1. Background: Cardiovascular diseases (CVDs) are India’s leading cause of mortality. This study aimed to recalibrate the original Framingham Risk Score (FRS) equations among adults in Kerala state. 2. Methods: Baseline survey data from the Kerala Diabetes Prevention Program were analyzed: 921 males and 567 females for lipid-based FRS scores and 1042 males and 646 females for BMI-based FRS scores. Recalibration of the original FRS scores was performed using local data on CVD risk factors and CVD mortality. 3. Results: Among males, the median 10-year CVD risk with the recalibrated lipid-based FRS score was 7.34 (IQR 4.33-12.42), compared with the original score of 8.88 (5.23-14.87) (p<0.001). For BMI-based FRS scores, the median 10-year CVD risk was 7.40 (4.27-11.83) with the recalibrated score, compared to 9.32 (5.40-14.80) for the original score (p<0.001). In females, the median 10-year CVD risk was 4.83 (2.90-8.36) with the recalibrated score, compared to 2.85 (IQR 1.71-4.98) with the original score (p<0.001). Similarly, the median 10-year CVD risk was 4.66 (2.74-8.81) with the recalibrated BMI-based FRS score, compared to 2.95 (1.72-5.61) with the original score (p<0.001). 4. Conclusions: Recalibrated FRS scores estimated a significantly lower 10-year CVD risk in males and a higher risk in females than the original FRS scores.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Background: The current review was conducted to determine the effectiveness of atenolol on all-cause mortality rate among Asian patients with chronic progressive diseases, mainly diabetes mellitus, primary hypertension, and coronary artery disease. Methods: We searched the COCHRANE, MEDLINE, TRIP, and EMBASE databases for published articles up to 31 March 2023. Studies that compared all-cause mortality rates among Asian patients who were on atenolol or other medications were included. Results: The review included 79603 Asian patients from three cohort studies. Out of the studied patients, 36046 were atenolol users and 43557 were non-atenolol users. The review revealed that atenolol users recorded lower all-cause mortality rates compared to non-users with a significant difference (OR= 0.57, CI= 0.44-0.75, P<0.001). The pooled estimate of the all-cause mortality rate was also lower among atenolol users (7.02%) compared to metoprolol tartrate users (13.15%) with a significant difference (OR= 0.50, CI= 0.47-0.53, p < 0.0001). Although the included studies were categorized as having a low risk of bias for most of the studied domains, significant heterogeneity was recorded across these studies (I2 =88%, P=0.001). Conclusion: This review found that atenolol when compared to a control or metoprolol tartrate, has a significant effect in reducing the all-cause mortality rate among Asian patients with chronic progressive disease.

Background: Ceramides are a new kind of lipid biomarkers and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague and has been addressed in the present study. Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the coronary event risk test (CERT) score which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). Results: Kaplan Meier survival curves revealed that the overall survival of patients has decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that every 1-step increase in category resulted in a 35% rise in overall mortality risk (HR=1.35 [1.16-1.58]). Multivariable adjustment, including amongst others age, T2DM, and statin treatment before baseline, did not abrogate this significant association (HR=1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin is significantly stronger in patients with a higher risk according to CERT. Conclusion: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.

Background: Patients with Inflammatory Bowel Disease (IBD) believe that diet is a key factor in the pathogenesis of their disease and in worsening their symptoms; they often follow restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found an association between eating disorders and IBD, particularly anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report the association with orthorexia nervosa, that is the obsession with healthy and natural foods. Aim: to assess the risk of orthorexia nervosa in patients with IBD. Methods: 158 consecutive subjects were recruited, including 113 patients diagnosed with IBD and 45 controls. The Donini standardized questionnaire ORTO-15 was administered to assess the risk of orthorexia; clinical and demographic data were also collected. Results: patients with IBD have a prevalence of orthorexia of 77%, significantly higher than the 47% observed in the control group. In patients with IBD, the risk of orthorexia is associated with lower BMI and history of previous surgery. Conclusion: Many patients with IBD develop orthorexia nervosa that impacts the patient's psychological and social sphere, exposes them to a high risk of nutritional deficiencies, and affects quality of life. Further high quality studies are warranted to evaluate the clinical impact of orthorexia and its correlation with clinical features and frank eating disorders.

Evidence points to a link between gluten-free diet or celiac disease and eating disorders, but not with orthorexia. This study is the first to examine adults with celiac disease in terms of the prevalence of risk of orthorexia. The study included 130 adults diagnosed with celiac disease. The standardized ORTHO-15 questionnaire was used to assess the risk of orthorexia. Cronbach's alpha test was used to determine the reliability of the ORTHO-15 questionnaire. Eating habits of the subjects were assessed using a questionnaire. The effect of celiac disease on diet was assessed on a 5-point scale. A risk of orthorexia was found in 69% of subjects with celiac disease. A statistically significant (p&lt;0.005) positive correlation was observed between age and ORTHO-15 test scores (rho=0.37). In the group with orthorexia risk, meals were more often self-prepared (93.3%) compared to those without orthorexia (80%) (p=0.023). For 80% of those at risk for orthorexia versus 20% without risk, mood was a factor influencing dietary choices (p=0.001). The study observed a strong association between celiac disease and the presence of orthorexia risk. The numerous risk factors for orthorexia suggest the need for holistic care, including nutritional and psychological support among individuals with celiac disease.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

Strengthening the analysis and risk assessment of the pig epidemic will help to better prevent and mitigate epidemic risks and promote high-quality development of the pig industry. Based on the systematic grasp of the situation of live pig epidemics, a risk assessment index system was constructed, and the spatial and temporal variation characteristics of the risk of pig epidemics in China were explored by the entropy method. In recent years, the overall trend in pig epidemics in time first increased and then decreased, and in space, the trend in the acceleration of the spread across the country continued to weaken. China still faces challenges, such as many types and a wide range of diseases, large total livestock breeding and weak epidemic prevention and control capacity, and a large risk of introduction of foreign animal epidemics. The spatial and temporal variation in the pig epidemic risk was obvious; there was one high-risk area, two higher-risk areas and 10 medium-risk areas in recent years, and the epidemic risk was highest in Beijing, Hainan, Liaoning, Tibet and Zhejiang. However, there were significant differences in the regional distribution of the risk of pig epidemics in different years. To further build a secure “defense system” for the high-quality development of the pig industry, it is recommended to improve the monitoring and early warning system of pig epidemic risk, perfect the pig epidemic prevention and control system, and strengthen the regional collaboration mechanism of epidemic prevention and control.

One of the major obstacles confronting the formulation of a mechanistic understanding for Alzheimer’s disease (AD) is its immense complexity – a complexity that traverses the full structural and phenomenological spectrum, including molecular, macromolecular, cellular, neurological and behavioural processes. This complexity is reflected by the equally complex diversity of risk factors associated with AD. However, more than merely mirroring disease complexity, risk factors also provide fundamental insights into the aetiology and pathogenesis of AD as a neurodegenerative disorder since they are central to disease initiation and subsequent propagation. Based on a systematic literature assessment, this review has identified 30 risk factors for AD and then extended the analysis to further identify neuroinflammation as a unifying mechanism present in all 30 risk factors. Although other mechanisms (e.g. vasculopathy) were present in multiple risk factors, dysfunction of the neuroimmune-neuroinflammation axis was uniquely central to all 30 identified risk factors. Though the nature of the neuroinflammatory involvement varied, activation of microglia and the release of pro-inflammatory cytokines was a common pathway shared by all risk factors. This observation provides further evidence for the importance of immunopathic mechanisms in the aetiopathogenesis of AD.

Rodents are known to be reservoir hosts for at least 60 zoonotic diseases and are known to play an important role in their transmission and spreading in different ways. We sampled different rodent communities within and around human settlements in Northern Senegal, an area subjected to major environmental transformations associated with global changes. Herein, we conducted an epidemiological study on their bacterial communities.One hundred and seventy-one (171) invasive and native rodents were captured, 50 from outdoors trapping sites and 121 rodents from indoors habitats, consisting on 5 species. DNA of thirteen pathogens have been successfully screened on the rodent’s spleens. We found: 2.3% of positive spleens to Piroplasmida and amplified one which gives a potentially new species Candidatus “Theileria senegalensis”; 9.35% of Bartonella spp. and amplified 10, giving three genotypes. 3.5% of filariasis species; 18.12% of Anaplasmataceae species and amplified only 5, giving a new potential species Candidatus “Ehrlichia senegalensis”; 2.33 % of Hepatozoon spp.; 3.5% of Kinetoplastidae spp; and 15.2% of Borrelia spp. and amplified 8 belonging all to Borrelia crocidurae.Some of the species of pathogens carried by the rodents of our studied area may be unknown because most of those we have identified are new species. In one bacterial taxon, Anaplasma, a positive correlation between host body mass and infection was found. Overall, male and invasive rodents appeared less infected than female and native ones, respectively.

The association between normal-range triglycerides and diabetes mortality remains unclear. This cohort study aimed to elucidate this relationship by examining 19,010 US adult participants with fasting serum triglycerides below 150 mg/dL. Cox proportional hazards models were employed to estimate mortality hazard ratios (HRs) and 95% confidence intervals (CIs). Participants were followed up for a mean of 15.3 years, during which 342 diabetes deaths were recorded. A 1-natural-log-unit increase in triglycerides was associated with a 57% higher risk of diabetes mortality (adjusted HR, 1.57; 95% CI, 1.04–2.38). Comparable results were obtained when triglycerides were analyzed in quartiles. Receiver operating characteristic curve analysis identified an optimal triglyceride cutoff of 94.5 mg/dL for diabetes mortality; individuals with triglyceride levels above this threshold faced a greater risk of diabetes mortality (adjusted HR, 1.43; 95% CI, 1.12–1.83). Further investigation revealed a positive association between normal triglyceride levels and all-cause mortality, though no association was observed between normal triglycerides and mortality from hypertension or cardiovascular disease. In conclusion, elevated triglycerides within the normal range were associated with an increased risk of diabetes mortality. Individuals with triglyceride levels of 95 mg/dL or higher may require vigilant monitoring for diabetes and its associated complications.

