In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individual’s resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled, re-vaccinated with two doses of Shanchol™ regardless of previous vaccination and followed-up for 90 days. Bloods collected at baseline before re-vaccination, at day 14 prior to second dosing and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60 and 90 across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

Background: This study aimed to identify the association between occupational stress and depression-well-being by proposing a comprehensive and flexible job burden-capital model with its corresponding hypotheses. Methods: For this research, 1618 valid samples were gathered from the electronic manufacturing service industry in Hunan Province, China; self-rated questionnaires were administered to participants for data collection after obtaining their written consent. The proposed model was fitted and tested through structural equation model analysis. Results: Single-factor correlation analysis results indicated that coefficients between all items and dimensions had statistical significance. The final model demonstrated satisfactory global goodness of fit (CMIN/DF=5.37, AGFI=0.915, NNFI=0.945, IFI=0.952, RMSEA=0.052). Both the measurement and structural models showed acceptable path loadings. Job burden and capital were directly associated with depression and well-being or indirectly related to them through personality. Multi-group structural equation model analyses indicated general applicability of the proposed model to basic features of such a population. Gender, marriage and education led to differences in the relation between occupational stress and health outcomes. Conclusions: The job burden-capital model of occupational stress-depression and well-being was found to be more systematic and comprehensive than previous models.

In patients with heart failure, the evaluation of left ventricular (LV) diastolic function is vital, offering crucial insights into hemodynamic impact and prognostic accuracy. Echocardiography stands as the primary imaging modality for diastolic function assessment, and using it effectively requires a profound understanding of the underlying pathology. This review covers four main topics: first, the fundamental driving forces behind each phase of normal diastolic dynamics, along with the physiological basis of two widely used echocardiographic assessment parameters, E/e' and mitral annulus early diastolic velocity (e'); second, the intricate functional relationship between the left atrium and LV in patients with varying degrees of LV diastolic dysfunction (LVDD); third, the role of stress echocardiography in diagnosing LVDD and the significance of parameter changes in this context; and fourth, the clinical utility of evaluating diastolic function from echocardiography images across diverse cardiovascular care areas.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p < 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

Background and Objectives: Wilson disease (WD) is a disorder of copper metabolism caused by genetic muta-tions in the ATP7B gene which lead to the accumulation of copper in the body. The aim of the present study is to investigate the severity of WD in patients in Romania. Materials and Methods: This study was conducted us-ing an online questionnaire consisting of 32 questions in a group of patients suffering from Wilson disease. Results: The study included 67 people aged 7 to 56 with WD. The most common symptoms of the participants were hepatic and neurological in 22 cases (32.8%). The most common neurological symptom in the assessed cases was muscle stiffness (49.5%), followed by tremor (45%), and speech disorders (40.5%). The Kay-ser-Fleischer ring was present in 50.7% of the participants. The most commonly used drug treatment in the participants was D-penicillamine (77.61%). Conclusions: The severity of WD is based on many aspects, the most important being early diagnosis and access to treatment throughout the year. The prognosis is favorable with early diagnosis and treatment, but it is crucial to diagnose individuals before they develop major symp-toms. Therefore, advances in WD screening can lead to an earlier diagnosis and better results.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or light chain (AL) origin may affect any structure of the heart, including the valves. Recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of epidemiology, diagnosis, treatment and prognosis of this dual pathology. Even though of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis is rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis including epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring V. cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 cholera patients enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titers. At this saliva titer, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between Vibrio Cholerae saliva and serum antibodies (rho=0.66, p&lt;0.001). In conclusion, saliva-based diagnostic cholera tests has high diagnostic accuracy, and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP, TRPC may form homo or heterotetrameric ion channel, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase of the expression of different TRPC isoforms has been observed in different animal model of heart infarcts, and in vitro experimental model of ischemia and reperfusion. TRPC-mediated increase of the intracellular Ca²⁺ concentration seems required for the activation of signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we will highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion, and to heart infarction.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Researchers have asserted that, as patients rely on external powerful sources to control their disorders, in addition to their own internal powers and virtues, examining their coping mechanisms can lead to a better understanding of the initiation and progression of chronic diseases and uncover potential opportunities to balance and enhance their psycho-spiritual well-being and possibly their treatment and recovery. This review serves as a user’s manual for investigators who choose to use the CSI-SF to conduct their research on coping behaviors. The CSI-SF that measures four coping strategies based on 16 items was first assessed using the Jackson Heart Study (JHS) cohort in 2007. The reliability and construct validity of the CSI-SF was also later assessed among hemodialysis patients across 13 countries. In this study, the CSI-SF was assessed to be a reliable and valid instrument for measuring coping strategies. The CSI-SF serves the purpose of developing an inner voice that can assist with understanding how people cope with everyday life. The information gathered from administration of the CSI-SF can inform investigators about environmental cues and triggers that can also impact individual health.

Following the era of GWAS studies, efforts are being made to identify genes underlying complex traits by merging eQTL and GWAS data and assessing the colocalization of eQTLs and GWAS signals. A problem that sometimes occurs in this context is the observation of association between several genes in a genomic region with a trait. This happens because genes in a region could be under the regulatory impact of common elements and coexpress. As such, computational approaches that rely on cis-eQTL information can not exactly pinpoint the causal gene. Here, I report an alternative solution, based on trans-eQTLs to test the association between a gene and a trait. Through the analyses applied to adjacent genes that coexpress and concordantly impact blood traits, I provide evidence that trans-eQTLs can resolve the problem of coexpression-causality without the interference of shared cis-regulatory SNPs.

Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and is ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful and which can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.

Mycobacterium tuberculosis was responsible for 1.3 million deaths worldwide in 2022. Bacillus Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB); however, it has limited protective efficacy in adults. In this study, we constructed a recombinant vaccinia virus expressing Ag85B from M. tuberculosis using a novel attenuated vaccinia virus (KVAC103). We then analyzed the immunogenicity of prime-boost inoculation strategies using recombinant KVAC103 expressing Ag85B (rKVAC85B) compared to BCG. In both the rKVAC85B prime-boost and the BCG prime-rKVAC85B boost inoculation regimens, rKVAC85B induced the generation of specific IgG and the secretion of IFN-γ by immune cells. In vitro analysis of Mycobacterium growth inhibition revealed a comparable immune-mediated pattern of outcomes. Furthermore, bacterial loads in the lungs were significantly lower in mice inoculated with the BCG prime-rKVAC85B boost, than in the BCG-only group following a rechallenge infection with both H37Rv and HN878 strains of M. tuberculosis. These findings collectively suggest that KVAC103, incorporated into a viral vector, is a promising candidate for a novel TB vaccine platform that is effective against multiple TB strains, including H37Rv and HN878, and that rKVAC85B effectively stimulates immune responses against TB infection.

