Search

This study investigated characteristics associated with two kinds of peer victimization--bullying victimization and adversarial victimization--distinguished by different balances of power between the perpetrator and victim. Specifically, we examined whether bullying victimization (victim has less power than perpetrator) would be experienced to a greater extent by vulnerable adolescents with psychosocial difficulties (fewer close friendships, emotional symptoms) and less peer esteem (physical attractiveness, perceived popularity, dating popularity, and prestige). In contrast, we investigated whether adversarial victimization, in which the victim has equal or greater power than perpetrator, would be experienced by adolescents perceived as rivals because they are held in high esteem by peers. A total of 599 adolescents aged 9 to 14 years (M = 11.93; SD = 1.40) completed a self-report measure of emotional symptoms and peer nomination measures of victimization, close friendship, physical attractiveness, dating popularity, perceived popularity, and prestige. Bullying victimization was negatively associated with close friendships, physical attractiveness, perceived popularity, and prestige, whereas adversarial victimization was positively associated with all four indicators of peer esteem. The results demonstrate the importance of measuring the power balance between the perpetrator and victim when studying peer victimization. Findings are discussed from an evolutionary perspective suggesting that victims of bullying are selected by perpetrators to achieve adaptive benefits while minimizing retaliatory, reputational, and social costs, whereas victims of adversarial aggression are targeted as rivals in competition for status and mates.

Civility is an important construct to be addressed in relation to child and youth development. The issue of classroom incivility is of particular interest, given its potential negative impacts to both the psychosocial well-being of adolescents and the overall learning environment. Therefore, the current study sought to investigate similarities and differences between perceptions of middle and high school students and teachers. Participants consisted of 40 intermediate and high school teachers and 52 students in Grades 7-12. Both students and teachers rated uncivil behaviour in the classroom based on how serious they thought it was and how often it occurred in their classroom. Further, participants responded to open-ended questions to allow for a deeper exploration of the viewpoints and lived experiences of both students and teachers. Findings suggest that adolescent students consider uncivil behaviours that may be seen as disrespectful towards the teacher as more uncivil than do teachers themselves. Teachers tended to focus on adolescents engaging in uncivil behaviuor towards each other as being more serious as well as a focus the negative implications of classroom incivility to the learning environment. These differing perceptions of uncivil behaviour in the classroom have important implications for intervention within educational settings.

Abstract Background Platelets play a key role in the natural history of aortic stenosis (AS) and after transcatheter aortic valve implantation (TAVI). An echo-based staging system stratifies patients with severe AS into 5 groups according to the associated cardiac damage phenotype. We aimed to correlate these AS stages with platelet indices in post-TAVI patients. Methods Patients with severe AS who underwent TAVI and were admitted to intensive cardiac care unit (ICCU) were prospectively identified and divided into 5 groups according to extra-valvular cardiac damage [no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4)]. Baseline characteristics and complete blood count including mean platelet volume (MPV) and immature platelet fraction (IPF) were collected within 2 h after the procedure and analyzed in relation to aortic stenosis staging. Results A total of 220 patients were included. The mean age was 81 years old and 112 (50.9%) were female. Two (1%) patients were classified in stage 0; 34 (15%) in stage 1; 48 (22%) in stage 2; 49 (22%) in stage 3 and 87 (40%) in stage 4. Higher mean MPV values were correlated with higher AS staging (10.8 fL, 11 fL, 11.3 fL and 10.8 fL in stages 1, 2, 3 and 4, respectively, P = 0.02) as well as lower hemoglobin values (12 mg/dl, 11.6 mg/dl, 11 mg/dl and 11.3 mg/dl in stages 1, 2, 3 and 4, respectively P = 0.04). Mean IPF values were 5.3%, 5.58%, 5.57% and 4.83% in stage 1, 2, 3 and 4, respectively (P = 0.4). In a multivariate logistic regression model only MPV (OR = 2.6, P = 0.03) and body mass index (BMI) (OR = 1.17, P = 0.004) were correlated with higher staging (0–3) of AS. Conclusions Although IPF and MPV levels increased in stages 0–3, there was a decrease in indices in stage 4, (probably due to bone marrow dysfunction) in this end-stage population. Higher levels of MPV and lower levels of hemoglobin were independently correlated with higher stages (0–3) of AS.

