Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that the violation of MN may be associated with various pathologies, including Parkinson’s disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LLRK2, α-synuclein, PINK1 and Parkin simultaneously proteins) under normal conditions and after hydrogen peroxide-induced stress. Fibroblasts with Pink1/Parkin mutation are the most different in morphology from fibroblasts obtained from conditionally healthy donors: MN is larger, contains longer mitochondria and accumulated individual mitochondria. In addition to MN, we evaluated other cellular parameters, such as: cytosolic and mitochondrial ROS production and mitochondrial membrane potential. It has been shown that mitochondria of fibroblasts with mutations in genes encoding PINK1, α-synuclein and Pink/Parkin tends to hyperpolarization and cytosolic ROS overproduction, while mitochondrial ROS production was higher only in fibroblasts with PINK1 and α-synuclein mutation.

Degenerative mitral valve disease (DMVD) consists of progressive degeneration of the mitral valve that can occur either in isolation or in association with the tricuspid valve, leading to incomplete coaptation of its leaflets and subsequent valve regurgitation. It's the most common cardiac condition in small animals, accounting for about 75% of cases of heart disease in dogs, mainly affecting elderly small-breed dogs. Breeds with a genetic predisposition such as Cavalier King Charles Spaniels and Bull Terriers tend to develop the disease early. It can be classified into 4 stages: A, B, C, and D, with B having subdivisions (B1 and B2). Animals in stages A, B1, and B2 are asymptomatic, showing clinical signs only from stage C onwards. The report details the case of a 13-year-old Fox Terrier diagnosed at stage B2 of the disease, progressing to stage C within two years. A cardiologist conducted annual monitoring.

Increasing the effectiveness of eradication therapy is an important task of gastroenterology. The aim was to evaluate the efficacy and safety of postbiotic (metabiotic) contained inactivated Limosilactobacillus reuteri DSM 17648 (Pylopass™; Helinorm™) as adjuvant treatment for Helicobacter pylori eradication in patients with functional dyspepsia (FD). This randomized, double-blind, placebo-controlled, multicenter, parallel study included H. pylori positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with the eradication therapy (esomeprazole 20 mg bid + amoxicillin 1000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after completion of eradication therapy. The eradication efficiency was 96.7% for the postbiotic group versus 86.0% for the placebo group (P=0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered. The postbiotic (metabiotic) contained inactivated L. reuteri DSM 17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.

Introduction: Depending on the kind of cancer and neurological disorders, there might be a direct or inverse link between neurodegeneration and cancer. The inverse interaction between cancer and Alzheimer's pathology has garnered substantial interest in medical research. While this inverse interaction between Alzheimer's pathology and cancer presents a fascinating scientific puzzle, there is still limited information and studies on the potential mechanisms involved in this inverse rela-tionship. Aim: This study aims to identify potential genes from Alzheimer's disease that may protect against cancer. Method: The Gene Expression Omnibus (GEO) database provided the Alzheimer's pathology dataset, and GEO 2R was utilized to examine genes that were differentially expressed. The expression of upregulated Alzheimer's pathology genes in breast, colorectal, and prostate cancer was compared using VENN 2.1, colorectal, and prostate cancer was compared using VENN 2.1, and colorectal and prostate cancers were compared using VENN 2.1. Results: Among the upregulated genes associated with Alzheimer's disease, 25 genes are shared among breast cancer, colorectal cancer, and prostate cancer, while 28 of these genes were exclusive to Alzheimer's dis-ease. Gene expression profiling interactive analysis among the shared genes revealed that AQP1, C4A, CSRP2, CRYAB, MACF1, HSPB2, and NEAT1 were downregulated in breast, colorectal, and prostate cancers. These genes have varying roles in cancer progression and suppression. Functional analysis of Alzheimer's disease-related upregulated genes revealed that C1orf56 and HIST1H2AC control cell proliferation, with HIST1H2AC playing a role in necroptosis. Additionally, C1orf56 worked as an oncogenic modifier to support DNMT3B's tumor suppressor properties. Conclusion: Given the role of HIST1H2AC and C1orf56 in the negative control of cell proliferation and their upregulation in Alzheimer's disease, there is a need to further investigate HIST1H2AC and C1orf56 as potential tumor suppressors responsible for Alzheimer's disease and cancer inverse association.

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

Fungal-bacterial co-colonization and co-infections are emerging among TB-suspected patients, yet the underlying mechanisms that enable and arise from their interactions are poorly understood. Understanding how environmental microbes such as fungi and bacteria co-evolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic co-infections. Our previous work has demonstrated that fungal-bacterial interactions can have dramatic impacts on fungal pathogenesis and drug resistance. Here, we, therefore, hypothesize that cross-kingdom synergistic interactions between environmental fungi and bacteria may influence both fungal and bacterial virulence, antimicrobial resistance patterns and aetiology. Through this, we aimed to establish the prevalence of fungal–bacterial microbial communities associated with chronic primary or opportunistic pulmonary infections. Concordantly, through surveilling 302 clinical samples from 151 patients, we established the prevalence of TB (0.7%) to be lower than that of fungi (1.3%) and non-TB bacterial (4.6%) mono-aetiologies Figure 2. However, our main observation was the unexpected taxonomic diversity with a striking twist of fungal-bacterial di-kingdom aetiological conformities. Interestingly, the majority of the patients presented with at least a di or mono-kingdom aetiological pairings. Importantly, fungi and non-TB bacteria formerly regarded as atypical opportunists are now frequently isolated as possible aetiology for chronic pulmonary infection. Hence, we revealed many di-kingdom aetiological pairings here but their significance remains a question of further examination. Among which Acremonium spp + K. pneumoniae (n=5), Acremonium spp +Streptococcus pneumoniae (n=4), Acremonium spp + C. albicans + K. pneumoniae (n=3) were among the most dominant aetiological pairings observed. Interestingly, Acremonium spp + K. pneumoniae pairings were also seen to be the most commonly associated with pulmonary TB both during and after treatment. Isolation from the same infection niche as seen here calls for further investigations into any interaction signatures that may exist between these organisms. Taken together, our data suggest that fungal-bacterial co-existence may influence their virulence attributes and antimicrobial resistance patterns, with relevance to patient outcomes. Therefore, our data reveals an array of fungal-bacterial pairings that may influence the prognosis of chronic pulmonary disease. Importantly, suggesting that the diversity of pulmonary infective fungi and bacteria, and their complex population structures may pose challenges to the analysis and interpretation of conventional data. Thus, there is a need to redirect our diagnostic approaches to encompass polymicrobial aetiology in order to enhance our suspicion index for better management of opportunistic fungal-bacterial co-infections.

In advanced Parkinson’s disease (PD), and especially in PD related dementia (PDD), psychotic symptoms are common. One of the manifestations of psychosis in PD is delusional misidentification syndrome, a phenomenon in which the patient believes the identity of a person, object or location has been duplicated or altered. Our patient, a 75-year-old female, was diagnosed with idiopathic Parkinson’s disease at the age of 68. Recently, her cognition deteriorated and she developed the believe that she lived in a replica of her real home. The delusion resolved completely with rivastigmine patches. Also visual hallucinations improved on treatment. This suggests that the dysfunctional connections were likely to be cholinergic.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin

Given the remarkable progress in global health and overall quality of life, the significant rise in life expectancy has become intertwined with the surging occurrence of neurodegenerative disorders (ND). This emerging trend is poised to pose a substantial challenge to the fields of medicine and public health in the years ahead. In this context, Alzheimer's disease (AD) is regarded as a ND that causes recent memory loss, motor impairment and cognitive deficits. AD is the most common cause of dementia in the elderly and its development is linked to multifactorial interac-tions between the environment, genetics, aging and lifestyle. The pathological hallmarks in AD are the accumulation of beta amyloid (A) peptide, the hyperphosphorylation of tau protein, neuro-toxic events and impaired glucose metabolism. Due to pharmacological limitations and in view of the prevailing glycemic hypometabolism, the ketogenic diet (KD) emerges as a promising non-pharmacological possibility for managing AD, an approach that has already demonstrated efficacy in addressing other disorders, notably epilepsy. KD consists of a food regimen in which carbohydrate intake is discouraged at the expense of increased lipid consumption, inducing met-abolic ketosis, whereby the main source of energy becomes ketone bodies, instead of glucose. Thus, under these dietary conditions, neuronal death through lack of energy would be decreased, inasmuch as the metabolism of lipids is not impaired in AD. In this way, the clinical picture of patients with AD would potentially improve, through the slowing down of symptoms and delaying the progression of the disease. Hence, this review aims to explore the rationale behind utilizing the KD in AD treatment while emphasizing the metabolic interplay between KD and the improvement of AD indicators, drawing insights from both pre-clinical and clinical investigations.

Induced pluripotent stem cells (iPSC) are derived from reprogrammed adult somatic cells. These adult cells are manipulated in vitro to express genes and factors essential for acquiring and maintaining embryonic stem cell (ESC) properties. This technology is widely applied in many fields, and there has been much attention to developing iPSC-based disease models to validate drug discovery platforms and study pathophysiological molecular processes underlying disease onset. Especially in neurological diseases, there is a great need for iPSC-based technological research, as these cells can be obtained from each patient and carry the individual’s bulk of genetic mutations and properties. Moreover, iPSC can differentiate into multiple cell types. These are essential characteristics since the study of neurological diseases is affected by limited access to injured sites, in vitro models composed of various cell types, the complexity of reproducing the brain’s anatomy, ethical issues, and the fact that post-mortem cell culture is challenging. Neurodegenerative diseases enormously impact global health due to their high incidence, symptoms severity, and usually lack of effective therapies. Recently, analyses using disease-specific iPSC-based models confirmed their efficacy for testing multiple drugs. This review summarizes the advances in iPSC technology used in disease modeling and drug testing with a primary focus on neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases.

Laboratory analyses reveal significant differences between vaccinated and unvaccinated patients in parameters like C-reactive protein, ferritin, and white blood cell counts. Univariate and multivariate Cox proportional hazards regression analyses identify several factors influencing mortality, including comorbidities, pneumonia development, and various inflammatory markers.

The recent introduction of foot-and-mouth disease virus serotype O (O/EA-2 topotype) in Southern Africa region has changed virus dynamics and the FMD vaccine requirements. This study describes an assessment of the heterologous antibody responses induced by O Manisa vaccine (three PD50/dose) against a representative O/EA-2 virus collected from an FMD outbreak in Zambia. Commercial and subsistence cattle herds were monitored following vaccination, where the benefits of employing a double vaccination schedule were compared to single-dose vaccination. Testing using virus neutralisation showed cattle that received two vaccine doses had a mean reciprocal log virus neutralisation titre of 2.02 (standard error [SE] = 0.16, n = 9) for commercial herds and 1.65 (SE = 0.17, n = 5) for subsistence herds , 56 days after first vaccination (dpv). Significantly lower mean titres were observed for single-dosed commercial herds (0.90, SE = 0.08, n = 9) and subsistence herds (1.15, SE = 0.18, n = 3), 56 dpv. Comparison of these results and those generated by solid-phase competitive ELISA by cohen’s kappa coefficient observed a statistically significant (ρ = 0.598 for 1:10 dilution, and ρ = 0.562 for 1:30 dilution of SPCE % inhibition results, p < 0.001 for both dilutions) positive correlation.

