Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Coronavirus disease 2019 (COVID-19) since its declaration as a pandemic by world health organization (WHO) has spread across the various continent with little known about the most effective public health response for containing and mitigating the transmission of the epidemic. It is important to state that some authors have published on the lessons learned from transmission and management of COVID-19 infection but only a few considered it from the Africa perspective. Despite the late arrival of the pandemic in Africa and the notion that the virus may not thrive because of the high temperature in the continent; today the narrative has changed with the number of infected patients increasing daily. Herein, the authors have shared their perspectives and opinions on the dynamics and response to COVID-19 from Africa context to create more awareness and approach in mitigating the spread of the virus should the continent becomes the epicenter of COVID-19.

Background: Research continues to search for blood-based biomarkers sensitive to Alzheimer’s disease (AD) pathology during the initial stages when symptoms of cognitive decline are not yet apparent. A blood-based biomarker candidate is metalloprotein p53, the conformation of which was previously found to be altered in peripheral cells from individuals with mild cognitive impairment (MCI) and AD, presenting as an unfolded p53 (U-p53) conformational variant. Methods: Plasma samples from the well-characterized Australian Imaging, Biomarkers, and Lifestyle (AIBL) cohort were used to identify the clinically relevant AZ 284^® peptide, specifically present in samples from individuals with symptomatic AD. The AZ 284^® peptide, which is a marker of the U-p53 conformational variant (U-p53^AZ), was identified by immunoprecipitation (IP) with a novel U-p53 conformational variant-specific antibody followed by liquid chromatography (LC) tandem mass spectrometry (MS/MS) and protein sequencing. Using IP-LC surface-activated chemical ionization (SACI) MS/MS analysis, the prognostic and diagnostic performance of U-p53^AZ were examined in the longitudinal AIBL cohort, including 252 plasma samples derived from 214 elderly individuals. For the prognostic analyses, U-p53^AZ levels were assessed at 36, 72, and 90 months after baseline assessment. Results: The prognostic performance of U-p53^AZ to predict the progression to AD from preclinical or prodromal AD was high, with area under the receiver operating characteristic curve (AUC) values close to or above 0.90. Furthermore, U-p53^AZ predicted the progression to AD more than 6 years prior to symptom onset with positive and negative predictive values of about 90%. Additionally, the estimated prognostic performance of U-p53^AZ was superior to other main risk factors (i.e., age, sex, and either alone or in combination with amyloid status. Furthermore, U-p53^AZ had high diagnostic performance to differentiate cognitively normal individuals from those with AD (AUC values >0.88). Conclusion: These findings support the use of U-p53^AZ as a prognostic blood-based biomarker accurately predicting the progression to AD dementia during the preclinical and prodromal stages at least 6 years before receiving the clinical diagnosis of AD dementia.

Alzheimer's is a disease for which there is no cure. Diagnosing Alzheimer's Disease (AD) early facilitates family planning and cost control. The purpose of this study is to predict the presence of AD using socio-demographic, clinical, and Magnetic Resonance Imaging (MRI) data. Early detection of AD enables family planning and may reduce costs by delaying long-term care. Accurate, non-imagery methods also reduce patient costs. The Open Access Series of Imaging Studies (OASIS-1) cross-sectional MRI data were analyzed. A gradient boosted machine (GBM) predicted the presence of AD as a function of gender, age, education, socioeconomic status (SES), and Mini-Mental State Exam (MMSE). A Residual Network with 50 layers (ResNet-50) predicted CDR presence and severity from MRI's (multi-class classification). The GBM achieved a mean 91.3% prediction accuracy (10-fold stratified cross validation) for dichotomous CDR using socio-demographic and MMSE variables. MMSE was the most important feature. ResNet-50 using image generation techniques based on an 80% training set resulted in 98.99% three class prediction accuracy on 4,139 images (20% validation set) at Epoch 133 and nearly perfect multi-class predication accuracy on the training set (99.34%). Machine Learning methods classify AD with high accuracy. GBM models may help provide initial detection based on non-imagery analysis, while ResNet-50 network models might help identify AD patients automatically prior to provider review.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

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

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

One of the principal hallmarks of Alzheimer’s disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists either in blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-Epigallocatechin-3-gallate, Quercetin, and Rosmarinic acid) with the amyloid-β(1-40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulate the double-layered structure stability.

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

The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), is an infectious disease responsible for the worldwide decline of amphibian species. To mitigate these declines, it is necessary to identify the various vectors by which the fungus can be transmitted between individuals and populations. The objective of this study was to determine whether adult female mosquitoes can carry and transfer Bd fungal cells. Mosquitoes were exposed to net soaked in a live Bd zoospore suspension to determine whether they are able to externally acquire the fungus. Another group was placed into containers with a sterile and Bd-inoculated agar plate to determine whether mosquitoes could transfer Bd between these surfaces. Bd DNA was found to be present on mosquito legs exposed to inoculated netting and agar plates suggesting that Bd can be transmitted by the mosquito over short distances This is the first study to demonstrate that an insect host may be a mechanical vector of Bd and suggests that we should begin to consider the role of mosquitoes in the dissemination and control of the fungus.

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 objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

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

The Armillaria genus represents one of the most common causes of chronic root rot disease in woody plants. The disease damage prompt assessment is crucial for pest management. However, the disease detection current methods are limited at the field scale. Therefore, an alternative approach that can enhance or supplement traditional techniques is needed. In this study, we investigated the potential of hyperspectral methods to identify the changes between fungi-infected and uninfected plants of Vitis vinifera in early detecting the Armillaria disease. The hyperspectral imaging sensor Specim-IQ was used to acquire images of leaves of the Teroldego Rotaliano grapevine cultivar. We analysed three groups of plants: healthy, asymptomatic, and diseased. Highly significant differences were found in the Near infrared (NIR) spectral region with a decreasing pattern from healthy to diseased plants attributable to internal leaf structure changes. Asymptomatic plants emerged from the other groups due to a smaller reflectance in the red-edge spectrum (around 705nm). Hypothetically associated with the presence of secondary metabolites involved in plant defence strategy. Furthermore, significant differences were observed in the wavelengths close to 550 nm in diseased plants versus asymptomatic. We used linear discriminant analysis from a machine learning context to classify the leaves based on the most significant variables (vegetation indices and single bands), with resulting overall accuracies of 85% and 84% respectively in healthy vs. diseased and healthy vs. asymptomatic. To our knowledge, this study represents the first report on the possibility of using hyperspectral data for root rot disease diagnosis on woody plants. Although further validation studies are required, it appears that the spectral reflectance technique, possibly implemented on unmanned aerial vehicles (UAV), could be a promising tool for a cost-effective, non-destructive method of Armillaria disease early diagnosis and mapping in the field, contributing to a significant step forward in precision viticulture.

Stripe rust ​​(caused by Puccinia striiformis f. sp. tritici) is one of the most devastating diseases of wheat and causes large-scale epidemics and severe yield loss. Applying fungicides during early epidemic development is crucial to controlling the disease but is often challenged by resource-limited human visual scouting. Deep learning has the potential to process images and videos captured from affordable devices to empower high-throughput phenotyping for early detection of stripe rust for timely application of fungicides and improve control efficiency. Here, we developed RustNet, a neural network-based image classifier, for efficiently monitoring fields for stripe rust. RustNet was built on a ResNet-18 architecture pre-trained with ImageNet Large-Scale Visual Recognition Challenge (ILSVRC) dataset using transfer learning. RGB images and videos of multiple wheat fields with different wheat types (winter and spring wheat), conditions (irrigated and non-irrigated), and locations were acquired using smartphones or unmanned aerial vehicles near the canopy. A semi-automated image labeling approach was conducted to improve labeling efficiency by combining automated machine labeling and human correction. Cross-validations across multiple categories (sensor platforms, wheat types, and locations) achieved Area Under Curve from 0.72 to 0.87. Independent validation on a published dataset from Germany achieved accuracies ranging from 0.79 to 0.86. The visualization of the last convolutional layer of RustNet demonstrated the identification of pixels with stripe rust. RustNet is freely available at https://zzlab.net/RustNet.

