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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Crimean-Congo hemorrhagic fever virus is one the most important and wide spread tick-borne viruses. Very little is known about the transmission from the tick and the early aspects of pathogenesis. Here, we generate human cutaneous antigen presenting cells: dermal dendritic cells and Langerhans cells, from umbilical cord progenitor cells. In order to mimic the environment created during tick feeding, tick salivary gland extract was generated from semi-engorged Hyalomma marginatum ticks. Our findings indicate that human dermal dendritic cells and Langerhans cells are susceptible and permissive to Crimean-Congo hemorrhagic fever virus infection, however, to different degrees. Infection leads to cell activation and cytokine/chemokine secretion, although these responses vary between the different cell types. Hyalomma marginatum salivary gland extract had minimal effect on cell responses, with some synergy with viral infection with respect to cytokine secretion. However, salivary gland extract appeared to inhibit antigen presenting cell (APC) migration. Based on the findings here we hypothesize that human dermal dendritic cells and Langerhans cells serve as early target cells. Rather affecting Crimean-Congo hemorrhagic fever virus replication, tick saliva likely immunomodulates and inhibits migration of these APC from the feeding site.

This research evaluates the feasibility of addressing computer vision problems with limited resources, particularly in the context of medical data where patient privacy concerns restrict data availability. (1) Background: The study focuses on diagnosing skin diseases using five distinct transfer learning models based on convolutional neural networks. Two versions of the dataset were created, one imbalanced (4092 samples) and the other balanced (5182 samples), using simple data augmentation techniques. Preprocessing techniques were employed to enhance the quality and utility of the data, including image resizing, noise removal, and blur techniques. The performance of each model was assessed using fresh data after preprocessing. According to the research findings, (2) Methods: the VGG-19 model achieved an accuracy of 95.00% on the imbalanced dataset. After applying augmentation on the balanced data, the best-performing model was VGG-16-Aug with an accuracy of 97.07%. (3) Results: These results suggest that low-resource approaches, coupled with preprocessing techniques, can effectively identify skin diseases, particularly when utilizing the VGG-16-Aug model with a balanced dataset. (4) Conclusions: The study addresses rare skin disorders that have received limited attention in past research, including acne, vitiligo, hyperpigmentation, nail psoriasis, and SJS-TEN. The findings highlight the potential of simple data augmentation techniques moreover, explainable AI: Grad-CAM interpreted the model outcome by showing image contours visually as well as identifying uncommon skin conditions and overcoming the data scarcity challenge. The implications of these research findings are significant for the development of machine learning-based diagnostic systems in the medical field. Further investigation is necessary to explore the generalizability of these findings to other medical datasets.

Background The operator's ability in performing carotid stenting (CAS) has improved clinical outcomes. However, more than 3% of patients need to be treated again after CAS. Most of the cases requiring further intervention are affected by hyperplasia. The recommended procedure is the DEBalloon. On the other hand, the literature reports a small number of carotid neoatherosclerosis cases and is recommended to be treated using elective Micronet-covered stent. Discriminating between the two types of in-stent-restenosis ISR (hyperplasia or neoatherosclerosis) is critical for a positive outcome.Case summary We describe a case in which a patient treated with carotid stenting 8 years before, was diagnosed with ISR. Due to the development of neurological symptoms and progressive increases in Peak Systolic Velocity (PSV) eight years following carotid stenting, a DEBalloon was used in a carotid in-stent-restenosis (ISR) standard procedure. About ten minutes after the procedure, the patient developed hemiplegia consistent with the treated carotid territory. The implantation of a MicroNet-covered stent excluded the thrombus and reverted symptoms with a normal MR control at 24 h. Conclusion This case illustrates that when in-stent stenosis evolves years after the stent implantation, neoatherosclerosis should be assessed, and a MicroNet-covered stent should be considered.

In this paper is described the obtention of fourteen derivatives from four natural labdane diterpenes isolated from Copaifera oleoresin, named ent-copalic acid (1), ¬ent-3beta-acetoxy copalic acid (2), ent-3beta-hydroxy copalic acid (3) and ent-agathic acid (4). All eighteen compounds were assayed against promastigote form of Leishmania amazonensis and trypomastigote forms of Trypanosoma cruzi, revealing two promising compounds related to leishmanicidal activity (IC50 = 5.94 micromolar and 5.31 micromolar) and three promising compounds with trypanocidal activity, two of them (IC50 = 13.31micromolar and IC50 = 15.05micromolar) displaying similar activity as the reference drug (IC50 = 13.12micromolar) and one of them even more potent with IC50 = 0.425micromolar.

Chronic obstructive pulmonary disease (COPD) is a condition that significantly impacts both patients and healthcare systems. The management of COPD involves various pharmacological intervention strategies, and addressing the issue of low adherence to these strategies has become a subject of significant interest. In response to this concern, there has been a shift towards utilizing telemedicine and mobile applications. The primary objective of this scoping review is to delineate the usage of mobile applications to enhance pharmacological therapeutic adherence in adult patients with COPD. The study involved a search of databases such as Medline, Google Scholar, Cochrane, and ClinicalTrial.gov, focusing on literature published in English and Spanish over the last decade. The selected studies assessed interventions involving mobile applications (mobile apps) designed to improve pharmacological adherence. Four digital aids were identified, available on online platforms, mobile apps, or both: m-PAC, myCOPD, Wellinks mHealth, and Propeller Health. Pro-peller Health, in particular, is an app that directly measures pharmacological adherence through electronic medication monitors attached to participants' inhalers. Opening the app was associated with higher odds of using control medications compared to participants who did not open the app. The findings suggest that these digital interventions serve as valuable tools to enhance patient adherence to treatment. Future research should focus on evaluating the effectiveness of different digital devices, such as digital inhalers and mobile applications, that directly measure pharmacological adherence.

In strawberry cultivation, precise disease management is crucial for maximizing yields and reducing unnecessary fungicide use. Traditional methods for measuring Leaf Wetness Duration (LWD), a critical factor in assessing the risk of fungal diseases such as botrytis fruit rot and anthracnose, have been reliant on sensors with known limitations in accuracy and reliability and difficulties with calibrating. To overcome these limitations, this study introduced an innovative algorithm for leaf wetness detection systems employing high-resolution imaging and deep learning technologies, including convolutional neural networks (CNNs). Implemented at the University of Florida's Plant Science Research and Education Unit (PSREU) in Citra, Florida, USA and expanded to three additional locations across Florida, USA, the system captured and analyzed images of a reference plate to accurately determine the wetness and, consequently, the LWD. The comparison of system outputs with manual observations across diverse environmental conditions demonstrated the enhanced accuracy and reliability of the artificial intelligence-driven approach. By integrating this system into the Strawberry Advisory System (SAS), this study provided an efficient solution to improve disease risk assessment and fungicide application strategies, promising significant economic benefits and sustainability advances in strawberry production.

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a) and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT’s target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

Accurate crop diseases classification is crucial for ensuring food security and enhancing agricultural productivity. However, existing crop disease classification algorithms primarily focus on a single image modality and typically require a large number of samples. Our research counters these issues by using pre-trained Vision-Language Models (VLMs), which enhances multimodal synergy for better crop disease classification than traditional unimodal approaches. Firstly, we apply the multimodal model Qwen-VL to generate meticulous textual descriptions for representative disease images selected through clustering from the training set, which will serve as prompt text for generating classifier weights. Compared to using solely the language model for prompt text generation, this approach better captures and conveys fine-grained and image-specific information, thereby enhancing prompt quality. Secondly, we integrate the cross-attention and the SE (Squeeze-and-Excitation) attention into the training-free mode VLCD (Vision-Language model for Crop Diseases classification) and the training-required mode VLCD-T (VLCD-Training) respectively for prompt text processing, enhancing classifier weights by emphasizing key text features. Experimental outcomes conclusively prove our method’s heightened classification effectiveness in few-shot crop disease scenarios, tackling data limitations and intricate disease recognition issues. It offers a pragmatic tool for agricultural pathology and reinforces the smart farming surveillance infrastructure.