CKD in HF patients is very common condition, their dysfunction is closely linked and influence each other, so their management required multidisciplinary and personalized approaches. The diagnosis of HF and CDK relies on signs and symptoms. Several tools, such as blood-based biomarkers and echography help us to clarify and discriminate the main characteristics of these patients. Evidence in improving survival due to new drug-employment in HF, has increasingly challenged physicians to manage patients with multiple diseases, especially in patients with CKD. The difficulty is in the safe administration of these drugs in patients with HF and CKD. Knowing up to which values ​​of creatinine or renal clearance any drug can be administered is fundamental. We wanted to summarize, on this sizable and complex topic, the experiences of various prior study to get clearer ideas and a more precise reference about the assessment and management of HF and CKD.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

This case study investigates the heart rate (HR) and heart rate variability (HRV) in a patient with coronavirus disease 2019 (COVID-19). We report the case of a 58-year old male who contracted COVID-19. During his disease, 24-hour Holter electrocardiography (ECG) was performed continuously. For comparison, his 24-hour Holter ECGs from the previous 10 years were available. In this patient, COVID-19 was associated with a decrease in HR and a paradoxical decline in HRV. An abrupt decline in HRV and a decrease in HR may signal the onset of COVID-19 before common symptoms such as dry cough or fever appear. In addition, HRV and HR measurements may help to evaluate the course of the disease.

Ambulatory heart rate (HR) monitors that acquire electrocardiogram (ECG) or/and photoplethysmographm (PPG) signals from the torso, wrists, or ears are notably less accurate in tasks associated with high levels of movement compared to clinical measurements. However, reliable estimation of HR can be obtained through data fusion from different sensors. These methods are especially suitable for multimodal hearable devices, where heart rate can be tracked from different modalities, including electrical ECG, optical PPG, and sounds (heart tones). Combined information from different modalities can compensate for single source limitations. In this paper, we evaluate the possible application of data fusion methods in hearables. We assess data fusion for heart rate estimation from simultaneous in-ear ECG and in-ear PPG, recorded on eight subjects while performing 5-minute sitting and walking tasks. Our findings show that data fusion methods provide a similar level of mean absolute error as the best single-source heart rate estimation but with much lower intra-subject variability, especially during walking activities. We conclude that data fusion methods provide more robust HR estimation than a single cardiovascular signal. These methods can enhance the performance of wearable devices, especially multimodal hearables, in heart rate tracking during physical activity.

Metabolic syndrome, diabetes and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise, and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. Also, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

Background We aimed to evaluate the effectiveness of the ALRYNGO channel-type video laryngoscope with an AI-based glottis guidance system in senior emergency medicine residents for endotracheal intubation. Methods We enrolled twenty patients would be adequate for each device (direct laryngoscope, Pentax-AWS, and ALRYNGO). Before intubation, six senior residents wore a personal protective equipment. To randomize the device in this clinical study, a sealed envelope containing a device-specific identification card was utilized. When intubation began, the person who measured the intubation time divided the total intubation time into three-time intervals. The primary outcome was the intubation time. The secondary outcomes were the glottis view using the Cormack-Lehane grade (C-L grade) and the glottis guidance performance of ALRYNGO’s artificial intelligence. Results In Pentax-AWS and ALRYNGO, all intubations were successful, but the intubation time was longer than with the direct laryngoscope. And among the three, the ALRYNGO and Pentax-AWS had the highest frequency of C-L grade I (easiest intubation) at 80%, and the direct laryngoscope had the lowest frequency of 10%. Conclusions Even if healthcare professionals without experience with the channel-type video laryngoscope improve their performance on airway mannequins after training, their intubation performance may differ when applied to actual patients.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Parkinson’s-disease (PD) is an incurable age-related neurodegenerative disease and its global prevalence of disability and death has increased exponentially. Although motor symptoms are the characteristic manifestations of PD, the clinical spectrum also contains a wide variety of non-motor symptoms, which are the main cause of disability and determinants of the decrease in a patient's quality of life. Noteworthy in this regard is the stress on the cardiac system that is often observed in the course of PD, however its effects have not yet been adequately researched. Here, an untargeted metabolomics approach was used to assess changes in cardiac metabolism in the 6-hydroxydopamine model of PD. Beta-sitosterol, campesterol, cholesterol, monoacylglycerol, α-tocopherol, stearic acid, beta-glycerophosphoric acid, o-phosphoethanolamine, myo-inositol-1-phosphate, alanine, valine and allothreonine, are the metabolites that significantly discriminate Parkinsonian rats from sham counterparts. Upon analysis of the metabolic pathways with the aim of uncovering the main biological pathways involved in concentration patterns of cardiac metabolites, biosynthesis of both phosphatidylethanolamine and phosphatidylcholine, glucose-alanine cycle, the glutathione metabolism and plasmalogen synthesis most adequately differentiated sham and Parkinsonian rats. Our results reveal that both lipid and energy metabolism are particularly involved in changes in cardiac metabolism in PD. These results provide insight into cardiac metabolic signatures in PD and indicate potential targets for further investigation.

Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae (n=676) isolated from patients hospitalized in 13 intensive care units (ICUs) in 6 European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. Majority were colistin-susceptible (CS) (n=597, MIC 2 µg/ml). 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS K. pneumoniae. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type and O-antigen type. Overall, 92% (618/671) of the K. pneumoniae were MDR with high prevalence among CS (540/592) and CR (98.7%, 78/79) isolates. In contrast, proportion of carbapenemase-producing K. pneumoniae (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.1%, 173/594). Proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and CS isolates (MDR: 91%, 539/592; CP-Kpn: 29.1%, 153/59). WGS analysis of PAP isolates showed diverse insertion elements in mgrB or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high ST diversity (Simpson’s diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, P ≤ 0.003). The widespread nature of CHR among MDR K. pneumoniae in our study urge the development of rapid HR detection methods to inform on the need for combination regimens.