In atherosclerosis patients, vascular endothelial dysfunction is commonly observed with damage of vascular endothelial glycocalyx, an extracellular matrix-bound to and encapsulating the endothelial cell lining the blood vessel wall. Unfavorable lifestyle; smoking and physical inactivity, also induces glycocalyx degradation. Moreover, the vascular endothelial glycocalyx is damaged by various unfavorable disease conditions like as dehydration, acute infectious disease, trauma, sepsis, ARDS, Kawasaki disease, preeclampsia, gestational diabetes mellitus, hypertension, diabetes, chronic kidney disease, atherosclerosis, stroke, dementia, microvascular angina, acute coronary syndrome, and heart failure. The vascular endothelial glycocalyx has been shown to be important not only as a physical cytoprotective barrier for vascular endothelial cells but also as a mechanism that regulates intracellular cell signaling. Therefore, vascular endothelial glycocalyx has great potential to explore new strategies for assessing the benefit conditions of our healthy vasculature.

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

Key features of glycogen metabolism in excitable tissues are not well-explained by current concepts. Glycogen stores in brain and skeletal muscle are generally considered to function as local glucose reserves, to be utilized during transient mismatches between glucose supply and demand; however, quantitative measures show that blood glucose supply is likely never rate-limiting for energy metabolism in either brain or muscle under physiological conditions. These tissues nevertheless do normally utilize glycogen during intervals of increased energy demand, despite the availability of free glucose, and despite the ATP cost of cycling glucose through glycogen polymer. This seemingly wasteful shunt can be explained by considering the effect of glycogenolysis on the amount of energy derived from ATP (ΔG’ATP). ΔG’ATP is diminished by elevations in Pi, such as occur at sites of rapid ATP hydrolysis and net phosphocreatine consumption. Glycogen utilization counters this effect by sequestering Pi in glycolytic metabolites (glycogen_n + Pi → glycogen_n-1 + glucose-1-phosphate → phosphorylated glycolytic intermediates), and thereby maintains the amount of energy obtained from ATP at sites of rapid ATP consumption. This thermodynamic effect may be particularly important in the narrow, spatially constricted astrocyte processes that ensheath neuronal synapses. This effect can also explain the co-localization of glycogen and cytosolic phosphocreatine in brain astrocytes, glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphorylase deficiency (McArdle’s disease).

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

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of kidney damage in Renovascular hypertension (RVH). The activation of the Renin-Angiotensin System (RAS) is crucial in the development and progression of hypertensive renal damage and TGF-β is closely associated with the activation of RAS. In the present study, we assessed the effect of boldine on the progression of kidney disease using the 2K1C hypertension model and identifying mediators in the RAS such as TGF-β, that could be modulated by this alkaloid. Toward this hypothesis, rats (n=5/group) were treated with boldine (50mg/kg/day, gavage) for 6 weeks after 2K1C surgery (pressure≥180mmHg). Kidney function was evaluated by measuring of proteinuria/creatininuria ratio (U prot/U Crea), oxidative stress (OS) by measuring thiobarbituric acid reactive substances (TBARS). The evolution of systolic blood pressure (SBP) was followed weekly. α-SMA and Col III were used as markers of kidney damage; ED-1 and Osteopontin (OPN) as markers of inflammation. We also explored the effect in RAS mediators, such as ACE-1 and TGF-β. Boldine treatment reduced UProt/UCrea ratio, plasma TBARS and slightly reduced SBP in 2K1C hypertensive rats, producing no effect in control animals. In 2K1C rats treated with boldine the levels of α-SMA, Col III, ED-1 and OPN were lower when compared to 2K1C rats. Boldine prevented the increase in ACE-1 and TGF-β in 2K1C rats, suggesting that boldine reduces kidney damage. These results suggest that boldine could potentially be used as a nutraceutic.

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

The growing population meet the challenge for agricultural production. CRISPR/Cas9 technology is based on plant research for the development of the new varieties as well as disease resistance crops. In addition the deletion of significant characters makes the new alleles from the CRISPR/Cas9. Recent and reliable molecular scissor for genetic engineering. The review is focused on the various application of the CRISPR/Cas9 technology in plant enhancement of plant disease resistance, stress burden in plant, nutritional improvement, and quality of crops from the CRISPR/Cas9 system. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein9 (cas9) is adopted from the prokaryotic type II system. CRISPR/Cas9 is simplicity and efficiency than ZENs and TALENs for the genome engineering. Due to rapid growing of the CRISPR/Cas9 system has been formulate the adaptation of many plant species. The current advancement of plants and future schemes of improve of CRISPR technology has been presented in contest of multiplex editing, knowledge on induced mutation whether the factor effect in CRISPR/Cas9 technology in plant. Remarkable perspective and challenges of CRISPR/Cas9 technology in significance of plant genetic modification.

The study of neurodegenerative diseases using pluripotent stem cells requires new methods to assess neurodevelopment and neurodegeneration of specific neuronal subtypes. The cholinergic system, characterized by its use of the neurotransmitter acetylcholine, is one of the first to degenerate in Alzheimer’s disease and is also affected in frontotemporal dementia. We developed a differentiation protocol to generate basal forebrain cholinergic neurons (BFCNs) from induced pluripotent stem cells (iPSCs) aided by the use of small molecule inhibitors and growth factors. Ten iPSC lines were successfully differentiated into BFCNs using this protocol. The neuronal cultures were characterised through RNA and protein expression, and functional analysis of neurons was confirmed by whole-cell patch clamp. We have developed a reliable protocol using only small molecule inhibitors and growth factors, while avoiding transfection or cell sorting methods, to achieve a BFCN culture that expresses the characteristic markers of cholinergic neurons.

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.

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B₁₂ (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.

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

1) Background: Ultrasound-based strain imaging is now available in several ultrasound (US) scanners. Strain ratio (SR) can be used to quantify strain recorded simultaneously in two different user-selected areas, ideally exposed to the same amount of stress. The aim of this study was to evaluate SR variability when assessed in an in-vitro setup with a tissue-mimicking phantom, on resected tissue samples and in live tissue scanning with endoscopic applications. 2) Material and methods: Retrospective analysis of SR for quantification of elastic contrasts in a tissue-mimicking phantom containing four homogenous inclusions, in 38 resected bowel wall lesions and in 48 focal pancreatic lesions examined in vivo. Median SR and the inter-quartile range (IQR) was calculated on all external and endoscopic US-applications. The IQR/median provides a measure of the SR variability focusing on the two percentiles of the data closest to the median value. 3) Results: The overall variability of SR was lowest in a tissue-mimicking phantom (mean QR/median SR: 0.07). In resected bowel wall lesions representing adenomas, adenocarcinomas or Crohn lesions, the variability increased (mean IQR/Median: 0.62). During an endoscopic examination of focal pancreatic lesions in vivo, the variability increased further (mean IQR/Median: 2.04). 4) Conclusion: SR variability increased when assessed on different targets with growing heterogeneity and biological variability as one moved from homogeneous media to live tissues and endoscopic application. This may indicate a limitation for the accuracy SR evaluation in clinical applications.

Background: Kidney damage is considered to be one of the risk factors for severity and mortality among COVID-19 patients. However, molecular nature of such observations remains unknown. Hypothesis: Altered gene expressions due to infection and in chronic kidney disease could explain severity in COVID-19 with kidney defects. Methods: We collected gene expression data from publicly available resources Gene Expression Omnibus CKD, Enrichr for deregulated genes in SARS-CoV infected cells in vitro, DisGeNET and others and carried out enrichment analysis using Enrichr. Result: Number of common genes altered in chronic kidney disease (CKD) and SARS-CoV infected cells was 2834. Enrichment analysis revealed that biological processes related viral life cycle and growth, cytokines, immunity, interferon, inflammation, apoptosis, autophagy, oxidative stress and others were significantly enriched with common deregulated genes. Similarly, significantly enriched pathways related to viral and bacterial infections, immunity and inflammation, cell cycle, ubiquitin mediated proteolysis, signaling pathways like Relaxin signaling pathway, mTOR signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway were enriched with the common deregulated genes. These processes and pathways are known to be related to kidney damage. DisGeNET terms enriched include and related to Dengue fever, chronic Hepatitis, measles, retroviridae infections, respiratory syncytial virus Infections and many others. Kidney dysfunction related terms ischemia of kidney, renal fibrosis and diabetic nephropathy. Conclusion: Common deregulated genes in SARS-CoV infected cells and chronic kidney disease, as well as their enrichment with molecular processes and pathways relevant for viral pathogenesis and renal dysfunctions, could explain the severity of COVID-19 with kidney disease. This observation not only provides molecular relation of severity in COVID-19 with renal dysfunctions but might also help in the management and treatment targets for these cases.