Presenting a case report about an occurrence of duodeno-duodenal intussusception in a 17-year-old female patient. Intussusception is typically observed in children. The patient has a history of recurrent pain and vomiting for four days. During the examination tenderness in the epigastric area worsened when the legs were elevated. An initial X-ray of the abdomen was done and the findings were normal. Subsequent ultrasound and abdominal CECT scans of the abdomen revealed intussusception involving the 2^nd, 3^rd, and 4^th part of the duodenum ampulla of Vater and pancreas without any identifiable cause for this condition. There was no abnormal thickening of the wall. This case shows how using radiological imaging and surgical management helps to prevent severe complications in cases like duodeno-duodenal intussusception in adults.

This study assesses the feasibility of hepatitis B and C elimination, using an analysis of trends of epidemiology data (1990-2019) from the global burden of disease. Joinpoint regression analysis was used to identify significant changing points in trends of Age-standardizes Prevalence Rate (ASPR) and Age-standardizes Mortality Rate (ASMR) and to estimate the annual percentage changes (APC) and the average annual percentage changes (AAPC) for the period. Sociodemographic Index (SDI) was used to analyze trends between countries. The total percentage change of the ASPR (2019/1990) was -31.4% and -12.8% for HBV and HCV worldwide respectively, the rate ratio (HBV/HCV) was 2.5. Mortality has decreased for HBV but not for HCV. The total percentage change for the ASMR (2019/1990) was -26.7% and 10.0%, for HBV and HCV respectively. While ASMR of HBV decreased, HCV increased during this period. The percentage change in ASMR of HBV was highest in countries with high-middle SDI and lowest in countries with high SDI. For HCV, the percentage change in ASMR was highest in countries with High SDI (increase) and only in countries with low SDI decreased. The global HBV and HCV rates have fallen with different AAPC associated with the SDI. Despite the advances, there is still a long way forward to achieve the 2030 elimination goals. An important challenge is related to finding a way to speed up the yearly rate at which the decline is happening.

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

Nurses focus more on curative aspects rather than health promotion and disease prevention, thus weakening primary health care and lessening engagement with the community. Providing a learning environment that can support the professional growth of nurses through engagement with local communities and educational institutions would strengthen primary health care in the community; however, this poses challenges due to the traditional mindset of nurses towards primary health care. This integrative review aimed to explore key features of the potential of the nursing center model as a contracting-out approach to strengthen primary health care services. This integrative review provides lessons for implementing the Nursing Centre model for any country, mainly where nurses are not fully utilized for health promotion and disease prevention.

The pathogenesis of Cerebral Small Vessel Disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from 3 groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the solely pathway altered in CTRLs related treatment. Indeed, 36 different biological processes turned out to be deregulated after PTs treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients’ plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate (GFR) decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRAs), and endothelin receptor antagonists (REAs), have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease (T2DKD), providing a new perspective on the clinical diagnosis and treatment of DKD.

The current recommendation to avoid non-steroidal anti-inflammatory drugs (NSAIDs) in management of dengue virus disease is, as it was adopted earlier in COVID-19, scientifically considered of very low to low certainty. In this perspective I argue, for the first time globally, basing on real-life practice that NSAIDs might be lifesaving in early management of dengue virus disease as I originally argued and proved rightful in COVID-19. Moreover, I also argue that the Egyptian immune-modulatory Kelleni’s protocol, including nitazoxanide as an integral component, can be safely and effectively used to early manage COVID-19, human metapneumovirus, dengue virus disease, Zika virus separate or co-infections similar to what has already been experienced and published with separate or conjoined infections with SARS CoV-2, influenza, RSV and Norwalk viruses without the need of prior serological or molecular investigations to determine the causative agent.

Purpose: Hormone Replacement Therapy (HRT), an FDA-approved treatment for menopausal conditions was found to be associated with increased risk of endometrial cancer and reduced oestrogen. Studies showing benefits of HRT in preventing chronic diseases lead to development of clinical guidelines by American College of Physicians. This study aims to assess effectiveness of HRT treatments across cardiometabolic measures including Triglycerides (TG), Follicle-Stimulating Hormone, LDL cholesterol, HDL cholesterol, and Estradiol in menopausal women. It reports gaps in scientific knowledge and clinical practice to enhance current guidelines and policies.Methods: A systematic methodology designed and published in PROSPERO (CRD42022346057) to report network meta-epidemiology analysis was utilised. We used databases by PubMed, Web of Science, ScienceDirect, EMBASE and MEDLINE for studies published between 30th of April 1980-2022. Effects of HRT treatments were explored using a mixed treatment comparison (MTC) model. Fixed and random-effects models were used to address heterogeneity in published studies. Publication bias was assessed and corrected using funnel plots and Egger’s test.Results: Of 45 eligible studies, our findings indicate a significant statistical heterogeneity between HRTs and reduction of TG, SFH, LDL-C alongside increase of HDL-C and Estradiol among menopausal women. The analysis suggests a lack of direct evidence to support their efficacy in reducing TG, SFH and LDL-C levels or to substantiate HRT’s effectiveness in increasing HDL-C and Estradiol. The results showed no significant publication bias in the meta-analysis of included studies.Conclusion: Our findings demonstrate that use of HRT interventions among menopausal women may reduce TG, FSH and LDL-C levels and increase levels of HDL-C and estradiol via oral and oral + transdermal administration. Our study reaffirms efficacy of HRT in supporting favourable lipid profile in menopausal women whilst highlighting the need for robust and inclusive epidemiology studies and clinical trials to further develop clinical guidelines and policies.

Alzheimer's disease (AD) is characterized by memory impairment and existence of amyloid-β (Aβ) plaques and neuroinflammation. Due to the pivotal role of oxidative damage in AD, natural antioxidative agents, such as polyphenol-rich fungi, have garnered scientific scrutiny. Here, the aqueous extract of mixed medicinal mushroom mycelia (MMMM) - Phellinus linteus, Ganoderma lucidum, and Inonotus obliquus - cultivated on a barley medium, was assessed for its anti-AD effects. A neuron-like PC12 cells, which were subjected to Zn2+, an Aβ aggregator, was employed as an in vitro AD model. The cells pretreated with or without MMMM assayed for Aβ immunofluorescence, cell viability, reactive oxygen species (ROS), apoptosis, and antioxidant enzyme activity. 5XFAD mice were administered with 30 mg/kg/day MMMM for 8 weeks and underwent memory function tests and histologic analyses. In vitro results demonstrated that the cells pretreated with MMMM exhibited attenuation in Aβ immunofluorescence, ROS accumulation, and apoptosis, and increment in cell viability and antioxidant enzyme activity. In vivo results revealed that 5XFAD mice administered with MMMM showed attenuation in memory impairment and histologic deterioration such as Aβ plaques accumulation and neuroinflammation. MMMM might mitigate AD-associated memory impairment and cerebral pathologies, including Aβ plaque accumulation, and neuroinflammation, by impeding Aβ-induced neurotoxicity.

Aquaculture assumes a pivotal role in meeting the escalating global food demand, and shrimp farming, in particular, holds indispensable significance for the global economy and food security, providing a rich source of nutrients for human consumption. Nonetheless, the industry faces formidable challenges, primarily attributed to disease outbreaks, and the diminishing efficacy of conventional disease management approaches, such as antibiotic usage. Consequently, there is an urgent imperative to explore alternative strategies to ensure the sustainability of the industry. In this context, the burgeoning field of epigenetics emerges as a promising avenue for combating infectious diseases in shrimp aquaculture. Epigenetic modulations entail chemical alterations in DNA and proteins, orchestrating gene expression patterns without modifying the underlying DNA sequence by utilizing DNA methylation, histone modifications, and non-coding RNA molecules. Exploiting epigenetic mechanisms presents an opportunity to enhance immune gene expression and bolster disease resistance in shrimp, thus revolutionizing disease management strategies and optimizing shrimp health and productivity. Additionally, the concept of epigenetic inheritability in marine animals holds immense potential for the future of the shrimp farming industry. To this end, this comprehensive review thoroughly explores the dynamics of epigenetic modulations in shrimp aquaculture, with a particular emphasis on its pivotal role in disease management. It accentuates the significance of harnessing advantageous epigenetic changes to ensure the long-term viability of shrimp farming while deliberating on the potential consequences of these interventions. Overall, this appraisal highlights the promising trajectory of epigenetic applications, propelling the field toward strengthening sustainability in shrimp aquaculture.

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote proinflammatory pathways also contributing to procoagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing molecular and clinical effects of inflammatory processes on the micro- and microvas-culature with a focus on peripheral artery disease.

Introduction. Streptococcus pneumoniae infections are a major cause of mortality and morbidity worldwide. In Jordan, pneumococcal conjugate vaccines (PCVs) are not included in the national vaccination program. Due to the current availability of several PCVs including PCV-10, PCV-13 and PCV-15, along with PCV-20, currently undergoing pediatric approvals globally, the decision to introduce PCVs and their selection should be based on valid local data on the common serotypes of Streptococcus pneumoniae. Methods: This cross-sectional study aimed to identify the frequency of serotypes of Streptococcus pneumoniae in children aged below 5 years hospitalized with invasive pneumococcal diseases (IPD) including pneumonia, septicemia and meningitis during the study’s duration in representative areas of Jordan. Serotyping for culture-positive cases was based on the capsular reaction test, known as the Quellung reaction. qPCR was conducted on blood samples of patients with lobar pneumonia identified via X-ray or on cerebrospinal fluid for those with a positive latex agglutination test for Streptococcus pneumoniae. Results. This study was based on the analysis of the serotypes of 1015 Streptococcus pneumoniae cases among children younger than the age of 5; 1006 cases with pneumonia, 6 cases with meningitis, and 3 cases with septicemia. Only 23 culture-positive cases were identified, in comparison to 992 lobar pneumonia cases which were PCR-positive but culture-negative, with a PCR positivity rate of 92%. Serotypes 6B, 6A, 14 and 19F were the most common serotypes identified in the study, with prevalence rates of 16.45%, 13.60%, 12.12% and 8.18%, respectively. PCV-10, PCV-13, PCV-15 and PCV-20 coverage rates were 45.32%, 61.87%, 64.14% and 68.47%, respectively. Discussion: To the best of our knowledge, this is largest prospective study from the Middle East and one of the largest studies worldwide showing the serotypes of Streptococcus pneumoniae. It reveals the urgency for the introduction of PCV vaccination in Jordan, utilizing recently developed vaccines with broader serotype coverage.

