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

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease among people over the age of 50 and occurs with symptoms such as musculoskeletal pain and stiffness in the neck, shoulders and hips. To date, corticosteroids represent the cornerstone of PMR treatment, although it is well known that their prolonged use is associated with several adverse effects, making it crucial to find therapeutic alternatives to their use. The purpose of this case report was to describe the effectiveness of 10 whole-body cryostimulation (WBC) sessions on a 74-year-old woman suffering from PMR. An improvement in disease impact, fatigue, pain, quality of sleep and total physical activity was observed after WBC. Moreover, the patient reduced her daily drug intake by 67% following WBC treatments. Given the increasing prevalence of PMR and considering the side effects that drug treatments can lead to, WBC could represent a valuable adjuvant and well-tolerated alternative for the treatment of PMR.

: Background: Parkinson’s disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence quality of life throughout the course of the disease. This study aimed to evaluate PD patients’ motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Methods: We evaluated 43 patients with Parkinson’s disease. Fourteen patients had tremor-dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients’ mean age was 65.21 years, and the disease’s mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, light headedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale’s gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusion: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients’ health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients’ well-being.

This review brings together the current knowledge regarding the risk factors, and the clinical, radiologic and histological features of both post-COVID-19 interstitial pul-monary fibrosis (PCPF) and Idiopathic Pulmonary Fibrosis (IPF) with a particular fo-cus on describing the similarities and the disparities between the fibrotic changes in these two diseases. It is important to highlight the common points of PCPF and IPF to observe if they are some targetable changes to improve patient outcomes. The litera-ture review was performed using numerous databases to identify relevant articles published in English through October 2022. This review would help clinicians, pathologists and researchers to make an accurate diagnosis, which can be useful in identifying the group of patients who can be selected for antifibrotic therapies, and future therapeutic perspectives.

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<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.

Human induced pluripotent stem cells (hiPSCs) have two characteristic abilities 1) self-renewal and 2) differentiation into all cell types in the human body. It is this ability of iPSCs to differentiate into any desired cell type that makes them amenable to disease modeling. iPSCs can further be engineered to carry a disease-specific mutation or be derived from patients to phenocopy the disease. To model neurodegenerative/neurodevelopmental disorders iPSCs are differentiated into neurons. This chapter describes protocols for two different approaches to generate neurons from iPSCs, first using dual SMAD inhibition to generate neural progenitor cells which are then differentiated into neurons, and second using single transcription factor (NGN2) over-expression to drive differentiation of iPSCs directly into neurons.

A retrospective study including 49 women with ovarian clear cell carcinoma between January 2009 and December 2021 at Oxford cancer centre was done. The mean age was 63 years, with 78% post-menopausal. All women underwent cytoreductive surgery with no residual disease (R0) in 39 women. The follow-up time ranged between 12-144 months, with mean of 105.5 months. The 3-year OS was 73.4%, and 3-year PFS was 81.3%, with a mean of 101.7months (95%CI, 84.63-118.93). As expected, women with stage 1 disease had the best outcome. In comparing OS in respect to absence or presence of residual disease, the 3-year OS was 88.6% (95% CI 108.6-141.8), compared to 12.5% (95% CI 4.48-32.11) respectively (P<0.001). In multivariant analysis the variables included were CA 125 (< or >200 IU/ml), Hb (< or >115 g/L), albumin (< or >40 g/L), associated endometriosis, ascites, residual disease, and FIGO staging. FIGO stage was the only independent prognostic indicator of OS with (p<0.05). Surgery to achieve no residual tumour is necessary to improve the prognosis in advanced OCCC. At present, the true challenge is to predict which patients with early-stage disease are at higher risk of recurrence and would most benefit from adjuvant treatments.

Background: Overall survival is the most important outcome for treatment response in feline chronic kidney disease (CKD). Beraprost has been shown to reduce the kidney function decline in cats with International Renal Interest Society (IRIS) stage 2 and 3 CKD. However, association with prolonged survival has not yet been examined. Objective: To assess the relationship between beraprost and overall survival in cats with CKD in real clinical practice. Animals: Client-owned cats with IRIS stage 3 CKD (n = 134), evaluated between 2017 and 2020. Methods: Retrospective cohort study based on data from electronic medical records of one hospital. Results: Multivariable Cox regression models on all treatment effects showed that beraprost only was related to better survival (P = 0.028). The cohort was divided into “beraprost therapy” and “no beraprost therapy” groups, and survival analyses revealed that overall survival was significantly longer in the beraprost therapy group, using Kaplan-Meier curves (P = 0.004). However, baseline phosphate is known to be an important prognostic indicator and was not well balanced between the two groups. Therefore, a subcohort of 97 cats was selected (those having baseline phosphate < 6.0 mg/dL) that allowed for this parameter to be balanced between groups. The survival data in this subcohort was consistent with that of the overall study cohort. Conclusions: In feline patients with CKD, beraprost therapy was associated with better overall survival.

In this paper we use quantum machine learning to detect and classify ocular diseases across age related macular degradation, cataract, diabetic, glaucoma, hypertension, and patological myopia categories versus a control group. We analyze fundus imagery from 1000 patients. Early findings indicate there may be benefit in terms of accuracy and loss function minimization of 2.07% and 1.979x respectively compared to a similar method implemented using traditional computers.

Alzheimer’s disease is a debilitating neurodegenerative condition which is known to be the most common cause of dementia. Despite its rapidly growing prevalence, medicine still lacks a comprehensive definition of the disease. As a result, Alzheimer’s disease remains neither preventable nor curable. In recent years, broad interdisciplinary collaborations in Alzheimer’s disease research are becoming more common. Furthermore, such collaborations have already demonstrated their superiority in addressing the complexity of the disease in innovative ways. However, establishing effective communication and optimal knowledge distribution between researchers and specialists with different expertise and background is not a straightforward task. To address this challenge, we propose the Alzheimer’s disease Ontology for Diagnosis and Preclinical Classification (AD-DPC) as a tool for effective knowledge sharing in interdisciplinary/multidisciplinary teams working on Alzheimer’s disease. It covers six major conceptual groups, namely Alzheimer's disease pathology, Alzheimer's disease spectrum, Diagnostic process, Symptoms, Assessments, and Relevant clinical findings. All concepts were annotated with definitions or elucidations and in some cases enriched with synonyms and additional resources. The potential of AD-DPC to support non-medical experts is demonstrated through an evaluation of its usability, applicability and correctness. The results show that the participants in the evaluation process who lack prior medical knowledge can successfully answer Alzheimer’s disease-related questions by interacting with AD-DPC. Furthermore, their perceived level of knowledge in the field increased leading to effective communication with medical experts.

Background: Liquid biopsy is widely recognised as an efficient diagnostic method in oncology for disease detection and monitoring. Though examination of circulating tumor cell (CTC) is mostly implemented for assessment of genomic aberrations, need of complex methodologies for their detection has impeded its acceptance in low resource settings. We evaluated the cell free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients. Methods: Total cell free DNA was extracted from plasma of breast cancer patients (n=167) with median follow up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247) and DNA Integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA was estimated by next-gen sequencing (NGS) in a subset of samples. Association of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and best performing model was evaluated by decision curve analysis. Results: DI and ALU 247 levels were significantly lower (p<0.0001) in the post-operative plasma when compared to their pre-surgery levels. DI and ALU 247 were found to be significantly higher in patients with metastasis (p<0.05). Patients with higher levels of ALU 247 in their post-operative plasma had significantly poor disease-free survival (p=0.005). Higher level of ALU 247 in circulation also correlated with low tumor-infiltrating lymphocytes (TIL) within their primary tumors in the ER-negative breast cancer subtype (p=0.01). Cox proportional hazard analysis confirmed ALU 247 as an independent variable of disease-free survival both in univariate and multivariate analysis [HR 1.3 (95% CI 1.047 to 1.613, p= 0.017)]. Nomogram model showed addition of ALU 247 with other variables significantly improved (C-index-0.823) the predictive ability of the model. Conclusion: Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragment of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (P<0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11mM glucose plus fatty acids (P=0.004, fatty acid x glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (P<0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (P=0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (P<0.001 for fatty acid x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x cell type interaction). Hence glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

Background: The COVID-19 outbreak has accelerated the huge difference between medical care and disease prevention in Chinese medical institutions. This study aimed to investigated the relationship between the symbiotic units, environments, models, and effects of the integration of medical and disease prevention. Methods: This cross-sectional study involved 762 employees of public hospitals in 11 cities in Zhejiang Province by random stratified sampling. We analyzed the influence paths of elements in the mechanism of integration of medical and disease prevention and the mediating effect of symbiotic models among symbiotic units, symbiotic environments, and effects for on this integration. Results: The path coefficient of symbiotic unit on the symbiosis model was 0.46 (p&lt;.001), the path coefficient of symbiotic environment on symbiosis model was 0.52 (p&lt;.001). The path coefficient of the symbiotic unit and environment was 0.91 (p&lt;.001). The symbiotic models exhibited a partial mediation effect between symbiotic units and the effect of this integration. Sobel test = 3.27, β = 0.152, and the mediating effect accounted for 34.6%. Conclusions: It is suggested that Health policy-makers and public hospital managers should provide sufficient symbiotic units, establish collaborative symbiotic models, and improve the effects of integration of medical and disease prevention in public hospitals.