Primary care pediatricians encounter a wide range of complex conditions in their daily clinical practice. It is not uncommon for their patients to get exposed to medical errors. Diagnostic errors, defined as missed, delayed, or wrong diagnosis, are of great importance as they may cause significant harm to the pediatric patient with severe disease. These errors often occur when the symptoms and signs of a disease are atypical or missing. Data on the most frequent misdiagnosed situations in pediatrics is scarce. One of these groups of conditions is that regarding cardiac diseases. The pediatric cardiology field has met rapid development over the past few decades. Primary care providers play a key role in diagnosis, management, and referral of children with heart disease, both congenital and acquired, because many common cardiac complaints are first addressed in the primary care setting. The scope of this review is to investigate the cardiac entities that are often missed by the general pediatricians. In particular, it aims to spot the most common of them, to describe their clinical presentation, their diagnostic options, red flags, and tips, and to provide the ways to avoid erroneous, delayed, or missed diagnosis.

New insights into the causes and mechanisms of congenital heart disease (CHD) have been gained through the use of next-generation sequencing. Examination of the whole exome sequence detects detrimental gene variations modifying single or contiguous nucleotides, that are characterised as pathogenicity based on statistical assessments of families. and correlates with congenital heart disease, elevated expression during heart development, and reduction of harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities enriched for gene classes meeting these criteria. CHDs and extracardiac defects, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data reveal the expression of genes associated with CHD in specific cell lineages, and emerging evidence suggests that genetic variants disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole genome sequence studies.

The World Health Organization (WHO) has released reports indicating that heart disorders hold the unfortunate distinction of being the primary cause of death worldwide. Shockingly, an astonishing estimated 17.9 million lives are claimed by heart diseases annually, accounting for an alarming 31% of all global deaths. With all the flaws in the clinical situation, it is frequently challenging to assess the severity of cardiac disease and forecast its course of progression due to heterogeneity and complex interplay of factors. Therefore, early heart disease detection is essential for effective therapy. To address these challenges, Machine Learning (ML) boosting algorithms play a pivotal role as the main components of predictive analytics required to do this. The main objective of this study is to develop a comprehensive comparative framework to predict heart diseases using state-of-the-art machine learning with boosting techniques such as Decision Tree, Random Forest, Gradient Boosting, Catboost, XGboost, Light GBM, and Adaboost. To evaluate the performance of the models, a large heart disorders dataset is used from the UCI machine learning repository, comprised of 26 feature-based numerical and categorical attributes with 8763 samples from all over the globe. The Experimental results reveal that AdaBoost attained the highest accuracy of 95% and outperforms other algorithms concerning various performance measures like precision= 0.98, recall= 0.95, specificity= 0.95, f1-score=0.01, Negative predicted value= 0.83, False positive rate= 0.04, False negative rate= 0.04 and False Development rate= 0.01.

This paper presents an effective heart disease prediction model through detecting the anomalies, also known as outliers, in healthcare data using the unsupervised K-means clustering algorithm. Most existing approaches for detecting anomalies are based on constructing profiles of normal instances. However, such techniques require an adequate number of normal profiles to justify those models. Our proposed model first evaluates an \textit{optimal} value of K using Silhouette method. Next, it intends to locate anomalies that are far from a certain threshold distance with respect to their clusters. Finally, the five most popular classification techniques such as K-Nearest Neighbor (KNN), Random Forest (RF), Support Vector Machines (SVM), Naive Bayes (NB), and Logistic Regression (LR) are applied to build the resultant prediction model. The effectiveness of the proposed methodology is justified using a benchmark dataset of heart disease.

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.

It has been well established that hypertension is considered as a predominant risk factor for the development of cardiovascular diseases. Despite the link between hypertension and cardiovascular diseases, hypertension may directly affect the cardiac function leading in heart failure, mostly with preserved ejection fraction (HFpEF). There are echocardiographic findings indicating hypertensive heart disease (HHD) defined as altered cardiac morphology (left ventricular concentric hypertrophy, left atrium dilatation) and function (systolic or diastolic dysfunction) in patients with persistent hypertension irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and kidney function impairment. In addition to classical echocardiographic parameters, novel indices, like speckle tracking of the left ventricle and left atrium, 3D volume evaluation, myocardial work in echocardiography may provide more accurate and reproducible diagnostic and prognostic data in patients with hypertension. However, their use is still underappreciated. An early detection and prompt therapy of HHD will greatly improve the prognosis. Hence, in the present review, we shed light on the role of echocardiography in the contemporary diagnostic and prognostic approach of HHD.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

This study aimed to evaluate the role of chest radiographs and electrocardiograms in predicting the hemodynamics of congenital heart disease (CHD). This retrospective study included 50 patients with a diagnosis of CHD who had undergone any form of cardiac intervention, either surgical or nonsurgical between September 2019 and September 2020. Chest radiographs and electrocardiograms were evaluated and compared with the diagnostic gold standard echocardiography. Chest radiographs had the highest sensitivity, specificity, and accuracy, with all being 100%, in detecting situs and cardiac position. There was a very good agreement between chest radiographs and echocardiography in the detection of both situs and cardiac position (κ = 1.00, p &lt; 0.001), while moderate agreement was observed for the detection of cardiomegaly, position of aortic knuckle, main pulmonary artery dilation, and right pulmonary artery dilation. Electrocardiograms had a high sensitivity (100.00%), but modest specificity and accuracy for the detection of left ventricle pressure overload. For the detection of left atrial enlargement and left ventricle volume overload, electrocardiograms had high specificity (94.12% and 94.29%, respectively) but low sensitivity and modest accuracy. There was a moderate agreement between electrocardiograms and echocardiography in the detection of right ventricle pressure overload (κ = 0.43, p = 0.002) and left ventricle volume overload (κ = 0.46, p &lt; 0.001). The study findings indicate that chest radiographs and electrocardiograms alone are not adequate for the assessment of hemodynamics of CHD and reinstates the recommendation that in addition to routine chest radiographs and electrocardiograms, echocardiography should be performed.