Structural magnetic resonance imaging (sMRI) is widely used in the clinical diagnosis of diseases due to its advantages: high definition and noninvasive. Therefore, computer-aided diagnosis based on sMRI images is broadly applied in classifying Alzheimer’s disease (AD). Due to the excellent performance of Transformer in computer vision, Vision Transformer (ViT) has been employed for AD classification in recent years. ViT relies on access to large datasets, while the sample size of brain imaging datasets is relatively insufficient. Moreover, the pre-processing procedures of brain sMRI images are complex and labor-intensive. To overcome the limitations mentioned above, we propose Resizer Swin Transformer (RST), a deep learning model that can extract information from brain sMRI images that are only briefly processed to achieve multi-scale and cross-channel features. In addition, we pre-trained our RST on a natural image dataset and obtained better performance. The experimental results of ADNI and AIBL datasets prove that RST can achieve better classification performance in AD prediction compared with CNN-based and Transformer models.

In this world that we share with them, they became unintended sentinels for the consequences of pollutant exposure, developing similar conditions to humans, and even earlier. This review focuses on the human-pet interaction and on the effects of the environment pets share with us. Alongside other species, canine and feline companions are veritable models in human medical research. The latency period for showing chronic exposure effects to pollutants is just a few years in them, compared to considerably more, decades in humans. Comparing the serum values of man's best friends to ours can indicate the degree of poisonous lead-load we are exposed to, for example, and of other substances as well. We can find 2.4 times higher perfluorochemicals from stain- and grease-proof coatings in canine companions, 23 times higher values for PBDEs in cats, and five times more mercury compared to the average levels obtained in humans. All these represent early warning signals. Taking into account all these, and the animal welfare orientation of today’s society, finding non-invasive methods to detect the degree of environmental pollution in our animals becomes paramount, alongside with the need to raise awareness on the risks carried by certain chemicals we knowingly use.

Background: Bleeding disorders can be divided into three categories: congenital coagulation disorders (CCDs), antiplatelet induced bleeding disorders (APBDs) and anticoagulant induced bleeding disorders (ACBDs). Implant placement can be challenging in this kind of patients. The aim of this study is to provide evidence on implant surgery in patient with bleeding disorders and to generate some practical recommendations for clinicians. Material & Methods: Pubmed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were screened. The latest search was performed in July 2022. Case Reports, Case Series, Cohort Studies, Cross-Sectional Studies, Case Control Studies, Reviews, Consensus Reports, Surveys and Animal Studies were included in the analysis. Results: Seventeen articles on CCDs were found, fourteen on APBDs, twenty-six on ACBDs. Most of these articles were case report or case series. Patients with CCDs can be treated after the infusion of the missing coagulation factor. Patients with APBDs can be treated without withdrawing the therapy. Patients with ACBDs should be treated depending on the anti-coagulative medication. Conclusion: Despite the low level of evidence, dental implants can be safely placed in patients with bleeding disorders. However, careful preoperative evaluation and the adoption of local and post-operative bleeding control measures are mandatory.

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

Background: Cell-free plasma DNA (cfDNA) is composed of circulating extracellular DNA originating from apoptosis or cell necrosis. It is generally present in healthy individuals, but its levels increase in different clinical conditions, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. Caspase-3 plays a central role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis of chronic kidney disease (CKD). Methods: We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating the modification of their concentrations according to CKD stage. We also analyzed the correlation between cfDNA and caspase-3 levels in CKD patients and the correlation between cfDNA and caspase-3 levels and creatinine and urea. Results: CfDNA and caspase-3 levels were higher in CKD patients compared to healthy subjects, in particular in patients with advanced renal disease. A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea was also observed. Conclusion: Patients with chronic kidney disease present higher levels of cfDNA and caspase-3 levels compared with healthy subjects. The worsening of renal damage and the increase in uremic toxin concentration are associated to higher levels of cfDNA and caspase-3 levels, thus reflecting a central role of apoptosis in the pathogenesis of CKD.

We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP) and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted to statistical analysis (α=0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD and CAL, which were statistically significant at 90 and 180 days (p<0.0001). Importantly, NSPT significantly reduced the blood level of CRP (p<0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune-system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years of age is steadily increasing and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g. infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.

3D printing is playing an important role in cardiovascular disease by use of personalised models with replication of normal anatomy and pathology with high accuracy and reliability. While 3D printed heart and vascular models are shown to improve medical education, preoperative planning and simulation of cardiac procedures, and enhance communication with patients, 3D bioprinting however, represents a potential advancement of 3D printing technology by printing cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs. In this review, we provide an overview of the use of 3D bioprinting in cardiovascular disease with a focus on technologies and applications in cardiac tissues, vascular constructs and grafts, heart valves and myocardium. Limitations and future research directions are highlighted.

Proteinuria is known to be associated with all-cause and cardiovascular mortality, and nephrotic syndrome is defined by the level of proteinuria and hypoalbuminemia. With advances in medicine, new causative genes for genetic kidney diseases are being discovered increasingly frequently. We reviewed articles on proteinuria/nephrotic syndrome, focal segmental glomerulosclerosis, membranous nephropathy, diabetic kidney disease/nephropathy, hypertension/nephrosclerosis, Alport syndrome, and rare diseases, which have been studied in mouse models. Significant progress has been made in understanding the genetics and pathophysiology of kidney diseases thanks to advances in science, but research in this area is ongoing. In the future, genetic analyses of patients with proteinuric kidney disease/nephrotic syndrome may ultimately lead to personalized treatment options.

Background and Objectives: HIV infection is a global public health problem that can lead to the progression of AIDS. Nutritional status and biochemical markers can significantly contribute to the progression of AIDS in HIV/AIDS patients. The main objective of this study is to examine the association between the nutritional and biochemical markers as well as BMI in HIV/AIDS patients in the kingdom of Bahrain. Methods: A retrospective cohort study, including 300 patients (248 males and 52 females) with HIV/AIDS in Bahrain. Various biochemical markers were collected from patients’ medical records including CD4^+ T cells counts, albumin, Hb, HCT, MCV, WBC, and creatinine. A semi-structured questionnaire using of a standardized food frequency questionnaire (FFQ) was used from which total energy and total macronutrients were calculate. Results: the mean BMI of participants was 27.20 kg/m2 with none of the participants had a BMI lower than 18.5 kg/m2 (underweight). The majority of patients’ dietary intake of macronutrients and total calories intake were either within or above the recommended RDA levels. The results also showed that all mean values of the nutritional and biochemical markers (CD4^+ T cells counts, albumin, Hb, HCT, MCV, WBC, and creatinine) are within the referenced normal ranges. A significant positive correlation of CD4^+ T cells counts, Hb, HCT and albumin at <0.05 level was found. There was no significant correlation between CD4^+ T cells counts and MCV, WBC and creatinine. A positive significant correlation was found between BMI, CD4^+ T cells counts, and WBC at <0.01 level. Conclusion: BMI values significantly correlated to biochemical markers of AIDS progression. Dietary pattern of participants was undiversified among participants, with high prevalence of obesity and overweight. Malnutrition among this study population was not present.

Alzheimer’s disease has become a major concern in the healthcare domain as it is growing rapidly. Many researches have been conducted to detect it from MRI images through various deep-learning approaches. However, the problem of the availability of medical data and the privacy of the patients still exists. To mitigate this issue in Alzheimer’s disease detection, we have implemented the federated approach which is found to be more efficient, robust, and consistent compared to the conventional approach. For this, we needed deep excavation on various orientations of MRI images and transfer learning architectures. Then, we utilized the publicly available two datasets (OASIS, and ADNI), and designed various cases to evaluate the performance of the federated approach. In almost all of them, the federated approach achieved better accuracy and sensitivity. In distinguishing between two classes equally, the capability of the models was better in the found model when trained with federated approach compared to the conventional approach. In this approach. MobileNet, which is a low-cost transfer learning architecture, achieved the highest 95.24%, 81.94%, and 83.97% accuracy in OASIS, ADNI, and merged (ADNI+OASIS) test set, which was way higher than the achieved performance in Conventional approach. Moreover, in this approach, only the weights of the model were shared which keeps the original MRI images in their respective hospital or institutions, mitigating the privacy concern in the healthcare domain.

Tungiasis has been included in the WHO list of Neglected Tropical Diseases, but systematic data on the occurrence are scarce. We analyzed data on the occurrence of tungiasis in the 184 munici-palities of Ceará State in Northeast Brazil, based on an online open rapid assessment question-naire focused on health professionals and other key stakeholders. Questions included the occur-rence of tungiasis, severe cases, cases in animals and seasonal variations of the disease. There were in total 1,265 individual data entries available (1 to 104 per municipality) from all munici-palities of the state. A total of 181 (98.3%) of municipalities reported the occurrence of tungiasis in the past or currently, 120 (65.2%) reported current occurrence, 155 (84.2%) severe cases in the past or currently; and 47 (25.5%) reported severe cases currently. A total of 132 (71.7%) municipalities reported tungiasis in animals, most commonly in dogs (97), pigs (80), cats (50), horses (20), cattle (8) and goats (6). Most municipalities mentioned the seasonality of tungiasis (n=146; 79.3%). There was no report of any specific tungiasis control program. Our data show that tungiasis and severe tungiasis commonly occur in Ceará state and that tungiasis is a significant public health issue for both humans and animals. An integrated One Health approach is needed to reduce dis-ease burden, including human and animal health, and the environment.

Parkinson’s disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin or tween-80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four h and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin reduced significantly the MPP+-induced damage compared to MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson’s disease, and since there is not currently a proteomic map of the Nigro striatum of rats, and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation are decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and for the first time the molecular mechanisms involved in this protective effect.

Dr. Jurg Tschopp created the word "inflammasome" in 2002. Inflammasome activation and its function in disease processes have been the subject of significant investigation over the last 15 years. Four important inflammasomes have been identified: NLRP1, NLRP3, NLRC4, and AIM2. When these inflammasomes are activated, they process and secrete inflammatory cytokines such as IL-1b and IL-18, as well as cause pyroptosis, an inflammatory form of cell death. In this review, we will look at how these inflammasomes have been connected to Periodontitis pathogenesis.