Research on the chemical mechanism and reciprocal behavior of the coronavirus relate to living organisms, engaging in the give and take of electrochemical mediators, is a very important, controversial and vital issue. What we should accept is the chemical identity of this scenario, and not preferably a characteristic of a biological system. This chemical reaction should be familiar, referring to the theory of chemical pathways involved in DNA/proteins in the body against aggressive guests (such as viruses). From the point of view of a chemist, this simple reaction is nothing more than an oxidation-reduction reaction (redox-stress signaling) which conducted and carried out by coronavirus in a biointerface medium. Thereby, oxidizing as well as reducing reagents should be very constructive, promoting development in such chemical process. We understand redox reactions as switchable thiol/disulfide exchanges (formation and cleavage of inherent disulfide bonds), then, we can hugely profit from redox-responsive nano-surfaces equipped with multiple new ionic and covalent interactions. This game-changing idea can substantiate by surface modified-nanoparticles to play powerful roles in synthesis of nano oxidizers as well as reducing agents in nanomedicine. Chemists and pharmacists must then explore new thoughts and present modern experiences/approaches of preparation nanoparticles and nanocomposites to create novel vaccines as well as coronavirus drugs. In this regard, this experience can also be so helpful for HIV/AIDS, which is caused by viruses.

Parkinson’s disease (PD) is the most common cause of movement disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. It is increasingly recognized as a complex group of disorders presenting widely heterogenous symptoms and pathology. Except for the rare monogenic forms, the majority of the PD cases result from an interaction between multiple genetic and environmental risk factors. The search for these risk factors and the development of preclinical animal models are in progress hand in hand, providing mechanistic insights into the pathogenesis of PD. This review summarizes the studies that capitalize on modeling sporadic (i.e. non-familial) PD using Drosophila melanogaster and discuss their methodology, new findings and future perspective.

Inflammatory Bowel Disease (IBD) is characterized by chronic remitting and relapsing inflammation of the lower gastrointestinal tract. The etiology underlying IBD remains unknown but is thought to involve a hypersensitive immune response to environmental antigen, including the microbiota. Diagnosis and monitoring of disease is heavily reliant on endoscopy, which is invasive and does not provide information regarding specific mediators. This review describes recent developments in imaging of IBD with a focus on PET and SPECT imaging of inflammatory mediators, and how this may be applied to the microbiota.

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

Defects in pre-mRNA splicing are frequently a cause of Mendelian disease. Despite the advent of next-generation sequencing, allowing a deeper insight into a patient’s variant landscape, the ability to characterize variants causing splicing defects has not progressed with the same speed. To address this, recent years have seen a sharp spike in the number of splice prediction tools leveraging machine learning approaches, leaving clinical geneticists with a plethora of choices for in silico analysis. In this Review, some basic principles of machine learning are introduced in the context of genomics and splicing analysis. A critical comparative approach is then used to describe seven recent machine learning-based splice prediction tools, revealing highly diverse approaches and common caveats. We find that, although great progress has been made in producing specific and sensitive tools, there is still much scope for personalized approaches to prediction of variant impact on splicing. Such approaches may increase diagnostic yields and underpin improvements to patient care.

The aim of this cross-sectional study was to assess the perceived medication-related burden among patients with multiple non-communicable diseases (NCDs), and to investigate the association between perceived burden and adherence to medication therapy. Medication-related burden was measured in three primary care clinics in Qatar using the Living with Medicines Questionnaire (LMQ) among adults with diabetes, with or without other comorbidities. Adherence was measured using the Adherence to Refills and Medications Scale (ARMS). Two hundred ninety-three eligible patients participated in the study. Majority of participants reported experiencing minimum (66.6%) to moderate (24.1%) medication-related burden. There was a significant positive correlation between the medication-related burden (measured by the LWQ) and medication adherence (measured by ARMS) (rs (253) = 0.317, p <0.0005). The duration of diabetes diagnosis, adherence score, marital status, employment status, and presence diagnosis of hypertension were significant predictors of medication burden. A considerable proportion of the patients in this study have reported experiencing medication-related burden. Healthcare providers should seek strategies to address this burden especially among patients with risk factors of cardiovascular diseases, non-adherent to their medication therapy, living alone, or non-employed.

It has recently been discovered that mere cell contact by human cytomegalovirus (CMV) particles leads to profound modulation of cellular gene expression. Reduced monocyte human leukocyte antigen (HLA-DR) expression is a novel biomarker of severity and outcome in many diseases. Modulation of CD14 protein by CMV was shown in vitro, but little is known about the phenomenon in vivo (during active cytomegalovirus disease). Therefore, we investigated monocyte CD14 and HLA-DR expression in CMV infected patients in relation to logarithmic phase of infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. After CD45/SSC gating monocyte CD14 and HLA-DR expression were determined by double-color flow-cytometry. Significant monocytosis and poor correlation between CMV replication and CD14+HLA-DR(-) cells prompted CD14 investigation. During logarithmic phase of CMV infection increased count and percentage of CD14low monocytes were observed which correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, most of CD14low monocytes are HLA-DR+. The increase of CD14low monocytes is also observed under the influence of high dose of glucocorticoids (20 mg of dexamethasone). The reduction in CD14 induced by CMV and dexamethasone indicates that the monocyte balance is disturbed between the classical and non-classical phenotype. A high percentage of CD14lowHLA-DR+ probably gives rise to adaptive and a decrease of innate immune response. In light of the logarithmic increase of viral load (with exponent between 3,23 and 5,77), high monocytosis above 1200 / µl is a hallmark of CMV replication.

Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.

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

The poultry industry is affected by many epidemics and Newcastle Disease (ND) is a constant threat, known as a devastating disease for poultry farmers around the world. According to the average death time of chicken embryos, virus strains can be classified as lentogenic, mesogenic, or velogenic. The current research will clarify the vulnerable host range as well as the epidemiology and geographic distribution of ND in Pakistan. The introduction of the virus into poultry can have serious economic consequences, including the loss of production of sick and dying poultry, the cost of control measures (such as population reduction and disinfection measures), and possible trade restrictions in the event of an outbreak. The virus is transmitted by direct contact with sick poultry or carriers. Infected birds can also spread the virus in their feces. It can also be spread through respiratory secretions, contaminated feed, equipment, water, or feces. We will also discuss vaccines that which vaccines are available for NDV in Pakistan and vaccines can fight against this disease or not? In this study, a qualitative risk analysis was carried out to assess Pakistan's vulnerability to the introduction of virulent NDV strains

Oats represents a promising alternative to small-grain cereals from Triticeae group (wheat, barley, rye) for persons suffering from any form of gluten intolerance, especially celiac disease (CD), since oat-specific prolamins avenins reveal generally lower gluten content and immunoreactivity. Recent studies on avenin molecular structure revealed large genetic variability in avenin sequences affecting the spectrum of gluten peptides produced by hydrolases in human digestive tract. The aim of the present review is to summarise recent knowledge obtained in laboratory in vitro studies focused on the effect of avenin-derived peptides on reactivity of crucial components of human immune system such as dendritic cells (DC) and T-cells. The other part of the review summarises the results of clinical studies with CD patients including oat products in their diet. Since different clinical studies revealed contradictory results regarding potential safety of oats for CD patients, the focus has to be directed at genetic variability in oat avenins. Identification of avenin isoforms with minimum CD immunoreactivity will open up ways leading to designing novel oat cultivars suitable for CD patients. Knowledge on immunoreactivity of gluten peptides together with breeding new oat cultivars revealing minimum avenin immunoreactivity with respect to CD as well as application of food processing technologies leading to gluten content reduction should result in development of gluten-free oats safe for celiacs.