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

One of the most frequent brain diseases, Alzheimer's is defined by poor cognitive function brought on by the build-up of Beta Amyloid plaques and the gradual death of neurons. Glucose metabolism and the development of amyloid plaques are being studied together. Under physiologically normal circumstances, glucose is the primary substrate for the adult human brain. The prodromal phases of AD are significantly influenced by glucose hypometabolism. Hypometabolism of glucose in the brain is a clear sign of mitochondrial dysfunction and bioenergetic system impairment. By regulating energy synthesis and cell death, mitochondria play a crucial role in the functioning of cells. Increased formation of reactive oxygen species (ROS) and oxidative stress are a result of mitochondrial dysfunction, which also accelerates the development of Alzheimer's disease. For the maintenance of balance, autophagy is crucial because it selectively destroys damaged mitochondria. AD affects this route for mitochondrial breakdown. Targeting specific mitochondrial ligands by interventions along this pathway might be a useful therapeutic approach. Due to a number of biological obstacles, this method has significant limitations. As a result, many nanocarriers have been created to improve drug delivery effectiveness. All potential nanotechnology-based treatments for AD have been examined in this study, with a particular emphasis on medication delivery to the mitochondria

The relationship between Parkinson's disease (PD), the second most common neurodegenerative disease after Alzheimer's disease, and palmitoylation, a post-translational lipid modification, is not well understood. In this study, we have analyzed the differential palmitome present in the cerebral cortex of PD patients compared to controls (n=4 per group) to better understand the role of protein palmitoylation in PD and the pathways altered in this disease. Data-mining of the cortical palmitome from PD patients and controls has allowed to: i) detect a set of 150 proteins with altered palmitoylation in PD subjects in comparison with controls, ii) describe the biological pathways and targets predicted to be altered by these palmitoylation changes, and iii) depict the overlap between the differential palmitome identified in our study with protein interactomes of the PD-linked proteins α-synuclein, LRRK2, DJ-1, PINK1, GBA and UCHL1. In summary, we have partially characterized the altered palmitome in the cortex of PD patients which is predicted to impact cytoskeleton, mitochondrial and fibrinogen functions, as well as cell survival. Our study points out that protein palmitoylation could have a role in the pathophysiology of PD, and that comprehensive palmitoyl-proteomics offers a powerful approach for elucidating novel cellular pathways modulated in this neurodegenerative disease.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and a decline in activities of daily life. Ventricular enlargement has been associated with worse performance on global cognitive tests and AD. Our previous studies demonstrated that brain sulfatides, myelin-enriched lipids, are dramatically reduced in subjects at the earliest clinically recognizable AD stages via an apolipoprotein E (APOE)-dependent and isoform-specific process. Herein, we provided pre-clinical evidence that sulfatide deficiency is causally associated with brain ventricular enlargement. Specifically, taking advantage of genetic mouse models of global and adult-onset sulfatide deficiency, we demonstrated that sulfatide losses cause ventricular enlargement without significantly affecting hippocampal or whole brain volumes using histological and magnetic resonance imaging approaches. Mild decreases in sulfatide content and mild increases in ventricular areas were also observed in human APOE4 compared to APOE2 knock-in mice. Finally, we provided Western blot and immunofluorescence evidence that aquaporin-4, the most prevalent aquaporin channel in the central nervous system (CNS) that provides fast water transportation and regulates cerebrospinal fluid in the ventricles, is significantly increased under sulfatide-deficient conditions, while other major brain aquaporins (e.g., aquaporin-1) are not altered. In short, we unraveled a novel molecular mechanism that may contribute to ventricular enlargement in AD.

Foot and Mouth Disease (FMD) is a viral disease, widespread and highly contagious affecting mainly cloven-hoofed domestic and wild animals. FMD can lead to high economic losses due to reduction in animals’ production such as drop of milk production, loss of body weight and high mortality rate in young ruminants. Sixteen nasal swabs and epithelial tissues were collected from animals showing typical clinical signs of FMD during the last FMD outbreak in Libya in 2018-2019. Blood samples, swabs and epithelial tissues impressions on Flinders Technology Associates (FTA) cards were shipped to the FMD Reference laboratory in Brescia, Italy, and tested for the detection of FMD viruses. Nucleic acids were extracted from the FTA cards and molecular testing of the examined FTA cards confirmed that the FMD virus circulating in Libya was serotype O. Sequencing analysis of the FMD virus VP1 gene confirmed that FMD virus strain was serotype O/East Africa 3 (O/EA-3) topotype. The phylogenetic of the VP-1 gene of the FMD virus showed very high nucleotide identity (99.8%) between the virus circulating in Libya and the Algerian FMD virus strains isolated in Algeria on 2018 and 2019.

Often yam varieties grown in different agro-ecologies show differential responses across production environments, a term known as genotype-by-environment interaction. Genotype-by-environment interaction makes selecting the best genotypes under varied production environments more complex. This study tested twenty yam genotypes evaluated in six test environments to assess genotype, environment, and the interaction between genotypes and environmental effect for tuber yield, yam mosaic virus, and dry matter content. The experiments were conducted in two seasons across three locations in Uganda using a randomized complete block design with three replications. The results showed a significant effect (p ≤ 0.001) for genotype (G), environment (E), and genotype by environment interaction for all the traits. Serere 2021 and Namulonge 2021 were identified as the most discriminating and representative environments for testing the yam mosaic virus, respectively. Serere 2021 was recognized as the most discriminating environment, whereas Arua 2021 was identified as the closest to an ideal environment for assessing yam tuber yields. The tested genotypes also exhibited high resistance to yam mosaic virus disease, high tuber yields, and high dry matter content. Genotypes UGY16020, UGY16034, UGY16042, and UGY16080 demonstrated great resistance to yam mosaic virus disease, high yielding, and considerable dry matter content and are thus potential parents for yam improvement. Further evaluation of the four genotypes should be done under farmers' production systems for selection, improvement, and release as new yam varieties for Uganda

Human Adenovirus (HAdV) infection occurs in 14-16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk to develop HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical or HLA mismatched parent) and severe lymphopenia (< 0.2 x 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold on blood (> 102-3 copies/ml) and/or on the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3-5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention applicable both in prevention and therapeutic setting.

A Mitochondrial dysfunction and oxidative stress are major contributors to the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease (AD). However, the mechanisms driving mitochondrial dysfunction and oxidative stress are unclear. Familial AD (fAD) is an early onset form of AD caused primarily by mutations in the presenilin-encoding genes. Previously, using Caenorhabditis elegans as a model system to study presenilin function, we found that loss of C. elegans presenilin orthologue, SEL-12, results in elevated mitochondrial and cytosolic calcium levels. Here, we provide evidence that elevated neuronal mitochondrial generated reactive oxygen species (ROS) and subsequent neurodegeneration in sel-12 mutants are a consequence of the increase of mitochondrial calcium levels and not cytosolic calcium levels. We also identify mTORC1 signaling as a critical factor in sustaining high ROS in sel-12 mutants in part through its repression of the ROS scavenging system SKN-1/Nrf. Our study reveals that SEL-12/presenilin loss disrupts neuronal ROS homeostasis by increasing mitochondrial ROS generation and elevating mTORC1 signaling, which exacerbates this imbalance by suppressing SKN-1/Nrf antioxidant activity.

Huntington’s Disease (HD) is a devastating neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, for which no disease modifying therapies are currently available. Much of the recent research has focused on developing therapies to directly lower HTT expression, and while promising, these therapies have presented several challenges regarding administration and efficacy. Another promising therapeutic approach is the modulation of HTT post-translational modifications (PTMs) that are dysregulated in disease and have shown to play a key role in HTT toxicity. Among all PTMs, modulation of HTT phosphorylation has been proposed as an attractive therapeutic option due to the possibility of orally administering specific kinase effectors. One of the kinases described to participate in HTT phosphorylation is Protein Kinase CK2. CK2 has recently emerged as a target for the treatment of several neurological and psychiatric disorders, although its role in HD remains controversial. While pharmacological studies in vitro inhibiting CK2 resulted in reduced HTT phosphorylation and increased toxicity, genetic approaches in mouse models of HD have provided beneficial effects. In this review we discuss potential therapeutic approaches related to the manipulation of HTT-PTMs with special emphasis on the role of CK2 as a therapeutic target in HD.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines, which are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5, in particular, play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in the liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokine’s receptor, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16 can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as potential therapeutic approaches.

Marburg virus disease (MVD) is a hemorrhagic fever and cause death up to 88% of people and is the same as Ebola virus, It is transmitted through skin contact or mucous membrane in the eyes, nose or mouth with blood or body fluids like urine, saliva sweat, feces and by object contaminated with body fluids. Despite these facts, yet there is no approved vaccine have been developed for the eradication of Marburg virus infections. Therefore, this study described a multi epitope-based peptide vaccine against Marburg virus viral protein 35, using several immunoinformatics tools combined with molecular docking studies. Utilizing Vaxijen 2.0 server, the V35 protein revealed to be antigenic with a score of 0.4316. Prediction of the T-cell and B-cell epitopes was then conducted. RTFDAFLGV epitope was found to be the most promising one with binding affinity to the highest numbers of MHC I alleles, a positive score in the Class I immunogenicity study and non-allergen. These results were further confirmed by the good interaction of RTFDAFLGV to the groove of HLA-A*02:01 with binding energy of -8.1 kcal/mole. Finally, the vaccine was cloned in silico to ensure its validity and efficiency of expression. To ensure its safety and immunogenic profile, in-vitro and in-vivo bioassays are recommended to confirm these findings.

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

Background: Chronic kidney disease, one of the most common diseases in the world, is characterized by irreversible impairment of the kidney’s metabolic, excretory, and endocrine functions. During end-stage renal disease, patients require renal replacement therapy, such as hemodialysis (HD). Protein-energy wasting is a common health problem among HD patients. However, this study aims to assess the nutritional status of HD patients at two HD centers in Jeddah, Saudi Arabia, and to determine its associated factors. Methods: A cross-sectional study was conducted at two different Dialysis Centers in Jeddah, Saudi Arabia; 211 female and male HD patients. Malnutrition was recognized using the Modified-SGA (M-SGA) comprising two parts: medical history and physical examination. Sociodemographic and health status for all patients were also determined. Patients were classified based on their M-SGA score into two groups: normal and malnourished. Results: Overall, 54.5% of the participants showed malnutrition. Unemployment, low muscle strength and mass, high level of medication use, and high dialysis vintage were positively (P&lt;0.05) associated with malnutrition. Conclusion: The M-SGA score indicates a high prevalence of malnutrition among HD patients. These results show the importance of regular assessment and follow-ups for HD patients ensuring better health and nutritional status.

The beneficial effects of solar radiation on human health are well documented. One necessary mechanism triggers the production of vitamin D whose insufficiency has been linked to a variety of disorders like diabetes, hypertension and more recently amyloidosis and Alzheimer disease. However, there are few architectural designs capable on ensuring adequate provision of solar radiation inside buildings. Conventional fenestration is not sufficient to provide for significant doses of sunlight even to prevent seasonal affective disorder (SAD). In this paper we discuss the effect of new design alternatives for skylights, especially in the refurbishment of obsolete facilities. After such complex retrofit is executed, we have analyzed the performance of a building in warm and sunny climates as is the case of southern Spain. It has been considered as a priority the study of the factors that relate sunlight and energy, as well as, to a certain extent, other aspects like ventilation and insulation. Many architectural designs are presented as correct if the thermal requirements alone are met, even at the risk of later energy waste in lighting devices and visual or physical discomfort. On the other hand, large glazed areas allow more daylight into a space, but they may also allow excessive heat gains or losses which increase the air-conditioning cooling or heating load. To avoid these problems, we have considered the combined effect of daylight and energy from the beginning of the skylight design-process. A daylighting software based on configuration factors that we have apply in former researches to study the problems of direct sun over architectural structures have been used. This question cannot be treated adequately with conventional programs for overcast skies. The skylights have already been constructed and on-site measurements in the offices have been taken to complement the computer simulations data. The results show that it is possible to achieve energy saving and high radiation levels in winter without increasing heat loads during the summer. All this is considered beneficial to improve the condition of users with cognitive diseases as Alzheimer’s disease by virtue of adapted spaces.