Cardiovascular disease (CVD) may sometimes unexpected loss of life. It affects the heart and blood vessels of body. CVD plays an important factor of life since it may cause death of human. It is necessary to detect early of this disease for securing patients life. In this chpter two exclusively different methods are proposed for detection of heart disease. The first one is Pattern Recognition Approach with grammatical concept and the second one is machine learning approach. In the syntactic pattern recognition approach initially ECG wave from different leads is decomposed into pattern primitive based on diagnostic criteria. These primitives are then used as terminals of the proposed grammar. Pattern primitives are then input to the grammar. The parsing table is created in a tabular form. It finally indicates the patient with any disease or normal. Here five diseases beside normal are considered. Different Machine Learning (ML) approaches may be used for detecting patients with CVD and assisting health care systems also. These are useful for learning and utilizing the patterns discovered from large databases. It applies to a set of information in order to recognize underlying relationship patterns from the information set. It is basically a learning stage. Unknown incoming set of patterns can be tested using these methods. Due to its self-adaptive structure Deep Learning (DL) can process information with minimal processing time. DL exemplifies the use of neural network. A predictive model follows DL techniques for analyzing and assessing patients with heart disease. A hybrid approach based on Convolutional Layer and Gated-Recurrent Unit (GRU) are used in the paper for diagnosing the heart disease.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Systemic inflammation and coronary microvascular endothelial dysfunction are essential pathophysiological factors in heart failure with preserved ejection fraction (HFpEF) that support the use of statins. The pleiotropic properties of statins, such as anti-inflammatory, antihypertrophic, antifibrotic, and antioxidant effects, are generally accepted and may be beneficial in HF, especially in HFpEF. Numerous observational clinical trials have consistently shown a beneficial prognostic effect of statins in patients with HFpEF, while the results of two larger trials in patients with HFrEF have been controversial. Such differences may be related to a more pronounced impact of the pleiotropic properties of statins on the pathophysiology of HFpEF and pro-inflammatory comorbidities (arterial hypertension, diabetes mellitus, obesity, chronic kidney disease) that are more common in HFpEF. This review discusses the potential mechanisms of statin action that may be beneficial for patients with HFpEF, as well as clinical trials that have evaluated the statin effects on left ventricular diastolic function and clinical outcomes in patients with HFpEF.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

Heart disease is a global health concern of paramount importance, causing a significant number of fatalities and disabilities. Precise and timely diagnosis of heart disease is pivotal in pre-venting adverse outcomes and improving patient well-being, thereby creating a growing demand for intelligent approaches to predict heart disease effectively. This paper introduces an Ensemble Heuristic-Metaheuristic Feature Fusion Learning (EHMFFL) algorithm for heart disease diagnosis. Within the EHMFFL algorithm, a diverse ensemble learning model is crafted, featuring different feature subsets for each heterogeneous base learner, including support vector machine, K-nearest neighbors, logistic regression, random forest, naive bayes, decision tree, and XGBoost. The primary objective is to identify the most pertinent features for each base learner, leveraging a combined heuristic-metaheuristic approach that integrates the heuristic knowledge of Pearson correlation coefficient with the metaheuristic-driven grey wolf optimizer. The second objective is to aggregate the decision outcomes of the various base learners through ensemble learning, aimed at constructing a robust prediction model. The performance of the EHMFFL algorithm is rigorously assessed using the Cleveland and Statlog datasets yielding remarkable results with an accuracy of 91.8% and 88.9%, respectively, surpassing state-of-the-art machine learning, ensemble learning, and feature selection techniques in heart disease diagnosis. These findings underscore the potential of the EHMFFL algorithm in enhancing diagnostic accuracy for heart disease and providing valuable support to clinicians in making more informed decisions regarding patient care.

Hepatitis C virus (HCV) is a major public health threat associated with serious clinical consequences worldwide. The WHO reports an estimated 58 million people globally living with chronic hepatitis C virus (HCV) infection, with 1.5 million new cases and over 350,000 deaths annually due to HCV-related diseases. Despite the existence of multiple diagnostic methods, the accessibility of diagnosis and treatment is often hindered across the continent by limited resources, insufficient healthcare infrastructure, and low public awareness of Hepatitis C virus Hepatitis C virus infection is a major public health concern in African countries, which have the highest prevalence rates of HCV in the world (1–26%). Egypt, African country which had the highest prevalence of Hepatitis C virus infection in the world. Its national hepatitis C elimination initiative emerges as an exemplary case of success an having screened over 60 million individuals, and treated more than 4 million, thereby markedly diminishing both the prevalence and incidence of the disease. The strategies employed by Egypt offer critical insights and adaptable frameworks for other African Countries facing analogous challenges. The Aim of this Review is to highlight the triumphs and hurdles of Egypt's approach, while also providing strategic guidance for African Countries to accelerate the journey towards the eradication of hepatitis C.

Diagnosing congenital heart disease (CHD) remains challenging because of its complex morphology. Representing the intricate structures of CHD on conventional two-dimensional flat screens is difficult owing to wide variations in the pathologies. Technological advancements, such as three-dimensional printed heart models (3DPHM) and virtual reality (VR), could potentially address the limitations of viewing complex structures using conventional methods. This study aimed to investigate the usefulness and clinical value of four visualization modalities across three different cases of CHD, including ventricular septal defect, double outlet right ventricle, and tetralogy of fallot. Seventeen cardiac specialists were invited to participate in this study, which was aimed at assessing the usefulness and clinical value of four visualization modalities, namely, DICOM images, 3DPHM, VR, and 3D PDF. Of these modalities, 76.4% of the specialists ranked VR as the best for understanding the spatial associations among cardiac structures and for presurgical planning. Meanwhile, 94.1% ranked 3DPHM as the best modality for communicating with patients and their families. Of the various visualization modalities, VR was the best tool for assessing anatomical locations and vessels, comprehending the spatial relationships among cardiac structures, and for presurgical planning. The 3DPHM models were the best tool for medical education as well as communication. In summary, both 3DPHM and VR have their own advantages and outperform the other two modalities, i.e., DICOM images and 3D PDF, in terms of visualizing and managing CHD.

Cadmium (Cd) is a metal with no nutritional or physiological value, but is found in most people because it is a contaminant in nearly all food types. The intestinal absorption rate determines the body burden of Cd because humans lack a physiologic mechanism for excretion of the metal. Most acquired Cd accumulates in the kidneys, in which the Cd content increases through age 50 but falls thereafter. The decline from maximal kidney content is probably due to release of Cd from injured tubular cells into urine and replacement of destroyed nephrons by scar tissue. Chronic kidney disease is diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2, or when albuminuria is present. Albuminuria is defined as an albumin-to-creatinine ratio ≥ 30 mg/g creatinine in women or ≥ 20 mg/g creatinine in men that persists for at least 3 months. Generally, Cd-induced reductions in eGFR are not reversible, and Cd nephropathy may progress to end-stage kidney disease. There is no evidence that elimination of current environmental exposure can reverse Cd nephropathy, and no theoretical reason to believe that such a reversal is possible. This review provides an update of knowledge concerning CKD in population environmentally exposed to Cd. Special attention is devoted to mechanisms of Cd-induced albuminuria concurrently with eGFR reductions, and the difficult challenge of exposure guidelines sufficient to eliminate the risk of Cd-induced CKD is addressed.