As recent history has shown, changing climate not only threatens to increase the spread of known disease, but also the emergence of new and dangerous phenotypes. This occurred most recently with West Nile virus: a virus previously known for mild febrile illness rapidly emerged to become a major cause of mortality and long-term disability throughout the world. As we move forward, into increasingly uncertain times, public health research must begin to incorporate a broader understanding of the determinants of disease emergence – what, how, why, and when. The increasing mainstream availability of high-quality open data and high-powered analytical methods presents promising new opportunities. Up to now, quantitative models of disease outbreak risk have been largely based on just a few key drivers, namely climate and large-scale climatic effects. Such limited assessments, however, often overlook key interacting processes and downstream determinants more likely to drive local manifestation of disease. Such pivotal determinants may include local host abundance, human behavioral variability, and population susceptibility dynamics. The results of such analyses can therefore be misleading in cases where necessary downstream requirements are not fulfilled. It is therefore important to develop models that include climate and higher-level climatic effects alongside the downstream non-climatic factors that ultimately determine individual disease manifestation. Today, few models attempt to comprehensively address such dynamics: up until very recently, the technology simply hasn’t been available. Herein, we present an updated overview of current perspectives on the varying drivers and levels of interactions that drive disease spread. We review the predominant analytical paradigms, discuss their strengths and weaknesses, and highlight promising new analytical solutions. Our focus is on the prediction of arboviruses, particularly West Nile virus, as these diseases represent the pinnacle of epidemiological complexity – solution to which would serve as an effective “gatekeeper”. We present the current state-of-the-art with respect to known drivers of arbovirus outbreak risk and severity, differentially highlighting the impact of climate and non-climatic drivers. The reality of multiple classes of drivers interacting at different geospatial and temporal scales requires advanced new methodologies. We therefore close out by presenting and discussing some promising new applications of AI. Given the reality of accelerating disease risks due to climate change, public health and other related fields must begin the process of updating their research programs to incorporate these much needed, new capabilities.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Studies have shown increased nontuberculous mycobacterial pulmonary disease (NTM) incidence with inhaled corticosteroid (ICS) use in patients with chronic respiratory diseases; however, this association in chronic obstructive pulmonary disease (COPD) remains insufficiently studied. Using a nationwide population-based database of the Korean National Health Insurance Service, newly diagnosed COPD patients (20052018) treated with inhaled bronchodilators were selected. An NTM case was defined by the presence of the first diagnostic code following inhaled bronchodilator use. Results indicated that ICS users did not have an increased risk of NTM disease compared to non-ICS users (hazard ratio [HR], 1.121; 95% confidence interval [CI], 0.9501.323; p = 0.1755). The highest quartile of the cumulative ICS dose was associated with the development of NTM (1.200, 0.9501.323, p = 0.0497). Medium (1.229, 1.0081.499, p = 0.0410) and high daily doses of ICS (1.637, 1.2412.160, p = 0.0005) were associated with an increased risk of NTM disease. There was no difference in the risk of NTM according to ICS type. ICS use may not increase the risk of developing NTM disease in patients with COPD. However, physicians should weigh the potential benefits and risks of ICS, especially when using high doses and prolonged durations.

El Niño is a quasi-periodic pattern of climate variability and extremes often associated with hazards and disease. While El Niño links to individual diseases have been examined, less is known about the cluster of multi-disease risk referred to as an ecosyndemic, which emerges during extreme events. The objective of this study was to explore a mapping approach to represent the spatial distribution of ecosyndemics in Piura, Peru at the district-level during the first few months of 1998. Using geographic information systems and multivariate analysis, two methodologies were employed to map disease overlap of 7 climate-sensitive diseases and construct an ecosyndemic index, which was then mapped and applied to another El Niño period as proof of concept. The main findings showed that many districts across Piura faced multi-disease risk over several weeks in the austral summer of 1998. The distribution of ecosyndemics were spatially clustered in western Piura among 11 districts. Furthermore, the ecosydemic index in 1998 when compared to 1983 showed a strong positive correlation, demonstrating the utility of the index. The study supports PAHO efforts to develop multi-disease based and interprogrammatic approaches to control and prevention, particularly for climate and poverty-related infections in Latin America and the Caribbean.

Peyronie's disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, understanding of the detailed mechanisms and risk factors involved in development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including genetic involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide better understanding regarding involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as provide insight into disease prevention and novel therapeutic interventions.

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.

The movement toward prevention trials in people at-risk for Parkinson’s is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with Parkinson’s disease (PD). These authors participated as speakers, panelists, and moderators in the “Planning for Prevention of Parkinson’s: A Trial Design Forum” hosted by Massachusetts General Hospital in 2021 and 2022. Other authors include a young onset person with Parkinson’s (PwP) and retired family physician, an expert in patient engagement in Parkinson’s, and early career and veteran movement disorders clinician researchers. Several themes emerged from the at-risk participant voice concerning the importance of early intervention, the legitimacy of their input in decision-making, and the desire for transparent communication and feedback throughout the entire research study process. Challenges and opportunities in the current environment include lack of awareness among primary care physicians and general neurologists about PD risk, legal and psychological implications of risk disclosure, limited return of individual research study results, and undefined engagement and integration of individuals at-risk into the broader Parkinson’s community. Incorporating the perspectives of individuals at-risk as well as those living with PD at this early stage of prevention trial development is crucial to success.

The purpose of the present study was to determine the relationship between healthy lifestyle behaviors, physical fitness and coronary risk factors in university students. 320 male and female (n_m:171; n_f:149) students from a university participated in this study voluntarily. For the determination of body composition and Body Mass Indexes (BMI), subjects’ height, body weight, and skinfold thickness were taken and body fat percentage (%Fat) was determined. Healthy lifestyle behaviors were determined using the healthy lifestyle behaviors questionnaire. Indicators of physical fitness included flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and a total of shuttle (TS), sprint performance, BMI, and body fat percentage (%fat). Coronary heart disease risk factors included mean arterial blood pressure (systolic (SBP) and diastolic (DBP)), fasting blood levels of triglycerides (TG), total cholesterol (TC), hematocrit (HT), and hemoglobin (HM). Results indicated subjects have normal body mass index, body fat percentage, SBP, DBP, TG, TCF, BS, KS. The results of the Pearson Product Moment Correlation Analysis, indicated that SBP, DBP, TG, TCF, BS, KS for male and female was significantly correlated with flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and total of shuttle (TS)), sprint performance. (p<0.01; p<0.05), In conclusion, the findings of the present study indicated that physical fitness and healthy lifestyle behaviors play a determinant role in coronary heart disease risk factors for male and female students from a university.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

The introduction of tenofovir-derived prodrugs has revolutionised the prevention and management of HIV, which has coincided with 23% reduction in new HIV incidences globally. To date, there are two formulations of tenofovir-derived nucleoside reverse transcriptase inhibitor (NRTI): tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and tenofovir alafenamide fumarate/emtricitabine (TAF/FTC). Although these prodrugs have shown favourable safety profile, their effects on cardiovascular health are differ from one another: TDF/FTC exhibits potential lipid-lowering effect, TAF/FTC demonstrates potential lipid-inducing effect, which is a major risk factor for cardiovascular diseases. However, this issue has not been previously elucidated, especially among the marginalised populations [lesbian, gay, bisexual and transgender (LGBT) and men who have sex with men (MSM)] who are likely be the main users of these prodrugs. This is of clinically significance as the cardiovascular health in these populations is often overlooked, in addition to a lack of appropriate cardiovascular risk prediction algorithm. Therefore, this review aims to (1) highlight the cardiovascular risks of tenofovir-derived prodrugs in the marginalized populations, and also to (2) establish the importance of having a cardiovascular risk prediction model that is specific to this particular populations so that their health management could be more comprehensive.

Patients with advanced chronic liver disease (ACLD) or cirrhosis undergoing surgery have an increased risk of morbidity and mortality in contrast to the general population. Retrospective, observational study of ACLD patients to evaluate the predictive capacity of previous surgical risk scores in a European cohort of patients. ACLD was defined by the presence of thrombocytopenia <150.000/uL and splenomegaly; AST-to-Platelet Ratio Index >2; nodular liver edge by ultrasound; transient elastography >15 kPa and/or signs of portal hypertension. We assessed variables related to 90-day mortality and the discrimination and calibration of current surgical scores (Child-Pugh, MELD-Na, MRS, NSQIP, and VOCAL-Penn). Only patients with ACLD and major surgeries included in VOCAL-Penn were considered (n=512). The mortality rate at 90 days after surgery was 9.8%. Baseline disparities between H. Mar and VOCAL-Penn cohorts were identified. Etiology, obesity, or platelet count not were associated with mortality. The VOCAL-Penn showed the best discrimination (C-statistic90D= 0.876) and overall predictive capacity (Brier90D= 0.054) but calibration was not excellent in our cohort. VOCAL-Penn was suboptimal in patients with diabetes (C-statistic30D= 0.770), without signs of portal hypertension (C-statistic30D= 0.555), or with an abdominal wall (C-statistic30D= 0.608) or urgent (C-statistic180D= 0.692) surgeries. Our European cohort has shown a mortality rate after surgery similar to those described in American studies. However, some variables included in the VOCAL-Penn score were not associated with mortality, and VOCAL-Penn’s discriminative ability decreases in patients with diabetes, without signs of portal hypertension, and with abdominal wall or urgent surgeries. These results should be validated in larger multicenter and prospective studies.

We explored the trends and the diversity of the mortality and risk factors of age-standardized cardiovascular diseases (CVD) and cerebrovascular disease (CBD) from 2000 to 2020 in five advanced Asian countries, including China, Japan, Singapore, South Korea, and Taiwan. Data were obtained from the Global Burden of Disease (GBD) report. Overall, the CVD mortality rates decreased gradually in all five Asian countries. Singapore had the highest rates before 2011, but Taiwan replaced Singapore as the nation of the highest mortality rates after 2012. Additionally, South Korea had the highest CBD mortality rates before 2016, while Taiwan experienced a peak in 2011 and remained high thereafter. The absolute difference (AD) and relative difference (RD) for CVD mortality rates showed clear declining trends in all five countries, with South Korea and China displaying the highest reductions, respectively. It is noteworthy that overweight and obesity exhibited an increasing trend in all these five Asian countries, with China demonstrating the highest AD and RD. Except for Taiwan, where a negative association of r=-0.732 was observed, CVD mortality was positively associated with CBD, hypertension, and DM mortality in all other four countries, therefore, further investigation into these relationships are needed.

Preeclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) in later life. Postpartum cardiovascular risk screening could identify patients who would benefit most from lifestyle interventions. However, there are no readily available methods to identify these high-risk women. We propose that placental lesions may be useful in this regard. Here, we sought to determine the association between placental lesions and lifetime CVD risk. Placentas from 85 PE women were evaluated for histopathological lesions. At 6 months postpartum, a lifetime cardiovascular risk score was calculated. Placental lesions were compared between CVD risk groups and the association was assessed using odds ratios. Multivariable logistic regression was used to develop prediction models for CVD risk with placental pathology. Placentas from high-risk women had more severe lesions of maternal vascular malperfusion (MVM) and resulted in a 3-fold increased risk of screening high-risk for CVD (OR 3.10[1.20-7.92]) compared to women without these lesions. MVM lesion severity was moderately predictive of high-risk screening (AUC 0.63[0.51,0.75]; sensitivity 71.8%[54.6,84.4]; specificity 54.7%[41.5,67.3]. When clinical parameters were added, the model’s predictive performance improved (AUC 0.73[0.62,0.84]; sensitivity 78.4%[65.4,87.5]; specificity 51.6%[34.8,68.0]. The results suggest that placenta pathology may provide a unique modality to identify women for cardiovascular screening.

This retrospective study aimed to investigate the effect of known risk factors on nonsurgical periodontal treatment (NSPT) response using a pocket depth fine-tuning multilevel linear model (MLM). Thirty-seven patients (24 males and 13 females) with moderate to severe chronic periodontitis were treated with nonsurgical periodontal therapy. Follow-up visits at 3, 6, and 12 months included measurement of several clinical periodontal parameters. Data were extracted from a database system. Probing depth (PD) and Clinical Attachment Loss (CAL) reductions after NSPT in an overall of 1416 initially affected sites (baseline PD ≥ 4 mm), distributed on 536 teeth, were analyzed against known risk factors at three hierarchical levels (patient, tooth and site). The variance component models fitted to assess the three-level variance of PD and CAL decrease for each post-treatment follow-up showed that all levels contributed significantly to the overall variance (P < 0.001). Patients that underwent NSPT and were continually monitored had very curative results. All three hierarchical levels included risk factors who had impact on the to influence the magnitude of PD and CAL reduction. Specifically, the tooth’s type, surfaces involved and teeth mobility site-level risk factors showed the highest influence on these reductions, being highly relevant factors for the NSPT success.

In recent years, Lassa fever has been announced as an infectious disease in the world, a few imported cases have been accounted for in various pieces of the world and there are developing worries of the possibilities of Lassa fever Virus as an organic weapon. Regardless of its assaulting impact, no substantial arrangement has been created to reduce the hazard of the ailment, about a large portion of 10 years after identifying it. A Review based on the documents from the literature search on PubMed, Scopus, Goggle Scholar and Science direct. Out of these, the final 16 articles that met the criteria were selected. Relevant information on epidemiology, the burden of management and control were obtained. Timely and effective containment of the Lassa fever disease in Lassa village four decades ago could have minimized the devastating effect and threats posed by this illness in the West African sub-region and indeed the entire globe. That was a hard lesson calling for much more proactive measures towards the eradication of the illness at primary, secondary, and tertiary levels of health care. Hence, the paper is aimed at appraising the threats associated with Lassa fever disease; its demands on curtailing the menace of the epidemic, and recommendations on important focal points.

The global SARS-Cov-2 which caused the coronavirus disease 2019 (COVID-19) pandemic has had a significant impact over the last 3.5 years, especially among healthcare workers (HCWs) who were constantly in the forefront of the pandemic. Due to the nature of their work, HCWs faced a potential risk of exposure. Therefore, this study investigated the individual-level factors associated with perceived COVID-19 risk among South African HCWs. We used an analytical cross-sectional study design to analyse data from the South African Health Care workers’ response to the Coronavirus (COVID-19) pandemic online survey conducted by the Human Sciences Research Council across the nine provinces in South Africa, from 11th April to 7th May 2020. In this study, only data (n= 5 579) with non-missing values for COVID-19 risk and individual-level factors (age, gender, educational level, occupational category, and race) was analysed. Univariate and Multivariate binomial logistic regression analyses were conducted. The crude and adjusted odds ratio and p-value ≤ 0.05, were used to describe the association between the individual-level factors and perceived COVID-19 risk, from low-medium to high. The binomial logistic regression was used to assess the factors associated with high perceived risk. Perceived COVID-19 risk among HCWs in South Africa was significantly associated with age, race, educational level and occupational category. Being 60 years and older, being “White”, having a Master’s and Doctorate degrees and being a healthcare worker other than a nurse practitioner and medical practitioner, all had higher odds of having high perceived COVID-19 risk. The findings may be used to guide policies and programs aimed at mitigating the impacts of COVID-19 and other similar pandemics.

Salmonellosis is a bacterial zoonosis with array of health conditions. Non-typhoidal salmonellosis (NTS) have a discrete adaptation to certain animals; in poultry, pullorum and fowl typhoid are its primary disease manifestations. The diseases are prevalent in the Nigerian poultry and have been well studied in Nigeria, but less so in the north central Nigeria (NCN). Using field sampling, laboratory methods and semi structured questionnaire in 1000 poultry farms from NCN, we explore the incidence and risk factors for the persistence of NTS infection in poultry. Approximately 41.6% of the farms have experienced NTS but only 6.3% have current infection with NTS. Farm experience of NTS moderately predicted awareness of salmonellosis. Increasing stock in smallholder farms, self-mixing of concentrate on the farm, usage of stream water, pen odour, non-adherence and partial adherence of farms to recommended poultry vaccination against pullorum and fowl typhoid, and lack of and non-adherence to biosecurity were identified risk factors that increased the odds of NTS infection in poultry. Antibiotic use practice may have reduced the isolation rate of NTS, yet NTS continues to challenge poultry farms in Nigeria. Identified risk practices must be mitigated intentionally and biosecurity and hygiene must improve to reduce the burden of NTS.

One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can estimate individual risk for common diseases. In practice, the current medical practice still predominantly relies on physiological and clinical indicators to assess personal disease risk. For example, caregivers mark individuals with high body mass index (BMI) as having an increased risk to develop type 2 diabetes (T2D). An important question is whether combining PRS with clinical metrics can increase the power of disease prediction in particular from early life. In this work we examined this question, focusing on T2D. We show that an integrated approach combining adult BMI and PRS achieves considerably better prediction than each of the measures on unrelated Caucasians in the UK Biobank (UKB, n=290,584). Likewise, integrating PRS with self-reports on birth weight (n=172,239) and comparative body size at age ten (n=287,203) also substantially enhance prediction as compared to each of its components. While the integration of PRS with BMI achieved better results as compared to the other measurements, the latter are early-life measurements that can be integrated already at childhood, to allow preemptive intervention for those at high risk to develop T2D. Our integrated approach can be easily generalized to other diseases, with the relevant early-life measurements.

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16-0.53) in specific parks, notably Wolfe’s Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities.

Multiple myeloma (MM) is a genetically heterogenous disease that includes a subgroup of 10-15% of patients facing dismal survival despite most intensive treatment. The aim of this review article is to provide an integrated clinical and biological overview on the high-risk MM discussing the novel therapeutic perspectives aimed to target the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug resistance can foster a better tailored clinical management of high-risk profile and refractoriness to therapy. Among the current clinical difficulties in MM, patient’s management manipulating the tumor niche represents a major challenge given the limited knowledge about the MM-milieu interaction. The angiogenesis and bystander infiltrate constitute pivotal mechanisms of mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy but variable and unpredictable responses in high-risk MM. Therefore, it would be worth to better select the population and the MM stage that could profit to a dual immune/vasculogenesis targeting. The comprehensive knowledge of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Despite significant improvements in the biology knowledge, MM is still a chronic and incurable neoplasia and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. Here, we corroborate previous biological findings providing a synthetic outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better personalize the patient-oriented clinical management.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

This research investigates the relationship among human knowledge, behavior, and risk as they relate to urban chicken husbandry in the U.S. Concern over zoonotic diseases has been on the rise, especially with increasing contact. In particular, avian influenza, or bird flu, Salmonella enterica (salmonella), and Escherichia coli (E. coli), can all cross species lines between people and poultry. This study analyzed knowledge and practices in urban chicken husbandry to assess how they relate to risk of disease acquisition, hypothesizing that certain practices associated with a lessened knowledge base may heighten the risk. This study used social surveys to examine the self-reported knowledge base of individuals involved in chicken husbandry as they relate to beliefs and behaviors associated with the care of these animals. These results identify key factors that may heighten the risk of disease transmission, and demonstrate that an increased knowledge base could act to lessen this risk.

The emergence of pathogenic fungi is a major and rapidly growing problem (7% increase) that affects human and animal health, ecosystems, food security and the economy worldwide. The Dermocystida group in particular has emerged relatively recently and includes species that affect both humans and animals. Within this group, one species in particular, Sphareothecum destruens, also known as the Rosette agent, represents a major risk to global aquatic biodiversity and aquaculture and has caused severe declines in wild fish populations in Europe and large losses in salmon farms in the USA. It is a species that has been associated with a healthy carrier for millions of years but the host has managed in recent decades to invade parts of Southeast Asia, Central Asia, Europe and North Africa. In order to better understand the emergence of this new disease, we have for the first time synthesised current knowledge on the distribution, detection, prevalence of S. destruens as well as the associated mortality curves, and the potential economic impact in countries where the healthy carrier has been introduced. Finally, we propose solutions and perspectives to manage and mitigate the emergence of this fungus in countries where it has been introduced.

Abstract: Cancer survivors are at an increased risk for cardiovascular disease (CVD). However, the association between particulate matter (PM) and CVD risk among cancer survivors (alive >5 years since diagnosis) is unclear. We investigated the risk of CVD among 40,899 cancer survivors within the Korean National Health Insurance Service database. Exposure to PM was determined by assessing yearly average PM levels obtained from the Air Korea database from 2008 to 2011. PMs with sizes <2.5 (PM2.5), <10 (PM10), or 2.5-10 (PM2.5-10) μm in diameter were compared, with each PM level exposure further divided into quintiles. Patients were followed up from January 2012 to date of CVD event, death, or December 2017, whichever came earliest. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated using Cox proportional hazards regression by PM exposure levels. Compared with cancer survivors in the lowest quintile of PM2.5 exposure, those within the highest quintile had a greater risk for CVD (aHR 1.31, 95% CI 1.07-1.59). Conversely, increasing PM10 and PM2.5-10 levels were not associated with increased CVD risk (p for trend 0.078 and 0.361, respectively). Cancer survivors who reduce PM2.5 exposure may reduce their risk of developing CVD.