Alzheimer’s disease is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients’ ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patients, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in Alzheimer’s disease have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acids species associated with Alzheimer’s disease from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.

Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2–related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.

Tick borne encephalitis virus (TBEV) is the causative agent of Tick borne encephalitis in humans, a severe zoonosis occurring in the Paleartic region mainly transmitted through ticks belonging to the genus Ixodes. In Italy, TBEV is restricted to few foci in the north-eastern part of the country. This report describes for the first time a case of clinical TBE in a roe deer, occurred in the Belluno province, Veneto region, an area highly endemic for the presence of the virus. The affected roe deer showed ataxia, staggering movements, muscle tremors and persistent teeth grinding causing hypersalivation. At necropsy, the macroscopic picture was inconclusive. RNA of TBEV was detected by real-time RT-PCR. Phylogenetic analysis revealed a close relationship to TBEV of the European subtype, and 100% similarity with a virus from the bordering Trento Province. The histological examination of the midbrain confirmed the viral etiology and specific immunofluorescence indicated the presence of a Flavivirus infection and characterized the pattern of infection in the neurons. This report underlines for the first time the occurrence of clinical encephalitic manifestations due to TBEV in a roe deer, thussuggesting to include this pathogen in the frame of differential diagnosis in this species.

In recent years, metabolomics has been used as a powerful tool to better understand the physiology of neurodegenerative diseases and identify potential biomarkers for progression. We used targeted and untargeted aqueous, and lipidomic profiles of the metabolome from human cerebrospinal fluid to build multivariate predictive models distinguishing patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and healthy age-matched controls. We emphasize several statistical challenges associated with metabolomic studies where the number of measured metabolites far exceeds sample size. We found strong separation in the metabolome between PD and controls, as well as between PD and AD, with weaker separation between AD and controls. Consistent with existing literature, we found alanine, kynurenine, tryptophan, and serine to be associated with PD classification against controls, while alanine, creatine, and long chain ceramides were associated with AD classification against controls. We conducted a univariate pathway analysis of untargeted and targeted metabolite profiles and find that vitamin E and urea cycle metabolism pathways are associated with PD, while the aspartate/asparagine and c21-steroid hormone biosynthesis pathways are associated with AD. We also found that the amount of metabolite missingness varied by phenotype, highlighting the importance of examining missing data in future metabolomic studies.

Introduction: The treatment of peritoneal dialysis in end-stage renal disease is increasing in clinical practice. The main purpose of this study was to evaluate the effect of far-infrared radiation therapy on inflammation and the cellular immunity of patients undergoing peritoneal dialysis. Materials and Methods: We recruited 56 patients undergoing peritoneal dialysis, and we included 32 patients from the experimental group and 24 patients from the control group in the final analysis. The experimental evaluation in our study was as follows: (1) We used abdominal computed tomography to measure the diameter and degree of hardening of the abdominal veins and large blood vessels to explore the changes in abdominal blood vessels. (2) The study compared the effects of peritoneal dialysis using albumin, blood urea nitrogen, creatinine, white blood cell, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, erythrocyte sedimentation rate, Hs-CRP clearance rate, and HBAlC. (3) We compared the cytokine concentration of blood between the two groups while controlling for GM-CSF, IL-2, IFN-γ, IL-6, IL-18, IL-4, IL-5, IL-13, IL-12p70, TNF-α, and IL-1β. Results and Discussion: (1) There was no significant difference in the abdominal blood vessels of the experimental group relative to the control group according to abdominal CT measured over 6 months. (2) Our study demonstrates the statistically significant effect of FIR therapy on the following parameters: albumin (p = 0.048*), creatinine (p = 0.039*), and Hs-CRP (p < 0.001**) decreased significantly, and glomerular filtration rate (eGFR, p = 0.043*) and glucose (p < 0.001**) increased significantly. Our study found that, in the experimental group, albumin and creatinine decreased significantly due to FIR therapy for 6 months. However, our study also found that, in the experimental group, glucose (p < 0.001**) increased significantly due to FIR therapy for 6 months. Peritoneal dialysis combined with FIR can reduce the side effects of glucose in dialysis buffer, which interferes with peritoneal inflammation and peritoneal mesothelial cell fibrosis. In addition, we also found that, in the experimental group, Hs-CRP (p < 0.001**) decreased significantly due to FIR therapy for 6 months. (3) No statistical significance in the inflammatory cytokines related to FIR therapy differences was observed in our study. IFN-γ (p = 0.124), IL-12p70 (p = 0.093), IL-18 (p = 0.213), and TNF-α (p = 0.254) did not exhibit significant improvements in peritoneal dialysis with FIR treatment over 6 months. IFN-γ and IL-18 in the plasma of patients in the experimental group and the control group were higher in the third month than in the first month. Conclusion: We found that the effect of peritoneal dialysis improved significantly with FIR therapy, and significant improvements in the peritoneal permeability and inflammatory response were observed. end-stage renal disease; peritoneal dialysis; far-infrared therapy (FIR)

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treat-ment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provided limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory conditions and experi-mental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model of human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, including podocyte loss. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by targeting NOTCH signaling pathway. JQ1 inhibited the gene expression of the NOTCH effec-tors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis.

When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that decon-struction of the extracellular matrix is essential to the remodeling of smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of in-ternal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content is low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension as demonstrated by straight-ening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.

Wheat gluten contains epitopes that trigger celiac disease (CD). A life-long strict gluten-free diet is the only treatment accepted for CD. However, very low-gluten wheat may provide an alternative treatment to CD. Conventional plant breeding methods are not sufficient to produce celiac-safe wheat. RNA interference technology, to some extent, succeeded in the development of safer wheat varieties. However, these varieties had multiple challenges in their implementation. Clustered Regularly Interspaced Short Palindromic Repeats-associated nuclease 9 (CRISPR/Cas9) is a versatile gene-editing tool that has the ability to edit the immunogenic gluten genes. So far, only a few studies have applied CRISPR/Cas9 to modify the wheat genome. In this article, we reviewed published literature that applied CRISPR/Cas9 in wheat genome editing to investigate the current status of the CRISPR/Cas9 system to produce a low-immunogenic wheat variety. We found that in recent years, the CRISPR/Cas9 system has been continuously improved to edit the complex hexaploid wheat genome. Although some reduced immunogenic wheat varieties have been reported, CRISPR/Cas9 has still not been fully explored in editing the wheat genome. We conclude that further studies are required to apply the CRISPR/Cas9 gene-editing system efficiently for the development of celiac-safe wheat variety and to establish it as a “tool to celiac safe wheat.”

Introduction: Dementia is a cognitive decline with patients often exhibit behavioural and psychological symptoms, severely affecting the quality of life and placing a heavy burden on caregivers. Acupressure has reported benefits for dementia. This study aims to critically review the available evidence for its use as a non-pharmacological therapy. Methods: Systematic search of major research databases for human clinical trials using acupressure as an intervention for dementia patients was conducted. Results were synthesised for the effects of acupressure on various outcome measures of interest for dementia.Results: Twelve clinical trials (N=973), including eight randomised control studies, were included in this review. The study sample was predominantly institutionalised residents with moderate to severe dementia. Baihui (GV20), Shenmen (HT7), Fengchi (GB20), Neiguan (PC6), Sanyinjiao (SP6), and Yingtang (EX-HN3) were the most used acupoints for intervention. Acupressure techniques employed in these clinical trials vary greatly with no standardised approach. This review finds inconsistent evidence in the effectiveness of acupressure in reducing agitation and behavioural disturbances. However, the treatment appears to improve their ease of care and reduce physical stress. Affixing acupressure devices on selected acupoints can also potentially improve psychiatric pain, anxiety, and depression. Long-term (6 months) treatment can potentially improve the cognitive function, activities of daily living, and quality of life of patients with mild to moderate dementia. The effect of acupressure on sleep disturbances remains unclear. Conclusion: More high-quality research on acupressure is needed to fill the gaps in knowledge and inform better care for dementia patients in the future.

Introduction: People with schizophrenia have poor cardiometabolic health, with elevated 10-year cardiovascular disease risk (CVD-R) scores and poor quality of life (QOL). There is lack of understanding of these issues in early psychosis. Aims: To quantify CVD-R in people with early psychosis and profile their obesity prevalence, lifestyle behaviours and QOL. Secondary aim was to explore associations between lifestyle behaviours/treatment characteristics and CVD-R/QOL. Method:Baseline data from 81 RCT participants were used to profile cardiometabolic health risks (QRISK®3, BMI and waist circumference). Participants self-reported lifestyle behaviours and QOL. Relationships between modifiable treatment/lifestyle factors and QOL/CVD-R were explored using bivariate analyses. Results: Participants’ relative risk for CVD over 10 years was 1.93 times higher than healthy counterparts; 39% also had an obese BMI and physical QOL was poor. No significant associations were observed between CVD-R or QOL with treatment characteristics and lifestyle factors. Discussion: Despite positive lifestyle behaviours, participants had elevated CVD-R scores and poor physical health related QOL. Quantifying CVD-R with QRISK®3 may highlight the need for health promotion interventions. Implications for practice: Mental health professionals should be alert to elevated cardiometabolic health risks in early psychosis, particularly as these can occur in the context of relatively healthy lifestyle behaviours.

This paper presents the evaluation of a fungal disease forecast model in vineyards for qualitative parameter analysis using the data from off the shelf sensors, i.e. temperature and air relative humidity, rain precipitation, and leaf wetness. The rules for the fungal disease models are digitalized as a decision support tool that serve as an indicator to farmers for the need of spraying of the chemical substances to ensure the best growing condition and suppress the level of parasites. The temperature and humidity contexts are used interchangeably in practice to detect the risk of the disease occurrence. By taking into account a number of influences on these parameters collected from the shelf sensors, new topics for research in the multidimensional field of precision agriculture emerge. In this study, the impact of the humidity is evaluated by assessing how different humidity parameters correlate with the accuracy of the Botrytis cinerea fungi forecast. Each humidity parameter has it’s own threshold that triggers the second step of the disease modeling - risk index based on the temperature. The research showed that for humidity a low-cost relative humidity sensor can detect in average 14.61% risk values, a leaf wetness sensor an additional 3.99% risk cases, and finally, a precipitation sensor will detect only an additional 0.59% risk cases.