Background: Sickle cell disease is a major public health issue in the DRC while it is still poorly understood by health professionals. The objective of this study was to assess the knowledge and practices of Congolese physicians treating sickle cell disease (SCD) in order to identify areas for improvement in clinical care. Methods: This is a descriptive observational study conducted on Congolese physicians using a questionnaire. Participants were evaluated on a pre-established answer grid. Results: A total of 460 physicians participated, including 81 women (18%) with an average age of 35 years (range 25–60 years). Most physicians were general practitioners. Although self-assessment of their level of knowledge on SCD was estimated as average to good, less than half of the participants (n= 460; 46%) reported adequate management of vaso-occlusive crisis but only 1% of them had received specific training on SCD. Most physicians reported difficulties both in terms of diagnostic (65%) and management (79%) options of SCD patients. This study showed also that 85% of them did not have access to diagnostic tools for SCD. Conclusions: Insufficient knowledge on SCD, poor diagnostic and treatment options may contribute to morbidity and mortality of patients living in the DRC. Interventions aiming at improving physician’s knowledge, patient’s follow-up and treatment access are needed. Specific training alongside existing programs (HIV, malaria), early diagnosis of the disease, and creation of patients’ advocacy groups should improve SCD patient’s care.

This paper examines interlinkages and hedging opportunities between nine major cryptocurrencies for the period between 30 September 2015 and 4 June 2020, which notably includes the coronavirus disease 2019 (COVID-19) outbreak lasting from early 2020 through the end of the sample period. The results of dynamic conditional correlation (DCC) analysis using a minimum connectedness approach show a high degree of correlation between cryptocurrencies throughout the sample period. However, the correlations reach their minimum values during the COVID-19 pandemic, which indicates that cryptocurrencies acted as a hedge or safe haven during the stressful period of the COVID-19 pandemic. The weight of cryptocurrencies was significantly reduced and their hedging effectiveness varied greatly during the pandemic, which indicates that investors’ preferences changed during the COVID-19 period.

Tomato (Solanum lycopersicum L.) is a valuable horticultural crop grown and consumed worldwide. Optimum production is hindered by several factors of which Verticillium dahliae, the cause of Verticillium wilt, is one of the major biological constraints in temperate production regions. V. dahliae is difficult to manage because it is a vascular pathogen, has a broad host range and worldwide distribution, and can persist in soil for years. Understanding the pathogen virulence and genetic diversity, host resistance, and plant-pathogen interactions can ultimately inform the development of integrated strategies to manage the disease. In recent years, considerable research has focused on providing new insight into these processes as well as the development and integration of environment-friendly management approaches. In this review, we discuss and summarize the recent findings on the race and population structure of V. dahliae; pathogenicity factors; host genes, proteins, and enzymes involved in defense; the emergent management strategies, and recent approaches to managing Verticillium wilt in tomatoes.

After an incubation period of weeks to months up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats: 27 households were identified containing 147 cats; 13 cats were treated for FIP and 109 others shed FCoV. A 4-7 day course of oral GS-441524 antiviral stopped faecal virus shedding. Follow-up was from 6 months to 3.5 years: 11 of 147 cats died, but none developed FIP. No FIP-recovered cat relapsed. Cats from 8 households recovered from chronic FCoV enteropathy. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group: 37 of 820 cats developed FIP: the difference was statistically significant (p = 0.0038). Conclusions: early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household then FIP can result. Further work is required to establish the role of FCoV in cats with inflammatory bowel disease.

A COVID-19 disease threatens the population and the economies of the countries significantly. Till now, this pandemic has affected 215 counties or territories. Unavailability of vaccine is the primary concern for the society. To avoid the spread of this disease, social isolation must be preserved and the inter and intra-population movement must be minimized. To reduce the possibility of transmission, the categorization of regions based on susceptibility to COVID-19 infection is a must.Due to the unavailability of a large amount of paper collection for this novel COVID-19 diseases, we used current literature available on a COVID-19 susceptibility of the diabetic patient, human reproductivity, hemodialysis patient’s, pregnant women and meteorological factors and geographical location. Countries in the cold region are more susceptible to the risk of COVID-19 transmission. There was no evidence of the spread of this disease from non-respiratory bodies. Diabetic patients and pregnant women were found to be more susceptible to COVID-19 infection. Anosmia was observed in the majority of the COVID-19 infected cases in European countries. No evidence indicates COVID-19's impact on the human reproductive system explicitly. No cases of vertical transmission of this disease have been observed until now. All the studies available till now is the small scale study. Correlation with something always does not mean causation. There are certain factor like pollution level, temperature Diurnal temperature range, geographical factor, humidity, pollution level, wind speed, population density, medical healthcare facilities social and political factor plays a critical role in transmitting the SARS-COV-2 virus. Besides the adverse effects, it has taught us to shed our selfish goals and to promote the welfare of all.

Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuro-inflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby lipopolysaccharides may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments which may relieve the characteristic non-motor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.

To evaluate whether autologous mesenchymal cells, adipose derived stem cells and platelet-rich plasma, grafted into the supracoroideal space by surgical treatment according to Limoli retinal restoration technique (LRRT), can produce growth factors in order to exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and divided based on retinal foveal thickness ≤ 190 or >190 µm into group A and group B, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed an improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of RP, it can be confirmed that further research is needed on tapeto-retinal degenerations both from a clinical and molecular point of view to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation times, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

Background: Understanding SARS-CoV-2 dynamics and transmission is a serious issue. Its propagation needs to be modeled and controlled. The Alsace region in the East of France has been among the first French COVID-19 clusters in 2020. Methods: We confront evidence from three independent and retrospective sources: a population-based survey through internet, an analysis of the medical records from hospital emergency care services, and a review of medical biology laboratory data. We also check the role played in virus propagation by a large religious meeting that gathered over 2,000 participants from all over France mid-February in Mulhouse. Results: Our results suggest that SARS-CoV-2 was circulating several weeks before the first officially recognized case in Alsace on February 26^th 2020 and the sanitary alert on March 3^rd. The religious gathering seems to have played a role for secondary dissemination of the epidemic in France, but not in creating the local outbreak. Conclusions: Our results illustrate how the integration of data coming from multiple sources could help trigger an early alarm in the context of an emerging disease. Good information data systems, able to produce earlier alerts, could have avoided a general lockdown in France.

Rapid increase in digital data coupled with advances in deep learning algorithms is opening unprecedented opportunities for incorporating multiple data sources for modeling spatial dynamics of human infectious diseases. We used Convolutional Neural Networks (CNN) in conjunction with satellite imagery-based urban housing and socio-economic data to predict disease density in a developing country setting. We explored both single (uni) and multiple input (multimodality) network architectures for this purpose. We achieved maximum test set accuracy of 81.6 per cent using a single input CNN model built with one convolutional layer and trained using housing image data. However, this fairly good performance was biased in favor of specific disease density classes due to an unbalanced data set despite our use of methods to address the problem. These results suggest CNN are promising for modeling spatial dynamics of human infectious diseases, especially in a developing country setting. Urban housing signals extracted from satellite imagery seem suitable for this purpose, under the same context.

Vitamin D (VD) is a pro-hormone essential for life in higher animals. It is present in few types of foods and is produced endogenously in the skin by a photochemical reaction. The final step of VD activation occurs in the kidneys involving a second hydroxylation reaction to generate the biologically active metabolite 1,25(OH)₂-VD. Extrarenal 1α-hydroxylation has also been described to have an important role in autocrine and paracrine signaling. Vitamin D deficiency (VDD) has been in the spotlight as a major public health-care issue with an estimated prevalence of more than a billion people worldwide. Among individuals with chronic kidney disease (CKD), VDD prevalence has been reported to be as high as 80%. Classically VD plays a pivotal role in calcium and phosphorus homeostasis. Nevertheless, there is a growing body of evidence supporting the importance of VD in many vital nonskeletal biological processes such as endothelial function, renin-angiotensin-aldosterone system modulation, redox balance and innate and adaptive immunity. In individuals with CKD, VDD has been associated with albuminuria, faster progression of kidney disease and increased all-cause mortality. Recent guidelines support VD supplementation in CKD based on extrapolation from cohorts conducted in the general population. In this review, we discuss new insights on the multifactorial pathophysiology of VDD in CKD as well as how it may negatively modulate different organs and systems. We also critically review the latest evidence and controversies of VD monitoring and supplementation in CKD patients.