Whole-body vibration (WBV) is a widely used training method to increase muscle strength and power. However, its working mechanisms are still poorly understood, and studies investigating the effects of WBV on muscle stiffness are scant. Therefore, the aim of this study is to investigate the acute effects of WBV on stiffness and countermovement jump (CMJ). Twenty-four recreationally active males, on separate days and in random order, performed a static squat under two different conditions: with WBV (WBV) or without vibration (CC). Muscle stiffness was assessed through the Wartenberg pendulum test, and CMJ was recorded. RM-ANOVA was employed to test differences between conditions in the above-mentioned variables. In the CC condition, stiffness was significantly lower after the exposure to the static squat (p = 0.006), whereas no difference was observed after the exposure to WBV. WBV and CC did not affect CMJ. No significant correlation was observed between changes in CMJ and changes in stiffness. Our results show that WBV may mitigate the reduction in muscle stiffness observed after static squats. However, current results do not support the notion that WBV exposure may account for an increase in CMJ performance.

Background: The study aimed to compare the prognostic importance of the heart rate (HR) and QT—corrected (QTc) according to Fridericia, Framingham, and Bazett with respect to all-cause mortality in a large non-selected population. Methods: The analysis of digital electrocardiograms archived from 2008 to 2022 in the metropolitan area of Modena, Italy, was carried out. The population under study was divided into three groups based on age, and survival analysis was performed. Results: 131,627 patients were enrolled and, during the follow-up (mean 1641.4 days), all-cause mortality was 8.9%. Both HR and QTc were associated with mortality. All-cause mortality significantly increased with HR values greater than 81 BPM and QTc values greater than 440 msec in young subjects and 455 msec in old subjects (values of the 75th percentiles/optimal operating point). A Cox analysis confirmed the better prognostic value of Bazett’s QTc and HR in the whole population and in the three age-groups. Conclusion: Bazett’s method performed better than the others, but, unexpectedly, the HR had the same or an even better correlation with all-cause mortality. Since the HR is simple and readily available, its evaluation should be improved. However, QTC and HR values are difficult to define, causing many confounding factors, and further population studies are required.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) presents a significant diagnostic challenge due to its complex and often nonspecific clinical manifestations. This review outlines a comprehensive approach to the diagnostic assessment of CTEPH, emphasizing the importance of a high index of suspicion in patients with unexplained dyspnea or persistent symptoms post-acute pulmonary embolism. We discuss the pivotal role of multimodal imaging, including echocardiography, ventilation/perfusion scans, CT pulmonary angiography, and magnetic resonance imaging, in the identification and confirmation of CTEPH. Furthermore, the review highlights the essential function of right heart catheterization in validating the hemodynamic parameters indicative of CTEPH, establishing its definitive diagnosis. Advances in diagnostic technologies and the integration of a multidisciplinary approach are critical for the timely and accurate diagnosis of CTEPH, facilitating early therapeutic intervention and improving patient outcomes. This manuscript aims to equip clinicians with the knowledge and tools necessary for the efficient diagnostic workflow of CTEPH, promoting awareness and understanding of this potentially treatable cause of pulmonary hypertension.

Recently, a novel method for the growth inhibition of malaria parasites using microwaves was proposed. However, the apparatuses used to demonstrate this method are high-cost and immovable, hindering the progression in this field of research, which is still in its early stages. This paper presents the redesign, construction, and validation of an equivalent system, converting it into a portable and low-cost system, capable of replacing the existing one. The proposed system is mainly composed of an RF generator (MAX2870), an RF amplifier (SKYWORKS 66292-11) and a graphical user interface. Likewise, the RF applicator proposed by the original study was redesigned, resulting in a five-fold improvement in return loss. The obtained results indicate that the proposed system achieves 90% parasite growth inhibition, matching the performance of its counterpart at less than 1% of its cost. These results represent a breakthrough for the creation of smaller, enhanced devices that open new possibilities for an alternative treatment to combat this devastating disease.