Rice has become the second major food among rural people. It is one of the most nutrient and low-cost food available in Asia. Rice is composed of two major subspecies as Japonica and Indica and it belongs to the Poaceae family. The World Bank predicts that rice demand will grow 51% faster than population growth in 2025. It is high time to develop a model which predicts the type of infected paddy leaf and avoids the loss of grains. In this paper, the proposed hybrid CNN model, three CNN networks with different layer properties are trained parallel. The extracted feature from these CNN networks is combined to provide the classification of the type of infected leaf. Fieldwork was carried and about 340 samples are collected from five different types of classes. The proposed hybrid model was tested with both the fieldwork dataset and also with an available dataset on the internet. The experimental results show that the proposed model outperforms the other CNN network and yields an accuracy value of 98%, a precision value of 95%, and a misclassification rate of 4% respectively.

Mulberry leaves, when infected by pathogens, can suffer significant yield loss or even death if early disease detection and timely spraying are not performed. To enhance the detection performance of mulberry leaf diseases in natural environments and to precisely locate early small lesions, we propose a high-precision, high-efficiency disease detection algorithm named YOLOv8-RFMD. Based on improvements to You Only Look Once version 8 (YOLOv8), we first proposed the Multi Dimension Feature Attention (MDFA) module, which integrates important features at the pixel-level, spatial and channel dimensions. Building on this, we designed the RFMD Module, which consists of the Conv-BatchNomalization-SiLU (CBS) module, Receptive-Field Coordinated Attention (RFCA) Conv, and MDFA, replacing the Bottleneck in the model’s Residual block. We then employed Adown down sampling structure to reduce the model size and computational complexity. Finally, to improve the detection precision of small lesion features, we replaced the complete intersection over union (CIOU) loss function with the Normalized Wasserstein Distance (NWD) loss function. Results show that the YOLOv8-RFMD model achieves an mAP50 of 94.3% and an mAP50:95 of 67.8% on experimental data, representing increases of 2.9% and 4.3% respectively compared to the original model. The model size is reduced by 0.53 MB to just 5.45 MB, and the number of floating-point operations is reduced by 0.3 G to only 7.8 G. The improved model meets the deployment requirements of mobile embedded devices and can provide a theoretical reference for the automated spraying operations of mulberry leaves.

Background and Objectives: The existing recommendations for female pelvic magnetic susceptibility weighted imaging MRI (FP-SWI) have not been optimized to capture the disease characteristics of the female pelvis. Therefore, it is imperative to explore acquisition parameters before conducting larger-scale studies. To establish optimized flip angle (FA) for acquiring FP-SWI to improve the image quality of female pelvic lesion sites. Materials and Methods: To evaluate signal quality and lesion conspicuity, regions of interest (ROIs) were manually drawn within the lesion on SWI sequences. Signal intensity was measured within the ROIs. Additionally, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for SWI sequences acquired at three FA: 10°, 15°, and 20°. Finally, a qualitative assessment of anatomical detail visualization, geometric distortion extent, artifacts, and lesion clarity was performed using a four-point scale. The Wilcoxon rank sum test was employed to compare the qualitative evaluation parameters. The intra-class correlation coefficient (ICC) was calculated to determine the consistency of subjective ratings between two observers. Results: FA=10° showed significantly higher SNR than FA=15° and 20° in most anatomical regions (P&lt;0.05), while the CNR was significantly higher than FA=15° and 20° (P&lt;0.05). Compared with FA=15° and 20°, the image quality of FA=10° was significantly higher, with less distortion and ghosting, and better image contrast (P&lt;0.05). Lesions with FA=10° exhibited higher clarity compared to FA=15° and 20° (P&lt;0.05). Conclusions: The image quality of FP-SWI images at FA=10° exceeds that at FA=15° and 20°. We recommend that when conducting SWI examination of the female pelvic cavity, the FA value should be set at 10° to stabilize the SWI sequence and improve image quality.

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR-type 2 angiogenesis and vascular morphogenesis as the tyrosin kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between vascular endothelial growth factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and is shared by stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

Background: Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with a rapidly increasing prevalence. Current therapeutic options primarily manage symptoms, not modifying the disease. Secretome-based therapies have emerged as a promising avenue for AD treatment in targeting multiple pathways and promoting neuroprotection and regeneration. This systematic review evaluated the preclinical and clinical evidences for secretome-based therapies in AD.Methods: A systematic search was conducted across Scopus, PubMed, ScienceDirect, and Cochrane Library. The SYRCLE risk of bias (RoB) tool was used for preclinical studies and Cochrane RoB 2.0 for clinical studies. We performed qualitative analysis of study results.Results: Included 21 in vivo studies and 2 clinical trials revealed promising outcomes of treatments involving secretomes, exosomes, and extracellular vesicles from different cell sources. The therapies could reduce amyloid plaque load, reactive gliosis, and enhance neuronal density. These findings suggested the treatments reveal mechanism of action in neuroprotection, neuroregeneration, and inflammation modulation, which are critical in AD pathology. Ongoing trials also supported the safety and efficacy of the treatment strategies. However, translational medical study faces several challenges regarding large-scale production, optimization of protocols, and understanding biomarkers. The heterogeneity in secretome-based therapies administration have complicated the comparison of study outcomes and the translation of preclinical findings into clinical settings. Deeper understanding of the secretome's mechanisms of action, optimal dosing, and delivery methods are needed to maximize therapeutic outcomes.Conclusion: Despite secretome-based therapies hold significant promise for AD treatment, addressing the identified gaps and limitations is crucial for advancing these therapies from preclinical research to clinical practice.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, manifests through dysregulation of brain function and subsequent loss of bodily control, attributed to β-amyloid plaque deposition and TAU protein hyperphosphorylation and aggregation, leading to neuronal death. Concurrently, similar cannabinoids to the ones derived from Cannabis sativa are present in the endocannabinoid system, acting through receptors CB1R and CB2R and other related receptors such as Trpv-1 and GPR-55, and are being extensively investigated for AD therapy. Given the limited efficacy and adverse effects of current available treatments, alternative approaches are crucial. Therefore, this review aims to identify effective natural and synthetic cannabinoids and elucidate their beneficial actions for AD treatment. PubMed and Scopus databases were queried (2014–2024) using keywords such as "Alzheimer's disease" and "cannabinoids". The majority of natural (THC, CBD, AEA, etc.) and synthetic (JWH-133, WIN55,212-2, CP55-940, etc.) cannabinoids included, showed promise in improving memory, cognition, and behavioral symptoms, potentially via pathways involving antioxidant effects of selective CB1R agonists (such as the BDNF/TrkB/Akt pathway) and immunomodulatory effects of selective CB2R agonists (TLR4/NF-κB p65 pathway). Combining anticholinesterase properties with cannabinoid moiety may enhance therapeutic responses, addressing cholinergic deficits of AD brains. Thus, the positive outcomes of the majority of studies discussed supports further advancing cannabinoids in clinical trials for AD treatment.