Background: The progression of periodontal diseases at national Portuguese level and its public awareness are of great interest, mainly due to the high burden of periodontitis. Objectives: To evaluate the prevalence progression of periodontal diseases in Portugal and correspondent public awareness, between 2004 and 2017, by using data from the Global Burden of Disease (GBD), Directorate-General of Health (DGH) and Google® Trends (GT). Methods: For the period 2004-2017, Portuguese national data of periodontal diseases prevalence were searched in the Institute for Health Metrics and Evaluation of GBD and DGH and for public awareness, GT comparison tool between Portuguese words for “Periodontitis”, “Gingivitis”, “Gums” and “Periodontal disease” trends was used. Results: For the period 2004-2017, the overall prevalence of periodontitis slightly increased from 11.3% to 11.7%. During that period the GT search term “Gums” (“Gengivas”) was the most relevant. It increased steadily over time while the search term “Periodontal disease” (“Doença periodontal”) decreased, being these search trends significantly correlated (

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an etiologic agent of the respiratory disease in humans that is known as coronavirus disease 2019 (COVID19). The first outbreak of the disease was initially documented in Wuhan, Hubei Province, China in late December 2019 where people had experienced SARS pneumonia-like symptoms with unknown etiology. Since then it has been observed that COVID-19 positive patients have been showing mild to severe upper respiratory illness symptoms. The type of virus is known to make its transfer from animals to humans and for the concerned virus; researchers have claimed its origin from bat coronavirus at whole-genome level with a 96 % sequence identity. The COVID-19 virus is very contagious and communicable in nature and has been spread throughout the globe since its first outbreak in China. On March 9, 2020, WHO declared it as a Pandemic, and within a month it was already reported to have shown its presence in 213 countries and territories or areas. As of April 29, 2020, this novel virus infected 3,218,183 people and caused 228,029 mortalities worldwide with a variable mortality rate from 3-13 % across the planet and also varied by age and gender. Diagnosis of the disease is a key component in understanding and controlling the spread of the virus and several techniques have been devised including RT-PCR, ELISA, and sequencing-based approaches. To cure COVID-19 patients as of now we do not have proven to be a safe and effective treatment. Therapeutic options currently under investigation in various parts of the world. However, there are various effective therapeutic targets to repurpose the present antiviral therapy for developing potential interventions against SARS-CoV-2. Boosting the immune system can also help to prevent and spread of COVID-19 using various medication and exercises. In this review, our goal to summarize and discussed the present scientific advancements to fight against this novel pandemic.

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was significantly increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia less than 50% of patients remain in a long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder which requires therapy in majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first line as well as relapsed setting. Rituximab is the preferred therapy for steroid refractory wAIHA and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of the rituximab and current literature its role in management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.

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

Air pollution has become a growing invisible killer in recent years and is major cause of morbidity and mortality globally. India stands 10th among the highly polluted countries with an average PM10 level of 134μg/m3 per year. It is also reported that 99% of India's population comes across air pollution level that exceed the World Health Organization Air Quality Guideline (AQG), PM2.5 permissible levels of 10 μg/m3. Maternal exposure to air pollution has a serious health outcome to the offspring because it can affect embryonic phases of development during the gestation period. Fetus is more prone to air pollution effect during embryonic developmental phases due to oxidative stress as antioxidant mechanisms are lacking at that stage. Any injury during this vulnerable period (embryonic phase) will have long-term impact on offspring health both in early and later in life. Epidemiological studies have revealed that maternal exposure to air pollution increases the risk of developing airways disease in offspring due to impaired lung development in utero. In this review, we discuss cellular mechanisms involved in maternal exposure to air pollution and how it can impact development of airways disease in offspring. Better understanding of these mechanisms in context of maternal exposure to air pollution can offer newer avenue to prevent development of airways disease in offspring.

We present a robust, fresh-frozen approach to immunohistochemistry (IHC), without committing the tissue to IHC via fixation and cryopreservation while maintaining long-term storage, using LiCor-based infrared (IR) quantification for sensitive assessment of TH in immunoreacted mid-brain sections for quantitative comparison across studies. In fresh-frozen tissue stored up to 1 year prior to IHC reaction, we found our method to be highly sensitive to rotenone treatment in 3-month-old Sprague-Dawley rats, and correlated with a significant decline in rotarod laten-cy-to-fall measurement by approximately 2.5 fold. The measured midbrain region revealed a 31% lower TH signal when compared to control (p<0.01 by t test, n=5). Bivariate analysis of in-tegrated TH counts versus rotarod latency-to-fall indicates a positive slope and modest but sig-nificant correlation of R2=0.68 (p<0.05, n=10). These results indicate this rapid, instrument-based quantification method by IR detection successfully quantifies TH levels in rat brain tissue, while taking only 5 days from euthanasia to data output. This approach also allows for the identifica-tion of multiple targets by IHC with the simultaneous performance of downstream molecular analysis within the same animal tissue, allowing for the use of fewer animals per study.

Background: Wheat root rot disease due to soil-borne fungal pathogens leads to tremendous yield losses worth billions of dollars worldwide every year. It is very important to study the relationship between rhizosphere fungal diversity and wheat roots to understand the occurrence and development of wheat root rot disease. Results: A significant difference in fungal diversity was observed between the diseased and healthy groups in the heading stage, but the trend was the opposite in the filling stage. The abundance of most genera with high richness decreased significantly from the heading to the filling stage in the diseased groups; the richness of approximately one-third of all genera remained unchanged, and only a few low-richness genera, such as Fusarium and Ceratobasidium, had a very significant increase from the heading to the filling stage. In the healthy groups, the abundance of most genera increased significantly from the heading to the filling stage; the abundance of some genera did not change markedly, or the abundance of very few genera increased significantly. Physical and chemical soil indicators showed that low soil pH and density, increases in ammonium nitrogen, nitrate nitrogen and total nitrogen contributed to the occurrence of wheat root rot disease. Conclusions: Our results revealed that in the early stages of disease, highly diverse rhizosphere fungi and a complex community structure can easily cause wheat root rot disease. The existence of pathogenic fungi is a necessary condition for wheat root rot disease, but the richness of pathogenic fungi is not necessarily important. The increases in ammonium nitrogen, nitrate nitrogen and total nitrogen contributed to the occurrence of wheat root rot disease. Low soil pH and soil density are beneficial to the occurrence of wheat root rot disease.

Parkinson’s disease (PD) is typically well-recognized by its characteristic motor symptoms (e.g., bradykinesia, rigidity, and tremor). The cognitive symptoms of PD are increasingly being acknowledged by clinicians and researchers alike. However, PD also involves a host of emotional and communicative changes which can cause major disruptions to social functioning. These include problems producing emotional facial expressions (i.e., facial masking) and emotional speech (i.e., dysarthria), as well as difficulties recognizing the verbal and non-verbal emotional cues of others. These social symptoms of PD can result in severe negative social consequences, including stigma, dehumanization, and loneliness, which might affect quality of life to an even greater extent than more well-recognized motor or cognitive symptoms. It is therefore imperative that researchers and clinicians become aware of these potential social symptoms and their negative effects, in order to properly investigate and manage the socioemotional aspects of PD. The present review provides an examination of the current research surrounding some of the most common social symptoms of PD and their related social consequences, and argues that proactively and adequately addressing these issues might improve disease outcomes.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

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

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

Mitochondria are involved in many cellular processes and their main role is cellular energy production. They constantly undergo fission and fusion, and these counteracting processes are under strict balance. The cytosolic dynamin-related protein 1, Drp1 or dynamin-1-like protein (DNM1L) mediates mitochondrial and peroxisomal division. Defects in the DNM1L gene results in a complex neurodevelopmental disorder with heterogeneous symptoms affecting multiple organ systems. Currently there is no curative treatment available for this condition. We have previously described a patient with a de novo heterozygous c.1084G>A (p.G362S) DNM1L mutation and studied the effects of a small molecule, Bezafibrate, on mitochondrial functions in this patient’s fibroblasts compared to controls. Bezafibrate normalized growth on glucose-free medium, ATP production, oxygen consumption and s improved mitochondrial morphology in patient’s fibroblasts, albeit concomitantly causing a mild increase ROS production. Further studies would be needed to show the consistency of the response to Bezafibrate, possibly using fibroblasts from patients with different mutations in DNM1L, and this treatment should be confirmed in clinical trials. However, taking into account the favorable effects in our study, we suggest that Bezafibrate could be a possible treatment option for patients with certain DNM1L mutations.