Lyme disease is a growing public health problem in Québec. Its emergence over the last decade is caused by environmental and anthropological factors that favour the survival of Ixodes scapularis, the vector of Lyme disease transmission. The objective of this study was to estimate the speed and direction of Lyme disease emergence in Québec and to identify spatiotemporal risk patterns. A surface trend analysis was conducted to estimate the speed and direction of its emergence based upon the first detected case of Lyme disease in each municipality in Québec since 2004. A cluster analysis was also conducted to identify at-risk regions across space and time. These analyses were reproduced for the date of disease onset and date of notification for each case of Lyme disease. It was estimated that Lyme disease is spreading northward in Québec at a speed varying between 18 and 32 km/year according to the date of notification and the date of disease onset, respectively. A high rate of disease risk was found in seven clusters identified in the south-west of Québec in the sociosanitary regions of Montérégie and Estrie. The results obtained in this study improve our understanding of the spatiotemporal patterns of Lyme disease in Québec, which can be used for proactive, targeted interventions by public and clinical health authorities.

Background: Superspreading events are important drivers of the SARS-CoV-2 pandemic. By analyzing two outbreaks associated with choir rehearsals in March 2020, we demonstrate the risk of indoor, long-range (LR) transmission and singing, to help prevent similar outbreaks. Methods: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses.Results: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively. WGS confirmed strain identity in both choirs and the primary case of choir 1 (transmitting presymptomatically). Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases’ emitted particles was 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (median: 89% vs. 18%, 95%CI: 80-95% vs. 6-36%). Observed AR in choir 1 (89%) was significantly higher than in choir 2 (24%). According to a risk model, first transmission in choir 1 occurred likely after 7 minutes of singing. The number of inhaled particles emitted by an infectious case, sufficient to infect 50% of exposed, was calculated to 1039-2883 particles (95%CI).Conclusions: Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. Given the potential for presymptomatic infectiousness, greatest caution is required wherever aerosols can accumulate.

Alzheimer’s disease is associated with prion-like aggregation of the amyloid β (Aβ) peptide and the subsequent accumulation of misfolded neurotoxic aggregates in the brain. Therefore, it is critical to clearly identify the factors that trigger the cascade of Aβ misfolding and aggregation. Numerous studies have pointed out the association between microorganisms and their virulence factors and Alzheimer’s disease; however, their exact mechanisms of action remain unclear. Recently, we discovered a new pathogenic role of bacterial extracellular DNA, triggering the formation of misfolded Tau aggregates. In this study, we investigated the possible role of DNA extracted from different bacterial and eukaryotic cells in triggering Aβ aggregation in vitro. Interestingly, we found that the extracellular DNA of some, but not all, bacteria is an effective trigger of Aβ aggregation. Furthermore, the acceleration of Aβ nucleation and elongation can vary based on the concentration of the bacterial DNA and the bacterial strain from which this DNA had originated. Our findings suggest that bacterial extracellular DNA might play a previously overlooked role in the Aβ protein misfolding associated with Alzheimer’s disease pathogenesis. Moreover, it highlights a new mechanism of how distantly localized bacteria can remotely contribute to protein misfolding and diseases associated with this process. These findings might lead to the use of bacterial DNA as a novel therapeutic target for the prevention and treatment of Alzheimer’s disease.

The authors present a stereotypical case presentation of x-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact Fibroblast Growth Factor 23 (FGF23) which lead to i) low serum phosphate levels, ii) increased fractional excretion of phosphorus, and iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in XLH patients is due to chronic hypophosphatemia. Additionally, XLH patients experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration’s (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

The redox chemistry of copper(II) is strongly modulated by the coordination to amyloid-β peptides and by the stability of the resulting complexes. Amino terminal copper and nickel binding motifs (ATCUN) identified in truncated Aβ sequences starting with Phe4 show very high affinity for copper(II) ions. Herein, we study the oxidase activity of [Cu-Aβ4-x] and [Cu-Aβ1-x] complexes toward dopamine and other catechols. The results show that the CuII-ATCUN site is not redox-inert, the reduction of the metal is induced by coordination of catechol to the metal and occurs through an inner sphere reaction. The generation of a ternary [CuII-Aβ-catechol] species determines the efficiency of the oxidation, although the reaction rate is ruled by re-oxidation of the CuI complex. In addition to the N-terminal coordination site, the two vicinal histidines, His13 and His14, provide a second Cu-binding motif. Catechol oxidation studies together with structural insight from the mixed dinuclear complexes Ni/Cu-Aβ4-x reveal that the His-tandem is able to bind CuII ions independently of the ATCUN site, but the N-terminal metal complexation reduces the conformational mobility of the peptide chain, preventing the binding and oxidative reactivity toward catechol of CuII bound to the secondary site.

Bone involvement occurs in 75% of patients with Gaucher disease (GD), and comprises structural changes, debilitating pain, and bone density abnormalities. Osteoporosis is a silent manifestation of GD until a pathologic fracture occurs. Thus early diagnosis is crucial for identifying high-risk patients to prevent irreversible complications. Thirty-one patients with GD were assessed prospectively to identify predictive markers associated with bone density abnormalities, osteopenia (OSN), and osteoporosis (OSR). Subjects were categorized into three cohorts based on T- or Z- scores of bone mineral density (BMD): In GD cohort with no bone complication (Z-score≥-0.9; T-scores≥-1), the OSN group (-1.8 ≥ Z-score ≥ -1; -2.5 ≥ T-score ≥ -1) and OSR group (Z-score ≤ -1.9; T-scores ≤ -2.5). Serum levels of TRAP5b, RANKL, OPG, and RANK were quantified by enzyme-linked immunosorbent assays. TRAP5b was increased in GD and showed a positive correlation with GD biomarkers, including plasma glucosylsphingosine (Lyso-Gb1), macrophage activation markers CCL18 and chitotriosidase. The highest levels of TRAP5b was measured in patients with osteoporosis. The elevation of RANKL and RANKL/OPG ratio correlated with osteopenia in GD. Elevation of TRAP5b, RANKL, and RANKL/OPG indicate osteoclast activation in GD. TRAP5b is a potential bone biomarker for GD with the ability to predict the progression of bone density abnormalities.

GPR4, a member of proton activated GPCRs group. Previously we have reported that GPR4 is constitutively active at physiological pH and knockout of GPR4 has shown to protect dopaminergic neuronal cells from caspase-dependent mitochondrial apoptotic cell death. In this study we have investigated the role of GPR4 in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) treated mice model of Parkinson’s disease. Subchronic administration of MPTP in mice produces oxidative stress induced apoptotic cell death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and motor deficits. Treatment with NE52-QQ57, a selective antagonist of GPR4 reduced dopaminergic neuronal loss MPTP-intoxicated C57BL6/J mice and improved motor deficit and memory impairment. Co-treatment with NE52-QQ57 significantly decreases the protein level of proapoptotic marker (Bax), and increases the antiapoptotic marker (Bcl-2) in the SNpc and striatum tissue collected from the brain of MPTP inflicted mice. Further, MPTP induced activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP) was significantly decreased in the SNpc and striatum tissue of NE52-QQ57 cotreated mice. Further mice receiving both MPTP and NE52-QQ57 mice showed significantly higher TH positive cells in the SNpc and striatum than MPTP treated mice alone. Moreover, NE52-QQ57 cotreatment improved the motor activity in the rotarod test and pole test and also improved spatial memory in Y maze test. Our findings suggest GPR4 as a potential therapeutic target for PD whereas the activation GPR4 is involved in the caspase mediated apoptotic cell death in SNpc and striatum of MPTP-intoxicated mice.

Freezing of gait (FOG), a debilitating symptom of Parkinson’s disease (PD), can be safely studied using the stepping in place (SIP) task. However, clinical, visual identification of FOG during SIP is subjective and time consuming, and automatic FOG detection during SIP currently requires measuring center of pressure on dual force plates. This study examines whether FOG elicited during SIP in 10 individuals with PD could be reliably detected using kinematic data measured from wearable inertial measurement unit sensors (IMUs). A general, logistic regression model (AUC = 0.81) determined that three gait parameters together were overall the most robust predictors of FOG during SIP: arrhythmicity, swing time coefficient of variation, and swing angular range. Participant-specific models revealed varying sets of gait parameters that best predicted FOG for each participant, highlighting variable FOG behaviors, and demonstrated equal or better performance for 6 out of the 10 participants, suggesting the opportunity for model personalization. The results of this study demonstrated that gait parameters measured from wearable IMUs reliably detected FOG during SIP, and the general and participant-specific gait parameters allude to variable FOG behaviors that could inform more personalized approaches for treatment of FOG and gait impairment in PD.

Cities worldwide are facing ever-increasing pressure to develop mitigation strategies for all sectors to deal with the impacts of climate change. Cities are expected to house 70% of the world’s population by 2050 and developing related resilient health systems is a significant challenge. Because of their physical nature, cities’ surface temperatures are often substantially higher than that of the surrounding rural areas, generating the so-called Urban Heat Island (UHI) effect. Whilst considerable emphasis has been placed on strategies to mitigate against the UHI-associated negative health effects of heat and pollution, the World Health Organization estimates that one of the main consequences of global warming will be an increased burden of such vector-borne diseases. Many of the major mosquito-borne diseases are urban and thus the global population exposed to these pathogens will steadily increase. Mitigation strategies beneficial for one sector may, however, be detrimental for another. Implementation of inter-sectoral strategies that can benefit many sectors (such as water, labour and health) do exist and would enable optimal use of the meagre resources available. Discussion among inter-sectoral stakeholders should be actively encouraged.

Vaccination against Newcastle disease (ND), a devastating viral disease of chicken, is often hampered by thermal inactivation of the live vaccines, in particular in tropical and hot climate conditions. In the past “thermostable” vaccine strains (I-2) have been proposed to overcome this problem. In the current study, we compared the thermal stability of 6 commercially available ND vaccines. Subjected to 37°C as lyophilized preparation, two vaccines containing I-2 strains were more sensitive to inactivation than a third I-2 vaccine or when compared to three other vaccines based on different strains. However, after reconstitution strains proved to have a comparable tenacity. Interestingly, all vaccines retained a sufficient virus dose for protection (106 EID50) after 1 day at 37°C, still. However, experiments exposing ND-vaccines to elevated temperatures of 51°C and 61°C, clearly demonstrated inactivation of all dissolved vaccines within 2 to 4 hours. The data indicate preparation that specific factors may influence thermal stability rather than strain specific characteristics. Regardless of the ND strain used, the appropriate cold chain is mandatory for live ND-vaccines.