Cognitive deficit is a frequent non-motor symptom in Parkinson 's disease (PD) with an unclear pathogenesis. Recent research indicates possible involvement of insulin resistance and glutamate excitotoxicity in PD development. We investigated cognitive performance and the brain glutamate and insulin signaling in a rat model of PD induced by bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). Cognitive functions were assessed with Passive avoidance (PA) and Morris Water Maze (MWM) tests. The expression of tyrosine hydroxylase (TH) and proteins involved in insulin (IR, pI3K, ERK) and glutamate receptor (AMPAR, NMDAR) signaling was assessed in the hippocampus (HPC), hypothalamus (HPT) and striatum (S) by immunofluorescence, Western blot and ELISA. Three months after 6-OHDA treatment, cognitive deficit was accompanied by decreased AMPAR activity and TH levels (HPC, S), while levels of the proteins involved in insulin signaling remained largely unchanged. Spearman’s rank correlation revealed a strong positive correlation for pAMPAR-PA (S), pNMDAR-pI3K (HPC) and pNMDAR-IR (all regions). Additionally, a positive correlation was found for TH-ERK and TH-pI3K, and a negative one for TH-MWM/errors and pI3K-MWM/time (S). These results suggest a possible association between brain glutamate (but not insulin) signaling dysfunction and cognitive deficit in a rat PD model, detected three months after 6-OHDA treatment.

Melioidosis, or Whitmore's disease, is an infectious disease initiated by a bacteria known as Burkholderia pseudomallei. This bacteria is commonly found in contaminated soil and water. In Malaysia, the mortality from melioidosis infection was reported to be higher than in other infectious diseases. The research on melioidosis is still limited in Malaysia but slightly increasing. The article's objective was to seek all the melioidosis research related to mortality in Malaysia. The information from the selected papers was then abstracted into two sections; Section 1: Review of literature and Section 2: Findings on mortality from melioidosis in Malaysia. In Section 1, the information on transmission and clinical features of melioidosis, demographic, severity of melioidosis, a clinical signs of melioidosis, diagnosis of melioidosis, management of melioidosis, the economic burden of melioidosis, and incidence of mortality from melioidosis were discussed in this paper. Meanwhile, in Section 2, the findings on mortality of melioidosis in Malaysia were discussed according to eight published articles. It is important to manage patients with melioidosis with appropriate treatment and management to reduce severe complications, high fatality rate, and relapse. More published research on melioidosis will provide input to the clinicians on a more detailed understanding of how to improve the diagnosis of melioidosis and the prognosis factors of this disease.

Rabies is a life-threatening and vaccine-preventable infectious disease and is triggered by an RNA virus, part of the Rhabdoviridae family, Lyssavirus genus. It is transmitted from infected saliva due to biting, but also from contact with infected blood or organs from rabid animals to humans. Children are at high risk due to their inability to defend themselves from infected animals and most deaths occur with a particularly high incidence in this category (under the age of 15 years). Postexposure prophylaxis (PEP) is standard and life-saving if given early after exposure. We are reporting the case of a ten-year-old female child, who was bitten by an unvaccinated cat ten days before admission to the Paediatric Intensive Care Unit at National Institute for Infectious Diseases „Prof. Dr Matei Bals”, Bucharest. The child had category III cat bites and did not receive PEP. Suggestive clinical manifestations such as an altered general state, psychomotor agitation, auditory and visual hallucinations, and hypersomnia followed by aerophobia and hydrophobia were present. Despite the maximal treatment introduced from early admission (Human Rabies Immunoglobulin, anti-rabies vaccination, orotracheal intubation plus mechanical ventilation, vital functions’ support, parenteral feeding, symptomatic drugs) the evolution of the patient was unfavourable, namely death two months after admission. The diagnosis was established in both pre-mortem by identifying the rabies virus in the cerebrospinal fluid based on reverse transcription-polymerase chain reaction (RT-PCR) and post-mortem by a histopathological examination (which reveals the presence of Babes-Negri bodies in the hippocampus). The objective is to understand the mechanism of infection and mortality from rabies virus in children. Conclusion: The most effective prevention methods are early administration of specific prophylaxis (immunoglobulin and vaccination) and, most importantly, early elimination of animal rabies outbreaks, while rapid diagnosis is helpful in the management of human rabies in humans. The rate of human exposure may be significantly decreased by controlling rabies through pet immunization programs.

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

Dry eye disease (DED) is one of the most common eye diseases. There is at least one DED patient in almost every five people. AI-based research methods increasingly become the focus of DED diagnosis research. This study utilizes a systematic review method on DED AI-based diagnosis. 2112 unduplicated records are extracted from Google Scholar, Web of Science (WOS), PubMed, China National Knowledge Infrastructure (CNKI), and Scopus databases. The most contributed countries, institutions, authors, journals, references, and disciplines are recognized. Keyword distribution and hot topics are identified. Popular databases of ophthalmic images, videos, and electronic demographic medical records are discussed. The DED diagnosis, classification, and grading criteria are identified. The major diagnosing methods are clustered, compared, and investigated. Findings show that diagnosing method research could be classified into three categories based on the relationship between AI techniques, which are (1) ground truth and/or comparable standards for AI DED diagnosis (TBUT, S Ⅰ T, TMH, and OSDI), (2) potential methods for AI-based methods have a great advantage(DED detection based on meibometry Images, CASPs, IVCM Images, OCT Images, blink videos and ultrasonic imaging), (3) and the potential direction and supplemented methods for AI-based DED detection (DED detections based on tear osmolarity, proteomic analysis, TCM and demographic information). AI-based approaches based on digital ophthalmologic images play an important role in early screening. Challenges and future perspectives are discussed at the end of this article, academically and practically.

Organisms release their nucleic acid in the environment including the DNA and RNA which can be used to detect their presence. eDNA/eRNA techniques are being used in different sectors to identify organisms from soil, water, air, and ice since long. The advancement in technology led to easier detection of different organisms without impacting the environment and the organism itself. These methods are being employed in different areas including surveillance, history, and conservation. eDNA and eRNA methods are being extensively used in aquaculture and fisheries setting to understand the presence of different fish species and pathogens in water. However, there are some challenges associated with the reliability of the results because of the degradation of nucleic acid by several factors. In aquaculture there are several diseases and parasites detected with these methods. In this review we discuss different aquaculture diseases and parasites detected with eDNA/eRNA approach and the fate of these nucleic acids when subjected to different water quality and environmental parameters. This review intends to help the researcher about the potential of eDNA/eRNA based detection of pathogens in aquaculture; this will be useful to predict the potential outbreak before it occurs. Along with that this paper intends to make people understand several factors that degrade and can hamper the detection of these nucleic acids.

The main objective of this study is to demonstrate proof of principle that computational fluid dynamics (CFD) modeling is a tool for studying the contribution of covert and overt vascular architecture to the risk of cerebrovascular disease in in sickle cell disease (SCD) as well as uncover one or more mechanism of response to therapy such as chronic red blood cell (cRBC) transfusion. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial, using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific potions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral artery such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arm. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had SCI) that developed neurovascular outcomes. CFD approaches allows for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions.

The association of the APOE4 (vs APOE3) isoform with an increased risk of Alzheimer’s Disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elu-cidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking apolipoprotein isoform to disease aetiology. APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several alterations in pathways of lipid homeostasis in the brains of mice expressing the human APOE4 versus APOE3 isoform. Carriers of APOE4 had deficient cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing poly-unsaturated fatty acids and an overall eleva-tion in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related with increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of AP-OE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

Alzheimer´s Disease (AD) has currently no effective treatment; however, preventive measures can significantly delay the progress/onset of the disease. Thus, accurate and early prediction of risk is an important strategy to alleviate the AD burden. Neuroinflammation is a major factor prompting the onset of the disease. Inflammation exerts its toxic effect via multiple mechanisms. Amongst others, it is affecting gene expression via modulation of non-coding RNAs (ncRNAs), such as miRNAs. Recent evidence supports that inflammation can also affect long non-coding RNAs (lncRNAs) expression. While the association between miRNAs and inflammation in AD has been extensively studied, the role of lncRNAs in neurodegenerative diseases has been less explored. In this review, we focus on lncRNAs and inflammation in the context of AD. Furthermore, since plasma-isolated extracellular vesicles (EVs) are increasingly recognized as an effective monitoring strategy of brain pathologies, we have focused on the studies reporting dysregulated lncRNAs in EVs isolated from AD patients and controls. The revised literature shows a positive association between pro-inflammatory lncRNAs and AD. However, the reports evaluating lncRNAs alterations in EVs isolated from plasma of patients and controls, although still limited confirm the value of specific lncRNAs associated with AD as reliable biomarkers. This is an emerging field that will open new avenues to improve risk prediction, patients’ stratification and may lead to the discovery of potential novel therapeutic targets for AD

Patients under immunosuppressive therapy for kidney diseases or on maintenance hemodialysis are more susceptible to infection than the general population since loss of renal function per se was an immunocompromised condition. Of relevance, CT imaging plays a crucial role in the detection and management of pulmonary infectious diseases. We hence presented diverse CT findings of pulmonary infections in the above said patients collected during our arduous work against a wide range of pathogens including klebsiella pneumoniae, staphylococcus aureus, candida parapsilosis, aspergillus, cryptococcus, mucor, pneumocystis carinii, cytomegalovirus, mycobacterium and nocardia. Notably, the pulmonary pathological changes were either primary pneumonia or secondary to the catheter-associated bloodstream infection. For a descriptive purpose, pulmonary manifestations of Wegener’s granuloma, lung cancer and diffuse alveolar hemorrhage/infection in vasculitis were also examined. As such, we retrospectively elaborated most likely CT features of each individual pathogen and briefly covered the differential diagnosis as well. Arguably, combination of pattern recognition with knowledge of the clinical setting could make a presumptive diagnosis and early treatment even more convenient. From the experience of first-line nephrologists, our work could make a substantial contribution to the expeditious and efficacious management of pulmonary infections in the pertinent patient population.

The High-Resolution Computed Tomography (HRCT) detection and diagnosis of diffuse lung disease is primarily based on the recognition of a limited number of specific abnormal findings, pattern combinations or their distributions, as well as anamnesis and clinical information. Since texture recognition has a very high accuracy percentage if a complex network approach is used, this paper aims to implement such a technique customized for diffuse interstitial lung diseases (DILD). The proposed procedure translates HRCT lung imaging into complex networks by taking samples containing a secondary lobule, converting them into complex networks and analyzing them in 3 dimensions: emphysema, ground glass opacity and consolidation. This method was evaluated on a 60 patient lot and the results show a clear quantifiable difference between healthy and affected lungs. By deconstructing the image on three pathological axes, the method offers an objective way to quantify DILD details which, so far, have only been analyzed subjectively.