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

Background: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic and life-threatening highly infectious disease. The people of Bangladesh are at high risk of COVID-19 and have already experienced various socio-economic, health and psychological (mental) consequences. Particularly, mental health problems are dominantly reported in the literature and should be controlled. The main objective of this epidemiological study is to assess the mental distress and identify its determinants using online-based survey. Such information is urgently needed to develop feasible strategies for Bangladesh. Methods: An online survey was conducted for this study from May 01 to May 05, 2020. A total of 240 respondents provided self-reported online responses. Respondent’s mental distress was measured by the General Health Questionnaire 12 (GHQ-12) and by the self-rated mental health (SRMH) question. Various kinds of statistical analyses ranging from simple to multivariable logistic recession were performed using SPSS 23.0. Results: About 31.3% and 48.3% of respondents were mentally distressed by GHQ-12 and SRMH question, respectively. Logistic regression analysis revealed that mental distress was significantly higher among those respondents, whose usual activity was affected by the coronavirus (OR = 6.40, 95% CI: 1.87 - 21.90, p<0.001) and whose financial stress was increased due to lockdown (OR = 2.12, 95% CI: 1.01 – 4.46, p<0.05) on GHQ-12. Female sex (OR = 1.97, 95% CI: 1.03 – 3.75, p<0.05) and respondents with poor mental health before the outbreak (OR = 3.38, 95% CI: 1.18 – 9.72, p<0.05) were also significantly affected by mental distress on SRMH. Conclusions: At least thirty percent of the respondents were found to be mentally distressed. Some of the study findings, particularly significant determinants, should be considered while developing strategies to reduce the burden of mental distress among study respondents or similar group in Bangladesh.

Background: This paper investigates the statistical relationship between bilingualism and the Onset Age (OA) of AD and MCI across a clinical sample, consisting of 580 Alzheimer's Disease (AD) subjects and 1264 Mild Cognitive Impairment (MCI) subjects, via a statistical analysis conducted on the sample retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Method: To investigate whether bilingualism has any correlation with the OAs of AD or MCI subjects, our study leverages the full potential of the ADNI dataset, a dataset that covers both the OA and the bilingualism status of both the AD and MCI subjects. Prior to performing any meaningful statistical analysis, a regression model and a probabilistic model were developed in parallel to fill in the missing OA and bilingualism values. A simple least-square regression model that consists of an independent variable of registered age for Mini-Mental State Examination (MMSE) score was used to estimate the OA of the AD and MCI subjects in the ADNI dataset. After filling in the missing OA values, the number of subjects relevant for the statistical analysis increased from 816 (AD: 371, MCI: 445) to 1844 (AD: 580, MCI: 1264), which greatly enlarged the representation of the AD and MCI sample in the ADNI population. With increased sample size, a novel probabilistic classification model was introduced to infer an ADNI subject’s bilingualism when relevant demographic information and deterministic outcome were not readily available from the ADNI dataset. The weighted average OA for the bilinguals and the monolinguals was then computed, where the weights for the probabilistic labels were assigned based on the percentage of bilingualism in the general US population. Finally, a statistical analysis was performed to test whether any statistically significant correlation exists between the OA and the bilingualism of the AD and MCI subjects within the ADNI dataset. Findings: Our preliminary study demonstrates no significant statistical difference between the OA of the bilinguals and the monolinguals within the ADNI dataset. Thus, the monolingual speakers within the ADNI dataset do not statistically manifest earlier onset, as compared to the bilingual speakers, which is slightly inconsistent with some earlier statistical findings that bilingual speakers enjoy certain distinctive advantages, such as late onset of AD, as compared to monolingual counterparts.

The basal ganglia (BG) are a central component of the brain, crucial to the initiation, execution and learning of adaptive actions. The BG are the major site of the action of dopamine. An important aspect of the BG architecture is the existence of two paths, direct and indirect, having different projection targets and dopamine receptor expression. To understand the BG, dopamine, and related disorders, it is imperative to understand the two paths. The standard account used in neuroscience research for decades posits that the role of the direct path is to support movements, while that of the indirect path is to suppress unselected or completed movements. This account is contradicted by converging evidence. Here, we explain why the arguments supporting the standard account are flawed, and present a new account, in which the role of the indirect path is completely opposite: to support automated execution. During acute events, the direct path allows coarse responses. These are refined by competition, and the resulting focused response is executed and learned by the indirect path, assisted by cholinergic interneurons and the subthalamic nucleus (STN). The new account allows a novel understanding of the symptoms of Parkinson's disease, in particular tremor and rigidity, and of its treatment by STN deep brain stimulation.

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of Tau^T231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)^Y216 while increasing Akt^S473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Medical brain image analysis is a necessary step in the Computers Assisted /Aided Diagnosis (CAD) systems. Advancements in both hardware and software in the past few years have led to improved segmentation and classification of various diseases. In the present work, we review the published literature on systems and algorithms that allow for classification, identification, and detection of White Matter Hyperintensities (WMHs) of brain MRI images specifically in cases of ischemic stroke and demyelinating diseases. For the selection criteria, we used the bibliometric networks. Out of a total of 140 documents we selected 38 articles that deal with the main objectives of this study. Based on the analysis and discussion of the revised documents, there is constant growth in the research and proposal of new models of deep learning to achieve the highest accuracy and reliability of the segmentation of ischemic and demyelinating lesions. Models with indicators (Dice Score, DSC: 0.99) were found, however with little practical application due to the uses of small datasets and lack of reproducibility. Therefore, the main conclusion is to establish multidisciplinary research groups to overcome the gap between CAD developments and their complete utilization in the clinical environment.

New experimental and clinical findings question the historic view of hydrocephalus and its 100-year-old classification. In particular, real-time MRI evaluation of CSF flow and detailed insights into brain water regulation on the molecular scale indicate the existence of at least three main mechanisms that determine the dynamics of neurofluids. (i) Inspiration is a major driving force (ii) Adequate filling of brain ventricles by balanced cerebrospinal fluid upsurge is sensed by cilia (iii) The perivascular glial network connects the ependymal surface to the pericapillary Virchow-Robin spaces. Hitherto, these aspects have not been considered a common physiologic framework improving knowledge and therapy for severe disorders of normal-pressure and post-haemorrhagic hydrocephalus, spontaneous intracranial hypotension and spaceflight disease.

Covid-19 has given a halt to all the activities in the world. Europe was most affected, followed by the United States of America. It has taken more than 350000 lives until now. In this study, we have assessed the severity of Covid-19 by analyzing the mortality rate of Covid-19 and other chronic diseases. The Covid-19 data and “death rate” data caused by other diseases were downloaded from the world health organization (WHO) website. A normalized method was used to see the mortality rate of Covid-19 in comparison to other diseases. The deaths caused by Covid-19 in April 2020 have overtaken the average number of deaths caused by Cancer, Cardiovascular diseases, and other diseases in Belgium, the United Kingdom (UK), Spain, France, and Ireland. Covid-19 was found to be strongly correlated with non-communicable respiratory diseases and Cancer with correlation coefficients 0.73 and 0.67 respectively. The severity of Covid-19 in the United States of America (USA) was moderate. The severity of Covid-19 in Asian countries was found to be low. Europe showed the highest diversity in the mortality rate of Covid-19. On average, except for a few European countries, Cardiovascular diseases, cancer, and non-communicable respiratory diseases were still more lethal and caused more deaths than Covid-19.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD remains poorly understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.