COVID-19 has substantially influenced healthcare systems, requiring early prognosis for innovative therapies and optimal results, especially in individuals with comorbidities. Healthcare practitioners have used AI systems for investigating, anticipating, and predicting diseases, through means including medication development, clinical trial analysis, and pandemic forecasting. This study proposes the use of AI to predict disease severity in terms of hospital mortality among COVID-19 patients. Methodology: A cross-sectional study was conducted the approval from the Research Ethics Committee of King Abdulaziz University (KAU), Saudi Arabia. The study used sequential sampling approaches to include 50 Real-Time Polymerase Chain Reaction (RT-PCR) positive COVID-19 patients from KAU's coronavirus isolation wards. A pre-designed form was used to collect each patient's demographic information, including age and gender, signs and symptoms, illness severity (mild, moderate, severe), and laboratory findings. Furthermore, the length of the hospital stay and the result, whether the patient recovered or died, were reported. Results: The study involved 50 patients with varying degrees of disease severity, most of whom suffered from fever, fatigue, cough, sore throat, and diarrhoea. Laboratory analysis of COVID-19 patients showed increased white blood cell and platelet counts, with C-reactive protein levels above normal. Elevated LDH levels indicated possible tissue damage, while ferritin levels were elevated. Other enzymes were in the normal range, but bilirubin levels were slightly elevated. Overall, the patient's lab results indicated inflammation and possible blood clot formation. The study evaluated the predictive accuracy for outcomes and mortality of COVID-19 patients based on factors such as CRP, LDH, Ferritin, ALP, Bilirubin, D-dimers, and hospital stay (p-value ≤0.05). The predictive accuracy mortality of patients with COVID-19 using AI showed Hospital stay, D-Dimers ALP, Bilirubin, LDH, CRP, and Ferritin significantly affected hospital mortality. (p ≤ 0.0001). Conclusion: Artificial Intelligence is crucial for identifying early coronavirus infections and monitoring patient conditions. It improves treatment consistency and decision-making via the development of algorithms. AI can track the crisis at various scales, facilitate research, and aid in developing treatment regimens, prevention strategies, and drugs and vaccines. It also aids in monitoring health and facilitating research on the virus.

Background and Objectives: Mycobacterium bovis Bacillus Calmette–Guérin (BCG) vaccine administration has been suggested to prevent glucose metabolism abnormalities and fatty liver in genetically obese ob/ob mice; however, it is not clear whether the beneficial effects of BCG are also observed in the progression of glucose intolerance induced by a high-fat diet (HFD). Therefore, the effects of BCG vaccination on changes in glucose tolerance and insulin response were investigated in HFD-fed C57BL/6 mice. Materials and Methods: We used the BCG Tokyo 172 strain to determine its effects on abnormalities in glucose metabolism. For vaccination, five-week-old male mice were injected intraperitoneally with BCG and maintained on an HFD three weeks later. The mice were regularly subjected to intraperitoneal glucose tolerance and insulin tolerance tests (IGTT and ITT). These tests were also performed in mice transplanted with bone marrow cells from BCG-vaccinated donor mice. Results: Significant effects of BCG vaccination on blood glucose levels in IGTT and ITT were observed from week 12 of the experiment. BCG vaccination significantly improved changes in fasting glucose and insulin levels, insulin resistance indexes, and glucagon-to-insulin ratios by HFD at the end of the experiment. Significant inhibitory effects in IGTT and ITT on glucose intolerance were also observed by transplantation with bone marrow cells derived from BCG-vaccinated donor mice. Conclusions: BCG vaccination significantly delayed glucose intolerance progression, suggesting a beneficial effect of BCG on the pathogenesis of type 2 diabetes. It has also been demonstrated that the effects of BCG vaccination may be at least partially due to an immune memory (trained immunity) for hematopoietic stem and progenitor cells of the bone marrow.

The potential adverse effects of coronavirus disease 2019 (COVID-19) vaccinations raise public concerns. Data from Taiwan’s Vaccine Injury Compensation Program (VICP) can provide valuable insights. This study analyzed preliminary application data for COVID-19 vaccine compensation in Taiwan’s VICP, focusing on applicants receiving vaccines between March 2021 and June 2022. Among the 2941 adverse events, 113 cases (3.8%) were deemed causally associated with vaccination, 313 (10.6%) were indeterminate, and 2515 (85.5%) had no causal association. Nearly half (47.6%) of applicants were over 60 years old, and 76.6% had a history of preexisting chronic dis-eases. Among the 426 vaccine-associated or indeterminate cases, the most common causes were hematological diseases and thrombosis. There were 920 mortality cases reported, and 97.4% were unassociated with vaccination. Only five deaths were judged to be associated with the COVID-19 vaccination, all involving the adenovirus vector vaccine and thrombosis with thrombocytopenia syndrome. In conclusion, most compensation applications were not causally linked to vaccination. Compared to other countries, the number of applications in Taiwan’s VICP is relatively high. These findings may indicate a need to adjust the application requirements for compensation in Taiwan’s program.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

Parkinson’s disease (PD) is the second most common degenerative disease which may cause blood pressure abnormalities due to autonomic dysfunction. Early morning rise of blood pressure which is called morning surge is found to be related with some cardiovascular diseases when it is exaggerated. We wanted to search the relation of Morning blood pressure surge (MBPS) and inflammation in PD. Method: Ambulatory blood pressure monitoring for 24 hours, fibrinogen to albumin ratio, hs-CRP are used in this retrospective study. Fifty idiopathic PD patients and 50 age and sex matched control cases were included. MBPS, it has been defined as the difference between morning BP (measured 2 hours after awakening) and the lowest night-time BP. Body mass index (BMI) is used as an independent variable. Results: Median value of MBPS for PD group (21,63) was significantly different from the control group values (18,63) (p

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

The legume-rhizobia symbiosis is one of the most important plant-microbe interactions in sustainable agriculture due to its ability to provide much needed N to cropping systems. This interaction is mediated by the mutual recognition of signaling molecules from the two partners, namely legumes and rhizobia. With legumes, these molecules are in the form of flavonoids and anthocyanins, which are responsible for the pigmentation of plants parts, such as seeds, flowers, fruits and even leaves. Seed coat pigmentation in legumes is a dominant factor influencing gene expression relating to N2 fixation, and may be responsible for the different N2-fixing abilities observed among legume genotypes under field conditions in African soils. Cowpea, Kersting’s bean and Bambara groundnut landraces with black seed coat color are reported to release higher concentrations of nod-gene-inducing flavonoids and anthocyanins when compared to the Red and Cream landraces, hence the black seed coat pigmentation is considered a biomarker for enhanced nodulation and N2 fixation. Cowpea, Bambara groundnut and Kersting’s bean with differing seed coat colors are known to attract different native soil rhizobia, confirmable by PCR-RFLP analysis of bacterial DNA from root nodules of these legumes. Even when seeds of the same legume with diverse seed coat colors were planted together in one hole, the nodulating bradyrhizobia clustered differently in the PCR-RFLP dendrograms. In one study, Kersting’s groundnut, Bambara groundnut and cowpea with differing seed coat colors were selectively nodulated by different bradyrhizobial species. Multilocus sequence analysis showed that different Bradyrhizobium species nodulated the Kersting's bean based on seed coat color. Phylogenetic analysis also placed the bradyrhizobial isolates in close proximity to different Bradyrhizobium species such as B. vignae 7-2T, B. subterraneum 58 2-1T, B. kavangense 14-3T, B. liaoningense 2281 (USDA 3622)T, B. yuanmingense LMG 21827T, B. huanghuaihaiense CCBAU 23303T, B. pachyrhizi PAC48T, and a reference type strain of B. elkanii according to seed coat color. Using 16S rDNA amplicon sequencing, we also found significant selective influences of seed coat pigmentation on microbial community structure in the rhizosphere of five Kersting’s groundnut landraces. For example, the rhizosphere of Belane Mottled landrace was dominated by Proteobacteria, while Bacteroidetes dominated the rhizospheres of the other landraces. With legumes, seed coat pigmentation therefore plays a dominant role in the selection of the bacterial symbiotic partner.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin may to some extent exacerbate every other kind of age-related damage. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss a method of removing it from single cells in vitro.