Chronic obstructive pulmonary disease (COPD) is increasingly being recognized as a systemic disease rather than a mere disorder of the lungs. Central (respiratory) and peripheral (limb) muscle weakness are among the main pronounced systemic effects of COPD. While the disease primarily affects the lower limb muscles and contributes to gait impairment, COPD is also associated with an increasing risk of falls in patients (COPDp). Previous studies have reported higher rates of falls among COPDp (1.17 to 1.20 falls/person-year), amounting to four times higher than an age-matched healthy group. Potential fall risk factors include muscle weakness, impaired daily activities, cognitive dysfunction, and gait and balance impairment. Although COPDp often manifest many of these risk factors, there remains a gap in literature regarding falls during walking in this population. This study aimed to 1. analyze the literature to identify the risk factors of falling in COPDp, and 2. investigate the underlying mechanisms by which these risk factors can lead to increased prevalence of falling. The results suggest that in addition to the known risk factors of falling, low back pain and mental fatigue should also be considered as relevant risk factors in the treatment process of these patients. Moreover, respiratory problems, which are common in this population, have demonstrated pronounced effects on energy expenditure, gait, and other types of activities of daily living (ADLs), leading to reduced intensity, disrupted coordination of the trunk-pelvic structure with the lower limbs during gait, and altered motor control performance due to activation of muscles in an inefficient synergic manner. These problems potentially lead to the increased vulnerability of these patients to external disturbances and higher incidence risk of falls and injuries. Cognitive problems, which are typically due to reduced oxygen received by the brain, as well as general inflammation caused by COPD, also play a significant role in gait disruption and balance. Future research is warranted to determine the prevalence of falls in COPDp by examining the response of these patients to Medio-Lateral (ML) and Anterior-Posterior (AP) disturbances during gait in association with traditional and recommended fall risk factors.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

Several recent epidemiological studies attempted to identify risk factors for Alzheimer's disease. Age, family history, genetic factors (APOE genotype, Down syndrome), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer's disease in Down syndrome patients and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer's disease, for Alzheimer's disease in Down syndrome, and Alzheimer's disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer's disease causes early pathological changes in Down syndrome patients, especially in the hippocampus and corpus callosum. The field needs more data about the neuroanatomical changes during childhood, how they change with increasing age, and the presence or absence of psychosocial risk factors. Further neuroimaging and psychosocial assessment-focused research is needed to understand the mechanisms leading to Alzheimer's disease at an early age and create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

This article explores the relationship between metabolic syndrome and cardiovascular disease, providing a comprehensive overview of its risk factors and prevalence. Metabolic syndrome, characterized by a cluster of interconnected risk factors, significantly increases the likelihood of developing cardiovascular disease and type II diabetes. The study, conducted over a one-year period, involved 117 patients with ages between 30 to 79 years old. Various elements such as gender, age, education level, background, smoking, alcohol consumption, dietary aspects, physical activity, and their contribution in developing the metabolic syndrome, were analysed.Central adiposity and high blood pressure emerged as prominent elements of the condition. The findings underscore the importance of a healthy lifestyle in the prevention and management of metabolic syndrome. Encouraging regular physical activity, maintaining a balanced diet, rich in fresh vegetables and fruits, and avoiding harmful behaviours, such as smoking or alcohol consumption, are essential in reducing the risk of metabolic syndrome and its associated cardiovascular complications. The study highlights the need for public health initiatives, as well as individualized preventive strategies to combat the rising prevalence of metabolic syndrome. Through promoting awareness of its risk factors and implementing effective interventions, healthcare professionals can contribute to better cardiovascular health worldwide. Further research in this area will continue to enhance our understanding of the metabolic syndrome and refine preventive and therapeutic approaches for its management.

Severe Acute Respiratory Disease Syndrome Coronavirus 2 has caused a global pandemic. Monoclonal antibodies, antiviral therapy (Remdesivir) and immunomodulatory agents represent one of the most promising therapies to prevent disease progression and reduce the relative risk of severe COVID-19. The aim of this study was to evaluate the impact on the disease progression of the main pharmacological options approved for the patients admitted in hospital with acute COVID-19 infection, according to their vaccination status.. We conducted a study including adult patients with confirmed COVID-19 admitted to the Infectious Diseases Unit of Alessandria’s Hospital in Italy, from October 2021 to March 2022. 102 patients were included in the analysis. The mean age was 69.2 ±15.4 years, 66.7% were males. According to the internal hospital’s guidelines, 47.06% patients with mild to moderate disease were treated with mAbs, 45.10% were treated with Remdesivir, of which 10.78% received combination therapy with mAbs. The most frequently complications were pneumonia (18.63%), respiratory failure (15.68%) and acute respiratory distress syndrome (13.72%). The mean length of hospitalization was 13.42 (±10.90) days and the mortality rate was 11.76%. The treatment with mAbs and immunomodulatory therapy for mild to moderate COVID-19 infection seem to be effective to improve the outcome reducing disease progression and mortality. C-reactive protein (CRP) and ferritin could be considered a good inflammatory marker of disease progression.

Background: This study aimed to assess the dementia literacy (DL) level of community-dwelling adults in the four cities (Hong Kong, Guangzhou, Macau and Zhuhai) of the Greater Bay Area of China and to determine the preferred mass media for receiving dementia information. Methods: A multi-city cross-sectional study with 788 community-dwelling adults completed the survey. Dementia literacy was indirectly measured by two validated scales, 30-item Alzhiemer’s Disease Knowledge Scale (ADKS) and 20-item Dementia Attitudes Scale (DAS). When the ADKS total score was <15 and DAS total score was <70, it was considered as ‘inadequate dementia literacy’. Participants were also asked to indicate whether they would like to receive dementia information via digital media or traditional media. Chi-square tests and logistic regressions were undertaken. Results: About one-third of the participants had inadequate dementia literacy. Those with young age or secondary education preferred to get dementia information from social media. But people living in public housing would like to get information from government or hospital websites. Middle-aged participants inclined to learn dementia from television or radio. Conclusion: It is worthy to conduct territory-wide public education in dementia and develop strategies according to their preferences in the types of mass media.

SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at the time of hospital admission are still missing. Here, we investigated whether this prediction is achievable by prospectively analysing the blood immunophenotype of 94 participants, including 20 uninfected and 37 acutely SARS-CoV-2-infected CVD patients and 37 healthy donors, using a 36-colour spectral flow cytometry panel. Unsupervised data analysis revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4+ T cells, and plasmablasts but fewer dendritic cells, CD16+ monocytes, innate lymphoid cells, and CD8+ T cell subsets. Moreover, we identified an immune signature characterised by mucosal-associated invariant T (MAIT) cells, intermediate effector CD8+ T cells, and natural killer T (NKT) cells that is predictive for CVD patients with a severe course of COVID-19. Thus, intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.

Short stature has been associated with increased various disease and all-cause death, but no reliable data exist the association between height and end-stage renal disease (ESRD) in diabetic patients. We investigated the relationship between short stature, development of ESRD, and mortality in type 2 diabetes. This study analyzed clinical data using the National Health Insurance Database in Korea. Height was stratified by five groups according to age and sex. Risk of ESRD and all-cause mortality was analyzed with Cox proportional hazards models. During a 6.9-year follow-up period, 220,457 subjects (8.4%) died and 28,704 subjects (1.1%) started dialysis. Short stature significantly increased the incidence of ESRD and all-cause mortality in the overall cohort analysis. In multivariable analysis, hazard ratios (HR) for development of ESRD comparing the highest versus lowest quartiles of adult height were 0.86 (95% confidence interval (CI), 0.83–0.89). All-cause mortality also decreased with highest height compared to patients with lowest height after fully adjusting for confounding variables (HR 0.79, 95% CI, 0.78–0.81). Adult height had an inverse relationship with newly diagnosed ESRD and all-cause in both males and females. Short stature is strongly associated with an increased risk of ESRD and all-cause mortality in type 2 diabetes.

There are potentially promising mitigation activities for epidemic and pandemic scenarios that are not currently the subject of significant research effort. Large epidemics and pandemics pose risks that are important to mitigate, even if the likelihood of the events is low and uncertain. While some efforts are the subject of extensive funding and consideration, other approaches are neglected. Here, we consider such neglected interventions which could significantly reduce the impact of such an epidemic or large-scale pandemic. These are identified via a narrative literature review of extant literature reviews and overviews of mitigations in epidemic and pandemic situations, followed by consideration of the economic value of information of further study of heretofore neglected interventions and approaches.Based on that analysis, we considered several classes of mitigations, and conducted more exploratory reviews of each. Those discussed include mitigations for (1) reducing transmission, such as personal protective equipment and encouraging improved hygiene, (2) reducing exposure by changing norms and targeted changes for high-risk or critical professions and activities, (3) reducing impact for those infected, and (4) increasing large scale resilience using disaster and infrastructure continuity planning.Some proposed mitigations are found to be of low marginal value. Other mitigations are likely to be valuable, but the concepts or applications are underdeveloped. In those cases, further research, resources, or preparation are valuable for mitigating both routine and extreme disease outbreak events. Still more areas of research are identified as having uncertain value based on specific but resolvable uncertainties. In both of the latter cases, there is no guarantee that mitigations identified as worthy of further consideration will be valuable, but the argument for further research is clear.

For children born with congenital heart defects (CHD), extracorporeal life support may be necessary. This study aimed to investigate the outcomes of children on extracorporeal membrane oxygenation (ECMO), focusing on various risk factors, including the type of CHD. The study was conducted as a retrospective single-center analysis at the Children's Hospital Zurich. All patients with CHD who required ECMO (veno-arterial or veno-venous) between 2009 and 2019 were included. Among the 88 patients, 36 (41%) had a single ventricle heart defect while 52 (59%) had a biventricular heart defect. Out of the total patients, 25 (28%) survived, with 7 (8%) having a single ventricle heart defect and 18 (20%) having a biventricular heart defect. Statistical analysis with a p-value of 0.19 revealed no significant difference in survival rates between the two groups. At the one-year follow-up, all children who survived to discharge were still alive. The rate of complications on ECMO was higher in children with a single ventricle (odds ratio [OR] 1.57, 95% confidence interval [CI] 0.67 - 3.7). The occurrence of a second ECMO run was more frequent in patients with a single ventricle compared to those with a biventricular physiology (22% vs. 9.6%). Although the study did not identify a significant difference in survival rates, it did indicate that patients with a single ventricle faced a higher risk of complications during ECMO and a greater likelihood of requiring a second ECMO run.

We report on the development of chemical vapour deposition (CVD) based graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO₂ substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalized with a linker molecule to immobile anti-hCG antibody on the surface of graphene. Binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s, Parkinson’s and Lewy body) and cardiovascular disorders.