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.

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

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

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..

Background: Inadequate meibomian glands (MGs) secretion can lead to dry eye signs and symptoms. Tear film lipid layer (TFLL) secreted by MGs protects and prevents rapid evaporation of tear film. Our purpose was to assess TFLL alteration and function in patients with evaporative dry eye (EDE) using tear interferometry after optimal pulse light technology (OPT) intense pulsed light (IPL). Methods: This prospective randomized examiner-masked sham- controlled study included 86 participants (142 eyes) with DED. IPL or sham procedure was performed on day 0, 21, and 42. Ocular Surface Disease Index (OSDI), non-invasive breakup time (NITBUT), interferometric fringe pattern determined TFLL quality, fluorescein staining (FS), and meibum gland (MG) were assessed at day 0, 21, 42 and 3-month. Results: At 3-month, TFLL, NITBUT, MG drop-out, MG quality, MG expressibility, FS and OSDI improved significantly (P<0.05) in the IPL group, while the sham group had no significant improvements. All DE parameters significantly correlated with the improvement in TFLL following IPL treatment. Additionally, artificial tears usage was significantly less in the IPL group from D-42 onwards. Conclusion: IPL treatment demonstrated the ability to improve TFLL quality and clinically reduced sign and symptoms of DED thereby reducing the frequency of artificial tears usage.

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

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

Abstract: Early life gut microbiota have been increasingly recognized as major contributors to short and/or long-term human health and diseases. Numerous studies have demonstrated that human gut microbial colonization begins at birth but continues to develop a succession of taxonomic abundances for two to three years until the gut microbiota reaches adult-like diversity and proportions. Several factors, including gestational age (GA), delivery mode, birth weight, feeding types, antibiotic exposure, maternal microbiome and diet influence the diversity, abundance and function of the early life gut microbiota. Gut microbial life is essential for assisting with the digestion of food substances to release nutrients, exerting control over pathogens, stimulating or modulating the immune system and influencing many systems such as the liver, brain, and endocrine system. Microbial metabolites play multiple roles in these interactions. Furthermore, studies provide evidence supporting that imbalances of the gut microbiota in early life, referred to as dysbiosis, are associated with specific childhood or adult disease outcomes, such as asthma, atopic dermatitis, diabetes, allergic diseases, obesity, cardiovascular diseases (CVD) and neurological disorders. These findings support that the human gut microbiota may play a fundamental role in the risk of acquiring diseases that may be programmed during the early life stage. In fact, it is critical to explore the role of the human gut microbiota in early life. In this review, we summarize the general understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the relationship between the gut microbiota composition and their metabolites, and immune functions, which could significantly influence long-term health and disease. We then review known pathophysiological interactions of the early gut microbiome with a number of well characterized diseases and pose potential etiological mechanisms.

The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second ¹²⁹Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized ¹²⁹Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD. Participants with Alzheimer’s disease (n=4) and healthy volunteers (n=4) were imaged using hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to determine the amount of retain xenon in the brain. At 60 sec post breath hold, AD patients retained significantly higher amounts of ¹²⁹Xe compared to healthy controls. Data was fit to a pharmacokinetic model and the xenon washout parameter was extracted. Xenon washout in white and grey matter occurs at a slower rate in Alzheimer’s participants (¹²⁹Xe half-life time of 42s and 43s, respectively) relative to controls (20s and 16s, respectively). Following larger scale clinical trials for validation, the xenon washout parameter has the potential to become a useful biomarker for the support of an AD diagnosis.

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

Background: Diabetes Mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis. Objective: This study aims to evaluate the side effect of Metformin for diabetic kidney diseases (DKD) patients. Method: This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library. Results: Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are considered to be below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension. Conclusion: Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.

Average of 41,900 patients are diagnosed annually with staphylococcus bacterial infection in California, 24,089 patients have Methicillin-resistant Staphylococcus Aureus (MRSA) and 17,810 patients have Methicillin-Sensitive Staphylococcus (MSSA). This paper demonstrates that there is a difference in mortality rate due to staphylococcus infection between males and females (P-value<0.05, CI 95%). Male patient diagnosed with S. aureus has 1.3 chance of mortality incidence than female patient. In addition, MRSA infection rate is 1.4 times MSSA infection (P-value<0.05, CI 95%), but the gap of infection is decreasing; however, mortality of both infections combined are more than threefold greater compared to three decades ago.

Recent studies supported a clinical association between Parkinson’s Disease (PD) and periodontitis. Hence, investigating possible protein interactions between these two conditions is of interest. In this study, we conducted a protein-protein network interaction analysis with recognized genes encoding proteins for PD and periodontitis. Genes of interest were collected via GWAS database. Then, we conducted a protein interaction analysis using STRING database, with a highest confidence cut-off of 0.9. Our protein network casted a comprehensive analysis of potential protein-protein interactions between PD and periodontitis. This analysis may underpin valuable information for new candidate molecular mechanisms between PD and periodontitis and may serve new potential targets for research purposes. These results should be carefully interpreted giving the limitations of this approach.

Huntington disease (HD) is an autosomal dominantly inherited fatal neurodegenerative disease. It affects motor, cognitive and psychiatric functions, and ultimately leads to death. The pathology of the disease is due to an expansion of CAG repeats in exon 1 of the huntingtin gene on chromosome 4, which produces a mutant huntingtin protein (mhtt). HD patients manifest a typical phenotype of sporadic, rapid, involuntary control of limb movement, stiffness of limbs, impaired cognition and severe psychiatric disturbances. A variety of symptomatic treatments (which target excitotoxicity, the dopamine pathway, caspases, aggregation, mitochondrial dysfunction, transcriptional dysregulation, mHtt, nucleic acid, neurodegeneration, fetal neural transplants, etc.) are currently available, and new symptomatic and potentially disease-modifying therapies are being actively developed. Recent advances in novel therapeutic strategies, including targeting mutant huntingtin (mhtt) and the htt gene, promise another wave of disease-modifying trials in the near future. A better appreciation of heterogeneous clinical phenomenology and immediate tractable treatment goals coupled with advances in new therapeutics heralds a golden age of HD treatment that will positively impact the quality of life and longevity of HD patients and inform advances in other inherited and neurodegenerative neurological disorders. In the present review literature, our aims to address the latest research on promising therapeutics based on influencing the hypothesized pathological mechanisms associated with HD.

Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease. We aimed to determine the effects of lactoferrin intervention on cognitive function from APP/PS1 mice, and possible mechanisms involved in. Both young and middle-aged male APP/PS1 mice were divided into control and lactoferrin group with 16 weeks’ intervention. Lactoferrin intervention had no effects on cognitive function from both young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered post lactoferrin intervention. In regards to gut microbiota profiles, in the young mice, lactoferrin elevated α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter, in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant post Lf intervention via LEfSe analysis. In the middle-aged mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus and Ruminococcus was significantly reduced post Lf intervention, additionally, S24_7, Bacteroidia, Bacteroidetes and Methylobacterium were specific via LEfSe analysis post lactoferrin intervention. In conclusion, dietary lactoferrin might be beneficial for gut microbiota homeostasis although might have no effects on cognition.

Sonic Hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh+ MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. In this study, the plasma number of Shh+ MPs in patients with peripheral artery disease (PAD) and control subjects without PAD. We found significantly higher number of Shh+ MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs – produced either by endothelial cells, platelets, leukocytes, and erythrocytes – was not different between PAD patients and controls. Interestingly, the concentration of Shh protein unbound to MPs – which was measured in MP-depleted plasma – was not different between subjects with PAD and controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel insights on the mechanisms through which the Shh signaling is reactivated during ischemia in humans, with potentially important fundamental and clinical implications.

