adults. We revisit the 1918/19 influenza and TB syndemic potential on the island of Malta. Borrowing from crisis studies that explore the harvesting effect, we used the method of assessing changes in pre-pandemic, pandemic, fallow, and post-pandemic mortality/life expectancy to reveal the syndemic experience. Pre-pandemic (1914–1917) life expectancy at birth was significantly higher, at 37.91 years, than during the pandemic (1918), when life expectancy dropped to 33.26 years (Z = 10.56, p < 0.0001). Post-pandemic (1919) life expectancy rose to 43.49 years, which was an even longer life expectancy than pre-pandemic (Z = 17.61, p < 0.0001). There were significant changes in TB mortality death rates during the four periods in those of reproductive age. Augmenting our framework for studies of syndemics involving short-term events, we proposed the identification of contributing, driving, and limiting factors. Underlying living conditions contributed to the syndemic. The exacerbation of housing conditions, the economy associated with the First World War, and meteorological measures—temperature, relative humidity, and rainfall—were driving factors. The early implementation of mitigation strategies, such as restrictions on mass gatherings, were limiting factors of the syndemic. Full article

This paper offers a philosophical account of the specific form of romantic love underlying the ideal of love-based marriages. Rather than examining the institution of marriage, it considers marriage as the promise of infinite love between finite persons. Although this promise may seem irrational, even those who never formally marry still invoke phrases like ‘I love you forever’. In three steps, this paper explores what we could possibly mean by infinite love and how it can be rationally promised throughout a finite life. First, I trace the concept of infinite love back to the metaphysical discussions surrounding the emergence of the love-based marriage among German Idealists and Jena Romanticists. Next, drawing on John Searle’s speech act theory, I examine how the ideal of infinite love can be articulated as a promise. Finally, I turn to early existentialist thought—particularly the notions of passion (Lidenskab, Leidenschaft), repetition (Gjentagelsen, Wiederkehr), and the moment (Øjeblik, Augenblick) as developed by Kierkegaard and Nietzsche—to justify the meaning of the marital promise. In short, I propose that instead of interpreting the marital promise as a description of an expected reality, we should approach it as a passionate necessity that discloses the world in a fundamentally indeterminate way. By reframing the marital promise in this light, I aim to show that marital love is compatible both with the ideal of personal autonomy and with an alternative conception of rationality and temporality. Full article

Sarcopenia is a prevalent and debilitating condition among stroke survivors, characterized by the progressive loss of muscle mass and function. This multicenter, randomized controlled trial aims to evaluate the effects of a community-based high-speed power training (HSPT) program tailored for individuals with post-stroke sarcopenia. The intervention bridges the gap between hospital-based rehabilitation and long-term community reintegration by offering physician-supervised, progressive resistance training sessions conducted twice weekly for eight weeks. Participants are assessed on muscle strength, physical performance, balance, body composition, and gait before and after the intervention. The study utilizes validated tools such as handgrip dynamometry, dual-energy X-ray absorptiometry (DXA), short physical performance battery (SPPB), and timed up and go (TUG) to comprehensively evaluate outcomes. Through stratified randomization and a double-blind design, the trial seeks to minimize bias and maximize clinical relevance. The results from this protocol are expected to inform evidence-based guidelines for stroke rehabilitation and support scalable community-based exercise programs aimed at improving functional recovery and quality of life in this population. Full article

Experimental research demands the selection of appropriate models to align with study objectives and conditions. Traditional experimental models, such as in vivo animal studies and in vitro systems like organoids, present nutraceutical and pharmaceutical research limitations such as high cost, ethical concerns, long lifespan, and difficult genetic manipulation. Caenorhabditis elegans has proved to be a valuable model as a result of its genetic and physiological similarities to higher organisms, fully sequenced genome, short life cycle, and transparency. These features enable high-throughput screening, molecular pathway analysis, and lifespan and healthspan assays. C. elegans has significantly advanced the discovery of bioactive molecules with therapeutic potential, shedding light on aging, neurodegeneration, metabolic disorders, and immune responses. Its utility in pharmacokinetics and validation of nutraceuticals underscores its role in longevity and metabolic health research. Additionally, its conserved stress response, apoptosis, and pathogen recognition pathways facilitate the study of pharmacological interventions for inflammation, oxidative stress, and infections. This study evaluates the applicability of C. elegans as a model for in vivo screening, analyses its role in drug efficacy testing, and discusses relevant advancements, associated difficulties, and what to expect of C. elegans in research. Full article