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.

Background: Studies exploring the possible protective effect of coffee and tea consumption on dementia showed inconsistent results so far. We aimed to investigate whether consumption of tea and different types of coffee at midlife are associated with dementia later in life and, whether sex or ApoE4 influence such association. Methods: We included 7381 participants from the Norwegian HUNT Study. Self-reported questionnaires assessed daily consumption of coffee and tea at baseline. After 22 years, individuals 70 years or older were screened on cognitive impairment. Results: General coffee consumption and tea consumption was not associated with dementia risk. Compared to daily consumption of 0-1 cups of coffee, daily consumption of ≥8 cups of boiled coffee was associated with increased dementia risk in women (OR:1.83, 95% CI: 1.10-3.04, p-value for trend=0.03) and daily consumption of 4-5 cups of other types of coffee was associated with a decrease in dementia risk in only men (OR 0.48, 95% CI: 0.32-0.72, p-value for trend =0.05). Furthermore, the association between boiled coffee and increased dementia risk was only found in ApoE4 non-carriers. Differences by sex or ApoE4 carrier status were not supported by strong statistical evidence for interaction. Conclusion: Type of coffee may play a role in the direction of the association between coffee-drinking habits and dementia later in life.

Machine Learning (ML) methods have become important to enhance the performance of decision-support predictive models. However, class imbalance is one of the main challenges for developing ML models, because it limits the generalization of these models, and biases the learning algorithms. In this paper, we consider oversampling methods for generating synthetic categorical clinical data aiming to improve the predictive performance in ML models, and the identification of risk factors for cardiovascular diseases (CVDs). We performed a comparative study of several categorical synthetic data generation methods, including Generative Adversarial Networks (GANs). Then, we assessed the impact of combining oversampling strategies and linear and nonlinear supervised ML methods. Lastly, we conducted a post-hoc model interpretability based on the importance of the risk factors. Experimental results show the potential of GAN-based models for generating high-quality categorical synthetic data, yielding probability mass functions that are highly close to real data, maintaining relevant insights, and contributing to increase the predictive performance. The GAN-based model and a linear classifier outperforms other oversampling techniques, improving 2\% the area under the curve. These results demonstrate the capability of synthetic data to help both in determining risk factors and building models for CVD prediction.

COVID-19 is an infectious disease spreading through human touch. This study explored the risk perception and knowledge towards COVID-19 infection among Bangladeshi adult participants. Two self-administered online surveys were administered at two different time points from 26-31 March 2020 (Early lockdown) and 11-16 May 2020 (Late lockdown) through social media on 1005 respondents (322 and 683 participants, respectively) during COVID-19 lockdown period in Bangladesh. Univariate and multiple linear regression models were used to examine factors associated with risk perception and knowledge towards COVID-19. The mean knowledge (8.4 vs. 8.1, P=0.022) and risk perception (11.2 vs. 10.6, P < 0.001) scores differ significantly between early and late lockdown. Compared to the early lockdown period, the scores for perceived risk of contracting COVID-19 decreased significantly while public knowledge about COVID-19 was lower but not statistically significant. Female participants who practiced high quarantine particularly those who did so at the public health order during the lockdown reported increased knowledge towards the spread of COVID-19 and perceived high risk of contracting COVID-19. Education intervention using awareness to increase public knowledge and perception towards COVID-19 in Bangladesh should target male participants who practiced low quarantine and are less worried about the spread of such novel coronavirus even as the physical distancing persists.

Risk of cardiovascular disease (CVD), common in childhood cancer survivors (CCSs), may be affected by diet. We assessed sodium (Na) and potassium (K) intake, estimated from food frequency questionnaires (FFQs) and morning urine spots, and its associations with cardiovascular risk in CCSs. We stratified CCS into three risk profiles based on A) personal history (CVD, CVD risk factors, or CVD risk free), B) body mass index (obese, overweight, or normal/underweight), and C) cardiotoxic treatment (anthracyclines and/or chest irradiation, or neither). We obtained a FFQ from 802, and sent a spot urine sample collection kit to 212, of which 111 (52%) returned. We estimated Na intake 2.9 g/day based on spot urine and 2.8 g/day based on FFQ; estimated K intake was 1.6 g/day (spot urine) and 2.7 g/day (FFQ). CCSs with CVD risk factors had a slightly higher Na intake (3.3 g/day), than CCSs risk free (2.9 g/day) or with CVD (2.7 g/day, p = 0.017), and obese participants had higher Na intake (4.2 g/day) than normal/underweight CCSs (2.7 g/day, p<0.001). Daily Na intake was above, and daily K intake below national recommended levels. Adult survivors of childhood cancer need dietary assistance to reduce Na and increase K intake.

Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of blood-brain barrier (BBB) seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote Aβ aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.

Amyotrophic lateral sclerosis (ALS) is also called "motor neuron disease”. In this review, we propose that ALS is not just a neuromotor disorder, but begins as a disorder of P53-modulated skeletal muscle metabolism, leading to failures at the energy state of the cells, incorrect redox states, motor denervation, and a loss of muscle fibers. Motoneurons die as a consequence of the lack of muscular feedback, and the oligomeric TDP43 aggregates progressively and relentlessly lead to mistakes in peripheral immune self-tolerance sustained over time. An effective treatment has not been found for this devastating pathology, as for 152 years the target has not been accurately defined. Scientists and doctors should consider new knowledge regarding ALS and consider immunomodulatory therapies that, based on genetic analysis and symptoms, can be combined with compounds that regulate metabolism and promote the elimination of useless organelles and cells. What if ALS could be cured as a result of seeing motor neuron disease differently? This review aims to develop that goal and change the paradigm of our understanding of ALS.

Cardiovascular disease (CVD) is considered to be one of the leading health issues in Thailand. CVD not only contributes to an increase in the number of hospital admissions year on year but also impacts on the rising health care expenditure for the treatment and long-term care of CVD patients. Therefore, this study is aimed at examining the impacts of risk reduction strategies on the number of CVD hospital admissions, Disability-Adjusted Life Years (DALYs) and the costs of hospitalisation. To estimate such impacts a CVD cost-offset model wasapplied using a Microsoft Excel spreadsheet. The number of the mid-year population was classified by age, gender and the CVD risk factor profiles from the recent Thai National Health Examination Survey (NHES) IV. This survey was chosen as the baseline population. The CVD risk factor profiles included age, gender, systolic blood pressure, total cholesterol, and smoking status. The Asia-Pacific Collaborative Cohort Study (APCCS) equation was applied to predict the probability of developing CVD over the next eight-year period. Estimates on the following were obtained from the model: (1.) the CVD events both fatal and non-fatal; (2.) the difference between the projected number of deaths and the actual number of deaths in that population; (3.) the number of patients who are expected to live with CVD; (4.) the DALYs from the estimated number of fatal and non-fatal events; (5.) the cost of hospital admissions. Four CVD risk strategy scenarios were investigated as follows: (1.) the do nothing scenario; (2.) the optimistic scenario; (3.) achieve the UN millennium development goal; and (4.) the worst-case scenario. The findings showed that over the next eight years there are likely to be 3,297,428 recorded cases of CVD; 5,870,049 cases of DALYs; and, approximately ฿57,000 million, ($1.9 billion), is projected as the total cost of hospital admissions. However, if the current health policy can reduce the levels of risk factors as defined in the optimistic scenario or such policy meets the specifications of the UN millennium development goal,there would be a significant reduction in the number of hospital admissions. These are estimated to be a reduction of 522,179 male and 515,416 female cases. With these results it is expected that health care costs would save approximately ฿9,000 million, ($298.3 million), for CVD and 900,000 million of DALYs over the next eight years. However, if there is an upward trend in the risk factors as predicted in the worst-case scenario, then there will be an increase of 428,220 CVD cases; consequently, DALYs cases may rise by 766,029 while the hospitalisation costs may increase by approximately ฿7,000 million, ($232.1 million). Based on our findings, reducing the levels of CVD risk factors in the population will drastically reduce: (1.) the number of CVD cases; (2.) DALYs cases; and (3.) health care costs. Therefore it is recommended that the health policy should enhance the primary prevention programs which would be targeted at reducing the CVD risk factors in the population.

Postural instability (PI) in Parkinson’s disease (PD) exposes patients to increased risk of falls (RF). Although dopaminergic therapy and deep brain stimulation (DBS) improve motor performance in advanced PD patients, their effects on PI and RF are not clear. PI and RF were assessed by a stabilometric platform in 6 advanced PD patients. Patients were evaluated on and off dopaminergic medication and four DBS conditions: bilateral-DBS, DBS of the more- or less-affected side and DBS-off. Dopaminergic medication alone worsened PI and RF, DBS alone worsened RF, and no medication/DBS combination produced an improvement in postural control with respect to the OFF-medication/DBS-off condition. When ON-medication, PI and RF significantly improved after turning the DBS on, regardless of medication condition. Among DBS conditions, bilateral-DBS provided the maximal improvement of PI and RF when ON medication, and minimal worsening of PI and RF when OFF medication, whereas patients performed worse when in most-affected side DBS condition. These results can help in developing the best therapeutic strategy for postural disorders in patients with advanced PD.

Background: Cardiovascular disease (CVD) has been one of the leading causes of death and disability-adjusted life years lost worldwide. Blood pressure, lipid, and cholesterol are good predictors of CVD risk and correspond upon age and physical fitness. However, few studies have explored the variation trend of CVD risk factors across different populations upon age and their muscle strength. Objective: to analysis the variation tendency of CVD risk factors in blood according to age and relative grip strength among different populations. Method: 25363 participants were recruited in this cross-sectional study and 24709 were included in the analysis. A logistic regression and a Bayesian probabilistic analysis based on Markov Chain Monte Carlo (MCMC) Modeling is conducted to build probability prediction models of hypertension, hyperlipidemia, and hypercholesterolemia according to age, relative grip strength, body weight conditions, and physical activity levels. Results: 1) age might be the main influence factor of hypertension, which is regarded as one of the primary CVD risk factors. However, although keeping a high level of physical activity might have positive effect on preventing hypertension because that individuals with normal body weight and higher physical activity shows a lower probability of being diagnosed with hypertension, it might could not prevent individuals from getting hypertension with age. 2) After 60, individuals of normal body weight seem more likely to have hyperlipidemia than those are overweight or obese. 3) Larger relative grip strength might not be able to offset the negative effects of obesity, overweight and physical inactivity on hyperlipidemia. 4) The probability of getting hypercholesterolemia varies less with age and relative grip strength. Conclusion: Body weight management and keeping high levels of physical activity are recommended at any age. It might benefit to increase some bodyweight after 60 years old.