Whole-body vibration (WBV) has been employed for performance-enhancing purposes. WBV may positively affect muscular endurance and its underlying neural mechanisms due to an enhanced muscular blood circulation and oxygen uptake. However, the effects of WBV on endurance-related torque signal complexity have been understudied. This study aims to investigate the acute effects of WBV on i) maximal isometric torque production; ii) isometric knee extensors fatigability and iii) torque signal complexity during an isometric endurance task.Thirty adult males performed an isometric intermittent endurance protocol on their dominant lower limb after performing: static half squat with WBV (WBV), static half squat without WBV (HS), and no exercise protocol (CC). For each repetition the maximal torque was identified. The maximal torque of the first repetition was identified as the PeakT. The Mean torque (MTorque) and fatigue index (pFatigue) were calculated as the mean and the percentage decay in torque across the entire set of eighteen repetitions (MTorque0–100 %, pFatigue0–100 %), and across shorter blocks of six repetitions (MTorque0–33 %, pFatigue0–33 %; MTorque34–66 %, pFatigue34–66 %, and MTorque67–100 %, pFatigue67–100 %). Torque fluctuations were analysed computing Sample Entropy (SampEn) and the coefficient of variation (CV).PeakT was significantly higher in CC than in WBV (p

Neonatal lupus (NLE) is a rare acquired autoimmune disorder caused by transplacental passage of maternal autoantibodies to Sjogren's Syndrome A or B (SSA-SSB) autoantigens (Vanoni et al. in Clin Rev Allerg Immunol 53:469-476, 2017) which target fetal and neonatal tissues for immune destruction. The cardiac trademark of NLE is autoimmune heart block, which accounts for more than 80% of cases of complete atrioventricular heart block (AVB) in newborns with a structurally normal heart (Martin in Cardiol Young 24: 41-46, 2014). NLE presenting with cardiac alterations not involving rhythm disturbances are described in the literature, but they are rare. Here, we report a case of a neonate with high anti-SSA antibodies who developed severe ventricular dysfunction in the absence of rhythm abnormalities, endocardial fibroelastosis, and dilated cardiomyopathy (Trucco et al. in J Am Coll Cardiol 57:715-723, https://doi.org/10.1016/j.jacc.2010.09.044 , 2011), the most common cardiac presentations of NLE. The patient developed severe multiorgan dysfunction syndrome that required prolonged critical care support but fully recovered and was discharged home. We highlight the unusual clinical features of this NLE case and the importance of timely treatment of NLE allowing complete recovery of a critically ill neonate.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how “incremental cost-effectiveness ratios” (ICERs) based on measures such as gains in “quality-adjusted life-years” (QALYs) may be used to determine a drug’s value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) presents with a high mortality rate. Two important features of PDAC contribute to this poor outcome. The first is metastasis which occurs in ~ 80% of PDAC patients. The second is cachexia, which compromises treatment tolerance for patients and reduces their quality of life. Although various mouse models of PDAC exist, recapitulating both metastatic and cachectic features have been challenging. Methods Here, we optimize an orthotopic mouse model of PDAC by altering several conditions, including the subcloning of parental murine PDAC cells, implantation site, number of transplanted cells, and age of recipient mice. We perform spatial profiling to compare primary and metastatic immune microenvironments and RNA sequencing to gain insight into the mechanisms of muscle wasting in PDAC-induced cachexia, comparing non-metastatic to metastatic conditions. Results These modifications extend the time course of the disease and concurrently increase the rate of metastasis to approximately 70%. Furthermore, reliable cachexia endpoints are achieved in both PDAC mice with and without metastases, which is reminiscent of patients. We also find that cachectic muscles from PDAC mice with metastasis exhibit a similar transcriptional profile to muscles derived from mice and patients without metastasis. Conclusion Together, this model is likely to be advantageous in both advancing our understanding of the mechanism of PDAC cachexia, as well as in the evaluation of novel therapeutics.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

The patient with obesity is at risk of developing cardiovascular disease and risk factors. Obesity negatively impacts prognosis and increases cardiovascular morbidity and mortality. Therefore, a comprehensive risk assessment is needed to define the cardiovascular risk of the patient and, thus, a tailored management and treatment. Chronic and successful management of these patients involves the evaluation of the various therapeutic strategies available (comprehensive lifestyle intervention, weight-loss medications, and bariatric surgery) and the diagnosis and treatment of cardiovascular complications (coronary artery disease, heart failure, and atrial fibrillation). Cardiac rehabilitation in patients with obesity is showing beneficial effect and a positive impact on weight loss, cardiovascular risk factors, mental health, functional capacity, and adherence to lifestyle interventions and pharmacological treatment. Long-term weight loss and maintenance represent a key objective during the management of the patient with obesity to reduce the risk of future adverse events. Multidisciplinary management and interventions are necessary to prevent and reduce overall cardiovascular risk and mortality. The aim of our review is to propose a comprehensive, critical and updated overview regarding risk assessment, physical activity, and the management of cardiovascular complications in patient with obesity.