To evaluate the efficacy of fish oil for protection against coronary heart disease (CHD), we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the use of fish oil for protection against CHD. We retrieved relevant articles published from January 1966 to January 2020 by searching the PubMed, EMBASE, Cochrane CENTRAL, and Web of Science databases. RCTs of fish oil in preventing CHD were selected. The study quality was evaluated using the Cochrane Risk of Bias tool with RevMan 5.3 software. The first selection involved 350 citations. After screening and evaluation of suitability, 19 RCTs adjusted for clustering were included in the meta-analysis. All selected manuscripts considered that fish oil was effective in preventing CHD, secondary outcome measures included angina, sepsis and death. Compared with the control group, fish oil may confer significant protection against CHD (odds ratio = 0.84; 95% confidence interval: 0.72–0.98). There was no significant difference in the incidence of secondary outcomes between the observation group and the control group (P > 0.05). The above results show that fish oil plays an important role in reducing CHD and cardiovascular events. However, because of the suboptimal quality of the studies included into the meta-analysis, these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Heart failure (HF) is a growing issue in developed countries and most patients present with a reduced ejection fraction. This condition significantly impairs quality of life and represents a threat not only for patients, but also for the entire healthcare system due to its high management cost. In the last decade, new medical treatments and devices have been developed to reduce HF hospitalizations and improve prognosis, while reducing the overall mortality rate. Medical therapy does not achieve the same results in all patients and, whenever it fails, technology comes in handy: novel devices for the management of HF have reduced symptoms. They have also improved the treatment of fluid retention and life threatening arrhythmias. The present review article gives to the readers a comprehensive overview of the most recent and important findings that need to be considered in HF with reduced ejection fraction patients. Both novel medical treatments and devices have been presented and discussed.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Background: Autonomic neuropathy commonly arises as a long-term complication in end stage kidney disease (ESKD) and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There is limited data about HRV using real-time ECG to predict HD efficiency in patients with ESKD who are routinely doing HD in real-world practice. Methods: Total of 50 patients (62.1 ± 10.7 years) with ESKD underwent continuous real-time ECG monitor (237.4 ± 15.3 min) during HD for HRV using remote monitoring system and checked electrolyte levels before/after HD. And we compared HRV according to electrolyte levels. Results: During the monitor, we checked total 2374 times of ECG and electrolyte level simultaneously of all patients. Both time and frequency domain HRV were higher when the patients had lower K+ level (&lt;0.5 mEq/L) and P+ level change (&lt;2 mEq/L) before/after HD as compared with those with higher K+ level (≥0.5 mEq/L) and P+ level (≥2 mEq/L) change respectively. In addition, there were higher incidence of arrhythmic events including atrial/ventricular premature complexes, even though no difference of mean heart rate in patients with lower K+ and P+ level change group (p &lt; 0.001). Conclusions: Higher HRV was independently associated with poor controlled K+ and P+ level during hemodialysis in patients with ESKD. This is further substantiated by independent continuous associations between real-time measures of higher HRV and K+ and P+ level. These data strongly suggest that cardiac autonomic dysfunction can be caused by lower change of electrolytes before/after hemodialysis alone.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

This review aims to explore the intricate relationship between epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorders' occurrence, development, and progression. The analysis encompasses various stress factors, including childhood trauma, work-related stress, and dietary deficiencies, alongside epigenetic changes such as DNA methylation and altered gene expression. Findings indicate that specific stress-related genes frequently exhibit epigenetic changes associated with affective disorders. Moreover, the review examines coping mechanisms in patients with bipolar disorder and major depressive disorder, revealing mixed associations between coping strategies and symptom severity. While active coping is correlated with better outcomes, emotion-focused coping may exacerbate depressive or manic episodes. Overall, this review underscores the complex interplay between genetic predisposition, environmental stressors, coping mechanisms, and affective disorders. Understanding these interactions is essential for developing targeted interventions and personalized treatment strategies for individuals with mood disorders. However, further research is needed to elucidate specific genomic loci involved in affective disorders and the clinical implications of coping strategies in therapeutic settings.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Synchronous electrical cardioversion is a relatively common procedure in the emergency department (ED), often performed for unstable supraventricular tachycardia (SVT) or unstable ventricular tachycardia (VT). However, it is also used for stable cases resistant to drug therapy, which carry a risk of deterioration. In addition to the inherent risks linked with procedural sedation, there is a possibility of malignant arrhythmias or bradycardia, which could potentially result in cardiac arrest following this procedure. Here, we present a case of complete heart block unresponsive to transcutaneous pacing and positive inotropic and chronotropic drugs for 90 minutes, resulting in multiple cardiac arrests. The repositioning of the transcutaneous cardio-stimulation electrodes, one of them placed in the left latero-sternal position and the other at the level of the apex, led to immediate stabilization of the patient. Extubation of the patient was performed the following day, while full recovery and discharge within 7 days, after insertion of a permanent pacemaker.

Background: The prevalence of physical inactivity has been rising in many countries in recent years, adding to the burden of non-communicable diseases and affecting overall health worldwide. The aim of this study is to determine the impact of physical activity on mortality from ischemic heart disease (IHD) separately for those respondents who were diagnosed with IHD and for those who were not diagnosed with IHD in their baseline health survey. Methods: In the baseline survey (2006–2008), 7100 men and women ages 45–72 were examined within the framework of the international study Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE). 6770 participants were available for statistical analysis (after excluding 330 respondents due to missing information on study variables). Physical activity was determined by leisure-time physical activities (hours/week). All participants in the baseline survey were followed up for IHD mortality events until December 31, 2018. Results: Using multivariate Cox regression analysis, it was found that moderate and higher levels of physical activity significantly reduced the risk of IHD mortality (HR=0.54 and HR=0.60 respectively) in men who were not diagnosed with IHD at baseline compared with physically inactive subjects. It was found that among men and women who were diagnosed with IHD at baseline, physical activity reduced the risk of mortality from IHD compared with those who were physically inactive (HR=0.54 and HR=0.41 respectively). Using mediation analysis, was found that physical activity directly predicted statistically lower IHD mortality (P&lt;0.05) in men and women. Conclusion: Physical activity was a significant factor that directly predicted statistically lower IHD mortality, regardless of whether subjects had IHD at baseline or not.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.