Sustainable tourism encompasses the evaluation of its present and prospective economic, social, and ecological consequences by prioritizing the demands of its natural environment and the local populations. This study examined how tourism affects critical socio-economic variables, such as life expectancy, energy intensity (EI), economic growth (EG), and population, on the environmental quality (EQ) of tourism-dependent countries. The authors employed the newly developed “residual augmented least squares (RALS) cointegration econometric method” to estimate the long-term associations between the study factors. On the other hand, the “autoregressive distributed lag (ARDL) model” was used to estimate long- and short-run estimates. The consequences revealed that, in the long run, the population, the EI, and tourism exert positive pressure on carbon emissions. However, in the short run, the EI, EG, life expectancy (LE), and population exert positive pressure to boost emissions, resulting in environmental degradation. Based on these findings, sustainable tourism management and green EG should be given priority to preserve environmental quality. Full article

Life expectancy and mortality rates are important indicators of public health and societal well-being, which are heavily influenced by environmental and economic factors. This study estimates the impacts of renewable energy consumption, transportation CO₂ emissions, and other variables on life expectancy and mortality in New Zealand using the dynamic autoregressive distributed lag simulations methodology during 1972–2022. The findings indicate that a 1% increase in renewable energy consumption and household expenditure leads to rises in life expectancy of 0.03% and 0.005%, respectively, in the long run. Urbanisation can also boost life expectancy in the long run by 0.43% if its value rises by 1%. However, if CO₂ emissions from the transport sector rise by 1% in the long run, it will contribute to a 0.07% decrease in life expectancy. However, the short-run results show that trade household expenditure, public health expenditure, and renewable energy consumption increase life expectancy, while capital formation and transport CO₂ emissions reduce it, but with lower impacts. The mortality results show that trade, public health expenditures, urbanisation, and renewable energy consumption can reduce mortality in the long run by 0.59%, 0.52%, 16%, and 0.66%, respectively, when their values increase by 1%, while transport CO₂ emissions increase it by 1.6%. However, capital formation can decrease mortality in the long run. It declines mortality by 0.21% when increased by 1%. These findings suggest the crucial role of renewable energy consumption and public health expenditure in decreasing mortality rates and improving life expectancy in New Zealand. Policymakers must prioritize these variables to achieve meaningful improvements in public health outcomes. Full article

Background/Objectives: As life expectancy rises and the epidemiological landscape of chronic diseases evolves, the necessity to assess and improve the overall health status of the population becomes increasingly fundamental. Therefore, evaluating health gains is a crucial challenge for modern health systems, particularly in the context of limited resources and increasing demand for services. The aim of this study is to assess health gains and their costs, with data provided by a private Italian clinic. Methods: We conducted a retrospective study on 129 patients admitted between June 2020 and August 2023 in a solvent ward for short-term planned hospitalization. The patients completed the EQ-5D-5L questionnaire at both admission and discharge. Quality-Adjusted Life Years (QALYs) were estimated based on the difference in EQ-5D-5L scores between discharge and admission, assuming that health gains persist up to two years post-discharge. Through QALYs value and hospitalization cost, a cost–utility analysis was performed. Descriptive and statistical analyses were carried out using STATA SE/14.0 software. Results: Of the studied sample, 55% was female, the median age was 81 [11] years old, and the median length of stay (LoS) was 16 [16] days. The patients gained, in median, 0.33 [0.38] in QALY, which was higher for males (0.35 [0.34]) than females (0.29 [0.45]). The QALY gained was greater for the non-geriatric patients (0.41 [0.42]) than geriatric ones (0.32 [0.38]) (p > 0.05). Those with a longer LoS showed a higher gain in QALY (0.35 [0.42]) than those with a shorter one (0.23 [0.29]) (p < 0.05). The cost per QALY gained was, in median, EUR 14,337, which was lower in males (EUR 13,803), in non-geriatric patients (EUR 13,743), and in patients with a shorter LoS (EUR 10,670) (p > 0.05). Conclusions: Although QALY gains differed among the groups, the median cost per QALY remained consistent. These results highlight the need for targeted interventions to optimize resource allocation, both by integrating data into allocation strategies and by employing a multidisciplinary approach to tailor interventions. Full article