Situbondo is one of the best mango producer city with a distinctive mango taste compared to other regions in East Java. Mango production in Situbondo in 2015 reached 222,471 quintals. One of the damage to post-harvest mango products is due to anthracnose disease. The purpose of this study was to determine the effect of hot water treatment in inhibiting anthracnose disease and maintaining the quality of mangoes. The study was conducted at the Plant Clinical Laboratory in January 2019 at the Faculty of Agriculture, University of Jember. The study design used was a completely randomized design with two factors, namely washing temperature (59 ± 1 ° C, 53 ± 1 °C, normal water temperature) and storage temperature (15.1 ± 1 ° C and 18.1 ± 1 ° C). Washing with a temperature of 53 ± 1 ° C can be used to clean fruit. Treatment with low temperature (15.1 ± 1 ° C and 18.1 ± 1 ° C) resulted in inhibiting changes in weight loss, fruit hardness, acid content (total titrated acid), and total dissolved solids while another treatment, 53 ± 1 ° C washing temperature with storage temperature 15.1 ± 1 ° C gives a good appearance that suppress the development of anthracnose, and inhibit fruit discoloration.

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that increasingly become a global threat for the elder people's health and life. Although there are some drugs in clinic for treating PD, these treatments only can alleviate the symptoms of PD patients but fail in curative therapies. Therefore, seeking other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable. In the last two decades, histone deacetylases as an important group of epigenetic targets in drug discovery have attracted much attention. This review is focused on the current knowledge about histone deacetylases involved in PD pathophysiology and their inhibitors used in PD study. Further perspectives related to small molecules that can inhibit or degrade histone deacetylases to treat PD are also discussed.

Transposable elements (TEs) ubiquitously exist in the human genome, and some have the ability to copy and paste themselves to other locations, resulting in new insertions. Organisms have evolved with mechanisms and machineries to repress such activity. TEs are also co-opted for beneficial functions by the host and are thus maintained in the genome. During the lifetime of humans, aberrant TE activity might cause or contribute towards diseases including neurological conditions such as Alzheimers Disease (AD) and cancer. While inflammatory pathways linked to TEs may be a part of the disease pathology, on the other hand altered TE activity involving inflammatory pathways could be recognised by disease suppression mechanisms. For this reason, TEs could be targeted for therapeutic applications aiming to prevent TE activity or reduce initial inflammatory pathways as well as to activate disease suppression mechanisms. In this review, we describe the contributory and potential preventative roles of TEs in neurological conditions and cancer from a molecular and evolutionary perspective. Evolutionary paradigms both at the unicellular and organismal level aid understanding the role of TEs in disease. These observations could pave the way for the development of novel therapeutic approaches targeting TEs.

Infectious diseases, as COVID-19 is proving, pose a global health threat in an interconnected world. In the last 20 years, resistant infectious diseases such as SARS, MERS, H1N1, Ebola, Zika and now COVID-19 have been impacting global health defences, and aggressively flourishing within the rise of global travel, urbanization, climate change and ecological degradation. In parallel, this extraordinary episode in global human health highlights the potential for artificial intelligence (AI)-enabled disease surveillance to collect and analyse vast amounts of unstructured and real-time data to inform epidemiological and public health emergency responses. The uses of AI in these dynamic environments are increasingly complex, challenging the potential for human autonomous decisions. In this context, our study of qualitative perspectives will consider a responsible AI framework to explore its potential application to disease surveillance in a global health context. Thus far, there is a gap in the literature in considering these multiple and interconnected levels of disease surveillance and emergency health management through the lens of a responsible AI framework.

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

Proteolytic processing of amyloid precursor protein (APP) plays a critical role in pathogenesis of Azheimer’s disease (AD). Sequential cleavage of APP by β and γ secretases leads to generation of Aβ40 (non-amyloidogenic) and Aβ42 (amyloidogenic) peptides. Presenilin-1 (PS1) or presenilin-2 (PS2) pay a role of catalytic subunit of γ-secretase. Multiple familial AD (FAD) mutations in APP, PS1, or PS2 result in increased Aβ42:Aβ40 ratio and accumulation of toxic Aβ42 oligomers and plaques in patient brains. In this study we performed molecular modeling of APP complex with γ-secretase and analyzed potential effects of FAD mutations in APP and PS1. We noticed that all FAD mutations in APP transmembrane domain are predicted to cause an increase in the local disorder of its secondary structure. Based on structural analysis of known γ-secretase structures we proposed that APP can form a complex with γ-secretase in 2 potential conformations – M1 and M2. In conformation M1 transmembrane domain of APP forms a contact with perimembrane domain that follows the transmembrane domain 6 (TM6) in PS1 structure. In conformation M2 transmembrane domain of APP forms a contact with transmembrane domain 7 (TM7) in PS1 structure. By analyzing effects of PS1-FAD mutations on local protein disorder index, we discovered that these mutations increase conformational flexibility of M2 and reduce conformational flexibility of M1. Based on these results we proposed that M2 conformation, but not M1 conformation, of γ secretase complex with APP leads to amyloidogenic (Aβ42-generating) processing of APP. Our model predicts that APP processing in M1 conformation is favored by a curved membranes, such as membranes of early endosomes. In contrast, APP processing in M2 conformation is likely to be favored by a relatively flat memranes such as membranes of late endosomes and plasma membrane. These predictions are consistent with published biochemical analysis of APP processing at different subcellular locations. Our results suggest that specific inhibitors of Aβ42 production could be potentially developed by selectively targeting M2 conformation of γ secretase complex with APP.

BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against high-fructose diet-induced metabolic derangements (MD) in a model mimicking children fed obesogenic diets. METHODS: Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocat-ed to and administered, for 8 weeks, five treatment regimens: 1 - standard rat chow (SC) + water (PW), 2 - SC + 20% (w/v) fructose solution (FS), 3 - SC + FS + fenofibrate at 100 mg/kg bwt/day, 4 - SC + FS + low dose MEFT (LD; 50 mg/kg bwt/day) and 5 - SC + FS + high dose MEFT (HD; 500 mg/kg bwt/day). Body weight, glucose load tolerance, fasting blood glucose and triglyceride, plasma insulin concentration, sensitivity to insulin, liver mass and fat content, steatosis and inflammation were determined. RESULTS: Fructose had no effect on the rats’ growth, glucose and insulin concentration, glucose tolerance and insulin sensitivity (P>0.05) but increased triglycerides in females; in-duced hepatic microsteatosis and inflammation in both sexes but macrosteatosis in females (P<0.05). In females, MEFT prevented fructose-induced plasma triglyceride increase. Low dose MEFT increased liver lipid content in females (P<0.05). The MEFT protected the rats against hepatic steatosis and inflammation but fenofibrate protected against hepatic mi-crosteatosis. CONCLUSION: MEFT can be used as prophylaxis against dietary fructose-induced ele-ments of MD but caution must be taken as low dose MEFT increases hepatic lipid accretion in females predisposing to fatty liver disease.

RTP801/REDD1 is a stress-regulated protein whose levels are increased in several neurodegenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases (HD). RTP801 downregulation ameliorates behavioral abnormalities in several mouse models of these disorders. In HD, RTP801 mediates mutant huntingtin (mhtt) toxicity in in vitro models and its levels are increased in human iPSCs, human postmortem putamen samples and in striatal synaptosomes from mouse models of the disease. Here, we investigated the role of RTP801 in the hippocampal pathophysiology of HD. We found that RTP801 levels are increased in the hippocampus of HD patients in correlation with gliosis markers. Although RTP801 expression is not altered in the hippocampus of the R6/1 mouse model of HD, neuronal RTP801 silencing in the dorsal hippocampus with shRNA-containing AAV particles ameliorates cognitive alterations. This recovery is associated with a partial rescue of synaptic markers and with a reduction of inflammatory events, especially microgliosis. Altogether, our results indicate that RTP801 could be a marker of hippocampal neuroinflammation in HD patients and a promising therapeutic target of the disease.

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

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of neurotoxin-induced PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD, and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

Meniere Disease (MD) is a multifactorial disorder of the inner ear characterized by vertigo attacks associated with sensorineural hearing loss and tinnitus with a significant heritability. Although MD has been associated with several genes, no epigenetic studies have been performed in MD. Here we performed whole genome bisulfite sequencing in 14 MD patients and 6 healthy controls, with the aim of identifying a MD methylation signature and potential disease mechanisms. We observed a high number of differentially methylated CpGs (DMC) when comparing MD patients to controls (N= 9,545), several of them in hearing loss genes such as PCDH15, ADGRV1 and CDH23. Bioinformatic analyses of DMCs and cis-regulatory regions predicted phenotypes related to abnormal excitatory postsynaptic currents, abnormal NMDA-mediated receptor currents and abnormal glutamate-mediated receptor currents when comparing MD to controls. Moreover, we identified various DMCs in genes previously associated with cochleovestibular phenotypes in mice. We have also found 12 undermethylated regions (UMR) that were exclusive to MD, including 2 UMR in an inter CpG island in the PHB gene. We suggest that the DNA methylation signature allows to distinguish between MD patients and controls. The enrichment analysis confirms previous findings of a chronic inflammatory process underlying MD.

Appropriate supplementation of vitamin D can affect infections, allergy, and mental and behavioral development. This study aimed to assess the effectiveness of monitored vitamin D supplementation in a population of preterm infants. 109 preterm infants (24 0/7–32 6/7 weeks of gestation) were randomized to receive 500 IU vitamin D standard therapy (n=55; approximately 800-1000 IU from combined sources) or monitored therapy (n=54; with an option of dose modification). 25(OH)D concentrations were measured at birth, 4 weeks of age, and 35, 40, and 52±2 weeks of post-conceptional age (PCA). Vitamin D supplementation was discontinued in 23% of infants subjected to standard treatment due to increased potentially toxic 25(OH)D concentrations (&gt;90 ng/mL) at 40 weeks of PCA. A significantly higher infants’ percentage in the monitored group had safe vitamin D levels (20–80 ng/mL) at 52 weeks of PCA (p=0.017). We observed increased vitamin D levels and abnormal ultrasound findings in five infants. Biochemical markers of vitamin D toxicity were observed in two patients at 52 weeks of PCA in the control group. Inadequate and excessive amounts of vitamin D can lead to serious health problems. Supplementation with 800–1000 IU of vitamin D prevents deficiency and should be monitored to avoid overdose.