Neuron degeneration is the most common old age complications worldwide. Alzheimer's disease (AD) is one of the most common neurodegenerative condition with limited drug options and significant adverse effects. Hence, there is a growing interest in exploring natural products for their potential pharmacological activities against AD. This study investigates the efficacy of Verbesina encelioides flower extract (VFE) in alleviating neurobehavioral damage induced by Scopolamine in rat mimicking AD model. GC-MS analysis showed that V. encelioides flower extract is rich in carotenoids like spirilloxanthin. Various behavioural models were used to assess the rats' learning and memory capabilities. Additionally, biochemical tests were conducted on the AD rat models to evaluate oxidative stress in the brain, including superoxide dismutase (SOD), nitric oxide (NO), reduced glutathione (GSH), and anti-acetylcholinesterase (AChE) enzyme assays. Findings from this study suggest that the VFE significantly improved the rats' cognitive aptitude and alleviated them from oxidative stress by reducing free radical generation. Based on the results obtained from GC-MS analysis, in silico interaction analysis of gingkolide A and spirilloxanthin with acetylcholinesterase was carried out. In summary, this study suggests that V. enceloides flower extract improves learning abilities and mitigates cognitive deficits caused by scopolamine. Thus V. enceloides could be potentially seen as natural therapeutic intervention against neurodegenerative disorders likes Alzheimer’s disease and dementia.

Novel therapies for treatment of familial dilated cardiomyopathy (DCM) are lacking. Triggers for the progression of the disorder commonly occur due to specific gene variants that affect the production of sarcomeric/cytoskeletal proteins. Generally these variants cause a decrease in tension by the myofilaments, resulting in signaling abnormalities within the micro-environment which over time result in structural and functional maladaptations leading to heart failure (HF). Current concepts support the hypothesis that the mutant sarcomere proteins induce a causal depression in the tension time integral (TTI) of linear preparations of cardiac muscle. However, molecular mechanisms underlying tension generation particularly in relation to mutant proteins and their impact on sarcomere molecular signaling, are currently the subject of controversy. Thus, there is a need for clarification as to how mutant proteins affect sarcomere molecular signaling in the etiology and progression of DCM. A main topic in this controversy is the control of the number of tension generating myosin heads reacting with the thin filament. One line of investigation proposes that this number is determined by changes in the ratio of myosin heads in a sequestered super-relaxed state (SRX) or in a disordered relaxed state (DRX) poised for force generation upon Ca-activation of the thin filament. Contrasting evidence from nanometer–micrometer-scale x-ray diffraction in intact trabeculae indicates that the SRX/DRX states may have a lesser role. Instead, the proposal is that myosin heads are in a basal OFF state in relaxation then transfer to an ON state through a mechano-sensing mechanism induced during early thin filament activation and increasing thick filament strain. Recent evidence about the modulation of these mechanisms by protein phosphorylation has also introduced a need for reconsidering control of tension. We discuss these mechanisms that lead to different ideas related to how tension is controlled and disturbed by mutant sarcomere proteins linked to DCM including cardiac myosin, myosin-binding protein C, titin filaments, and thin filaments. Resolving the various mechanisms and incorporating them into a unified concept is crucial for gaining a comprehensive understanding of DCM. This deeper understanding is not only important for diagnosis and treatment strategies with small molecules, but also for understanding the reciprocal signaling processes that occur between cardiac myocytes and their micro-environment. By unraveling these complexities, we can pave the way for improved therapeutic interventions for managing DCM.

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

Disease outbreaks can severely affect populations in the wild. However, their ecological consequences are poorly understood. Here, we used a multi-site capture-recapture model to investigate the impacts of a yellow fever outbreak on the endangered golden lion tamarin Leontopithecus rosalia, in the Atlantic forest, Brazil. We show that the annual adult survival rate severely declined in 2017-2018, coinciding with the outbreak period. Simultaneously, dispersal patterns changed temporarily, with a slight reduction of dispersal between groups of the same forest fragment from 3.6 to 2.8%, and a strong increase of dispersal between forest fragments, from 0.4 to 4.3%. Those results suggest that disease transmission potential was low, especially between forest fragments and advocate for a better integration of host movements and landscape configuration when evaluating species response to vector-borne diseases

Abstract: The VSI represents a significant advancement in the assessment of gastrointestinal-specific anxiety among patients with Irritable Bowel Syndrome (IBS) and other Chronic Inflammatory Bowel Diseases (IBD). However, an Italian version of the instrument is not yet available for the reference population. This study utilized a national sample of 500 individuals, including healthy controls and patients with Ulcerative Colitis and Crohn's Disease, to test the validity and reliability of the Italian VSI. Using back-translation methodology to ensure translation fidelity, the research applied a questionnaire and the VSI through an online format to 500 participants. Data analysis revealed that the Italian VSI had excellent psychometric properties, demonstrating high internal consistency (Cronbach’s α = 0.95) and construct validity. The scale proved sensitive in detecting significant differences in visceral sensitivity among groups, highlighting its utility as a clinical and research assessment tool. Specifically, the Italian VSI exhibited a unidimensional factorial structure and maintained a strong correlation with other measures of anxiety and the severity of gastrointestinal symptoms, confirming its role in enhancing the understanding and management of IBS and IBD in Italy.

(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

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

Helicobacter pylori is a gastric oncopathogen that infects over half of the world’s human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.

Therapies targeting amyloid, such as monoclonal antibodies like Lecanemab, Aducanumab, and Donanemab, have garnered FDA approval but remain controversial due to limited clinical benefits and significant side effects against Alzheimer. The present theorical work utilized Virtual Screening and Docking techniques to explore potential small natural molecules' interactions with the KIBRA protein, a promising target for drug development. Kibra protein is considered a biomarker for synaptic dysfunction and cognitive decline. Employing Autodock Vina and Pyrx software, on several natural compounds and found Hypericin to exhibit the lowest binding energy of approximately -9 kcal/mol. Previous studies have highlighted Hypericin's strong affinity for Alzheimer's Disease-associated targets like ABAD and BACE1. These findings suggest Hypericin could be as a potential therapeutic agent for Alzheimer's Disease. Further research is warranted to validate its efficacy and safety for clinical use.

Mutations of PKD1 coding for polycystin-1 (PC1) account for most of the autosomal dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these is the leucine-rich repeats (LRR) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRR in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal axis curvature and pronephric cyst formation. We found that overexpression of LRR suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRR structurally predicted to bind laminin-511 disrupted LRR-laminin interaction in vitro and neutralized the ability of LRR to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1-deficiency.