Objectives: This study explores the development and evaluation of a bilayer sustained-release (SR) tablet formulation of ruxolitinib. As a BCS Class 1 drug, ruxolitinib requires twice-daily dosing due to its short half-life. We designed a bilayer tablet that integrates immediate-release (IR) and SR components in varying ratios to achieve sustained plasma concentrations, which we evaluated using discriminative analysis. Methods: Bilayer tablets combining IR and SR components were prepared in different ratios. In vitro dissolution tests and pharmacokinetic studies were conducted using Beagle dogs, followed by the evaluation of in vivo–in vitro correlation (IVIVC), along with a discriminative pharmacokinetic analysis focused on the SR layer. Results: A discriminative pharmacokinetic and IVIVC analysis was applied to all bilayer tablets, offering clearer insights into the plasma concentration and dissolution profiles. Pharmacokinetic studies showed that test formulation F4, which has a 20:20 IR-to-SR ratio, is expected to provide a similar area under the curve (AUC) while prolonging exposure compared to the reference IR tablet. Conclusions: This study highlights the potential of a bilayer tablet approach, combined with discriminative pharmacokinetic and IVIVC analysis, for creating a sustained-release dosage form of ruxolitinib. Full article

Background and Objectives: Intertrochanteric fractures of the femur are common in the elderly due to the increase in longer life expectancy. However, unstable intertrochanteric fractures in the elderly population were still a significant concern for the postsurgical period after total hip arthroplasty (THA). This study aimed to compare the demographics, operative time, dislocation rate, and length of stay of the novel interfragmentary technique (IFT) and the conventional posterolateral approach (CPA) for unstable intertrochanteric femoral fractures treated with THA in the elderly. Materials and Methods: This retrospective study investigated community-dwelling elderly patients with type III, IV, and V unstable femoral intertrochanteric fractures according to the Evans–Jensen classification, treated with THA by a well-experienced single surgeon. The patients were separated into IFT (n = 74) and CPA (n = 67) groups. Patient demographics (age, gender, and body mass index), total surgical duration, dislocation rates, length of stay and follow-up, and complication rates were recorded. Results: The mean age was 80.37 years in the IFT and 80.14 in the CPA groups (p = 0.838). Body mass index, gender, complication, and revision rates did not differ between groups (p > 0.05). The mean follow-up of the IFT group was 4.15 years, and 10.25 years in the CPA group (p = 0.001). Total surgical duration was comparable, with 69.98 min in the IFT group and 69.55 min in the CPA group (p = 0.697). The dislocation rate was 2.7% (n = 2) in the IFT group and 9% (n = 6) in the CPA group (p = 0.109). The mean length of stay was 66.97 h in the IFT group and 67.83 h in the CPA group (p = 0.729). Conclusions: The interfragmentary surgical technique, a novel technique for unstable intertrochanteric fracture surgery, shows promising clinical outcomes. Preserving the short rotator muscles and posterior capsule utilizing the novel IFT can be advantageous for the risk of dislocation without increasing surgical duration. It can be concluded that performing THA using IFT emerges as a practical and viable procedure for treating unstable intertrochanteric fractures in elderly patients. Full article