This review is aimed at providing an overview of the application of liquid chromatography-high resolution mass spectrometry (LC-HRMS) in the metabolomic study of cereal grains, with special emphasis on wheat, maize, barley, and rice. The significant role of untargeted metabolomics in identifying and quantifying metabolites is highlighted, thereby elucidating biochemical pathways involved in flavour, disease detection, and the development of disease-resistant varieties. The use of stable isotope labelling for enhanced compound annotation and the exploration of metabolic pathways involved in plant defence mechanisms and stress resilience are also discussed. The integration of cutting-edge analytical techniques is becoming of fundamental importance to enhance the understanding of metabolic reconfigurations in response to various conditions, thereby contributing to the improvement of cereal quality and ensuring food safety. The potential health benefits of phytochemicals in human nutrition and the role of specific metabolites as biomarkers for crop resistance and susceptibility to diseases, pests, and abiotic stresses are discussed. Overall, valuable insights into the advancement of analytical chemistry and its applications in agricultural science are provided by this review.

When the COVID-19 pandemic was declared in March 2020, the lives of families all over the world were disrupted. Many adults found themselves working from home while their children were unable to go to school. To better understand the potential impact of these educational disruptions, it is important to establish what learning looked like during the first school shutdown in the spring of 2020, particularly for the youngest learners who may feel the longest lasting impacts from this pandemic. Therefore, the purpose of the current descriptive study was to gather information on how kindergarten teaching and learning occurred during this time, what the biggest barriers were, and what concerns educators had regarding returning in person to the classroom setting. The sample for the current study was 2569 kindergarten educators (97.6% female; 74.2% teachers, 25.8% early childhood educators) in Ontario, Canada. Participants completed a questionnaire consisting of both quantitative scales and qualitative open-ended questions. Educators reported that parents most often contacted them regarding technological issues or how to effectively support their child. The largest barrier to learning was the ability of both parents and educators to balance work, home life, and online learning/teaching. With regards to returning to school, educators were most concerned about the lack of ability of kindergarten aged children to do tasks independently and to follow safety protocols. Our findings highlight unique challenges associated with teaching kindergarten during the pandemic, contributing to our understanding of the learning that occurred in Ontario during the first COVID-19 shutdown.

IntroductionWith the proliferation of smartphones, social media access and use is ubiquitous. As such, many adolescent friendships now comprise both in-person and online contexts. Our paper explores the relationship between these contexts in two parts: the first is an exploratory comparison of in-person and online friendship networks with peers at school using descriptive social network analysis; the second, an investigation of how the use of different social media platforms relates to the importance placed on social media for connectedness and friendship closeness.MethodsParticipants were 547 adolescents (M = 15.25 years, 52% male, 55% white) from six schools in Southern Ontario, Canada. Participants completed a peer nomination survey on their relationships with peers at school and a self-report survey on social media use.ResultsWhile in-person and online networks are largely overlapping, there are important differences between the two. Results from the path analyses suggest that length of cell phone usage, Instagram, Snapchat, and YouTube were positively associated with the importance placed on technology for social connection and that this importance was also positively associated with feelings of friendship closeness. Daily cell phone usage, Instagram, and Snapchat use were positively indirectly associated with friendship closeness through the importance of technology for social connection.DiscussionOur findings also suggest slight gender differences, with daily time spent on a smartphone only significantly positively associated with the importance of technology for social connection for girls. Implications for future study are discussed.