Background. Carotid artery disease is prevalent among patients with coronary heart disease. The concomitant severe lesions in the carotid and coronary arteries may necessitate either simultaneous or staged revascularization, involving coronary bypass and carotid endarterectomy. However, there is presently a lack of consensus on the optimal choice of surgical treatment tactics for patients with significant stenoses in both carotid and coronary arteries. The aim of the current study was to compare the 30-day and long-term outcomes of coronary and carotid artery revascularization surgery based on the simultaneous or staged surgical tactics. Material and Methods. The single-center, non-randomized retrospective study involved 192 patients with concurrent coronary artery disease and carotid artery stenosis ≥70%, of whom 106 patients underwent simultaneous intervention (CABG+CEA), and 86 patients underwent staged CABG/CEA. The mean time between stages ranged from 1 to 4 months (mean 1.88±0.9 months). Endpoints included death from any cause, nonfatal stroke, nonfatal myocardial infarction (MI), and major adverse cardiovascular events (MACE) (death + nonfatal MI + nonfatal stroke) within 30 days after the last intervention and in the long-term follow-up period (median follow-up - 6 years). Results: The 30-day all-cause mortality, incidence of postoperative nonfatal MI, nonfatal stroke, and MACE did not exhibit differences between the groups after single-stage and staged interventions. However, the overall risk of postoperative complications (adjusted for the risk of any complication per patient) (OR 2.214, 95% CI 0.214-0.954, p=0.034), as well as the duration of ventilatory support (p=0.004), were elevated in the group after simultaneous interventions compared with the staged intervention group. However, this difference did not result in an increased incidence of death and MACE in the group after simultaneous interventions. In the long-term follow-up period, there were no significant differences observed when comparing simultaneous or staged surgical tactics in terms of overall survival (54.9% and 62.6% in groups 1 and 2, respectively, P log-rank = 0.068), nonfatal stroke-free survival (45.6% and 33.6% in groups 1 and 2, respectively, P log-rank = 0.364), nonfatal MI-survival (57.6% and 73.5% in groups 1 and 2, respectively, P log-rank = 0.169), and MACE-free survival (7.1% and 30.2% in groups 1 and 2, respectively, P log-rank = 0.060). Risk factors associated with an unfavorable outcome included age, smoking, BMI, LV EF, and atherosclerosis of lower limb arteries. Conclusions: This study revealed no significant difference in the impact of simultaneous CABG+CEA or staged CABG/CEA on the incidence of death, stroke, MI, and MACE over a 30-day and long-term follow-up period. Although the immediate results indicated an increased risk of a complicated course (attributable to overall complications) after simultaneous CABG+CEA compared with staged CABG/CEA, this did not lead to an increase in fatal complications. Therefore, performing both tactics is deemed safe and eligible after a meticulous postoperative risk assessment.

Walnut (Juglans regia L.) is a monoecious species and although it exhibits self-compatibility, presents incomplete overlap of pollen shed and female receptivity. Thus, cross-pollination is prerequisite for optimal fruit production. Cross-pollination can occur naturally by the wind, the insects, artificially, or by hand. Pollen has been recognized as one possible pathway for Xanthomonas arboricola pv. juglandis infection, a pathogenic bacterium responsible for walnut blight disease. Other than the well-known cultural and chemical control practices, artificial pollination technologies with the use of drones could be a successful tool for walnut blight disease management of orchards. Drones may carry pollen and release it over crops or mimic the action of bees or other pollinators. Although this new pollination technology could be regarded as a promising tool, pollen germination and knowledge of pollen as a possible pathway for the dissemination of bacterial diseases remain crucial information for design and manufacture of aerial pollinator robot for walnut trees. Thus, our purpose was to describe a pollination model with fundamental components, the identification of the “core” pollen microbiota, specify an appropriate flower pollination algorithm, design an autonomous precision pollination robot, and minimize the average errors of flower pollination algorithm parameters through machine learning and meta-heuristic algorithms.

In this research, we present the first steps taken towards a data-driven agent-based model (ABM) specifically designed for simulating infectious disease dynamics in Greece. Amidst the ongoing COVID-19 pandemic caused by SARS-CoV-2, this research holds significant importance as it can offer valuable insights into disease transmission patterns and assist in devising effective intervention strategies. To the best of our knowledge, no similar study has been conducted in Greece. We constructed a prototype ABM that utilizes publicly accessible data to accurately represent the complex interactions and dynamics of disease spread in the Greek population. By incorporating demographic information and behavioral patterns, our model captures the specific characteristics of Greece, enabling accurate and context-specific simulations. By using our proposed ABM, we aim to assist policymakers in making informed decisions regarding disease control and prevention. Through the use of simulations, policymakers have the opportunity to explore different scenarios and predict the possible results of various intervention measures. These may include strategies like testing approaches, contact tracing, vaccination campaigns, and social distancing measures. Through these simulations, policymakers can assess the effectiveness and feasibility of these interventions, leading to the development of well-informed strategies aimed at reducing the impact of infectious diseases on the Greek population. This study is an initial exploration toward understanding disease transmission patterns and a first step towards formulating effective intervention strategies for Greece.

Several studies have already demonstrated the relationship between the loss of natural habitats and the incidence of diseases caused by vectors, such as dengue, which is an acute fever disease, considered a serious public health problem. The aim of the present study was to analyze the relationship between land use changes between 2009 and 2019 and the occurrence of dengue fever in 2015 and 2019 by municipality, using the state of Minas Gerais as a case study. For this, secondary data obtained from openly available sources were used. Natural vegetation cover data were obtained from the MAPBiomas platform and dengue occurrence data from the Ministry of Health, in addition to socioeconomic indicators from the Brazilian Institute for Geography and Statistics. Between 2015 and 2019, 1,255,731 cases of dengue were recorded throughout the state of Minas Gerais, ranging from 0 to 227 per thousand inhabitants between municipalities. The occurrence of dengue was distributed throughout all regions of Minas Gerais, affected by climatic and socioeconomic aspects. In general, municipalities with net loss of natural vegetation, predominantly located in the Cerrado biome, had the highest number of dengue cases in the studied period. Despite the significant positive relationship between these two variables, three of the eight socioeconomic parameters analyzed also affected the occurrence of dengue: population density, human development index (both positively) and Gini inequality index (negatively). These results indicate that, contrary to expectations, municipalities with better social conditions had more dengue cases. Our study indicates that natural vegetation is, directly or indirectly, involved in the ecosystem service of dengue control, despite the occurrence of this disease being affected by multiple factors that interact in a complex way. Thus, policies towards reducing deforestation must be complemented by a continuous investment in public health policies and reduction of social inequalities to efficiently control dengue fever.

In this study, we introduce a neural-learning based approach for the early detection of Parkinson Disease using DaT SPECT imaging, a promising technique in neurodegenerative disease diagnosis. Leveraging the advanced capabilities of deep learning, we developed a convolutional neural network model based on the Inception V3 architecture, which has been enhanced by modulating custom layers to fine-tune the model specifically for the analysis of DaT SPECT images. The imaging dataset was obtained through the Parkinson's Progression Markers Initiative (PPMI), and the model was trained to classify whether a patient had Parkinson Disease through a binary classification of their DaT SPECT Scan using the fine-tuned InceptionV3 model. This specialized adaptation allows for more accurate and nuanced interpretation of the scans, a crucial factor in early and reliable diagnosis of Parkinsonian syndromes. Our model underwent rigorous hyperparameter tuning, focusing on learning rates, the number of neurons in the dense layer, and dropout rates, to ensure optimal performance. Remarkably, the proposed model demonstrated a significant improvement in accuracy, achieving 74.65%, compared to a standard Sequential Model, which only reached an accuracy of 51.41%. Diagnosis of Parkinson Disease through DaT SPECT Scans is a promising approach not only as a more effective diagnostic tool but also as a beacon for future research in the application of deep learning to medical imaging for neurodegenerative diseases. By building layers on the InceptionV3 Architecture, we achieve a higher accuracy on DaT SPECT Scan diagnosis and pave the way for automated diagnosis of patients with Parkinson Disease, allowing for easier medical accessibility and paving the way for advancements in early diagnosis and personalized medicine strategies for Parkinson's disease and related disorders.