The implications of the adult congenital heart disease anatomic and physiological classification (AP-ACHD) for risk assessment have not been adequately studied. A retrospective cohort study was conducted using data from an ongoing national, multicentre registry of patients with ACHD and atrial arrhythmias (AA) receiving apixaban (PROTECT-AR study, NCT03854149). At enrollment, patients were stratified according to Anatomic class (AnatC, range I to III) and physiological stage (PhyS, range B to D). Follow-up was conducted between May 2019 and September 2021. The primary outcome was a composite of death from any cause, any major thromboembolic event, major or clinically relevant non-major bleeding, or hospitalization. Cox proportional-hazards regression modeling was used to evaluate the risks for the outcome among AP-ACHD classes. Over a median 20-month follow-up period, 47 of 157 (29.9%) ACHD patients with AA experienced the composite outcome. Adjusted hazard ratios (aHR) with 95% confidence intervals [CI] for the outcome in PhyS C and PhyS D were 1.84 (95% CI 0.73 to 4.61) and 7.88 (95% CI 1.54 to 40.41) respectively, as compared with PhyS B. The corresponding aHRs in AnatC II and AnatC III were 1.10 (95% CI 0.39 to 3.06) and 0.99 (95% CI 0.24 to 4.10) respectively, as compared with AnatC I. In conclusion, the PhyS component of the AP-ACHD classification was an independent predictor of net adverse clinical events among ACHD patients with AA receiving apixaban.

Objective: In this pilot study, we described the gross motor development of infants aged 4 to 24 months with congenital heart disease (CHD) and assessed through a systematic develop­mental screening programme, with individualised motor interventions. Methods: Thirty infants who had cardiac repair underwent gross motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results: Based on AIMS, 80% of 4-month-old infants had a delay in gross motor development and required physical therapy. Gross motor abilities significantly improved by 24 months. Infants who benefited from regular physiotherapy tended to show better improvement in motor scores. Conclusion: Our study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in those at-risk. Further research is needed to assess the effectiveness of systematic developmental screening and individualized inter­vention programmes at identifying at risk patients, and their impact on developmental outcomes.

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.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

ABSTRACT Purpose: Tongue image analysis for disease diagnosis is an ancient traditional non-invasive diagnosis technique widely used by traditional medicine practitioners. Deep Learning based multi-label disease detection models offer tremendous potential to clinical decision support systems, by facilitating preliminary diagnosis. Methods: In this work, we propose a multi-label disease detection pipeline, where in observation and analysis of tongue images captured and received via smartphones assist in predicting the health status of an individual. All images are voluntarily given by subjects consulting collaborating physicians. Images thus acquired are first and foremost classified either into a diseased or a normal category by a 5-fold cross-validation algorithm using a convolution neural network (MobileNetV2) model for binary classification. Once the diseased label is predicted, the image is used to diagnose multiple diseases using the prediction algorithm based on DenseNet121. Results: Average accuracy of 93 % was achieved in classifying diseased from normal healthy tongue by detection model with MobileNetV2 architecture. Multilabel disease classification produced more than 90% accurate results for the seven class labels considered. Conclusion: AI based image analysis shows promising results and an extensive dataset could provide further improvements to this approach. Rather than employing high-cost sophisticated image capturing setup, experimenting with smartphone images opens opportunity to provide preliminary health status to individuals on smartphone prior to further line of treatment and diagnosis.

Apple replant disease (ARD) is a complex issue caused by various fungal, oomycetes pathogens and parasites which can differ in their abundance between sites within a geographic region. Knowledge of the specific etiology of ARD at a particular site is required in order to develop commercially viable soil management strategies to combat specific/individual components of the disease. In this study we analyzed the soil from six ARD sites for the presence of fungal, bacterial and oomycetes communities and plant parasitic nematodes. Five fungal, and 17 bacterial classes were differentially represented in the microbiomes from different locations. Mortierellomycetes was the most abundant fungal taxa represented followed by Sordariomycetes. Mortierella exigua a fungal endophyte was the most abundant fungal amplicon sequence variant (ASV) in the core microbiome. Proteobacteria was the most prevalent phylum identified in orchard soils. Several potential phytopathogenic fungi involved in ARD and endophytes including Fusarium oxysporum, F. solani, Nectria ramulariae, Ilyonectria robusta and Nectriaceae were identfied in the orchard soil. Pythium attrantheridium (Globisporangium attrantheridium), P. monospermum and P. ultimum (Globisporangium ultimum) were the most abundant oomycete taxa identified in these soil samples. Six different groups of plant-parasitic nematodes were found across the six orchards soil. Root-lesion nematodes, Pratylenchus spp., which are commonly associated with ARD, were identified in all orchards soil at population densities ranging from 12 to 33/100 cm3 soil. This research contributes valuable understanding of the ARD complex as the apple industry needs alternative approaches to combat the disease.

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.

Aim: To investigate the effects of intensive physical exercise on retinal microvascular regulation in healthy volunteers by the adaptive optics retinal camera measurement. Methods: We included healthy volunteers (11 men and 14 women) aged 20.6± 0.9. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were recorded before and after a submaximal physical exertion of continuously riding a training ergometer. The superior temporal retinal artery measurements were captured using the adaptive optics (AO) camera rtx1TM (Imagine Eyes, Orsay, France) without pupil dilatation. We compared measures of vessel diameter (VD), lumen diameter (LD), two walls (Wall 1, 2), wall-to-lumen ratio (WLR), and wall cross-sectional analysis (WCSA) before and immediately after the cessation of exercise. Results: Cardiovascular parameters: After exercise, SBP, DBP and HR changed significantly from 130.2±13.2 to 159.7±15.6 mm Hg, 81.2±6.3 to 77.1±8.2 mm Hg and 80.8±16.1 to 175.0±6.2 bpm, respectively (p < 0.002). Retinal microcirculation analysis: Before the exercise, the mean LD was 96.0±6.8, VD 118.5±8.3, WLR 0.234±0.02, WCSA 3802.8±577.6. The mean LD and Wall 1 did not change significantly after exercise but slightly decreased. The VD, Wall 2, WLR and WCSA decreased significantly (p