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a severe and complex condition that evolves from unresolved pulmonary embolism, leading to fibrotic obstruction of pulmonary arteries, pulmonary hypertension, and potential right heart failure. The cornerstone of CTEPH management lies in a multifaceted therapeutic approach tailored to individual patient profiles, reflecting the disease's heterogeneity. This review delves into the current therapeutic strategies for CTEPH, including surgical pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and targeted pharmacological treatments such as PDE5 inhibitors, endothelin receptor antagonists, sGC stimulators, and prostanoids. Lifelong anticoagulation is also highlighted as a preventive strategy against recurrent thromboembolism. Special emphasis is placed on the interdisciplinary nature of CTEPH care, necessitating collaboration among PEA surgeons, BPA interventionists, PH specialists, and thoracic radiologists to ensure comprehensive treatment planning and execution. The review underscores the importance of selecting an appropriate treatment modality based on the patient's specific disease characteristics and the evolving landscape of CTEPH treatment, aiming to improve patient outcomes through integrated care strategies.

Abstract Storage or transportation temperature is very important for preserving the quality of fruit. However, low temperature in sensitive fruit such as peach can induce loss of quality. Fruit exposed to a specific range of temperatures and for a longer period can show chilling injury (CI) symptoms. The susceptibility to CI at low temperature varies among cultivars and genetic backgrounds. Along with agronomic management, appropriate postharvest management can limit quality losses. The importance of correct temperature management during postharvest handling has been widely demonstrated. Nowadays, due to long-distance markets and complex logistics that require multiple actors, the management of storage/transportation conditions is crucial for the quality of products reaching the consumer. Peach fruit exposed to low temperatures activate a suite of physiological, metabolomic, and molecular changes that attempt to counteract the negative effects of chilling stress. In this review an overview of the factors involved, and plant responses is presented and critically discussed. Physiological disorders associated with CI generally only appear after the storage/transportation, hence early detection methods are needed to monitor quality and detect internal changes which will lead to CI development. CI detection tools are assessed: they need to be easy to use, and preferably non-destructive to avoid loss of products. Graphical Abstract

Pathogenic variants localized in the gene coding for the Fukutin-Related Protein (FKRP) are responsible for Limb-Girdle Muscular Dystrophy type 9 (LGMDR9), Congenital Muscular Dystrophies type 1C (MDC1C), Walker–Warburg Syndrome (WWS), and Muscle–Eye–Brain diseases (MEBs). LGMDR9 is the fourth most common hereditary Limb Girdle Muscular Dystrophy in Italy. LGMDR9 patients with severe disease show an overlapping Duchenne/Becker phenotype and may have secondary dystrophin reduction on muscle biopsy. We conducted a molecular analysis of the FKRP gene by direct sequencing in 153 patients from Southern Italy (Calabria) with Duchenne/Becker-like phenotypes without confirmed genetic diagnosis. Mutational screening of the patients (112 men and 41 women, aged between 5 and 84 years), revealed pathogenic variants in 16 subjects. The most frequent variants identified were c.427C > A, p.R143S, and c.826C > A, p.L276I (NM_024301.5). The results obtained show that the Duchenne/Becker-like phenotype is frequently determined by mutations in the FKRP gene in our cohort and highlight the importance of considering LGMDR9 in the differential diagnosis of dystrophinopathies in Calabria. Finally, this study, which, to our knowledge, is the first conducted on Calabrian subjects, will contribute to the rapid identification and management of LGMDR9 patients.

Apple cultivars ‘Annurca’ and ‘Limoncella’ are grown locally in the Campania region of Italy and are valued for their distinctive flavour and characteristics, including a high content of nutritionally important bioactive compounds. However, apples are typically stored chilled for several months before consumption, so it is important to assess if the valuable characteristics are still present after postharvest storage. Here, we compare the quality, nutritional parameters, and aroma of these two cultivars with two widely grown international cultivars, ‘Golden Delicious’ and ‘Fuji’, after 60 days of storage. The aroma profiles of all four apples were analysed using thermal desorption and gas chromatography–time-of-flight mass spectrometry. We show that the local cultivars are distinct from the international cultivars in their bioactive compound content and their antioxidant activity. ‘Limoncella’ shows high sugar content, which may be acting as a cryoprotectant during storage, and high total phenolics in the flesh, which is of nutritional interest. We identified 104 volatile organic compounds (VOCs) and showed that the overall aroma profile is distinct for each cultivar, containing 11 published odorant compounds. The ‘Annurca’ profile is uniquely low in esters. Seven VOCs retain good discrimination across the four cultivars and, together with the quality and nutritional data, separate the two local cultivars from the international cultivars by hierarchical clustering. Overall, the data emphasize the unique characteristics of the two local cultivars and their value.