Adrenal crisis (AC) is an unexpected and possibly lethal situation of stressful interventions in patients with Addison’s disease (AD). Despite being rare in dentistry, it is to be noted that evidence indicates that 5-8% of patients with AD necessitate emergency glucocorticoid administration to treat AC annually. For that, dentists must be aware of this condition and be prepared when the clinical signs and symptoms occur.

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb) that affects approximately a millions people worldwide. It is characterized by a single nucleotide substitution on the β-globin gene, leading to the production of abnormal sickle hemoglobin with multi-system consequences. Mutated Hb leads to profound changes in: i) red blood cell metabolism and physiology; ii) endothelial signaling; and iii) immune response. Oxidative stress is an important hallmark of SCD. It plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e. by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

Understanding the motor patterns underlying the movement of people with Parkinson's disease (PD) is fundamental to the effective targeting of non-pharmacological therapies. This study aims to analyze the gait pattern in relation to the evolutionary stage between I-II and III-IV according to the Hoehn and Yahr scale (H&amp;Y) in people affected by PD. The study was conducted with the participation of 37 PD patients, with a mean age of 70.09±9.53 years, and of whom 48.64% were women. The inclusion criteria were: 1. To be diagnosed with PD; 2. To be in an evolutionary stage of the disease of between I and IV and; 3. To be able to walk independently and without any assistance. Kinematic and spatial-temporal parameters of the gait were analyzed. The results show differences in speed of movement, cadence, stride length, support duration, swing duration, step width, walking cycle duration and double support time between the stages analyzed. These results confirm the differences in PD gait pattern between stages I-II and III-IV. Different behaviors of the same variable were recorded depending on whether the right or left sides were affected by PD.

Learning systems have been very focused on creating models that are capable of obtaining the best results in error metrics. Recently, the focus has shifted to improvement in order to interpret and explain their results. The need for interpretation is greater when these models are used to support decision making. In some areas this becomes an indispensable requirement, such as in medicine. This paper focuses on the prediction of cardiovascular disease by analyzing the well-known Statlog (Heart) Data Set from the UCI’s Automated Learning Repository. This study will analyze the cost of making predictions easier to interpret by reducing the number of features that explain the classification of health status versus the cost in accuracy. It will be analyzed on a large set of classification techniques and performance metrics. Demonstrating that it is possible to make explainable and reliable models that have a good commitment to predictive performance.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function with neuronal damage. Although the precise pathobiology of AD is still elusive, accumulating evidences suggest that mitochondrial dysfunction is one of the underlying causes of AD. Mutations of mitochondrial or nuclear DNA that encode mitochondrial constituents may cause mitochondrial dysfunctions. In particular, dysfunction of electron transport chain complexes along with interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunctions in AD. Mitochondrial dysfunction causes an imbalance in reactive oxygen species, leading to oxidative stress (OS) and vice-versa. Neuroinflammation is another potential contributory factor to induce mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense system, and thereby protect against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Pharmacological intervention through neuroprotective phytochemicals can, therefore, be a potential strategy to combat mitochondrial dysfunctions as well as AD. This review focuses on the role of phytochemicals to mitigate mitochondrial dysfunction in the therapy of AD pathogenesis.

The complex interplay among pathogens, host factors, and the integrity and composition of the endogenous microbiome determine the course and outcome of gastrointestinal infections. The model organism Yersinia entercolitica (Ye) is one of the five top frequent causes of bacterial gastroenteritis based on the Epidemiological Bulletin of the Robert Koch Institute (RKI) published on September 10, 2020. A fundamental challenge in predicting the course of an infection is to understand whether co-infection with two Yersinia strains differing only in their capacity to resist killing by the host immune system may decrease the overall virulence by competitive exclusion or increase it by acting cooperatively. Herein, we study the primary interactions among Ye, the host immune system and the microbiota, and their influence on Yersinia population dynamics. The employed model considers two host compartments, the intestinal mucosa and lumen, commensal bacteria, the co-existence of wild-type and mutant Yersinia strains, as well the host immune responses. We determine four possible equilibria: the disease-free, wild-type-free, mutant-free, and co-existence of wild-type and mutant equilibrium. We also calculate the reproduction number for each strain as a threshold parameter to determine if the population may either be eradicated or persist within the host. We conclude that the infection should disappear if the reproduction numbers for each strain fall below one, and the commensal bacteria’s growth rate exceeds the pathogens’ growth rates. These findings will help inform public health control strategies. The supplement includes MATLAB source script, Maple workbook, and figures.

Molluscan aquaculture is a major contributor to global seafood production, but is hampered by infectious disease outbreaks which can cause serious economic losses. Selective breeding has been widely used to improve disease resistance in major agricultural and aquaculture species, and has clear potential in molluscs, albeit its commercial application remains at a formative stage. Advances in genomic technologies, especially development of cost-efficient genomic selection, have potential to accelerate genetic improvement. However, tailored approaches are required due to the distinctive reproductive and lifecycle characteristics of molluscan species. Transgenesis and genome editing, in particular CRISPR/Cas systems, have been successfully trialled in molluscs, and may further understanding and improvement of genetic resistance to disease through targeted changes to the host genome. Whole organism genome editing is achievable on a much greater scale compared to other farmed species, making genome-wide CRISPR screening approaches plausible. This review discusses the current state and future potential of selective breeding, genomic tools, and genome editing approaches to understand and improve host resistance to infectious disease in molluscs.

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

This case study examined changes in body composition, resting metabolic rate (RMR), aerobic capacity, and daily physical activity in a patient who had ulcerative colitis who underwent ileal pouch‒anal anastomosis (IPAA) surgery. Body composition, RMR, and VO2 peak were assessed prior to, 4, 8, and 16 weeks after IPAA surgery. Daily physical activity data was extracted from a wrist-worn activity tracker preoperatively and 16 months postoperatively. At baseline, total body mass was 95.3 kg; body fat, 11.6 %; lean body mass, 81.1 kg; RMR, 2,416 kcal/d; and V̇O2peak, 42.7 mL/kg/min. All values decreased from baseline at 4 weeks postoperatively, body mass was 85.2 kg (-10.5%); body fat, 10.9% (-6.0%); lean body mass, 73.1 kg (-9.9%); RMR 2,210 kcal/d (-8.5%) and V̇O2peak, 25.5 mL/kg/min (-40.3%). At 16 weeks postoperatively, most parameters were near their baseline levels (within 1%-7%); exceptions were V̇O2peak, which was 20.4% below baseline, and RMR, which increased to nearly 20% above baseline. After the patient had an IPAA surgery, his total and lean body masses, RMR, and aerobic capacity were markedly decreased. Daily physical activity decreased postoperatively and likely contributed to the decreased aerobic capacity, which may take longer to recover compared to body composition and RMR parameters.

Aim: Abnormal laboratory findings have been shown to be associated with severe COVID-19. However, all aspects of this association have not been reviewed systematically. Therefore, the aim of this meta-analysis was to explore crucial laboratory parameters in severe COVID-19 infection. Methods: We performed the literature review of scientific articles indexed in electronic databases. Scientific search engines were used to perform the electronic literature search. After the removal of duplicates and selection of articles of interest, 30 studies were eligible to include. If heterogeneity was high (I²>50%), a random-effects model was applied to combine the data. Otherwise, a fixed-effects model was used.Results: A total of 5586 individuals were assessed (1555 patients with severe COVID-19 infection and 3452 with non-severe infection). Platelets, lymphocytes and serum albumin were significantly lower in severe patients while other biochemical and immunological parameters including prothrombin time, ALT, AST, total bilirubin, LDH, procalcitonin, CRP, IL-6, and IgA were significantly higher in patients with severe infection. Neutrophil and monocyte counts as well as hemoglobin level, D-dimer, hypersensitive troponin I, IL-2R, IgG and IgM levels were different between two groups; however, the difference was not statistically significant (All P-values >0.05). Conclusions: Lymphopenia, elevated liver enzymes, and high levels of inflammatory biomarkers are associated with severe COVID-19 infection.

As a major infectious disease in chickens, Newcastle disease causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 dpi after infection at day21 with a lentogenic Newcastle disease virus in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV challenged and nonchallenged groups, 526 differentially expressed genes (DEGs) (FDR &lt; 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, IPA analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis and angiogenesis. Upregulation of Interferon Induced Protein with Tetratricopeptide Repeats 5 (IFIT5) in response to NDV was consistent between the current and most previous studies. Sprouty RTK Signaling Antagonist 1 (SPRY1), a DEG in the current study is located in a significant QTL associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.

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.

The outbreak across the globe due to coronavirus disease 2019 (COVID-19) has spread abruptly by infected humans worldwide. The continuous efforts by scientists is on way to understand how pandemic of COVID-19 resembles and differs from serve acute respiratory syndrome coronavirus (SARS-CoV) at transcriptomic and genomic level. The SARS-CoV and COVID-19 exploits the angiotensin converting enzyme 2 (ACE2) receptor to gain entry inside the cells.We analyzed the entry COVID-19 into host cell due to receptor binding domain (RBD) of spike glycoprotein. The proposed simulation data shows similar ternary structures from two viruses shares approximately 80 percent identity in amino acid sequences. Our molecular modeling investigation signifies that angiotensin converting enzyme 2 (ACE2) has stronger interaction with COVID -19 RBD. The Amino acid phenylaniline F486 LOOP plays vital role due to its penetration into hydrophobic pocket in ACE2.The said investigation of S-Glycoprotein RBD of COVID-19 or SARS-CoV-2 via ACE2 provides post genome analysis of protein-protein interaction for rapid assessing transmission of infected patients by deadly CoVID-19. The scientific data extracted implies early guidance to control and viral prevention of CoVID-19.

In the end of April nearly 100 cases of children aged between 6 month and 9 years with Kawasaki like disease were reported (mostly in Europe) probably linked to COVID-19. With the increasing awareness of this condition the number of cases reported is increasing worldwide. We aim to sum up the known data about this new entity based on published data (in a case report, a series of 8 cases and in newspapers and society statement) and using our knowledge of classical Kawasaki disease. It seems to be a post infectious disease with an onset between 2-4 weeks after the infection, probably in genetically predisposed children aged between 6 month to 17 years. A very rough estimation of incidence based on current data from Bergamo, Italy, and New York State and a lot assumption is between 0.016% (95% CI:0.013-0.02%) - 0.31% (95% CI: 0.2-0.47%) of infected children. Clinical signs overlaps with Kawasaki disease in some children, but another feature is prominent gastrointestinal manifestations. For the 9 detailed patients most had incomplete presentation for Kawasaki disease (with a mean 1.7 (+/-1.2) criteria per patient for the 5 non fever criterion) and only one had a classical form. In some cases, presentation is closer to toxic shock syndrome or isolated myocarditis. Persistent fever seems to be constant and biological exploration are consistent with inflammation (elevated CRP, ferritin and D-Dimers). Management is described as supportive and children seem to improve rapidly, but can require cardiac or respiratory support. In date of 11 may 2020 there is 4 deaths confirmed linked to these new entities (1 in UK and 3 in New York). Paediatricians and general practitioners need to be aware of these possible evolution following COVID-19 infection. However it seems to be rare and children are probably still spared from most morbidities and mortality linked to COVID-19 infection .There are need of published detailed cohorts to better delineate these entities.