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence show that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Background. The type-2 sodium-glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate, in a real-world population from a single center, the feasibility of introducing SGLT2i and their interaction with other recommended drug classes. Methods. We evaluated the consecutive patients affected by chronic heart failure (CHF) since January 2022. At baseline clinical visit the therapy taken by the patients as well as that prescribed were accurately collected. During a 6-12 month follow-up the the changes in concomitant therapy were analyzed. Results. At baseline, among 350 patients evaluated, only 17 (5%) were already taking SGLT2i, 13 with HFrEF, 2 with CHF with mild reduced (HFmrEF) and 2 with preserved ejection fraction (HFpEF). After baseline evaluation, SGLT2i were prescribed to 220 (63%) of all the patients enrolled, among whom 178 (84%) of HFrEF patients, 25 (42%) of HFmrEF and 17 (22%) of HFpEF. After follow-up, SGLT2i therapy was highly tolerated and it was associated with a significant increased prescription of sacubitril/valsartan and a reduced use of diuretics. Finally, a significant improvement in functional status and left ventricular systolic function after SGLT2i therapy was observed. Conclusions. In this single center “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. Moreover, a further optimization in prescribed ther-apy was observed during a short term follow-up. These data further support the use of this thera-peutic approach in routine clinical practice.

We document for the first time epsilon waves on the electrocardiogram of a patient with Dravet syndrome (DS) who does not exhibit structural cardiac pathology. DS, a severe form of pediatric epilepsy, involves mutations in the SCN1A gene, which disrupt sodium ion flow and increase the risk of sudden unexpected death in epilepsy. The epsilon waves, typically associated with arrhythmogenic right ventricular dysplasia, may also suggest a link between neuronal and cardiac dysfunctions. In our case, the epsilon waves appear to originate from abnormalities in sodium channels rather than structural changes in the myocardium. This finding underscores the importance of assessing both neurological and cardiac manifestations in patients with severe epilepsy, opening new avenues for the research and treatment of these interactions in DS.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

Elevated serum uric acid (sUA) is associated with risk of developing cardiovascular disease (CVD). Here, we examined the prognostic significance of sUA and exercise capacity in 411 Japanese adults (age, ≥65; mean, 81 years) hospitalized for worsening CVD. Mean sUA was significantly higher in the 23% of patients on an sUA-lowering agent than in those not. When the patients were stratified by sUA into three groups (7.0 mg/dL), the high sUA group had significantly worse peak VO2 and composite endpoint (rehospitalization due to worsening CVD and all-cause mortality) compared with low and moderate sUA groups (P < 0.001). When the patients were stratified by sUA into five groups (sUA 10.0 mg/dL), the incidence of the composite endpoint was significantly higher in the highest sUA group compared with that in the reference group, but only in women. Univariate Cox regression analysis, but not a multivariate analysis, indicated that sUA was significantly associated with the composite endpoint. Although sUA and exercise capacity may have some degree of prognostic significance in older patients with CVD, this significance may differ between men and women.

Visual exploration of complex data helps interpretation, especially in the case of omics data analysis in life sciences and clinical research. Generating and analysing omics data requires bioinformatic skills, while they are interpreted by domain experts, for whom parsing large and complex data structures may be challenging. However, outcomes of visual analytics are often difficult to quantify, which emphasises precision and reproducibility, especially for research on human diseases. Here, we propose a workflow combining a reproducible computational environment with a dedicated visualisation functionality for systems biology diagrams. By linking the Galaxy with the MINERVA Platform, we visualise and explore COVID-19 transcriptomic data to demonstrate the utility of our workflow. Visualised data recapitulate findings of the original publication and offer new insights about the COVID-19 pathology. Our results offer a blueprint for quick prototyping of computational workflows that facilitate communication and exploration of complex data in biomedical research.

We aimed to evaluate the association between daily dietary calcium intake and the risk of cardiovascular disease (CVD) in postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES). This cross-sectional study included 12,348 women aged 45–70 years who had reached natural menopause. They were classified into three groups according to daily dietary calcium intake: &lt; 400 mg, 400–800 mg, and &gt;800 mg. The risks of CVD, stroke, angina, and myocardial infarction were assessed in each group. Further, we performed subgroup analysis according to the post-menopause duration (≤10 vs. &gt;10 postmenopausal years). We performed logistic regression analysis with adjustment for age, menopausal age, income, urban area, education, insulin use, body mass index, hypertension, diabetes mellitus, dyslipidemia, high alcohol intake, smoking, exercise, oral contraceptive use, and hormonal therapy use. Calcium intake level was not significantly associated with the risk of CVD in the total population and the ≤10 postmenopausal years subgroup. However, in the &gt;10 postmenopausal years subgroup, daily calcium intake &gt;800 mg was associated with significantly decreased risks of all CVD (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11–0.64), stroke (OR, 0.06; 95% CI, 0.01–0.42), and myocardial infarction (OR, 0.27; 95% CI, 0.11–0.64). Our findings suggest that a dietary calcium intake of &gt;800 mg/day decreases the risk of CVD events in women who have been menopausal for &gt;10 years.

Pregnancy is a complex biological process which is associated with significant metabolic and hemodynamic changes of the maternal body which allow a normal fetal growth. The inability to adapt to these changes can affect the cardiovascular health. During pregnancy, women may experience mood swings, anxiety and emotional ambivalence. These symptoms can lead to stress and have a negative impact on the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women in order to manage these cases properly. The current narrative review explores and summarizes the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. Understanding the physiological adaptations that the body undergoes throughout pregnancy is crucial for educating and supporting individuals as well as healthcare professionals. This enables them to recognize any risk factors or pathological conditions that may exacerbate pregnant women's health. In order to reduce maternal morbidity and mortality from cardiovascular disease, a psychological and cardiovascular risk factor screening that is done either before or during pregnancy may be able to identify situations that call for particular medical and/or psychological therapies.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of aerodynamic diameter < 10 μm (PM10) on the incidence of ACS. Results: Desert dust intrusion on days 0 to 5 after ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM10 concentrations 1, 2, 3, 3, 4 and 5 days before ACS onset (for changes of 10 µg/m3) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18) and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of premature coronary heart disease.