Under the pressure of fluoroquinolones, Pasteurella multocida (PM) can easily develop resistance to fluoroquinolones mediated by QRDR target mutation. It is imperative to find new drug resistance inhibitor targets to combat the rapid development of drug resistance. In order to overcome these problems, we sequenced the transcriptome of PM with different levels of resistance to ENR(0.03 μg/mL; 8 μg/mL; 32μg/Ml, Enrofloxacin). The results showed that with the increase of resistance to fluoroquinolones, the expression of satP gene was significantly up-regulated. The satP gene deletion strain and replenishment strain were constructed, and their drug resistance and tolerance were determined. The results showed that the deletion of satP gene did not affect the resistance of PM to fluoroquinolones, rather affected the time when PM developed resistance to fluoroquinolones. After 10 generations of drug induction, the MIC (minimum inhibitory concentration) of fluoroquinolones for wild strain was 64 μg/mL, while the MIC for satP gene deletion strain was only 8 μg/mL. The MDK99 test (time to kill 99% bacteria),agar diffusion test and mutation frequency test showed that the tolerance of satP gene deletion strain was significantly lower than that of wild strain. At the same time, the virulence of gene deletion strain and wild strain was tested, and about 400 times decreased virulence was observed for satP gene deletion strain. The mouse infection model confirmed that mice infected with satP gene deletion strains were more likely to be treated with ENR than mice infected with wild-type bovine PM strains. The results show that satP has potential to be a target of fluoroquinolone resistance inhibitors.

The long-term impact of treatment of dogs with steroid-responsive enteropathy (SRE) on the fe-cal microbiome and metabolome has not been investigated. Therefore, this study aimed to evaluate the fecal microbiome and metabolome of dogs with SRE before, during, and following treatment with standard immunosuppressive therapy and an elimination diet. We retrospec-tively selected samples from 9 dogs with SRE enrolled in a previous clinical trial, which received treatment for 8 weeks, and had achieved remission as indicated by the post-treatment clinical scores. Long-term (1 year) samples were obtained from a subset (5/9) of dogs. Samples from 13 healthy dogs were included as controls (HC). We evaluated the microbiome using 16S rRNA sequencing and qPCR. To evaluate the recovery of gut function, we measured fecal metabolites using an untargeted approach. While improvement was observed for some bacterial taxa after 8 weeks of treatment, several bacterial taxa remained significantly different from HC. Seven-ty-five metabolites were altered in dogs with SRE, including increased fecal amino acids and vitamins, suggesting malabsorption as a component of SRE. One year after treatment, however, all bacterial species evaluated by qPCR and 16S rRNA gene sequencing, and all but thirteen me-tabolites were no longer different from healthy controls.

Inherited retinal diseases (IRD) comprise a heterogeneous set of clinical and genetic disorders that lead to blindness. Given the emerging opportunities in precision medicine and gene thera-py, it has become increasingly important to determine whether DNA variants with uncertain significance (VUS) are responsible for the patients’ IRD. This research was performed to assess the functional consequence of six VUS identified in patients with IRD. Clinical assessments in-cluded an ophthalmic examination, best corrected visual acuity, and kinetic perimetry. Imaging was acquired with the Optos ultra-widefield camera and spectral-domain optical coherence to-mography (SD-OCT). Genetic testing was performed by Molecular Vision Laboratories. VUS that were predicted to alter splicing were analyzed with a minigene assay which revealed that VUS in the genes OPA1, CNGB1, and CLUAP1 altered spicing mechanisms. Due to the emerging gene and cell therapies, these results expand the genotype-phenotype correlations for patients diag-nosed with an IRD.

Silverleaf is an important trunk disease of fruit crops, like Japanese plum. It is known that Chondrostereum purpureum produces wood discoloration, leaves silvering and tree decline, however, the information about the effects on fruit production is scarce. Therefore, the objectives of this study were to determine C. purpureum pathogenicity on Prunus salicina and effects on physiology, fruit yield and quality, in Chile, in 2019 and 2020. Wood samples from affected plum trees were collected in the Chilean plum productive area. Fungi were isolated plating wood sections from the necrosis margin on culture media. Isolates colonies morphological and molecular characteristics accorded to C. purpureum (98%). Representative isolates were inoculated on healthy plum plants and after 65-d incubation, wood necrotic lesions and silver leaves were visible. Fungi were reisolated, fulfilling Koch’s postulates. To determine Silverleaf effects, water potential, and fruit yield and quality were measured in healthy and Silverleaf diseased plum plants cv. ‘Angeleno’. Water potential was altered on diseased trees, and their yield was reduced in 51% (2019) and 41% (2020), compared to fruit from healthy plants. Moreover, cover-colour, equatorial-diameter and weight were reduced, and fruit were softer, failing to meet the criteria to be properly commercialized and exported to demanding markets.

Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..

I wish to suggest a physiological function for alpha-synuclein (a-syn) that has the potential to explain its role in pathology. Intraneuronal proteinaceous Lewy Bodies (LBs), the pathological hallmark of Parkinson’s disease and other synucleinopathies, consist majorly of a-syn. Ample evidence suggests that LBs are not the result of simple amyloidosis of cytosolic a-syn. Benign soluble unstructured a-syn gets converted into toxic species which preferentially accumulates in LBs. But how these aberrant a-syn molecules are produced in the cytosol, is still not clear. The present hypothesis is an effort to relate a metabolic reaction specific to neuronal function, that is, phase transition, with the pathobiology of a-syn. During high frequency stimulation, which entails rapid phase transition reactions at the presynaptic compartment, aberrant interaction of a-syn with the membrane occasionally generates toxic a-syn molecules. My conjecture is that the physiological function of a-syn is to modulate membrane fluidity by a process wherein it goes through a conformation cycle driven by a flux of energy from mitochondria. It is the range of toxic a-syn produced during aberrant phase transition reaction that is responsible for pathology, not the normal a-syn that reenters the conformation cycle, thereby, resolving the paradox of the Janus-face of a-syn.

Influenza epidemics in temperate regions display dynamics that are characterized by pronounced seasonal peaks during the winter. The general lack of influenza cases during the off-season may result from the virus physically disappearing at the end of the season, in which case it must be imported annually. Alternatively, it may result from persistent asymptomatic carriers or unnoticed local transmission chains that develop into local epidemics as conditions become conducive. Here I attempt to understand these differing explanations by analyzing the global distribution of the four major subtypes that comprise influenza over a period of 18 years based on FluNet data, the surveillance network and database compiled by the WHO, and the NCBI influenza data resource, a repository of relevant genetic information. Examining the annual proportion of each subtype, I find considerable variations in subtype annual proportions between the regions. Moreover, I find that seasonal influenza subtypes can remain confined to specific temperate regions, without showing measurable global presence. These results indicate that although largely undetected during the off-season, influenza is likely to persist locally, and imply a ‘local-global’ model where annual influenza epidemics are a mixture of local strains undergoing reactivation together with an influx of global variants.

The gut microbiome is important in the homeostasis of gut health and has pivotal roles in digestion, immune regulation, and metabolic processes. The gut microbiome has been implicated in range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We have yet to identify a single microbe that causes either ulcerative colitis or pouchitis, however, perturbations in the gut microbiome are associated with disease states. Importantly, we can manipulate the gut microbiome using dietary interventions, medications, and faecal microbiota transplantation. This review will summarise our knowledge of gut microbiome therapies in ulcerative colitis and pouchitis.

Physical activity is considered a promising preventive intervention to reduce the risk of developing Alzheimer’s disease (AD). However, the positive effect of exercise therapy has not been proven conclusively yet, likely due to confounding factors such as varying activity regimens and life or disease stages. To examine the impact of different routines of physical exercise in the early disease stages, we subjected young 5xFAD and wild-type mice to 1-day (acute) and 30-day (chronic) voluntary wheel running and compared them with age-matched sedentary controls. We observed a significant increase in brain lactate levels in acutely trained 5xFAD mice relative to all other experimental groups. Subsequent brain RNA-seq analysis did not reveal major differences in transcriptomic regulation between training durations in 5xFAD mice. In contrast, acute training yielded substantial gene expression changes in wild-type animals relative to their chronically trained and sedentary counterparts. The comparison of 5xFAD and wild-type mice showed the highest transcriptional differences in the chronic and sedentary groups, whereas acute training was associated with much fewer differentially expressed genes. In conclusion, our results suggest that different training durations did not affect the global transcriptome of 3-month-old 5xFAD mice, whereas acute running seemed to induce a similar transcriptional stress state in wild-type animals as already known for 5xFAD mice.

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction referred for surgical myectomy. Plasma was collected at the surgical preoperative visit approximately one month prior to surgery and then at the post surgical visit approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p value of <0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of the differentially expressed proteins such as interferon-, TGF-1 and TNF. Biological pathways affected by the surgery included organ inflammation, migration and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function.

Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry, Newcastle disease (ND). ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease egg productions, mortality, and morbidity. Although, significant advances have been made in the vaccine development, but outbreaks are reported in vaccinated birds leading to overall decreased growth rate. In this study, we report the damage caused by the NDV infection in the pancreatic tissues of vaccinated as well as specific pathogen free chickens. The histopathological examination of the pancreas showed sever damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, and apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone, somatostatin, were observed in NDV infected chicks at 3 and 5-day post infection (DPI). Slight decrease in the plasma concentrations of the insulin were noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection has decreases the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in pancreas, decrease the activity and expression of pancreatic enzymes and increase plasma corticosterone and somatostatin.

Faba bean (Vicia faba L.) was considered a minor crop in the Canadian prairies until recently, but its potential for cultivation is increasing due to its positive environmental impact and economic value. This review provides a historical summary of faba bean improvement in western Canada. Although traditional breeding methods have proved useful, in the last decade faba bean improvement has benefited from advances in genetics, biochemistry and molecular breeding tools. The overall breeding goal is to develop high yielding germplasm with improved agronomic characteristics that will be of economic value to the emerging faba bean sectors, including the plant protein industry. To maximize value and acceptance by producers, processors and the food industry as a source of protein and dietary fibre, future faba bean varieties need to be high-yielding, have diverse seed size classes, disease resistance, genetically low vicine-convicine concentration, and have wider adaptation to different agro-ecological zones of Canada. The experiences over the last 40 years of faba bean improvement in western Canada may be useful to other breeding programs globally located in regions with similar agroecology. In the past 10–15 years, faba bean genetic development in Canada has benefited greatly from research and development interactions with most of the faba bean research programs in northern Europe.

Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases in the world, which is characterized by memory dysfunction and the formation of tau and amyloid β (Aβ) aggregate in multiple brain regions, including the hippocampus and cortex. The formation of senile plaques involving tau hyperphosphorylation, fibrillar Aβ, and neurofibrillary tangles (NFTs) are used as pathological markers of AD, and eventually produces aggregation or misfolded protein. Importantly, it has been found that failure to degrade these aggregate-prone proteins leads to pathological consequences, such as synaptic impairment, cytotoxicity, neuronal atrophy, and memory deficits associated with AD. Recently, increasing evidences have been suggested that autophagy pathway plays a role as a central cellular protection system to prevent the toxicity induced by aggregate or misfolded proteins. Moreover, it has also been related that AD-related protein aggresomes could be selectively degraded by autophagosome and lysosomal fusion through autophagy pathway which is known as aggrephagy. Therefore, the regulation of autophagy might be served as a useful approach to modulate the formation of aggresome associated in AD. This review focuses on the recent improvements in the application of natural compounds and small molecules as a potential therapeutic approach for AD prevention and treatment via aggrephagy.