COVID19 is a current pandemic disease due to the novel coronavirus SARS-CoV-2. The scientific community mounted a strong response by accelerating research and innovation, and rapidly setting the basis to the understanding of molecular determinants of the disease for the development of targeted therapeutic interventions. The replication of the viral genome within the infected cells is a key step of SARS-CoV2 life cycle. It is a complex process involving the action of several viral and host proteins in order to perform RNA polymerization, proofreading and final capping. This review provides an update of structural and functional data on key actors of the replicatory machinery of SARS-CoV-2, filling the gaps in the current availability of structural data using homology modelling. Moreover, learning from similar viruses, we collect literature data to reconstruct the pattern of interactions among protein actors of the SARS-CoV-2 RNA polymerase machinery. In this pattern, an important role is played by co-factors, like Nsp8 and Nsp10, not only as allosteric activators but also as molecular connectors holding the entire machinery together to enhance the efficiency of RNA replication.

Deforestation and associated changing landscapes are major components of environmental changes, with important implications for ecosystem functioning and biodiversity conservation. Tropical forests are hot spots of biodiversity and provide multiple goods and ecosystem services which benefit people in many ways Forest also play an important role in health-related legends, myths, and fairy tales from all over the world, and are important sources of new potential emerging microbial threats to human. Although plausibly numerous abundant microbial forms with a forest origin may exist, our systematic literature review shows that forest-derived infection studies are relatively unexplored, and both taxonomically and geographically biased. Since biodiversity has been associated with emergence of novel infectious diseases at macro-scale, we describe the main biogeographical patterns in the emerging infection-biodiversity-forest loss nexus. Then, we illustrate four fine-scale case studies to decipher the underlying processes of increased infection risk in changing forest clearing landscapes. Finally, we identify scientific challenges and regional management measures required to mitigate these important new emerging threats.

As of 26 March 2020, Pakistan had 1179 cases of COVID-19, with most 421 cases from Sindh, 394 cases, 131 cases, 123 cases, 84 cases, 25 cases and 01 cases from Punjab, Balochistan, Khyber Pakhtunkhwa, Gilgit-Baltistan, Islamabad Capital Territory, and Azad Jammu and Kashmir respectively. Travel-related cases were the main source of SARS-CoV-2 infection during the early phase of the pandemic in Pakistan. Nevertheless, cases of local virus transmission are increasing day by day. As of 26 March 2020, nine deaths have been reported from COVID-19. The case fatality rate is 0.8%, which is less compare to China, Italy, USA, and Iran. The SIR (Susceptible-Infected-Recovered) model of epidemiological analysis predicts that almost 90 million population will be infected in the coming days with 5% critical cases that need health care facilities. However, the Pakistan health care system cannot provide services to this much population. Hence, we need to act timely to reduce this number by restricting local transmission of the disease. This can be done by mass testing, quarantine, isolation and social distancing of the active coronavirus cases in Pakistan. Moreover, better communication between the authorities is very much required to control disease transmission.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

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

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

Disease related malnutrition (DRM) is prevalent in hospitals and is associated with increased care needs, prolonged hospital stay, delayed rehabilitation and death. Nutrition care process related activities such as screening, assessment and treatment has been advocated by scientific societies and patient organizations but implementation is variable. We analyzed the cross-sectional nutritionDay database for prevalence of nutrition risk factors, care processes and outcome for medical patients. In 59126 medical patients included between 2006-2015 the prevalence of recent weight loss (45%), history of decreased eating (48%) and low actual eating (53%) was more prevalent than low BMI (8%). Each of these risk factors was associated with a large increase in 30 days hospital mortality. Nutrition care processes increases slightly with presence of risk factors but never done in more than 50% of patients. Only a third of patients not eating in hospital receive oral nutritional supplements or artificial nutrition. We suggest that political action should be taken to raise awareness and formal education on all aspects related to DRM for all stakeholders, to create and support responsibilities within hospitals, and to create adequate reimbursement schemes. Collection of routine and benchmarking data is crucial to tackle DRM.

Background: Alzheimer’s disease (AD), the most threatening neurodegenerative diseases, is characterized by the loss of memory and language function, an unbalanced perception of space and other cognitive and physical manifestations. Pathology of the AD is characterized by neuronal loss, and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in the AD is being studied actively, and nutrition is certainly one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest in recent times, with varying and often conflicting results. Scope and approach: This review aims to critically summarize the most recent studies conducted to clarify the relationship between wine drinking and AD, as well as whether effects are influenced by quantity and/or frequency of drinking. Key findings and Conclusion: Overall, based on the interpretation of various studies, it can be concluded that there is no indication that light to moderate alcohol drinking is detrimental to cognition and dementia, and it is not possible to define whether alcohol could be used as a means to reduce risk of developing AD.

Sickle cell disease (SCD) is an inherited condition characterized by chronic haemolytic anaemia. SCD is associated with moderate to severe anaemia, hypercoagulable state and inconsistent platelet count and function. However, studies have yielded conflicting results with regards to the effect of anaemia on coagulation in SCD. The purpose of this study was to determine the effect of anaemia severity on selected coagulation parameters of SCD patients. Four milliters of venous blood samples were taken from the participants (SCD and non-SCD patients) and used for analysis of full blood count and coagulation parameters. Data was analyzed using SPSS version-16. From the results, it was seen that individuals with SCD had a prolonged mean PT, APTT and high platelet count compared to the controls. There was also significant difference in the mean PT (p=0.039), APTT (p=0.041) and platelet count (p=0.010) in HbSS participants with severe anaemia. Mean APTT also showed significant difference (p=0.044) with severe anaemia in HbSC participants. It can be concluded that SCD patients have prolonged PT, APTT and increased platelet count which might predispose them to bleeding episodes and thrombocytosis. Significant difference was also seen between severity of anaemia and mean PT, APTT and platelet count in HbSS individuals.

Nutrition is crucial for the management of patients affected by chronic kidney disease (CKD) to slow down disease progression and to correct symptoms. The mainstay of the nutritional approach to renal patients is protein restriction coupled with adequate energy supply to prevent malnutrition. However, other aspects of renal diets, including fiber content, can be beneficial. This paper summarizes the latest literature on the role of different types of dietary fiber in CKD, with special attention to intestinal microbiota and the potential protective role of renal diets. Fibers have been identified based on aqueous solubility, but other features, such as viscosity, fermentability, and bulking effect in the colon should be considered. A proper amount of fiber should be recommended not only in the general population but also in CKD patients, to achieve an adequate composition and metabolism of intestinal microbiota and to reduce the risks connected with obesity, diabetes, and dyslipidemia.

The association between the choice of general anesthetic agents and the risk of acute kidney injury (AKI) and long-term renal function after nephrectomy has not yet been evaluated. We reviewed 1087 cases of partial or radical nephrectomy. The incidence of postoperative AKI, new-onset chronic kidney disease (CKD) stage 3a and CKD upstaging were compared between different general anesthetic agent groups: propofol, sevoflurane, and desflurane. Four different propensity score analyses were performed to minimize confounding for each pair of comparison (propofol vs sevoflurane; propofol vs desflurane; sevoflurane vs desflurane; propofol vs volatile agents). Study outcomes were compared before and after matching. Kaplan-Meier survival curve analysis was performed to compare renal survival determined by the development of CKD stage 3a between groups up to 36 months after nephrectomy before and after matching. Propofol was associated with a lower incidence of AKI, CKD upstaging and a higher three-year renal survival after nephrectomy compared to sevoflurane or desflurane group after matching (AKI: propofol 23.2% vs. sevoflurane 39.5%, P=0.004, vs. desflurane 34.3%, P=0.031; CKD upstaging: propofol 27.2% vs. sevoflurane 58.4%, P<0.001, vs. desflurane 48.6%, P=0.017; Log-rank test propofol vs. sevoflurane P<0.001, vs. desflurane P=0.015). Propofol was also associated with a lower incidence of new-onset CKD after nephrectomy compared to sevoflurane after matching (P<0.001). However, there were no significant differences between sevoflurane and desflurane. In conclusion, propofol, compared to volatile agents, may be the reasonable choice of general anesthetic agent for nephrectomy to attenuate postoperative renal dysfunction. Randomized prospective trials are warranted to test this hypothesis.

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

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

Gluten is a complex mixture of storage proteins in cereals like wheat, barley and rye. Prolamins are the main components of gluten. Their high content in proline and glutamine makes them water-insoluble and difficult to digest in the gastrointestinal tract. Partial digestion generates peptide sequences which trigger immune responses in celiac and gluten-sensitive patients. Gluten detection in food is challenging because of the diversity, in various food matrices, of protein proportions and their immunogenicity. Attempts to develop standard reference materials have been unsuccessful. We present here a summary of recent studies reporting the detection of dominant Gluten Immunogenic Peptides (GIP) sharing epitopes presented in the α-gliadin 33-mer, the most important celiac disease-immunogenic sequence within gluten. GIP were not only detectable and quantifiable in very different kind of difficult to analyze food, but also in stool and urine of celiac patients on a supposedly gluten-free diet (GFD), providing the first simple and objective means to assess adherence to the GFD. Methods to specifically and sensitively detect the most active GIP in food and biological fluids are rational candidates may use similar analytical standard references for determination of the immunopathological risk of gluten exposure in gluten-related diseases.