Organ-on-a-Chip (OoC) systems bring together cell biology, engineering, and material science for creating systems that recapitulate the in vivo microenvironment of tissues and organs. The versatility of OoC systems enables in vitro models for studying physiological processes, drug development, and testing in both academia and industry. This paper evaluates current platforms from the end-user perspective, elaborating on usability, complexity, and robustness. We surveyed 165 peers in over 30 countries and grouped the responses according to preliminary knowledge and the source of the OoC systems that are used. The survey clearly shows that current commercial OoC platforms provide a substantial level of robustness and usability - which is also indicated by an increasing adaptation of the pharmaceutical industry but a lack of complexity can challenge their use as a predictive platform. Self-made systems on the other hand are less robust and standardized but provide the opportunity to develop customized and more complex models which are often needed for human disease modeling. This review serves as a guide for researchers in the OoC field and encourages the development of next-generation OoCs.

The import and export of tree seed carries with it risks of inadvertent introduction of pests and pathogens to hitherto unaffected regions. Although trade in seed of specified trees is regulated, phytosanitary requirements for most tree species are minimal, even those related to the most important forest tree species in a given region. A better understanding of the microbiome associated with seed intended for commercial production or ornamental use, and their potential risk with the transport from the source origin of distributors, will help regulatory agencies implement measures to prevent new and emerging risks. In this study we used high throughput sequencing to show that highly diverse fungal communities were associated with seed of 14 different Pinus species obtained from seed banks (seed orchards) and retail sources (online distributors) in North America and Europe. Fungal diversity differed among the 23 seedlots tested. Community composition did not relate to the species of Pinus nor the country of origin. Assigned potential functions based on sequence identity using FUNGuild provided an overall understanding of the likely life strategies associated fungal OTUs. Of those sequences classified to a trophic level, 453 were plant pathogens, with the Dothideomycetes having the highest prevalence. The most common plant pathogens detected included Sydowia polyspora, Lasiodiplodia theobromae, Diplodia intermedia and Diplodia sapinea. The evidence presented here illustrates an urgent need for plant protection authorities, practitioners and the general public to recognize the potential risk of introducing harmful pathogens through innocent transport of seed.

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

Exercise training influences the risk of vascular thrombosis in patients with peripheral arterial disease (PAD). Mitochondrial functionalities in platelets involve the cellular bioenergetics and thrombogenesis. This study aimed to elucidate the effect of cycling exercise training (CET) on platelet mitochondrial bioenergetics in PAD patients. Forty randomly selected patients with PAD engaged in general rehabilitation (GR) with CET (i.e., cycling exercise at ventilation threshold for 30 min/day, 3 days/week) (GR+CET, n=20) or to a control group that only received GR course (n=20) for 12 weeks. Systemic aerobic capacity and platelet mitochondrial bioenergetics that included oxidative phosphorylation (OXPHOS) and electron transport system (ETS) were measured using automatic gas analysis and high-resolution respirometry, respectively. The experimental results demonstrated that GR+CET for 12 weeks significantly (i) elevated VO2peak and lowered VE-VCO2 slope, (ii) raised resting ankle-brachial index and enhanced cardiac output response to exercise, (iii) increased the distance in 6-minute walk test and raised the Short Form-36 physical/mental component scores, and (iv) enhanced capacities of mitochondrial OXPHOS and ETS in platelets by activating FADH2 (Complex II)-dependent pathway. Moreover, changes in VO2peak levels were positively associated with changes in platelet OXPHOS and ETS capacities. However, no significant changes in systemic aerobic capacity, platelet mitochondrial bioenergetics, and health-related quality of life (HRQoL) occurred following GR alone. Hence, we conclude that CET effectively increases the capacities of platelet mitochondrial bioenergetics by enhancing Complex II activity in patients with PAD. Moreover, the exercise regimen also enhanced functional exercise capacity, consequently improving HRQoL in PAD patients.

The basic pattern of MHC variation in fish, with MHC class I versus class II, and polymorphic classical versus nonpolymorphic nonclassical, is similar in fish and mammals. Nevertheless, in many or all teleost fishes, important differences with mammalian or human MHC were observed: (1) The allelic/haplotype diversification levels of classical MHC class I genes tend to be much higher than in mammals; (2) Teleost fish classical MHC class I and class II loci are not linked. The present article summarizes previous studies that performed quantitative trait loci (QTL) analysis for mapping differences in teleost fish disease resistance, and discusses them from MHC point of view. Overall, those studies suggest the possible importance of genomic regions including classical MHC class II and nonclassical MHC class I genes, whereas similar observations were not made for the genomic regions with the highly diversified classical MHC class I alleles. The present study is a review and discussion of the fish MHC situation.

As metabolomics is widely used in the study of disease mechanisms, more and more studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with a HFD for 30 and 50 days. Results indicated quercetin exhibited hepatoprotective activity in HFD-induced NAFLD rats in 30 days by regulating fatty acids related metabolites (adrenic acid, etc.), inflammation related metabolites (arachidonic acid, etc.), oxidative stress related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin couldn’t improve NAFLD in 50 days maybe it couldn’t reverse the inflammation condition induced by long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD at early stages. Furthermore, combining metabolomics and experimental approaches opens up avenues of effects and mechanisms of drugs for complex diseases.

Neurodegenerative diseases of protein misfolding affect humans and animals. In humans, these diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC). Mineral exposure may be important in the pathogenesis of protein misfolding cascades. The possible association of bentonite, montmorillonite, and mineral risk factors with Alzheimer’s disease, Parkinson’s disease, ALS, and Western Pacific ALS/PDC is analyzed and discussed.

Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGFs, a group of proteins with roles in neuronal ion channel regulation and synaptic transmission. We have previously demonstrated that a male Fgf14-/- mouse model recapitulates salient endophenotypes of synaptic dysfunction and behaviors associated with schizophrenia (SZ). As the underlying etiology of SZ and its sex-specific onset remain elusive, the Fgf14-/- model provides a valuable tool to interrogate pathways that might be related to the disease mechanism. Here, we performed label free quantitative proteomics and bioinformatics to identify enriched pathways at the proteome level in the male and female hippocampi from Fgf14+/+ and Fgf14-/- mice. We discovered that many differentially expressed proteins in Fgf14-/- animals are associated with SZ. In addition, measured changes in the proteome and signaling pathways were predominantly sex-specific with the male Fgf14-/- being distinctly enriched for pathways associated with neuropsychiatric disorders and addiction and the female exhibiting modest changes. In the male Fgf14-/- mouse the major protein changes that could in part explain the previously described neurotransmission and behavioral phenotype of this model were loss of ALDH1A1 and PRKAR2B. ALDH1A1 has been shown to mediate an alternative pathway for GABA synthesis, while PRKAR2B is essential for dopamine 2 receptor signaling, which is the basis of current antipsychotics. Collectively, our results provide new insights in the role of FGF14 and support the use of the Fgf14-/- mouse as a useful preclinical model of SZ for generating hypothesis on the disease mechanism, sex-specific manifestation and therapy.

Depending on the characteristics of the industrial area, toxicity evaluation of human body, risk assessment and health impact assessment may directly cause cancer due to air pollution. Environmental data collection is from August 2018 to January 31, 2019, and the average, minimum, and maximum values of air pollution data respectively. According to the global data on global trends using the Big Data, high blood pressure is confirmed at 33rd place in the world, and myocardial infarction among the environmental diseases is confirmed to be lower than Korea. Disease that occurred in Jeolla province industrial complex considering the characteristics of our country was identified as representative. Air pollutants are considered to be the causes of allergic diseases in Korea. PM10 was found to be higher than the control area (28.8804348 (㎍ / ㎥), 31.7065217 (㎍ / ㎥) and 32.8532609 (㎍ / ㎥). The mean concentrations of PM2.5 in the middle and high exposure areas were lower than those of the control areas, but the highest in the intermediate exposure areas was 16.5978261 (㎍ / ㎥), 16.1086957 (㎍ / ㎥) and 17.1847826 (㎍ / ㎥) respectively. The relationship between the major variables of environmental exposure in Yeosu was confirmed to be correlated with high blood pressure, chronic obstructive pulmonary disease (COPD), bronchitis, cerebrovascular, diabetes, thyroid disease, sinus infection, anemia and pneumonia.

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