This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and –regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood triglyceride and HDL-cholesterol showed the highest Q statistics and I2 values, respectively. Other than blood HDL-cholesterol, total cholesterol, and triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p<0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in enhancing the quality of human life.

Polyphenols represent a group of secondary metabolites of plants which have been analyzed as potent regulators of multiple biological processes, including cell proliferation, apoptosis and autophagy, among others. These natural compounds exhibit beneficial effects and protection against inflammation, oxidative stress and related injuries including metabolic diseases, such as cardiovascular damage, obesity and diabetes and neurodegeneration. In the present review, we report the main biological effects in relationship to autophagy regulation in response to different dietary polyphenols and its impact on metabolic and neurodegenerative diseases

There is still an ambiguous opinion on oat regarding its safety for people with celiac disease (CD). Some studies have confirmed different content of oat immunoreactive epitopes in different cultivars while others explain the differences in consequence of cross-contamination with gluten-rich species or as ELISA cross-reactivity of oat homological epitopes with antibodies against wheat gliadin. Our study was based on a two-year mapping of oat immunoreactive epitopes in a set of 132 oat cultivars using the G12-based ELISA kit. Although repeated evaluation confirmed high interannual variability (RSD ≥ 30%) in approximately 2/3 of the cultivars, the permitted gluten content (20 mg kg-1) has not been exceeded except for contaminated cultivar Sirene. The polymorphism of purified avenins determined by SDS-PAGE revealed the occurrence of 2 bands around 30 kDa in oat cultivars with relatively high gluten content (12-16 mg kg-1) except for the cultivar Leo while this pattern occurred only in 50% oat cultivars with low gluten content. Quantification of gluten epitopes on purified avenin unit further revealed the three materials (Mojacar, Maris Oberon, SG-K 16370) with the lowest gluten content and presence of one band at 30 kDa. The band pattern at 30 kDa thus represents a promising breeding marker.

Sea star wasting disease (SSWD) is a condition that has affected asteroids for over 120 years, yet mechanistic understanding of wasting etiology remains elusive. We investigated temporal virome variation in two Pisaster ochraceus specimens that wasted in the absence of external stimuli and two specimens that did not experience SSWD for the duration of our study, and compared viromes of wasting lesion margin tissues to both artificial scar margins and grossly normal tissues over time. Global assembly of all SSWD-affected tissue libraries resulted in 45 viral genome fragments represented in &gt;1 library. Genome fragments mostly matched densoviruses and picornaviruses with fewer matching nodaviruses, narnaviruses and sobemoviruses. Picornavirus-like and densovirus-like genome fragments were most similar to viral genomes recovered in metagenomic study of other marine invertebrates. Read recruitment revealed only 2 picornavirus-like genome fragments that recruited from only SSWD-affected specimens, but neither was unique to wasting lesions. Wasting lesion margin reads recruited to a greater number of viral genotypes (i.e. richness) than did either scar tissue and grossly normal tissue reads. Taken together, these data suggest that no single viral genome fragment was associated with SSWD. Rather, wasting lesion margins may generally support viral proliferation.

Background: Alzheimer’s disease affecting about 24 million people world-wide. The socio-economic burden on world-economies costing more than 172 billion US $ annually for the US alone. Objectives: To prepare aqueous extract of T. foenum graecum seeds (FSE) to explore the possible treatment for cognitive deficit in experimental animals. Materials and methods: FSE was subjected to preliminary phytochemical evaluation and antioxidant effect using free radical scavenging method (DPPH). All the animal behavior was video recorded with no human intervention during observation and animal groupings were blinded to avoid investigator bias. Different doses of FSE (5%, 10% and 20%), control, standard (Piracetam, 200 mg/kg, IP.) were given for male albino mice a period of 15 days followed by cognitive assessment in elevated plus maze and novel objection recognition tests. Ttransfer latencies and time exploring novel and familiar objects were recorded in respective tests. Retention of this learned-task was examined again 24 h later and inflexion ratio (IR) and discriminative index (DI) were calculated respectively. Next in the second set of experiment same groups and treatments were continued but scopolamine was administered to all the groups except normal control one hour after the last dose and examined similarly. Results: FSE showed potential antioxidant effect and a dose dependent increase in transfer latency and improved DI indicating a nootropic effect. FSE at 20% showed significant reversal of scopolamine induced dementia in the second set of experiment. Conclusion: FSE improved memory as well as reversed the chemically induced memory deficits in experimental mice.

In this review we summarize the recent development in understanding the role of PIP2 in cellular function and signaling. We first discuss the effect of PIP2 on actin binding proteins addressing the mechanism of the actin cytoskeletal dynamics such as polymerization or depolymerization of the filamentous network or the coupling to membrane to generate forces. Next, we outline the role of PIP2 in membrane dynamics. We summarized how the membrane organization depends upon PIP2 in the presence of ions or transmembrane proteins that are sensitive to membrane curvature. We discuss how clathrin coated pits interact with adaptor proteins during the endocytosis process, which is facilitated by PIP2. Finally, we discuss the role of PIP2 in cell signaling and diseases.

Necroptosis is a caspases-independent form of programmed cell death exhibiting intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development, tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis has been associated to chronic inflammatory diseases and cancer. Drugs that inhibit necroptosis could, therefore, be used therapeutically for the treatment of these diseases, and researches to develop such inhibitors are already underway. In this Review, we outline pathways for necroptosis and its role in chronic inflammation and cancer. We also discuss current and developing therapies that target necroptosis machinery.

Substantial studies have focused on early detection of Alzheimer's disease (AD). Cerebral amyloid beta (Aβ), is hallmark of AD, can be observed in vivo via positron emission tomography imaging using amyloid tracer or cerebrospinal fluid assessment, but costly expensive. The current study aims to identify and compared predictability in magnetic resonance imaging (MRI) markers and neuropsychological markers to predict cerebral Aβ status in AD cohort using machine learning (ML) approaches. The predictability in candidate markers for cerebral Aβ status was examined by analyzing 724 participants from the ADNI-2 cohort. Demographic variables, structural MRI markers, and neuropsychological test scores were used as input in several ML algorithms to predict cerebral Aβ positivity. Out of five combination of candidate markers, neuropsychological markers with demographics showed the most cost-efficient result. A feature selection model could distinguish abnormal levels of Aβ with the predictability of 0.85, indicating the same performance with MRI-based models. The result has first to identified the predictability in MRI markers using ML approaches, and secondary to demonstrate the neuropsychological model with demographics could predict Aβ positivity, suggesting a more cost-efficient method for detecting cerebral Aβ status compared to MRI markers.

Smallholder livestock farmers utilize their existing communication networks as information sources. This study explored these information sources, frequency of contacts and perceived usefulness of information from these sources. Using descriptive and correlation analysis, it categorized respondents according to total information score and explored the relationship between their scores and socio-economic characteristics. Findings show that 65% of farmers in the area scored a high reliance on fellow farmers and extension officials. Mass media sources such as radio and television scored low on perceived usefulness. The correlation coefficients for age (-0.228), farming experience (0.183), extension visits (0.002) and information contacts (0.214) were significant (p<0.05). Level of education (0.256), herd size (0.067) and perceived usefulness of information contacts (0.252) were also significant (p<0.01). Gender, household size, income, cooperative participation and access to financial services were not correlated to the total information scores of respondents. It was recommended that mass media sources in the area be supported by extension communication specialists to disseminate livestock-health related information.

The consequences of Sickle Cell Disease (SCD), including ongoing hematopoietic stress and hemolysis, vascular damage and chronic therapies , such as blood transfusions and Hydroxyurea on hematopoietic stem and progenitor cell (HSPC) have not been characterized. We have quantified the frequencies of nine HSPC populations by flow cytometry in the peripheral blood of pediatric and adult patients stratified by treatment and controls. We observed broad differences between SCD patients and healthy controls. SCD is associated with 10 to 20-fold increase in CD34dim cells, and two to five-fold more CD34bright cells, a depletion in Megakaryocyte-Erythroid Progenitors and an increase in hematopoietic stem cells, when compared to controls. SCD is also associated with abnormal expression of CD235a and by very high levels of expression of the CD49f antigen. These findings were present to varying degrees in all patients, whether or not they were naïve or on chronic therapy. HU treatment tended to normalizes many of these parameters. Chronic stress erythropoiesis, inflammation caused by SCD and hydroxyurea therapy have long been suspected of causing premature aging of the hematopoietic system, and potentially increasing the risk of hematological malignancies. An important finding of this study was that the observed concentration of CD34bright cells and of all the HSPCs decreased logarithmically with time of treatment with HU. This correlation was independent of age and specific to HU treatment. Although the number of circulating HSPCs is influenced by many parameters, our findings suggest that HU treatment may decrease premature aging and hematologic malignancy risk compared to the other therapeutic modalities in SCD.

Alzheimer’s disease is a prominent neurological disorder, which leads to progressive dementia. The microtubule-associated protein Tau is been considered as one of the major causes of Alzheimer’s disease. Physiologically Tau assists in the stabilization of microtubules, contrary to this the pathological state of Tau results in the formation of neurotoxic tangles of Tau. The posttranslational modifications, such as GSK-3β-mediated Tau phosphorylation results in the generation of Tau pathology. Neuroinflammation generated in Alzheimer’s disease, contributes to elevated body temperature. The aim of present work is to study the effect of high temperature on Tau phosphorylation. The neuroblastoma cells were exposed to heat stress for 40 minutes. The immunofluorescence and western blot studies suggested that high temperature increases the levels of GSK-3β in cells. Heat stressed cells was also observed to have elevated levels of phosphorylated Tau. Additionally, heat stressed cells found to have modulated nuclear transport as the level of Ran was reduced. The results of present work suggested that increased temperature could be considered as a risk factor in Alzheimer’s disease as it elevated the GSK-3β levels in cells thus, resulting in increased Tau phosphorylation.

The crux of the paper is to present a detailed analysis of COVID-19 data which is available on global basis. This analysis is performed using some specific package of R software. It provides various insights from the data and help to understand the current status of this pandemic in India so that effective measures can be formulated by policymakers. These insights include global summary of this disease, growth rate of this pandemic and performance of SIR model for the given global data. The analysis has been presented in different tables and graphs to understand the outputs of the problem in a more detailed point of view.