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.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

Brain hemispheres develop rather symmetrically except in the case of pathology or intense training. As school experience is a form of training, the current study tested the influence of pedagogy on morphological development through the cortical thickness (CTh) asymmetry index (AI). First, we compared CTh AI of 111 students aged 4 to 18 with 77 adults aged > 20. Second, we investigated CTh AI in the students, as a function of schooling background (Montessori or traditional). At the whole-brain level, CTh AI was not different between the adult and student groups, even when controlling for age. However, the pedagogical experience was found to impact CTh AI in the temporal lobe, within the parahippocampal (PHC) region. The PHC has a functional lateralization, with the right PHC having a stronger involvement in spatiotemporal context encoding, while the left PHC is involved in semantic encoding. We observed CTh asymmetry toward the left PHC for participants enrolled in Montessori schools and toward the right for participants enrolled in traditional schools. As these participants were matched on age, intelligence, home life, and socioeconomic conditions, we interpret this effect found in memory-related brain regions to reflect differences in learning strategies. Pedagogy modulates how new concepts are encoded, with possible long-term effects on knowledge transfer.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproductive function in mice. However, the effects of fetal ASD exposure on male reproductive function have not been investigated. The present study investigated the effects of fetal ASD exposure on reproductive function in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproductive function of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproductive function of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Volatile organic compounds (VOCs) released from plants have been correlated with disease-status. Analysis of VOCs using GC-MS is time-consuming, laboratory-based, and requires specialist training. Electronic nose devices (E-nose) provide a portable alternative. Three different E-nose devices were compared to assess how accurately they could detect Mango Twig Tip Dieback and Panama disease in banana. The devices were initially trained on known volatiles, then pure cultures of Pantoea sp., Staphylococcus sp., and Fusarium odoratissimum, and finally, on infected and healthy mango leaves and field-collected, infected banana pseudo-stems. The experiments were repeated three times with six replicates for each host-pathogen pair. The variation between healthy and infected host materials was evaluated by principal component and linear discriminant analysis, cross-validation and chemometric data analysis. GC-MS analysis was conducted contemporaneously and identified an 80% similarity between healthy and infected plant material. The portable C 320 was 100% successful in discriminating known volatiles but had a low capability in differentiating healthy and infected plant substrates. The advanced devices (PEN 3 / MSEM 160) successfully detected healthy and diseased samples with a high variance. The results suggest that E-nose devices are more sensitive and accurate in detecting changes of VOCs between healthy and infected plants compared to headspace GC-MS.

Background: The adoption of self-care behaviors among patients with congestive heart failure (CHF) is essential for the management of their health condition. However, there is a lack of tools for estimating self-care in CHF patients. We aim to develop and validate the Hippocratic heart failure self-care scale (HHFSCS). Methods: the scale includes 22 items which are reviewed by a committee of experts. Individuals indicate the frequency at which they follow each self-behavior on a five-point Likert scale. Adult patients with CHF (n=250) from a General Hospital, in Athens, were participated in the study from June 2020 to March 2021. Reliability coefficients and Explanatory Factor Analysis (EFA), using a Varimax rotation and the Principal Components Method were used to assess the psychometric measurements. Results: The Cronbach’s alpha coefficient of the HHFSCS was 0.807. The exploratory factor analysis identified two domains that accounted for 88.44% of the variance of the scale items; however, each sub-scale could not be used as an independent scale. Finally, the test-retest showed a significant strong correlation (r=0.973, p&lt;0.001). Conclusions: The HHFSCS is a reliable and valid tool for assessing self-behaviors in CHF patients. Health professionals can use it in their clinical practice to improve the management of patient’s health conditions.

Heart failure (HF) has become a public health problem, but exact pathophysiology is still unknown. Western diet characterised with high sugar, high fat, red meat and processed meat, eggs, fried foods and sweetened beverages, may cause oxidative stress and inflammation, leading to oxidative dysfunction and adverse effects on cardiac-ultra-structure. However, only little is known about oxidative function of the of the myocardium and how oxidative dysfunction predispose Ca-overloading resulting in to physio-pathological remodelling leading to HF. Antioxidants such as flavonoids and polyphenolics, omega-3 fatty acids, vitamins, minerals as well as essential and nonessential amino acids that are rich in Indo-Mediterranean type of diets, may have protective roles in maintaining oxidative functions of the heart. The cardiac cells use fatty acids and glucose for the metabolic functions depending upon physiological and metabolic requirements. Apart from glucotoxicity, lipotoxicity is also damaging to cardiac cells which worsen in presence of deficiency of endogenous antioxidants and lower exogenous antioxidants in the diet. There is increased production of ceramide, advanced glycation end products (AGE) and triamino-methyl-N-oxide (TMAO) due to high sugar and high fat diets, leading to oxidative dysfunction and Ca-overloading. The biological changes may begin with physiological remodelling to pathological remodelling due to oxidative damages. High fat diet in combination with inducible nitric oxide synthase (NOSi) via N-arginine methyl ester has been found to preserve ejection fraction in a mouse model of HF. It is possible that increased supplementation of High Exogenous Antioxidant Restorative Treatment (HEART) diet; polyphenolics and flavonoids, vitamins, minerals, arginine, with omega-3 fatty acids, and cessation of red meat and egg may further improve the oxidative function of cardiac cells, resulting in the prevention and improvement in the earliest of the Six Stages of HF. Cohort studies and randomised, controlled trials would be necessary for demonstration of the role of HEART diet in the management of HF.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Cardiovascular disease is the leading cause of death worldwide. A key factor in assessing the risk of cardiovascular disease is left ventricular functional evaluation. Left ventricular (LV) systolic function is evaluated by measuring the left ventricular ejection fraction (LVEF) using echocardiography data. Therefore, quick and accurate left ventricle segmentation is important for estimating the LVEF. However, it is difficult to accurately segment the left ventricle due to changes in the shape and area of the left ventricle during cardiac cycles. In this study, we proposed a framework that considers changes in the shape and area of the left ventricle during the cardiac cycle by applying the convolutional long short-term memory (CLSTM) approach. In addition, we evaluated the left ventricular segmentation and multidimensional quantification of the proposed system in comparison to manual and automated segmentation methods. In addition, to assess the validity of CLSTM, the values of multi-dimensional quantification metrics were compared and analyzed using graphs and Bland–Altman plots on a frame-by-frame basis. We demonstrated that the CLSTM method effectively segments the left ventricle by considering the LV activity. In conclusion, we demonstrated that LV segmentation based on our framework may be utilized to accurately estimate LVEF values.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.