Safety management assessment systems for national level units’ in South Korea focus on responding capacity to cope with impending accident occurrence and danger occurrence. Since the four stage systems for prevention-preparation-response-recovery, which are core elements of national disaster management, assess the capacities by item such as those of individuals, disaster management departments, institutions, and management networks, there is no assessment function for the organic operation states of the entire systems. Therefore, for efficient disaster management, systematic evaluation indices that will enable active pre-checks in departments in organizations should be developed in place of the existing simply checking methods. In this study, an assessment model that will enable active disaster management centered on practice was developed using resilience engineering techniques. This model consists of disaster management items from the viewpoint of proactive responses instead of prevention. A total of 56 items that constitute four capacities; which are prediction (13 items), monitoring (14 items), proactive response (15 items), and safety learning (14 items) capacities were adopted in this model through Delphi analysis. Institutional capacities for infectious disease disaster management were evaluated based on this model and the resultant scores were prediction 4.41, monitoring 4.63, proactive response 4.69, safety learning 4.56 out of the full score of 5.0 points with an overall average of 4.51. This is an excellent capacity management score comparable to the score 4.57 of diagnosis of similar capacities by the WHO\_JEE (The Joint External Evaluation) in 2017. In fact, in 2015, when infectious disease capacity management was poor, in case of MERS (Middle East Respiratory Syndrome) infectious disease spread in South Korea, 36 patients died and 6,729 patients were isolated. However, through capacity reinforcement, in the case of MERS occurrence in South Korea in September 2018, a management capacity that prevented spread was shown as one confirmed case was completely cured in 10 days and 21 contacts were isolated and tested negative. Therefore, this capacity management assessment model is judged to be usable in enhancing disaster response and management capacities.

Enteric septicemia of catfish, columnaris disease, and streptococcosis, caused by Edwardsiella ictaluri, Flavobacterium columnare, and Streptococcus iniae, respectively, are the most common bacterial diseases of economic significance for the pond-raised channel catfish Ictalurus punctatus industry. Several management practices are used by catfish farmers to prevent large financial losses from these diseases such as the use of commercial antibiotics and other chemicals. In order to discover environmentally benign alternatives, using a rapid bioassay, we evaluated a crude extract from the roots of muscadine Vitis rotundifolia against these fish pathogenic bacteria and determined that the extract was most active against F. columnare. Subsequently, several isolated compounds from the root extract were further evaluated against F. columnare. Among these isolated compounds, (+)-hopeaphenol (2) and (+)-vitisin A (3) were found to be the most active against F. columnare, with 24-h 50% inhibition concentrations of 4.0±0.7 and 7.7±0.6 mg/L, respectively, and minimum inhibitory concentrations of 9.1±0 mg/L for each compound. Efficacy testing of 2 and 3 is necessary to further evaluate the potential for these compounds to be used as antibacterial agents for managing columnaris disease.

Gait abnormalities are one of the distinguishing symptoms of patients with Parkinson's disease (PD) that contribute to fall risk. Our study compares the gait parameters of people with PD when they walk through a predefined course without assistance, with a conventional walker, and with a motorized walker under different speed cues. Six PD subjects were recruited at the New York Institute of Technology College of Osteopathic Medicine to participate in this study. Spatial posture and gait data of the test subjects were collected via a VICON motion capture system. We developed a framework to process and extract gait features and applied statistical analysis on these features to examine the significance of the findings. The results showed that motorized walkers with haptic cues significantly improved gait symmetry of PD subjects. Specifically, the asymmetry index of the gait cycle time was reduced from 6.7% when walking without assistance to 0.56% and below when using a walker. Furthermore, the double support time of a gait cycle was reduced by 4.88% compared to walking without assistance.

Photoplethysmography (PPG) is a simple-to-perform vascular optics measurement technique that can detect changes in blood volume in the microvascular tissue bed. Beat-to-beat analysis of the PPG waveform enables the study of the variability of pulse features such as amplitude and pulse arrival time (PAT), and when quantified in the time and frequency domains, has considerable potential to shed light on perfusion changes associated with peripheral arterial disease (PAD). In this pilot study innovative multi-site bilateral finger and toe PPG recordings from 43 healthy control subjects and 31 PAD subjects were compared (recordings each at least 5 minutes, collected in a warm temperature-controlled room). Beat-to-beat normalized amplitude and PAT variability was then quantified in the time-domain using SD and IQR measures and in the frequency-domain bilaterally using Magnitude Squared Coherence (MSC). Significantly reduced normalized amplitude variability (healthy control 0.0384 (IQR 0.0217-0.0744) vs PAD 0.0160 (0.0080-0.0338) (p<0.001) and significantly increased PAT variability (healthy control 0.0063 (0.0052-0.0086) vs PAD 0.0093 (0.0078-0.0144) (p<0.001) was demonstrated in PAD using the time-domain analysis. Frequency-domain analysis demonstrated significantly lower MSC values across a range of frequency bands for PAD patients. These changes suggest a loss of right-to-left body side coherence and cardiovascular control in PAD. This study has also demonstrated the feasibility of using these measurement and analysis methods in studies investigating multi-site PPG variability for a wide range of cardiac and vascular patient groups.

Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor (P-elF2α) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

The aim of this study was synthesize and evaluate the effects of Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of metformin (PLGA+ Met) on inflammation, and bone loss in a ligature-induced periodontitis rat model. The prepared NPs were characterized by mean diameter, size particle, polydispensity index and encapsulation efficiency by Atomic force microscopy (AFM). Male albino Wistar rats were randomly divided into four groups of 20 rats in each group, and given the following treatments for 10 days to evaluate in vivo activity: (1) Sham: no ligature + water; (2) Positive control: ligature + water (with Periodontal disease and Diabetes); (3) ligature + PLGA+ 10 mg/kg Met (With Periodontal disease and Diabetes); and (4) ligature + PLGA+ 100 mg/kg Met (with Periodontal disease and Diabetes). Water or PLGA + Met was administered orally by gavage. Maxillae were fixed and scanned using Micro-computed Tomography (μCT) to quantify linear of bone loss. Histopathological characteristics were assessed through immunohistochemical staining for Osteocalcin, Cathepsyn K, RANKL/RANK/OPG pathway. IL-1β and TNF-α from gingival tissues were analysed by Elisa immunoassay. Quantitative RT-PCR reaction was used to evaluate gene expression of AMPK, NF-κB p-65, Hmgb1 and TAK-1 from gingival tissues. Statistical analysis was performed using one-way ANOVA at 5% significance. The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm with a polydispersity index of 0.285, zeta potential: 8.16 ± 1.1 mV and entrapment efficiency (EE) was 70%. The results suggest that the addition of MET in the core slightly affected the particle sizes. Treatment with PLGA+ 10 mg/kg Met showed low inflammatory cells, decreased bone loss and integrity cement and levels of IL-1β, and TNF-α (p < 0.05) were significantly reduced. Additionally, weak staining was shown by RANKL, Cathepsyn K, OPG, and osteocalcin. Radiographically, linear measurements showed a statistically significant reduction in bone loss after treatment with PLGA+ 10 mg/kg Met compared to the positive control (p < 0.05). RT-PCR showed increased AMPK expression (p < 0.05) and decreased expression of NF-κB P65, HMGB1 and TAK-1 after PLGA+ 10 mg/kg Met (p < 0.05). The PLGA nanoparticle + 10 mg/kg Met decreased glucose levels and also decreased the inflammatory response, and bone loss in ligature-induced periodontitis in rats.

Background: Coronary tortuosity is a common angiographic finding. Scarce data is available on clinical profile of patients with coronary tortuosity (CT) and its relation with coronary artery disease (CAD). Method: A total 224 patients undergoing angiography for suspected CAD were included in the study. CT was defined by the presence of ≥3 consecutive bends of > 45 degree measured at end-diastole in an epicardial artery ≥2 mm in diameter. CT was present in 45(20.08%) patients in the study and another 45 patients without CT was randomly selected as control (NCT group). Clinical profile of CT and NCT group was compared. Results: Incidence of CT was significantly higher in females (p=0.000) and hypertensives (p=0.001) patients. CT was most commonly seen in Left circumflex coronary artery. Incidence of CAD was significantly lower in CT group as compare to NCT group (0.02). Risk factors for CAD was associated with reduced incidence of CT. Majority (88.46%) patient with CT without CAD presented with chronic stable angina out of which (65.21%) had an objective evidence of myocardial ischemia. Conclusion: CT is more commonly seen females and hypertensive patients. It has negative correlation with CAD. Risk factors of CAD do not predict CT. CT itself can lead to myocardial ischemia.

Chemokine C-C receptor 6 (CCR6) and its exclusive ligand CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple organ systems, including lung, liver, kidney, skin, brain, eye, joints, gonads and the gut in the human body. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, HIV and cancer metastasis. CD4⁺ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between pro-inflammatory T_H17 cells and regulatory T_reg cells. Although the exact immune regulatory role is not elucidated yet, CCR6/CCL20 axis is implicated as a front runner which determines the polarization of T_H17 and T_reg cells and consequently the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems thereby hoping to accentuate its value in future therapeutic modalities.

In the last years evidence has emerged that neurodegenerative diseases (NDs) are strongly associated with the microbiome composition in the gut. Parkinson’s disease (PD) is the most intensively studied neurodegenerative disease in this context. In this review, we performed a systematic evaluation of published literature comparing changes in colonic microbiome in PD to the ones observed in other NDs including Alzheimer’s Disease (AD), Multiple system atrophy (MSA), Multiple sclerosis (MS), Neuromyelitis optica (NMO) and Amyotrophic lateral sclerosis (ALS). To warrant comparability of different studies, only human case-control studies were included. Several studies showed an increase of Lactobacillus, Bifidobacterium, Verrucomicrobiaceae and Akkermansia in PD. A decrease in PD was observed of Faecalibacterium spp., Coprococcus spp., Blautia spp., Prevotella spp. and Prevotellaceae. On low taxonomic resolution, like phylum level, the changes are not disease specific and inconsistent. However, on higher taxonomic resolution like genus or species level, a minor overlap was observed between PD and MSA, both alpha synucleinopathies. We show that a methodical standardization of sample collection and analysis is necessary for ensuring the reproducibility and comparability of data. We also provide the evidence, that assessing the microbiota composition at high taxonomic resolution, reveals changes in relative abundance, that may be specific or characteristic for one disease, or a disease-group and might evolve discriminative power. The interactions between bacterial species and strains and moreover the co-abundances must be more deeply investigated before assumptions of the effects of specific bacteria on the host can be made with certainty.

Background: Gluten neuropathy (GN) is defined as an otherwise idiopathic peripheral neuropathy in the presence of serological evidence of gluten sensitivity (positive antigliadin and/or transglutaminase or endomysium antibodies). We aimed to compare the quality of life (QoL) of GN patients with control subjects and to investigate the effect of a gluten free diet (GFD) on the QoL. Methods: All consecutive patients with GN attending a specialist neuropathy clinic were invited to participate. Overall Neuropathy Limitations Scale (ONLS) was used to assess the severity of neuropathy. The SF-36 questionnaire was used to measure participants’ QoL. A strict GFD was defined as effectively been able to eliminate all circulating gluten sensitivity-related antibodies whilst on the diet. Results: Fifty-three patients with GN and 53 age and gender matched controls were recruited. Compared to controls, GN showed significantly worse scores in physical functioning, role limitations due to physical health, energy/fatigue and general health subdomains of SF-36. After having adjusted for age, gender and disease severity, being on a strict GFD correlated with better SF-36 scores on the pain domain of the SF-36 (beta 0.317, p=0.019) and the overall health change domain of the SF-36 (beta 0.306, p=0.017). Conclusion: In GN physical dysfunctioning is the major determinant of poor QoL compared to controls. Routine checking for elimination of gluten sensitivity-related antibodies that results from a strict GFD should be encouraged as such elimination ameliorates the overall pain and health scores, indicating better QoL.