We investigated whether cigarette smoking and dietary acid load (DAL) are associated with the risk of chronic obstructive pulmonary disease (COPD) in middle-aged healthy Korean men. Healthy men without diagnosed chronic disease (40-64 yrs) from the KNHANES-VI (2013–2015) included in the analysis (n=774) were subdivided by smoking status and DAL levels as estimated by the net endogenous acid production (NEAP) quartile. Current smokers tended to have a higher risk of COPD than non-smokers before and after the adjustment. When divided by the DAL quartile, the Q4 tended to have a higher risk of COPD than the Q1. Additionally, current smokers with lower (Q2), modest (Q3), and highest NEAP scores (Q4) showed more than 4-fold higher risks of COPD than the non-smokers with the lowest NEAP scores (Q1). Ex–smokers with higher NEAP scores (Q3 and Q4) showed more than 4-fold higher risks of COPD than the Q1. Interestingly, the risk of COPD was also more than 6-fold higher in non-smokers with the highest NEAP scores compared to the Q1. NEAP scores and smoking status synergistically increased the risk of COPD in middle-aged healthy Korean men. It suggests that DAL levels are an important factor for the prevention and management of COPD.

(1) Background: Alcohol abuse has a high impact on the mortality and morbidity related to a great number of diseases and is responsible for the development of alcoholic liver disease (ALD). It remains challenging to detect and evaluate its severity, which is crucial for prognosis. In this work, we studied if urinary EVs (uEVs) could serve in diagnose and evaluate cirrhosis in ALD. (2) Methods: uEVs characterization by cryo-electron microscopy (Cryo-EM), Nanoparticle Tracking Analysis (NTA) and Western blotting (WB) was performed in a cohort of 21 controls and 21 cirrhotic patients. Then, proteomics of urinary EVs (uEVs) was carried out in a second cohort of 6 controls and 8 patients in order to identify new putative biomarkers for cirrhosis in ALD. (3) Results: uEVs concentration, size and composition were altered in cirrhotic patients. A total of 1304 proteins were identified in uEVs, and 90 of them were found to be altered in cirrhotic patients. (4) Conclusions: uEVs could be considered as a tool and a supplier of new biomarkers for ALD, whose application would be especially relevant in chronic patients. Yet, further research is necessary to obtain more relevant result in clinical terms.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are fast becoming the most common chronic liver disease and are often preventable with healthy dietary habits and weight management. Sugar-sweetened beverage (SSB) consumption is associated with obesity and NAFLD. However, the impact of different types of SSB, including artificially sweetened beverages (ASB), is not clear after controlling for total sugar intake and total caloric intake. In this study, we examined the association between different SSB consumption and the risk of NAFLD and NASH. A total of 3,739 US adults aged ≥20 years old who had completed 24-hour dietary recall interviews and measurements, including dietary, SSB, smoking, physical activity, and liver stiffness measurement, using the National Health and Nutrition Examination Survey 2017-2020 surveys were included in this study. Chi-square tests, t-tests, and weighted logistic regression models were utilized for analyses. The prevalence of NASH was 20.5%, and NAFLD (defined without NASH) was 32.7% of .S.U.S. adults. We observed a higher prevalence of NASH/NAFLD in men, Mexican-Americans, sugar intake from SSB, light-moderate alcohol use, individuals with lower physical activity levels, higher energy intake, obesity, and medical comorbidities. Heavy sugar consumption through SSB was significantly associated with NAFLD (aOR=1.60, 95% CI=1.05-2.45). In addition, intake of ASB only (compared to non-SSB category) was significantly associated with NAFLD (aOR=1.78, 95% CI=1.04-3.05), after adjusting for demographic, risk behaviors, and body mass index. Higher sugar intake from SSB and exclusive ASB intake are both associated with the risk of NAFLD.

Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous systemic syn-drome that often coexists with multiple comorbidities. In high-complex COPD patients the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. Objective. To determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. Methods. 105 adults with COPD were included in this prospective study. All participants at baseline had at least 2 moderate exacerbations or 1 leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during 12-months follow-up. Results. CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with mMRC, CAT and a negative correlation with FEV1, FVC, FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS-Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS-Severity Index: HR = 1.21 (95% CI: 1.12-1-31); CIRS-Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). Conclusions. Among patients with COPD, comorbidity number and severity, assessed by the CIRS score, influence the risk in moderate to severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function

Conducting computational stress-strain analysis using finite element methods (FEM) is a common approach when dealing with the complex geometries of atherosclerosis, which is a leading cause of global mortality and complex cardiovascular disease. The considerable expense linked to FEM analysis encourages the substitution of FEM with a considerably faster data-driven machine learning (ML) approach. This study investigated the potential of end-to-end deep learning tools as a more effective substitute for FEM in predicting stress-strain fields within 2D cross sections of arterial wall. We first proposed a U-Net based fully convolutional neural network (CNN) to predict the von Mises stress and strain distribution based on the spatial arrangement of calcification within arterial wall cross-sections. Further, we developed a conditional generative adversarial network (cGAN) to enhance, particularly from the perceptual perspective, the prediction accuracy of stress and strain field maps for arterial walls with various calcification quantities and spatial configurations. On top of U-Net and cGAN, we also proposed their ensemble approaches to further improve the prediction accuracy of field maps. Our dataset, consisting of input and output images, was generated by implementing boundary conditions and extracting stress-strain field maps. The trained U-Net models can accurately predict von Mises stress and strain fields, with structural similarity index scores (SSIM) of 0.854 and 0.830 and mean squared errors of 0.017 and 0.018 for stress and strain, respectively, on a reserved test set. Meanwhile, the cGAN models in a combination of ensemble and transfer learning techniques demonstrate high accuracy in predicting von Mises stress and strain fields, as evidenced by SSIM scores of 0.890 for stress and 0.803 for strain. Additionally, mean squared errors of 0.008 for stress and 0.017 for strain further support the model's performance on a designated test set. Overall, this study developed a surrogate model for finite element analysis, which can accurately and efficiently predict stress-strain fields of arterial walls regardless of complex geometries and boundary conditions.

Parkinson’s disease (PD) is characterized by motor deficits and a wide variety of non-motor symptoms. The age of onset, rate of disease progression and the precise profile of motor and non-motor symptoms display considerable individual variation. Neuropathologically, the loss of substantia nigra dopaminergic neurons is a key feature of PD. The vast majority of PD patients exhibit alpha-synuclein aggregates in several brain regions, but there is also great variability in the neuropathology between individuals. While the dopamine replacement therapies can reduce motor symptoms, current therapies do not modify the disease progression. Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification. It has been suggested that the heterogeneity of PD is a major contributing factor to the failure of disease modification trials, and that it is unlikely that a single treatment will be effective in all patients. Precision medicine, using drugs designed to target the pathophysiology in a manner that is specific to each individual with PD, has been suggested as a way forward. PD patients can be stratified according to whether they carry one of the risk variants associated with elevated PD risk. In this review we assess current clinical trials targeting two enzymes, leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), which are encoded by two most common PD risk genes. Because the details of the pathogenic processes coupled to the different LRRK2and GBA risk variants are not fully understood, we ask if these precision medicine-based intervention strategies will prove “precise“ or “personalized“ enough to modify the disease process in PD patients. We also consider at what phases of the disease that such strategies might be effective, in light of the genes being primarily associated with the risk of developing disease in the first place, and less clearly linked to the rate of disease progression. Finally, we critically evaluate the notion that therapies targeting LRRK2 and GBA might be relevant to a wider segment of PD patients, beyond those that actually carry risk variants of these genes.

This study aimed to assess the prevalence and identify risk factors for schistosomiasis among school-aged children in low- and middle-income communities. A retrospective cross-sectional study was conducted, involving the examination of 24 034 children for Schistosoma haematobium ova. Data were analyzed using IBM Statistical Package for the Social Sciences (SPSS) version 27. Logistic regression was employed to determine the factors associated with schistosomiasis. The overall prevalence of schistosomiasis in the study population was 75%, with higher rates observed in rural-dominated areas, particularly Bushbuckridge (73%) and Nkomazi (51%). Age, a history of bilharzia, and the presence of blood in urine were significantly associated with schistosomiasis, while being a female child was found to be a protective factor. This study underscores the importance of implementing robust screening procedures and the necessity for health education to mitigate the high prevalence of schistosomiasis and prevent its further spread.

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.

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, in-cluding iPTH, vitamin D, FGF-23, fetuin-A, sclerostin and VC scores (Adragao method). Preva-lence of VC was similar in both groups, but HD patients had more frequent VC scores ≥6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A levels were higher in pre-HD, while FGF-23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin and no vitamin D treatment, while in HD patients with higher sclerostin, FGF23 and urea, and lower iPTH. Conclusion. Progression of CKD from the pre-HD to the HD stage is accompanied by a decreased effect of the inhibitor and an increase in the promoter VC. However, mineral imbalance, hormonal regulation, treatment options, and patient-specific fac-tors should be considered. Further studies are needed to elucidate the underlying pathways.

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

This study investigated the effects of whole-body circuit training using a weighted vest on plasma resistin, cardiovascular disease risk factors, and cardiorespiratory fitness for normal-weight obese women. In this study, thirty- six normal-weight obese women were divided into three groups: Weighted Vest Circuit Training (WVCT) (n = 12), Body Weight Circuit Training (BWCT) (n = 12), and Control (CON) (n = 12). Whole-body circuit training was conducted three times a week for eight weeks to compare and analyze plasma resistin, cardiovascular disease risk factors, and cardiorespiratory fitness before and after training. Although there was no significant baseline difference between the groups regarding skeletal muscle mass, it significantly increased for the WVCT group after eight weeks. percent body fat significantly decreased for the WVCT and BWCT groups, and there was a significant difference when the percent body fat of these two groups were compared to that of the control group. Moreover, the WVCT and BWCT groups displayed a significant decrease in plasma resistin, showing a significant difference from the CON group. The WVCT and BWCT group showed a significant decrease in plasma IL-6, whereas the CON group showed a significant increase. VO2max significantly increased post-training compared to before in the BWCT group and the WVCT group, and the WVCT group showed differences between groups compared to the BWCT group and the CON group. None of the three groups displayed significant changes in plasma hs-CRP, yet there was a significant difference between the hs-CRPs of the WVCT and BWCT group and that of the CON group. In conclusion, whole-body circuit training using a weighted vest efficiently improves body composition, plasma resistin, and cardiopulmonary fitness, reducing cardiovascular disease risk factors in normal-weight obese women.