It is estimated that 15-22% of students have high levels of test anxiety (von der Embse, Jester, Roy, & Post, 2018), which can be associated with greater academic stress and poorer educational performance (e.g., Steinmayr, Crede, McElvany, & Withwein, 2016). First-generation students (where neither parent has completed post-secondary education) are a critical group to study given that they are at higher risk for poorer educational attainment and being unsuccessful at the post-secondary level. Therefore, the purpose of this study was to examine the link between basic psychological needs and test anxiety in a sample of first-generation Ontario high school students across two points in time (N = 147; M[subscript age] = 14.82, SD = 1.28). Self-report data was collected as a part of an on-going longitudinal study focusing on students attending a high school with specialized programming to enhance the transition to post-secondary institutions. Results from cross-lagged path analyses indicated that being older, female, and having higher levels of needs frustration significantly predicted higher levels of test anxiety over time within this sample. Our results highlight important educational implications, emphasizing the importance of fostering classroom environments where students perceive their psychological needs to be met, particularly within this unique population of students.

In social groups, such as school-based peer networks, youth often vie for power and dominance over others. Different strategies may be used to gain power (i.e., coercive and/or cooperative strategies), and with varying levels of success. Using a social networks approach, we examined whether and how social network centrality and social network prestige were associated with social strategies, social power, and peer reputation. Participants were fifth- to eighth-grade elementary school students (N = 466, 51% girls, 63% White) in southern Ontario, Canada. Peer nominations were used to assess social network centrality and prestige (via friendship nominations), social power strategies (coercive and cooperative strategies), social power, and peer reputation (popularity and likeability). Results indicated that coercive and cooperative strategies were used by youth high in both centrality and prestige, but that only high prestige related to power, popularity, and likeability. Results have implications for the usefulness of a social networks approach to understanding the structure of youths' social relationships and power in school settings, as well as practical implications for teachers and other school staff.

Background Sepsis is a life-threatening condition that results from a dysregulated host response to infection, leading to organ dysfunction. Despite the prevalence and associated socioeconomic costs, treatment of sepsis remains limited to antibiotics and supportive care, and a majority of intensive care unit (ICU) survivors develop long-term cognitive complications post-discharge. The present study identifies a novel regulatory relationship between amyloid-β (Aβ) and the inflammasome-caspase-1 axis as key innate immune mediators that define sepsis outcomes. Methods Medical ICU patients and healthy individuals were consented for blood and clinical data collection. Plasma cytokine, caspase-1 and Aβ levels were measured. Data were compared against indices of multiorgan injury and other clinical parameters. Additionally, recombinant proteins were tested in vitro to examine the effect of caspase-1 on a functional hallmark of Aβ, namely aggregation. Results Plasma caspase-1 levels displayed the best predictive value in discriminating ICU patients with sepsis from non-infected ICU patients (area under the receiver operating characteristic curve=0.7080). Plasma caspase-1 and the Aβ isoform Aβx-40 showed a significant positive correlation and Aβx-40 associated with organ injury. Additionally, Aβ plasma levels continued to rise from time of ICU admission to 7 days post-admission. In silico, Aβ harbours a predicted caspase-1 cleavage site, and in vitro studies demonstrated that caspase-1 cleaved Aβ to inhibit its auto-aggregation, suggesting a novel regulatory relationship. Conclusions Aβx-40 and caspase-1 are potentially useful early indicators of sepsis and its attendant organ injury. Additionally, Aβx-40 has emerged as a potential culprit in the ensuing development of post-ICU syndrome.

s Kyrgyzstan undergoes significant demographic transitions, with an increasing aging population, the intersection of healthy aging and cardiovascular health emerges as a critical aspect of public health. We explore the relationship of healthy aging and cardiovascular health, underlining both the opportunities and challenges inherent in this demographic shift. Applying the World Health Organization's concept of "intrinsic capacity" and the "Integrated Care for Older People" (ICOPE) approach, we suggest strategies for addressing these crucial public health issues.