The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, has been declared by the World Health Organization (WHO) as a pandemic. Unfortunately, finding a vaccine or developing drugs from the scratch is a time-consuming luxury given the widespread and high fatality rates of the virus. In the short term, repurposing of drugs already in use seem to be the most rational step to quickly and effectively curb the virus. Several antiviral agents had been proposed as possible remedies, but the 4-aminoquinolines, Chloroquine (CHQ) and hydroxychloroquine (HCHQ) appear to be generating more interest. They are generic, cheaply available and have proven efficacy against malaria parasites in Africa. The human immunodeficiency virus (HIV), on the other hand, targets the immune system thereby reducing the patient’s ability to fight infections. Sadly, 68% of the global HIV burden occur in Africa. It is therefore anticipated that incidence of severe forms of COVID-19 could occur in Africa because of associated endemic conditions that compromise the immune system. With CHQ and HCHQ being considered for clinical use against COVID-19, there is a need to highlight their potential merits and confounding variables in the subgroup of patients with or without HIV.

Background: On late December 2019, a viral pneumonia known as coronavirus disease 2019 (COVID-19), was originated from China and spread very rapidly in the world. Therefore, COVID-19 became a global concern and health problem. Methods: We presented four patients in this study. They were selected from patients who presented with pneumonia symptoms and were suspicious for COVID-19 and referred to the intended centers for COVID-19 diagnosis and management of Shiraz University of Medical Sciences in the south of Iran. Two nasopharyngeal and oropharyngeal throat swab samples were collected from each patient and tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR), and also samples were sent for influenza viruses and all the respiratory panel. Results: In the present report, four patients were diagnosed in the starting days of COVID-19 disease in our center in south of Iran with co-infection of SARS-CoV-2 and influenza virus. Conclusions: This co-infection of COVID-19 and influenza highlights the importance of considering SARS-CoV-2 PCR assay regardless of other positive findings for other pathogens in the primary test during the epidemic.

Alzheimer's disease (AD) has been the subject of extensive investigation as to its biological underpinnings. However, this has produced little of therapeutic benefit or indeed provided any accepted biomarkers that could tailor treatment. This chapter reviews data on the main pathophysiologic processes that have been widely shown to be altered in AD, including circadian dysregulation, mitochondrial dysfunction, gut dysbiosis, and immune-glia-platelet activation. It is proposed that alterations in the gut microbiome, including gut dysbiosis and increased gut permeability drive changes in mitochondrial function that are intimately associated with significant variations in sirtuin expression. Both mitochondria-located and nucleus/cytoplasm located sirtuins can act on mitochondrial function in different cells and body systems to co-ordinate the ageing-associated changes that underpin AD. The sirtuins are therefore key aspect to a developmental model of AD that is more 'holistic' in perspective, thereby providing a framework for the detection of earlier biomarkers and more successful treatment for the heterogenous nature of AD pathoetiology.

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

Sphingomonas paucimobilis is an opportunist pathogen bacillus gram-negative aerobic with a rare occurrence. We present a case in an immunocompetent man successfully treated by surgical debridement, purulent drainage and with an associated course of antibiotics. A large necrotic infection, approximately 5 cm x 3 cm, in a 74-year-old man was identified. Empirical antibiotic therapy with ciprofloxacin 400mg EV 12/12 hours, associated with clindamycin 600mg EV 6/6 hours and pain control was done through dipyrone 1gr, tramadol 400 mg. Deep venous thrombosis was prevented through the prescription of enoxaparin 40mg subcutaneous once a day during hospitalization. The case was well illustrated with pictures throughout treatment. Complete healing was achieved after 90 days. Herein, we present a case of cutaneous contamination. The presented case is the third cutaneous contamination case reported in the literature and the first reported case in the Amazonia region in Brazil.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson’s disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results. Improvements in phonation and declines in articulation have frequently been reported during different speech tasks under different stimulation conditions. Questions remain about preferred STN-DBS stimulation settings. Seven right-handed, native speakers of English with PD treated with bilateral STN-DBS were studied off medication at three stimulation conditions: stimulators off, 60 Hz (low frequency stimulation - LFS), and the typical clinical setting of 185 Hz (High frequency - HFS). Spontaneous speech was recorded in each condition and excerpts were prepared for transcription (intelligibility) and difficulty judgements. Separate excerpts were prepared for listeners to rate abnormalities in voice, articulation, fluency, and rate. Intelligibility for spontaneous speech was reduced at both HFS and LFS when compared to STN-DBS off. Speech produced at HFS was more intelligible than that produced at LFS, but HFS made the intelligibility task (transcription) subjectively more difficult. Both voice quality and articulation were judged to be more abnormal with STN-DBS on. STN-DBS reduced the intelligibility of spontaneous speech at both LFS and HFS but lowering the frequency did not improve intelligibility. Voice quality ratings with STN-DBS were correlated with the ratings made without stimulation. This was not true for articulation ratings. STN-DBS exacerbated an existing voice disorder and may have introduced new articulatory abnormalities.

Changes in land-use have been observed in banana-based systems in the African Great Lakes region affected by Xanthomonas wilt disease (XW) of banana. Through participatory focus group discussions (FGDs) and the 4-cell method, changes in land-use were retrospectively assessed in 13 XW-affected landscapes/villages along a 230 km transect from Masisi (XW arrived in 2001) to Bukavu (XW arrived around 2014) in eastern Democratic Republic of Congo during 2015. The four-cell chart ranked land-use by mapping the area under production and the number of households involved in production. Farmers’ perceptions on the sustainability of new land-uses were also documented. Soil nutrient content and erosion levels were measured for five major land-use options/ trajectories on 147 fields across 55 farms in three landscapes along the transect. From being ranked the most important crop (92% of landscapes i.e. produced on large areas of land and by many households) before XW outbreaks, its importance had declined with most households in 36% of the landscapes growing it on smaller farms while in 64% of cases by few households on smaller pots. Farmers uprooted entire banana mats or fields, expanding land under other crops, mainly beans, taro, sweet potato, cassava, maize, coffee and eucalyptus. Species richness did not change at landscape level, though 21 crops were introduced at farm level. Land-use for banana is however still perceived to be more sustainable due to its multi-functional roles. Soils under banana plots were found in general to be better in their chemical attributes while high erosion levels (Mg ha-1 year-1) were observed under cassava (1.7-148.9) compared with banana (0.3-10.7) and trees (0.3-5.9). The current shift away from banana could thus have profound effects on supply of key services and sustainability of the production systems. This study offers a good basis/entry point for interventions in the XW-affected landscapes.

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

The key issue in the post-genomic era is how to systematically describe the association between small molecule transcripts or translations inside cells. With the rapid development of high-throughput “omics” technologies, the achieved ability to detect and characterize molecules with other molecule targets opens up the possibility of investigating the relationships between different molecules from a global perspective. In this article, a Molecular Associations Network(MAN) is constructed and comprehensively analyzed by integrating the associations among miRNA, lncRNA, protein, drug, and disease, in which any kind of potential associations can be predicted. More specifically, each node in MAN can be represented as a vector by combining two kinds of information including the attributes of the node itself (e.g. sequences of ncRNAs and proteins, semantics of diseases and molecular fingerprints of drugs) and the manner of the node in the complex network (associations with other nodes). Random Forest classifier is trained to classify and predict new interactions or associations between biomolecules. In the experiment, the proposed method achieves a superb performance with 0.9735 AUC in 5-fold cross-validation, which show that the proposed method can provide new insight for exploration of the molecular mechanisms of disease and valuable clues for disease treatment.

In recent years, using multispectral cameras on UAVs has provided an opportunity to capture separate bands that offer the extraction of spectral features used for early detection of diseased plants. One of the main steps in disease detection is radiometric calibration that converts digital numbers to reflectance values commonly using white reference panels. This paper focused on the necessity of radiometric calibration to distinguish disease trees in orchards based on aerial multi-spectral images. For this purpose, two study sites with various climate conditions and tree species as well as different disease types were selected where multispectral images were taken using a multirotor UAV. The impact of radiometric correction on plant disease detection was assessed in two ways: 1) comparison of separability between the healthy and diseased classes using T-test and entropy distances; 2) radiometric calibration effect on the accuracy of classification. The experimental result showed the insignificant effect of radiometric calibration on separability criteria. Furthermore, based on T-test and entropy distances criteria, NIR and R spectral features made highest distances between healthy and Greening infected citrus trees, respectively, at the first study site while NDRE and BNDVI spectral features made highest distances between healthy and peach leaf curl infected trees, respectively, at the other study site. In the second strategy, the experimental result showed that radiometric calibration had no effect on the accuracy of classification. As a result, the overall accuracy and kappa values for both un-calibrated and calibrated orthomosaic classifications of the citrus orchard were 96.6% and 0.94%, respectively, using five spectral bands as well as DVI, NDRE, NDVI and GNDVI vegetation indices using a random forest classifier. The experimental results were also similar at the other study site. Therefore, the overall accuracy and kappa values for both the un-calibrated and calibrated orthomosaic classifications were 96.1%, 0.92, respectively, using five spectral bands as well as NDRE, BNDVI, GNDVI, DVI, and NDVI vegetation indices.

Disease classification based on biological data is an important area in bioinformatics and biomedical research. It helps the doctors and medical practitioners for the early detection of disease and support them as a computer-aided diagnostic tool for accurate diagnosis, prognosis, and treatment of disease. Earlier Microarray gene expression data have wide application for the classification of disease, but now Next-generation sequencing (NGS) has replaced the Microarray technology. From the last few years, RNA sequence (RNA-Seq) data are widely used for the transcriptomic analysis. Hence, RNA-Seq based classification of disease is in its infancy. In this article, we present a general framework for the classification of disease constructed on RNA-Seq data. This framework will guide the researchers to process RNA-Seq, extract relevant features and apply the appropriate classifier to classify any kind of disease.

Metal nanoparticle has been reported to have a high antimicrobial activity against fungi, bacteria, and yeasts. In this study, silver nanoparticles (AgNPs) were synthesized using a chemical reduction method, at 90 oC, and used as an antifungal coating in paper packaging, to control the growth of C. gloeosporioides in cut orchid flowers during shipping. AgNPs were characterized by UV-Vis spectroscopy and atomic force microscope (AFM). The results indicated that the shape of AgNPs was spherical and homogenous with an average size of 47 nm. Twenty and 50 particles per million (ppm) concentration of AgNPs, mixed with starch, were prepared as the coating solution. The paper coated with 50 ppm AgNPs exhibited a significant antifungal activity against C. gloeosporioides compared to 20 ppm AgNPs coating. The AgNPs coated paper had a better water resistance and mechanical properties compared to paper without coating. We observed a significant reduction in the number of anthers, of orchid inflorescences, infected by C. gloeosporioides, when stored in the coated boxes. The current study demonstrates that paper boxes coated with AgNPs are a potential solution to control the infection of C. gloeosporioides in the storage of cut orchid flowers.