Neutropenia is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with esti-mated glomerular filtration rate (eGFR) 60–89 ml/min/1.73m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophy-laxis of FN. The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of cre-atinine assessment enabled the use of the newly recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration. Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR<60ml/min/1.73m2, while 15 (62.5%) eGFR< 90ml/min/1.73m2. The relative risk of neutro-penia in patients with impaired eGFR was over six times higher than in patients with eGFR>90 ml/min/1.73m2 (RR=6.08; 95%CI:1.45–27.29; p< 0.01). Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

Cannabidiol is a well-known non-psychotropic phytocannabinoid from Cannabis sativa, which exerts a broad range of neuropharmacological activities in the central nervous systems. Over the past years, compelling evidence from preclinical and clinical studies support therapeutic potentials of cannabidiol in various neurological disorders, including neurodegenerative diseases. Neurodegenerative diseases are characterized by the accumulation of misfolded or aggregated protein due to the defective protein homeostasis or proteostasis network, termed as proteinopathies. Because of its role in the protein homeostasis network, cannabidiol could be a potent molecule to revert not only age-associated neurodegeneration but also other protein misfolding disorders. In this review, we discuss the potentiality of cannabidiol as a pharmacological modulator of the proteostasis network, highlighting its neuroprotective and aggregates clearing system inducing potentials in the neurodegenerative diseases.

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. In Bolivia it is cultivated in different parts of the High Andes and in the Interandean Valleys. The species is affected by several fungal diseases which reduce production, but before 2016 hardly any mention had been made of virus disease in the region. The aims of the present work were: 1) to describe the symptomology of this apparent viral disease, and ii) determine its effects on the yield of different alfalfa cultivars available from the CIF-UMSS. In 2016, a plot was established at Tiquipaya (Dept. of Cochabamba) (altitude 2480 m) was planted with 12 alfalfa cultivars. Disease incidence values were estimated and the area under the disease progress curves (AUDPC) calculated. The disease progress curves themselves were analyzed using logit functions for polycyclic diseases, and yields were determined. Disease symptoms included deformation of the folioles, thickened veins, the presence of vein enations and papillae on the abaxial leaves, reduced plant size - all symptoms of infection apparently caused by Alfalfa Dwarf Virus. The different cultivars returned different incidence values. They also returned different apparent infection rates ranging from 0.072/day for Cóndor, to 0.113/day for Tamborada. The different cultivars returned different dry weight yields, with yields inversely related to the AUDPC. In conclusion, based on the foliar symptoms registered, the viral disease is associated with the Alfalfa Dwarf Virus. The twelve cultivars evaluated presented different incidence levels of the viral disease.

Crohn's disease (CD) results from an aberrant immune response against the commensal microbiota in genetically susceptible hosts. However, the nature of the immune defects, the microflora involved and the genetic susceptibility remain incompletely defined and controversial. Extraintestinal manifestations occur in up to 25-35% of patients and generally precede the onset of gastrointestinal symptoms, which are often of a colonic nature and are influenced by disease activity. Renal manifestations can be considered dependent on the same immune mechanism that determines inflammatory bowel disease in CD. This review seeks to describe the current state of association between CD and kidney disease.

Crohn's disease (CD) results from an aberrant immune response against commensal microbiota in genetically susceptible hosts. However, the nature of immune defects, the microflora involved, and genetic susceptibility remain incompletely defined and controversial. This review seeks to describe the present state of association between CD and renal disease; moreover, we highlight the convergence of CD with amyloidosis that can trigger sustained inflammation, producing the pathological alteration observed in both diseases. The following MESH terms were searched in PubMed, PubMed Central (PMC), and Web of Science: “Crohn´s disease” and “renal disease.” The R RISmed package was used for PubMed and PMC. The abnormal humoral immune response is described along with alterations in immune cell migration mechanisms in CD during inflammation.

Introduction: Crohn's disease (CD) is a chronic inflammatory granulomatous disease that can affect the entire gastrointestinal tract. It is characterized by various extraintestinal manifestations (EIM), of which oral manifestations (OM) are often possible. One of the possible OM is periodontal disease (PD) a chronic inflammatory condition of the supporting tissues of the teeth. This study aimed to show the existence of a mutual relationship between the clinical activity of PD and the clinical and endoscopic activity of CD. Materials and methods: Using one clinical and two endoscopic indexes for the assessment of CD activity and clinical attachment loss (CAL), bleeding on probing (BOP), pocket probing depth (PPD) and radiographic bone loss (RDL) on dental panoramic tomogram to assess PD in CD patients. Results: A total of 38 patients underwent the entire study process, of which 20 patients with CD and 18 patients with CD and PD. Considering all CD activity scores, there were 26 patients with active disease, and half of them had PD, and 85.7% of operated patients had active CD. Values of CAL, PPD, BOP and RBL were higher in active CD than remission, except BOP when compared to CDAI score which was higher in remission of CD. Discussion and conclusion: The results of this study indicate that there is a connection between the activity of CD and the worse condition of the supporting tissues of the gums in the oral cavity which is important to keep in mind the necessity of referring patients with CD to a dentist for timely and adequate therapeutic measures.

Weeds that infest crops are a primary factor limiting agricultural productivity world-wide. Weedy rice, also called red rice, has experienced independent evolutionary events through gene flow from wild rice relatives and de-domestication from cultivated rice. Each evolutionary event supplied/equipped weedy rice with competitive abilities that allowed it to thrive with cultivated rice and severely reduce yields in rice fields. Under-standing how competitiveness evolves is important not only for noxious agricultural weed management but also for the transfer of weedy rice traits to cultivated rice. Molec-ular studies of weedy rice using simple sequence repeat (SSR), restriction fragment length polymorphism (RFLP) and whole genome sequence have shown great genetic variations in weedy rice population globally. These variations are evident both at whole genome and at single allele level, including Sh4 (shattering), Hd1 (heading and flower-ing), and Rc (pericarp pigmentation). The goal of this review is to describe the genetic diversity of current weedy rice germplasm and the significance of weedy rice germplasm as a novel source of disease resistance. Understanding these variations, es-pecially at an allelic level, is also crucial as individual locus that control important traits can be of great target to rice breeders.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

Over the last decade, advances in our understanding about the genetic architecture of complex traits and common diseases, have increased our ability to perform susceptibility genetic testing for diseases in asymptomatic individuals. These technological developments raise complex ethical, legal and social considerations. Here we discuss a series of ethical issues associated with susceptibility genetic testing for Alzheimer's and Parkinson's disease. These include, amongst others, informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. As knowledge of the genetic basis of these diseases continues growing, and as genetic testing becomes more widespread, we anticipate that it will become increasingly important for scientists and clinicians to engage in the conversation about the ethical, social and policy implications of these technologies.

Background: Meniere's disease (MD) has been recently linked to gluten assumption. Approximately 75% of MD patients show positive skin test to food and about 50% of the positive responses are specific to the gliadin acid extract fraction. Aim of this study was to investigate the humoral immune responses to wheat antigens and related autoantigens in MD patients. Methods. We assessed the reactivity of sera from 28 patients with definite MD and 100 healthy controls against a repertoire of 51 antigens usually associated with immune reaction to gluten. Results. MD patients showed an increase of anti-wheat IgA, anti-cerebellar peptide IgA and anti-glutamic acid decarboxylase (GAD) 65 IgM compared to healthy controls. In particular, the increase of anti-wheat IgA and GAD 65 IgM has been confirmed in a subgroup of MD patients symptomatically responding to a gluten free diet (GFD). Conclusion. In MD patients, an increase of the antibody production against gluten biomarkers was observed; in particular, anti-wheat IgA seems to be associated to clinical response to GFD.

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

Introduction: Sarcopenia, muscle loss, often coexists with MASLD, a common liver disorder, which is more prevalent in those with sarcopenia. Sarcopenia also increases the risk of liver conditions like steatosis and fibrosis. Studies on sarcopenia in MASLD are common in developed countries, but fewer follow the EWGSOP2 guidelines in Brazil. Aim: to assess sarcopenia prevalence in MASLD patients. Methods: Cross-sectional study conducted at the Gastroen-terology/Hepatology Service of ISCMPA with patients diagnosed with MASLD. The EWGSOP2 criteria were used to evaluate sarcopenia. Categorical data presented as absolute and relative frequency; parametric continuous data ex-pressed as mean±standard deviation; non-parametric continuous data as me-dian and IQR. Gender differences in were analyzed using Fisher's Exact Test or Chi-squared tests, and for continuous variables, T Student tests (parametric) and Mann-Whitney U tests for independent samples (non-parametric). The significance level was set at 5% (p<0.05). Results: The study involved 103 MASLD patients with an average age of 60.39 years, comprising 48 (46.60%) adults and 55 (53.40%) older individuals. Concerning sarcopenia diagnosis, four individuals exhibited decreased muscle strength; two had reduced MME (sarcopenia); and one showed decreased walking speed (severe sarcopenia). Among the participants, 63 (60.6%) were physically active. 35 (62.5%) had mild to moderate steatosis, while 21 (37.5%) had severe steatosis. In terms of EHNA, 13 subjects (24.08%) had moderate to severe EHNA. Regarding fibrosis classi-fication, 68 (72.34%) individuals had undetermined or high probability based on the NAFLD score, with higher prevalence in males (n=23; 88.5%). Fibrosis assessment via liver biopsy revealed 27 (28.72%) in F1 and F2 and 15 (16.96%) in F3 and F4. Stratification of fibrosis into F3 and F4 was more com-mon among men (n=9; 47.4%). Conclusion: Most of the population was physi-cally active. The parameters indicating sarcopenia exceeded the thresholds recommended by EWGSOP2. The prevalence of sarcopenia was low in individuals with MASLD.

Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and memory loss subsequently become cardinal features of Alzheimer’s disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson’s disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity. Importantly, both diagnoses are accompanied by hyperinflammation and intrathecal cytokine changes. Thus far, numerous clinical trials for investigational drugs have produced nothing effective for AD or PD, yet the anti-inflammatory and regenerative potential of platelet-rich plasma (PRP) remains largely unexamined in this context. This report explores a proposed Phase I study on intrathecal condensed plasma growth factors processed from autologous thrombin-activated PRP as monotherapy for AD or PD. The concept gains support from related work where cytokines of platelet origin successfully lowered inflammation, corrected background fibrosis, deactivated abnormal cells, and recovered local tissue function—all desirable outcomes in AD and PD. PRP-mediated effects on membrane potentials, electrolyte balance, and water clearance are less well characterized, but experimental evidence suggests these pathways could likewise influence glymphatic drainage to ameliorate proteinopathies. As a well-tolerated ‘orthobiologic’ with no hypersensitivity risk, intrathecal PRP and its derivatives bring advantages distinct from synthetic pharmaceuticals. If age-associated neuroinflammation in AD and PD is an upstream event contributing to neural disruption, then dampening local oxidative stress by a patient’s own platelet cytokines (as already proven in other tissues) could offer therapeutic relevance to these neurodegenerative conditions as well.