Modern gastroenterology, which occupies the pages of scientific journals without alternative, began as an initiative of manufacturers of diagnostic equipment. For widespread advertising, they selected practical doctors who were not familiar with the methodology of science and superficial knowledge of physiology. This is how a group led by DeMeester arose, which in 1976 published the DeMeester score, i.e., the normal limit for esophageal pH monitoring. pH <4, less than 4% of the time per day was considered normal, i.e., it was unreasonably claimed that such reflux is physiological. This article proves that this study was carried out with numerous methodological errors, which led to an erroneous conclusion. For a long time, pH monitoring was considered the gold standard and with its help hypotheses were proposed that form the basis of modern gastroenterology. The article proves the fallacy of 13 hypotheses, which are presented as theories. Numerous articles using pH monitoring have publicized this method. Practitioners became "great scientists", equipment manufacturers became successful businessmen. Over time, they found other groups of practitioners to promote devices for impedance ph monitoring, high-resolution manometry, and many others. At the same time, a network of reviewers who believe in the infallibility of the luminaries do not allow studies that contradict their faith to be published. Thus, fundamental science was destroyed, which alone could assess the harm of false research both for science and for patients. Conclusion This study provides a list of hypotheses, that were previously considered theories, but since scientific evidence has proven these assumptions to be false, they should be excluded from subsequent use and citation.

Locally Advanced Breast Cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant Chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognised, a small number of patients show Progressive Disease (PD). No standard Salvage Treatment (ST) has been defined and different strategies can be adopted, such as second line systemic therapies, radiation therapy, and surgery. Herein a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment in each patient.

We evaluated diagnostically differential radiological findings between focal nodular hyperplasia (FNH)-like lesions and hepatocellular carcinoma (HCC). We studied pathologically confirmed FNH-like lesions in 13 alcoholic-cirrhosis patients who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography (CT) and magnetic resonance imaging (MRI), including superparamagnetic iron oxide (SPIO) and/or gadoxetic acid-enhanced MRI. Seven patients underwent angiography-assisted CT. Evaluated lesion features included arterial enhancement pattern, washout appearance (low density compared to surrounding liver parenchyma), signal intensity on T1-weighted image (T1WI) and T2-weighted image (T2WI), central scar presence, chemical shift on in- and out-of-phase images, and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and on SPIO-enhanced MRI. Eleven patients had multiple small lesions (&lt;1.5 cm). Radiological features of FNH-like lesions included hypervascularity despite small lesion, lack of “corona-like” enhancement in the late phase on CT during hepatic angiography (CTHA), high-intensity on T1WI, slightly high- or iso-intensity on T2WI, no signal decrease in out-of-phase images, and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid. Pathologically, like HCC, FNH-like lesions showed many unpaired arteries and sinusoidal capillarization. In summary, FNH-like lesions have unique radiological findings useful for differential diagnosis. Specifically, SPIO- and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.

Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals in Europe, Asia, and North America. In this study, we aimed to characterize circulating EVs derived from patients with chronic Chagas disease (CCD) experiencing reactivation of acute symptoms. Blood samples collected in EDTA were processed to isolate plasma and subsequently subjected to ultracentrifugation for particle isolation and purification. The EVs were characterized using nanoparticle tracking analysis and enzyme-linked immunosorbent assay (ELISA). Our findings revealed distinctive differences in size, concentration, and composition of EVs between immunosuppressed patients and those with CCD. Importantly, these EVs play a critical role in the pathophysiology of Chagas disease and demonstrate significant potential as biomarkers in the chronic phase of the disease. Overall, our findings support the potential utility of the CL-ELISA assay as a specific sensitive tool for detecting circulating EVs in chronic chagasic patients, particularly those with recurrent infection following immunosuppressive treatment or with concurrent HIV and Chagas disease. Further investigations are warranted to identify and validate the specific antigens or biomarkers responsible for the observed reactivity in these patient groups, which may have implications for diagnosis, monitoring of treatment and prognosis.

Venous thromboembolism (VTE) is a prevalent medical condition with high morbidity, mortality, and associated cost. Anticoagulation remains the main treatment for VTE, though the decision on when, how, and for how long to administer anticoagulants is increasingly complex. This review highlights the different phases of VTE management, special circumstances for consideration such as antiphospholipid syndrome, coronary artery disease, cancer associated thrombus and COVID, and future anticoagulation options. Anticoagulation management will continue to be a complex decision, applying evidence-based medicine to individual patients with the hope to maximize effectiveness while minimizing risks.

4-(2-Methyloxazol-4-yl)benzenesulfonamide was synthesized by the reaction of 4-(2-bromoacetyl)benzenesulfonamide with an excess of acetamide. The obtained compound was evaluated as a potential inhibitor of human monoamine oxidase (MAO) A and B and was found to inhibit these enzymes with IC50 values of 3.47 μM for MAO-B and 43.3 μM for MAO-A. Thus, the new selective MAO-B inhibitor was identified, which may be used as the lead compound for development anti-Parkinson’s disease agents.

Diseases pose a significant and pressing concern for the sustainable development of the aquaculture sector, particularly as their impact continues to grow due to climatic shifts such as rising water temperatures. While various approaches, ranging from biosecurity measures to vaccines, have been devised to combat infectious diseases, their efficacy is disease- and species-specific and contingent upon a multitude of factors. The field of genetics and genomics offer effective tools to control and prevent disease outbreaks in aquatic animal species. In this study, we present the key findings from our recent research, focusing on the genetic resistance to three specific diseases: White Spot Syndrome Virus WSSV) in white shrimp, Bacterial Necrotic Pancreatitis (BNP) in striped catfish and skin fluke (a parasitic ailment) in yellowtail kingfish. Our investigations reveal that all three species possess substantial heritable genetic components for disease resistant traits, indicating their potential responsiveness to artificial selection in genetic improvement programs tailored to combat these diseases. Also, we observed a high genetic association between disease traits and survival rates. Through selective breeding aimed at enhancing resistance to these pathogens, we achieved substantial genetic gains, averaging 10% per generation. These selection programs also contributed positively to the overall production performance and productivity of these species. Although the effects of selection on immunological traits or immune responses were not significant in white shrimp, they yielded favourable results in striped catfish. Furthermore, our genomic analyses, including shallow genome sequencing of pedigreed populations, enriched our understanding of the genomic architecture underlying disease resistance traits. These traits are primarily governed by a polygenic nature, with numerous genes or genetic variants, each with small effects. Leveraging a range of advanced statistical methods, from mixed models to machine and deep learning, we developed prediction models that demonstrated moderate to high levels of accuracy in forecasting these disease-related traits. In addition to genomics, our RNA-seq experiments identified several genes that undergo upregulation in response to infection or viral loads within the populations. Preliminary microbiome data, while offering limited predictive accuracy for disease traits in one of our studied species, underscore the potential for combining such data with genome sequence information to enhance predictive power for disease traits in our populations. Lastly, this paper briefly discusses the roles of precision agriculture systems, AI algorithms, and outlines the path for future research to expedite the development of disease-resistant genetic lines tailored to our target species. In conclusion, our study underscores the critical role of genetics and genomics in fortifying the aquaculture sector against the threats posed by diseases, paving the way for more sustainable and resilient aquaculture development.