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

Pattern recognition receptors such as nucleotide-binding oligomerization domain (NOD)-containing protein receptors (NLRs) and the pyrin and HIN domain (PYHIN) receptors initiate the inflammatory response following cell stress or pathogenic challenge. When activated some of these receptors oligomerize to form the structural backbone of a signalling platform known as the inflammasome. The inflammasome promotes the activation of caspase-1 and the maturation of the proinflammatory cytokines, interleukin (IL)-1β and IL-18. In the gut dysregulation of the inflammasome complex is thought to be a contributing factor in the development of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD). The importance of inflammasomes to intestinal health has been emphasized by various inflammasome deficient mice in dextran sulphate sodium (DSS) models of intestinal inflammation and by the identification of novel potential candidate genes in population based human studies. In this review we summarise the most recent finding with regard to formation, sensing and regulation of the inflammasome complex and highlight their importance in maintaining intestinal health.

Although the European reports highlight an increase in community-acquired Legionnaires’ disease cases, the risk of Legionella spp. in private houses is underestimated. In Pisa (Italy) we performed a three-year survey on Legionella presence in 121 buildings with an independent hot water production (IB); 64 buildings with a central hot water production (CB); and 35 buildings with a solar thermal system for hot water production (TB). From all the 220 buildings Legionella spp. was researched in two hot water samples collected either at the recirculation point or at on the first floor and on the last floor, while the potable water quality was analyzed in three cold water samples collected at the inlet from the aqueduct network, at the exit from the autoclave, and at the most remove remote? tap. Legionella pneumophila sg1, Legionella pneumophila sg2-16 and not-pneumophila Legionella species were detected in 26% of the hot water networks, mostly in CB and TB. In these buildings we detected correlations between the presence of Legionella and the total chlorine concentration decrease or/and the increase of the temperature. Cold water resulted free from microbiological hazards, with the exception of Serratia liquefaciens and Enterobacter cloacae isolated at the exit from two different autoclaves. We observed an increase in total microbial counts at 22 and 37°C between the samples collected at the most remote taps compared to the ones collected at the inlet from the aqueduct. The study highlights a condition of potential risk for susceptible categories of population and supports the need for measures of risk assessment and control.

The main objective of this work is the assessment of the annual number of hospital admissions for respiratory disease (HARD) due to the exposure to in-healable particulate matter (PM10), within the greater Athens area (GAA), Greece. Towards this aim, the time series of the particulate matter with aerodynamic diameter less than 10μm (PM10) recorded in six monitoring stations located in the GAA, for a 13-year period 2001-2013, is used. Initially, a descriptive statistical treatment of PM10 concentrations took place. Furthermore, the AirQ2.2.3 software developed by the WHO was used to evaluate adverse health effects by PM10 in the GAA during the examined period. The results show that, during the examined period PM10 concentrations present a significant decreasing trend. Also, the mean annual HARD cases per 100,000 inhabitants ranged between 20 (suburban location) and 40 (city centre location). Approximately 70% of the annual HARD cases are due to city centre residents. In all examined locations, a declining trend in the annual number of HARD cases is appeared. Moreover, a strong relation between the annual number of HARD cases and the annual number of days exceeding the European Union daily PM10 threshold value was found.

Leishmaniasis is the third most common vector-borne disease and a very important protozoan infection. Cutaneous leishmaniasis is one of the most common types of leishmaniasis infectious diseases with up to 2 million occurrences of new cases each year worldwide. A dynamic transmission multivariate time series model was applied to the data to account for overdispersion and evaluate the effects of three environmental layers as well as seasonality in the data. Furthermore, ecological niche modeling was used to investigate the geographical suitable conditions for cutaneous leishmaniasis using temperature, precipitation and altitude as environmental layers, together with the leishmaniasis presence data. A retrospective analysis of the cutaneous leishmaniasis spatial data in Afghanistan between 2003 and 2009 indicates a steady increase from 2003 to 2007, a small decrease in 2008, then another increase in 2009. An upward trend and regularly repeating patterns of highs and lows was observed related to the months of the year which suggests seasonality effect in the data. Two peaks were observed in the disease occurrence-- January to March and September to December -- which coincide with the cold period. Ecological niche modelling indicates that precipitation has the greatest contribution to the potential distribution of leishmaniasis.

Psychosis in Alzheimer's disease (AD) is a prevalent phenomenon, marked by delusions and hallucinations, along with other neuropsychiatric symptoms such as agitation, depression, anxiety, and apathy. These neuropsychiatric symptoms, also known as behavioral and psychological symptoms of dementia (BPSD), affect up to 97% of Alzheimer's patients. The presence of psychosis in AD significantly impacts patients' daily lives and places a considerable burden on caregivers. The development of AD-related psychosis (ADP) is influenced by a range of factors, including genetic predispositions and life-acquired factors. AD affects cognitive function and various brain regions, resulting in widespread brain atrophy. In addition to its neurological impact, AD can induce pathological physiological changes that serve as biomarkers for ADP. Research efforts have focused on developing pharmacological treatments for psychosis in AD, aiming to minimize side effects. Brexpiprazole has emerged as a promising medication for ADP, alongside other antipsychotics. Treatment approaches for ADP extend beyond pharmacology, incorporating methods such as sensory stimulation and digital therapeutics. This review will explore the characteristics of psychosis in Alzheimer's disease, the pathological underpinnings of ADP, and the current therapeutic landscape, highlighting emerging opportunities for managing this challenging condition.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

Background. Chronic kidney disease (CKD) is a progressive condition with limited treatment options that often lead to significant morbidity. Recent studies suggest that oxyhydrogen nanobubbles (HHOnb) may offer therapeutic benefits due to their antioxidative and anti-inflammatory properties. This case series examines the effects of intravenous HHOnb therapy on three patients with varying stages of CKD.Methods. Three patients with CKD underwent a series of ten HHOnb infusions over a period of two to three months. The patients, aged 43 to 70, presented with additional comorbidities including hypertension, diabetes mellitus, and polycystic kidney disease. Clinical parameters, including glomerular filtration rate (GFR), serum creatinine, blood pressure, and uric acid levels, were monitored alongside subjective health improvements.Results. Patient A. A 70-year-old woman with CKD grade 3a experienced a reduction in serum creatinine from 0.98 mg/dL to 0.82 mg/dL and an improvement in GFR from 59 mL/min/1.73 m² to 73.2 mL/min/1.73 m². She reported reduced leg swelling and increased vitality. Patient B. A 52-year-old man with CKD grade 4 and class III obesity showed a decrease in serum creatinine from 3.0 mg/dL to 2.86 mg/dL, an increase in GFR from 23 mL/min/1.73 m² to 24.4 mL/min/1.73 m², and improved sleep quality. Blood pressure reduced from 167/82 mmHg to 145/85 mmHg. Patient C. A 43-year-old man with CKD grade 4 and massive polycystic kidney disease reported reduced fatigue and normalized urination. His serum creatinine decreased from 3.26 mg/dL to 3.09 mg/dL, and his GFR improved from 22 mL/min/1.73 m² to 23.6 mL/min/1.73 m².Conclusion. Intravenous HHOnb therapy demonstrated potential benefits in improving renal function and overall health in CKD patients. These findings suggest that HHOnb could be a promising complementary treatment for CKD, though larger, controlled studies are needed to confirm its efficacy and safety.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today we are talking about a new paradigm - cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies.

The concept of Palliative Care (PC) is more and more known in medicine and the need for this type of approach is growing in a world with great longevity and exponentially increasing chronic diseases. More and more cases from internal medicine, gastroenterology or cardiology wards could benefit from a better care if their medical team would align with the PC concept and principles. In this sense we try to present the specifical needs for Romanian patients in accordance with the current standards of care and how they must be adapted to the reality of the medical system in which they are cared for. We consider also that for medical staff from chronic disease wards it may be necessary to recapitulate the most important principles that govern medical practice of palliation, emphasizing some important aspects of applicability in daily clinical activity.

This review highlights the therapeutic potential of epigallocatechin gallate (EGCG) and forskolin in managing retinal diseases, with a focus on glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. EGCG, a potent polyphenol from green tea, exhibits significant antioxidant, anti-inflammatory, and neuroprotective effects, making it a promising candidate for reducing oxidative stress and inflammation in ocular tissues. Forskolin, a diterpene from Coleus forskohlii, increases cyclic AMP (cAMP) levels, which helps lower intraocular pressure (IOP) and provides neuroprotection. Both compounds target critical pathways involved in retinal disease progression, including oxidative stress, mitochondrial dysfunction, and inflammation, offering complementary therapeutic benefits. The review consolidates preclinical and clinical studies, highlighting the potential of EGCG and forskolin as adjunctive or alternative treatments for retinal diseases. Future research should explore the synergistic effects of these compounds, particularly in combination therapies aimed at addressing multiple pathogenic mechanisms in retinal health.

Background/Objectives: To understand the lived experiences of the informal caregivers of people with chronic noncommunicable diseases and their interpretations of the significance of that care. The perspectives of men and women interacting with people in a situation of chronicity are examined. Methods: This qualitative phenomenological-hermeneutic study was based on Van Manen’s comprehensive and interpretative vision. Criterion-oriented non-probability random sampling was used. In-depth interviews were used to collect the information. Twenty caregivers participated in the study. Results: The following five themes emerged: transformation of the caregiver’s world; uncertainty of care; tireless guardianship and unwavering devotion; isolation and emotional exhaustion; and imbalance between caring for others and the self. Conclusions: The experience of informal caregivers reveals that both men and women face significant challenges, albeit from gender-differentiated perspectives and experiences. Men and women elaborate different meanings of caregiving, reflecting their gender roles and expectations. Therefore, an inclusive and equitable approach that recognizes and addresses these gender differences is essential in order to improve the support and quality of life for all informal caregivers, respecting and valuing their unique voices and experiences. An inclusive and equitable approach that recognizes gender intersections is required to improve support and the quality of life for caregivers.