Crop disease classification has always been a critical and persistent problem in the field of agricultural and forestry sciences, where often we do not have access to a sufficient number of samples to know the distribution of real-world samples. How to make full use of the existing data is the starting point of our thinking. To address this problem, this paper proposes a supervised image augmentation method Negative Contrast, which uses the contrast images of existing disease samples after removing disease areas as negative samples for image augmentation when samples are relatively scarce. Numerous experiments have shown that several classical models using this augmentation method have improved in disease classification of four crops, rice, wheat, corn, and soybean, with a maximum accuracy improvement of 30.8%. In addition, the comparative analysis of attentional heat map shows that the model using Negative Contrast is more accurate and intense on the area of interest of diseases, and thus reflects better generalization ability in real-world disease classification. Our dataset and codes can be found in https://www.kaggle.com/datasets/w970704112/corn-wheat-rice-soybean and https://github.com/hiter0/contrastaug .

Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.

Assessment of cardiac function is the leading parameter when evaluating the state of the cardiovascular system of patients undergoing chronic hemodialysis. The aim of the paper: to assess the state of the cardiovascular system of these patients using new sensitive echocardiography and Doppler techniques and thus advance the prevention of cardiovascular disease.Method: Twenty children with end-stage renal insufficiency on chronic hemodialysis and twenty healthy controls underwent echocardiographic monitoring using standard Doppler and tissue Doppler imaging. Structural and functional changes in the left ventricle were evaluated.Results: Patients on hemodialysis had significantly greater left ventricular mass indices compared to the controls (p<0.001). The patients on hemodialysis had preserved systolic function – their fractional shortening, ejection fraction and Sm (systolic myocardial velocity) did not differ significantly compared to the controls (p>0.05). Early diastolic function in children on hemodialysis was also preserved: the E/A and Em/Am ratio did not differ significantly from the control group (p>0.05). Children on hemodialysis exhibited impaired late diastolic function (compliance index), that is, considerably higher E/Em compared to controls (p<0.00). Myocardial Performance Index values showed statistically significant elevation in children on hemodialysis compared to the control group (p<0.001).Conclusion: Tissue Doppler in tandem with conventional Pulsed Doppler can provide additional information on left ventricular filling pressures (E/Em) in children on hemodialysis. It is therefore recommended to perform routine measuring of Em waves and the E/Em ratio, not only in order to evaluate myocardial relaxation and ventricular filling pressures, but primarily to stratify risk and provide a prognosis.

Google Trends data can be informative for infectious disease incidences, including Lyme disease. However, the use of Google Trends for predictive purposes is underutilized. In this study, we tested the ability of Google Trends search data to predict monthly state-level Lyme disease case counts in the United States. We requested Lyme disease data for the years 2010-2021. We downloaded Google Trends search data on terms for Lyme disease, symptoms of Lyme disease, and diseases with similar symptoms as Lyme disease. We built mixed negative binomial models based on a training dataset (2010-2016) and tested the models on a test dataset (2017-2021). A model was built for each search term and monthly lags of search terms were included as predictors. The highest performing models had high predictive ability, indicated by low Root Mean Squared Errors (RMSEs) and close association between observed and predicted case counts. The highest performing model was for the search term “Summer Flu”, which indicates low specificity of some of the terms. We outline challenges of using Google Trends data, including data availability and a mismatch between geographic units. We discuss opportunities for Google Trends data, including prediction of additional zoonotic diseases and incorporating environmental and companion animal data.

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with a low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology ranging from clinical activity to genealogical reconstruction of families/populations along the centuries, creation of databases, and molecular/genetic research, has been modelled on the characteristics of the Calabrian population for more than three decades. This methodology allows to the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, in this population it has been reported a higher prevalence of several hereditary neurodegenerative diseases such as Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Niemann Pick type C disease, Spino-cerebellar ataxia, Creutzfeldt–Jakob disease and Gerstmann Straussler Scheincker disease. Thus, Calabria constitutes a model for the study of neurodegenerative diseases, a sort of "outdoor laboratory" useful for the advancement of knowledge in this field. Here, we summarize and discuss some results of research data supporting the view that Calabria is a genetic isolate and could represent a useful model for the study and characterization of neurodegenerative diseases.

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.

The Neurodegenerative Diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to have an exponential growth thanks to numerous advancements in tech, shifts in the understanding of the disease as a phenomenon, and the change of perspective regarding gene editing and the upsides of this action. The aim of this paper is to analyse the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and Amyotrophic Lateral Sclerosis. We intend through this review to focus on the newest treatment, diagnosis and predictions plans regarding this large group of diseases, in order to obtain a better accuracy analysing and spotting the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide future evidence of possible novelty therapies that target the specific genes and could be useful to be taken into consideration when the classical approaches fail to shed light.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies suggested relations between neurodegenerative diseases for many years, e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways. Within this study, publicly available genomic, transcriptomic and proteomic data were gathered from 188 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases and the analyzed omics-layers within conditions. The results show a remarkably high number of shared genes between the transcriptomic and proteomic levels for all diseases while showing a significant relation between genomic and proteomic data only in some cases. A set of 139 genes was found to be differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented GO-Terms and pathways mainly involved in stress response, cell development, cell adhesion, and the cytoskeleton. Furthermore, the overlap of two and three omics-layers per disease were used to search for overrepresented pathways and GO-Terms. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis on the transcriptomic and proteomic level by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring these omics-layers simultaneously holds new insights that do not emerge from analyzing these omics-layers separately. Our data therefore suggests addressing human patients with neurodegenerative diseases as complex biological systems by integrating multiple underlying data sources.

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in GBA1, characterized by glucocerebrosidase dysfunction and glucocerebroside and glucosylsphingosine accumulation. Since phenotypes of murine models of GD often differ from those in patients, careful characterization of Gba1 mutant mice is necessary to establish their ability to model GD. We performed side-by-side comparative biochemical and pathologic analyses of four murine Gba1 models with genotypes L444P/L444P (p.L483P/p.L483P), L444P/null, D409H/D409H (p.D448H/p.D448H), and D409H/null, along with matched wildtype mice, all with the same genetic background and cage conditions. All mutant mice exhibited significantly lower glucocerebrosidase activity (p < 0.0001) and higher glucosylsphingosine levels than wildtype, with the lowest glucocerebrosidase and highest glucosylsphingosine levels in mice carrying a null allele. Although glucocerebrosidase activity in L444P and D409H mice was similar, D409H mice showed more lipid accumulation. No Gaucher or storage-like cells were detected in any of the Gba1 mutant mice. Quantification of neuroinflammation, dopaminergic neuronal loss, alpha-synuclein levels and motor behavior revealed no significant findings, even in aged animals. Thus, while the models may have utility for testing the effect of different therapies on enzymatic activity, they did not recapitulate the pathological phenotype of patients with GD, and better models are needed.

Background: Autoimmune inner ear disease (AIED) is a rare autoimmune condition characterized by progressive sensorineural hearing loss with hearing fluctuations over weeks to months, presenting significant challenges in both diagnosis and treatment. Due to its rarity, treatment responses and prognosis in AIED remain poorly understood. Methods: This study reviewed medical records from Taipei Medical University Hospital documented between August 2016 and August 2021. Among 67 patients experiencing fluctuating hearing loss, 11 met the diagnostic criteria for AIED and underwent regular follow-up assessments within a 5-year timeframe. ROC curve was used to discriminate the power of these prognostic parameters. Results: In this study, several factors including younger age, milder initial hearing loss, meeting criteria for bilateral Meniere's disease (MD), having an ascending audiogram pattern, longer time interval between hearing impairment attacks in contralateral ears and responding well to steroids were associated with better prognosis. ROC curve demonstrated the diagnostic value of specific parameters such as the presence of bilateral MD (AUC 0.825, 95% CI 0.640–1.000), pretreatment HI ≤ 45 dB HL (AUC 0.808, 95% CI 0.610–1.000), response to steroids (AUC 0.800, 95% CI 0.595–1.000), and ascending audiogram (AUC 0.858, 95% CI 0.683–0.858). Conclusions: This study identified key prognostic factors for AIED, providing valuable insights for predicting AIED prognosis and facilitating personalized patient management.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Bacterial Extracellular Vesicles (BEVs) generated from the bacteria has high feasibility of intracellular interactions with other cells, can be used as a cargo to deliver any therapeutic substances like monoclonal antibodies, proteins, plasmids, siRNA and small molecules for the treatment of neurodegenerative diseases (NDs). BEVs have a high ability for delivering therapeutic molecules across the blood-brain barrier to treat Alzheimer's Disease (AD) via various mechanisms. In this review, we have sum up in-depth research details of the role and advancement of BEVs in NDs, AD and its Therapeutics. Moreover, details about offensive and defensive functions of BEVs in ND pathogenesis and examine the critical BEV networks in the microbiome-gut-brain axis and their role in neurodegenerative disorders. Additionally determining the roles of BEVs in the neuroimmune system and their interaction with neurodegenerative disorders and exploring the risk factors of BEVs in the autophagy-lysosomal pathway and their possible effects on neurodegenerative disorders are summarised in detail. In conclusion, this review seeks to contribute to a better understanding of the potential function of BEVs in NDs and to identify new therapeutic intervention strategies.

Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.

Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders related to aging. Though several risk factors are shared between these two diseases, the exact relationship between these two diseases is still unknown. In this paper, we analyzed how these diseases relate to each other from a genomics viewpoint. Using an extensive literature search, we accumulated the list of genes from the major genome-wide association (GWAS) studies. However, we found only one gene (HLA-DRB5) reported in these GWAS studies that are common between AD and PD. We also listed all the miRNAs that have been previously reported for AD and PD. Here we found 15 different miRNAs that were reported in both diseases. In order to get better insights, we predicted the gene coexpression network for both AD and PD. Network analysis on these networks show six clusters of genes related to AD and four clusters of genes related to PD.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.