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

The cancer burden is increasing worldwide with contrasting national patterns. Therefore, providing national estimations is necessary to understand and control this health issue. Herein, we comparatively describe incidence, mortality, and disability-adjusted lived years (DALYs) due to 29 groups of cancer in Mexico from 1990 to 2019 by sex and age. Using public data from the Global Burden of Disease Study 2019, we assessed the national burden of cancer using counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and their trends using the annual percentage of change from 1990 to 2019. In 2019, cancer caused 222,060 incident cases, 105,591 deaths, and 2,86,054 DALYs in the general population. Nonmelanoma skin cancer, prostate cancer, and breast cancer had the highest incidence, and six groups of cancer (lung, colorectal, stomach, prostate, breast, and pancreatic) caused 53% of the deaths in 2019. From 1990 to 2019, incidence and mortality showed an increasing trend that varied between 10% and 436% among the groups of cancer, whereas the crude and age-standardized rates showed cancer-specific sex disparities. Our results demonstrate a substantial growth of the national burden of cancer with sex-specific patterns of change. These results may guide national efforts toward reducing health loss due to cancer.

Mosquito-borne diseases (MBDs) are a group of illnesses transmitted by mosquitoes and can be caused by bacteria, viruses, or parasites. These diseases represent a significant global burden of infectious diseases, including morbidity and mortality. This systematic review delves into the multifaceted factors contributing to the spread of mosquito-borne diseases (MBDs) in the Middle East and North Africa (MENA) region. Following PRISMA guidelines, a thorough analysis of peer-reviewed articles from May 1990 to Jan 2023 was conducted, highlighting the interplay of population, environmental, disease, and mosquito factors in disease transmission and prevalence. The review incorporated 31 studies that revealed a complex relationship between various risk factors and the presence of MBDs. Significant associations were observed with age, certain occupations, environmental conditions such as rainfall and temperature, sanitation practices, specific pathogen variants, clinical symptoms, and Aedes aegypti mosquitoes. Conversely, gender, socioeconomic status, educational status, and certain sanitation-related factors showed inconsistent association with the spread of MBDs. The review underscores the need for targeted interventions, including vector control, improved sanitation, and educational campaigns to mitigate the spread of MBDs in the MENA region. This review could guide research studies to address data gaps and assist in developing effective surveillance programs in the MENA region. This work emphasizes the need for region-specific public health strategies and further research to understand and curb the burden of these diseases effectively.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.

Chronic hemodialysis (HD) patients have very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. Aim: To study acute vascular changes during HD. In 29 consecutive chronic HD patients (age: 65.6±10.4 years) pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. SDC-1 levels increased during HD (p=0.004). Males had higher ET-1 levels. Patients were divided into 2 groups based on pulse wave velocity (PWV): PWV≥12 m/s and PWV<12 m/s. Pre-HD and mid-HD SDC-1 levels were higher in the group with PWV≥12 m/s (10.174±2.568 vs. 7.928±1.794 ng/ml, p=0.013, and 10.319±3.482 vs. 8.248±1.793 ng/ml, p=0.044, respectively). Post-HD ET-1 levels were higher in the patient group having PWV≥12 m/s (10.88±3.00 vs. 8.05±3.48 pg/l, p=0.027). Patients having PWV≥12 m/s had higher pre-HD peripheral and aortic systolic blood pressure (p<0.05). Total cholesterol correlated with the SDC-1 decrease during HD (r=0.539; p=0.008). Pre-, mid-, and post-HD SDC-1 correlated with the ultrafiltration (r=0.432, p=0.019; r=0.377, p=0.044; and r=0.401, p=0.012, respectively). SDC-1 and ET-1 contribute to vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Renal angiogram is a promising tool for diagnosing renal vasculature and structural alterations in renal diseases. In renal diseases, the vascular changes were observed earlier than the structural and other changes. However, the literature on angiograms in kidney diseases was limited. Six client-owned dogs with chronic kidney diseases with International Renal Interest Society (IRIS) stage II and III were selected for this study. Under general anesthesia, the femoral arterial catheterization was performed. With a Cobra (C2) catheter, Iohexol saline (50:50) was administered to evaluate the vascular changes of Renal failure, using selective and non-selective angiograms. The procedures were completed successfully with minimal complications. Serum biochemistry and urine protein creatinine ratio were estimated sequentially and quality of life was monitored. Due to contrast agent complications, a dog died within 14 days and necropsy was conducted. Though the renal angiogram has complications, it is a reliable tool for the diagnosis of vasculature changes associated with kidney diseases, in veterinary medicine.

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

Carbohydrates such as fructooligosaccharides (FOS) are associated with improved gastrointestinal health and prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFA). Sixty C57BL/6 mice received diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed: animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profile; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; SCFA in the feces. Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There was found statistical differences in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

Blood biomarkers represent a promising future for studying cognitive impairment, particularly in Alzheimer's Disease (AD), as they offer a non-invasive alternative to cerebrospinal fluid tests and have potential as population screening tools. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations between Amyloid-β, Total Tau, Phosphorylated Tau (p-tau), Neurofilament Light (Nfl), and Glial Fibrillary Acidic Protein (GFAP) with cognition. The reviewed studies are heterogeneous, varying in design and population (mixed, cognitively impaired, or unimpaired), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-tau measures tend to show stronger associations with cognitive functions than other biomarkers, no single blood marker has emerged as predominantly associated with a specific cognitive domain. These findings add to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical evaluations of cognition.

This work focused on Diplectanum aequans, a gill parasite of Dicentrarchus labrax. Analyzes allowed us to detect factors regulating parasites distribution on Corsican fish-farms, and to highlight the ecological structure of D. aequans communities on gills of fish. The study of parasite distribution showed that bigger fish appear more parasitized and that the infection dynamics of D. aequans can be explained by several factors such as biotic factors or farm environment conditions. The study of gill repartition of D. aequans showed that parasites tend to have a homogeneous distribution with no statistically significant difference in infection between two sides on each fish. However, the distribution of the number of parasites on gill arches varies according to the total number of parasites. Results differ depending on infection degree and host weight. When parasites are numerous, the individuals are distributed on the gill arches according to an antero-posterior gradient, while with low rates of infection, the parasites are randomly distributed on the 4 arches. The spatial distribution of D. aequans appears to be determined by the differential action of water flow through gill arch and the size of anterior arches. We also proposed a tool in order to reduce the sampling effort and allow optimal exploitation for fish farmers.

The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have been attracted attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. This review explores the emerging role of omega-3 FAs and their specialized pro-resolving mediators (SPMs) in the context of macrophage polarization, with a focus on chronic liver diseases. Omega-3, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have promising effects in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. SPMs, such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties. These mediators modulate the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLD, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3 and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. However, the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment require further investigation. Understanding the intricate relationship among SPM and macrophage polarization holds unlimited potential for the development of novel therapeutic strategies for chronic liver diseases.

Marek’s disease (MD) is an important neoplastic disease caused by serotype 1 Marek's disease virus (MDV-1), which results in severe economic losses worldwide. Despite vaccination practices that have controlled the MD epidemic, current increasing MD-suspected cases indicate the persistent viral infections circulating among vaccinated chicken farms in many countries. However, the lack of available information about phylogeny and molecular characterization of circulating MDV-1 field strains in Taiwan reveals a potential risk in MD outbreaks. This study investigated the genetic characteristics of 18 MDV-1 isolates obtained from 17 vaccinated chicken flocks in Taiwan between 2018 and 2020. Based on the sequences of the meq oncogene, phylogenetic analysis demonstrated that the circulating Taiwanese MDV-1 field strains were predominantly in a single cluster that showed high similarity with strains/isolates from countries of East Asian region. Because the isolated strains were obtained from CVI988/Rispens vaccinated chicken flocks and the molecular characteristics of the Meq oncoprotein showed the features like vvMDV and vv+MDV strains, the circulating Taiwanese MDV-1 field strains may have higher virulence compared with vvMDV pathotype. In conclusion, the presented data demonstrate the circulation of hypervirulent MDV-1 strains in Taiwan and highlight the importance of routine surveillance and precaution strategies in response to the emergence of enhanced virulent MDV-1.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

Background: Recommended CKD first-line diagnostics is based on GFR-determination by Creatinine. Cystatin C-use may provide better assessment. Methods: We compared creatinine- and cystatin C-derived eGFR determination in first-line di-agnostic of 112 hospital patients aged >60 years (median=76 years). Patients were judged kid-ney-sane according to first-line diagnostic recommendations (N=61, eGFR (CKD-EPI) ≥60ml/min/m2, total urine protein <150mg/g creatinine, urinary red and white blood cells not increased) or classified at-risk for kidney insufficiency due to aortic valve dysfunction (N=51). Plausibility of eGFR-values was evaluated retrospectively by final case diagnoses. Results: eGFR (CAPA) was found linearly correlated to eGFR (CKD-EPI) (R2=0.5, slope=0.69, p<0.0001). In 93/112 (>80%) cases, eGFR (CAPA) yielded lower values (on average ≈20%). In 55/112 (49%) cases CKD-stage decreased. CKD-reclassification from kidney-sane to kid-ney-insufficient state (i.e. CKD1/2 to CKD3a/b or 4) or reclassification to more severe kidney in-sufficiency (i.e. CKD3a3b/4 or 3b4) was found in 41/112 (37%) cases. Worsening of CKD-classification (kidney-sanekidney-insufficient) based on eGFR (CAPA) was in 30% of cases plausible in the light of final case-diagnoses. Conclusion: In elderly patients (>60 years), renal function appears systematically overestimated by creatinine-based eGFR (CKD-EPI) heralding for this group employment of cystatin C-based eGFR (CAPA) as first-line diagnostic.

The number of people with gluten-related illnesses has been increasing and the available treatments include the introduction of a gluten-free diet. In the bakery industry, there are problems with gluten-free products, namely the important characteristics that this component gives to doughs and the low nutritional value they present. A disease that has also increased in recent years is diabetes mellitus, which is characterized by a lack of insulin and the effectiveness of its action (type 1 diabetes) or tissue insensitivity to the hormone (type 2 diabetes). In terms of treatments, there are several approaches: inhibition of digestive enzymes (α-amylase and α-glucosidase) or techniques based on mechanisms of action (stimulation of insulin production and release, insulin transport and decreased glucose absorption). Hyperglycemia is also associated with the production of reactive oxygen species, which leads to cell apoptosis. On the other hand, there was also an association with high levels of cholesterol in the body, which contributed to the development of other types of diseases. In this sense, macroalgae have been studied as a source of natural compounds and used as food supplements, due to their protein, amino acid and mineral content, and the anti-diabetic effect in controlling the glycemic index, oxidative stress and cholesterol have already been demonstrated. Seaweed emerges as a promising source of bioactive nutraceuticals for individuals with coeliac disease, diabetes, and hyperglycemia. The rising prevalence of gluten-related illnesses calls for effective treatments, and seaweed's potential in enhancing the nutritional value of gluten-free products is noteworthy. Additionally, its demonstrated anti-diabetic effects, including glycemic index control, oxidative stress reduction, and cholesterol management, make it a valuable dietary supplement. Further research is needed to explore the specific bioactivities of seaweed compounds and their mechanisms of action. Integrating seaweed-based nutraceuticals into diets could complement traditional treatments, offering potential health benefits to those with coeliac disease and diabetes.

The best form of prevention against human infection through bacteria, viruses and other parasites is ozone disinfection of wastewater and drinking water as a highly effective, well-known method. As a therapeutic measure, various preclinical studies showed promising results, which are being revisited and reconsidered in times of pandemics and led to interesting results in recent clinical trials and reports, as presented by the example of protective measures against covid-19 in particularly vulnerable clinical personnel. In patients with rheumatoid arthritis, repeated ozone treatments have led to new findings in the "immunomodulation" through ozone. The more effective immune response is discussed as the response of innate immune memory and opens interesting aspects for complementary treatment of autoimmune diseases.

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD such that AD may be a form of brain insulin resistance. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography-mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.

Brain disorders pose a significant global healthcare challenge due to their complexity and profound impact on individuals and society. This review explores recent advancements in brain disease research, deepening our understanding and progress towards treatments. Technological innovations, like high-resolution imaging and optogenetics, play a pivotal role in illuminating cellular structures and dissecting neural circuits. Genetic analysis identifies dis-ease-associated genes and mutations, yet translating findings to clinical applications remains challenging. Epigenomics, transcriptomics, and proteomics provide molecular insights, un-covering disrupted pathways in conditions like Alzheimer's disease. Stem cell models elucidate developmental mechanisms, and immunotherapies, including CAR T cells, emerge as prom-ising strategies for brain cancers like glioblastoma. Genome editing tools, exemplified by CRISPR, enable precise modification of disease genes in models, deepening our understanding of pathogenesis. Multifaceted approaches integrating human studies, animal models, and bi-oinformatics propel the field forward. However, complexities persist, as disease specificity for cell types or brain regions remains an enigma, and genetic factors interact with environmental influences, highlighting disease intricacies. Ultimately, interdisciplinary efforts combining bi-ophysical and psychospiritual perspectives are essential to fully understand brain health and unlock transformative treatments for these debilitating disorders. A comprehensive under-standing of brain disorders is vital to improve the quality of life for millions and alleviate the global burden of neurological afflictions. Continued collaborative research will lead to an era of improved brain health worldwide.

About half of the transcatheter aortic valve replacement (TAVR) recipients exhibit some degree of coronary artery disease (CAD), and controversial results have been reported regarding the impact of the presence and severity of CAD on clinical outcomes post-TAVR. In addition to coronary angiography, promising data has been recently reported on the use of both cardiac computed tomography angiography and the functional invasive assessment of coronary lesions whether by FFR or iFR in the work-up pre-TAVR. Despite mitigated available data, percutaneous revascularization of significant coronary lesions has been the routine strategy in TAVR candidates with CAD. Also, scarce data exists on the incidence, characteristics and management of coronary events post-TAVR, and increasing interest exist on potential coronary access challenges in patients requiring coronary angiography/intervention post-TAVR. This review provides an updated overview of the knowledge of CAD in TAVR recipients, focusing on its prevalence, clinical impact, pre- and post-procedural evaluation and management.

Background: Peyronie’s disease (PD) represents a challenging urological disease, due to not optimal post-operative surgical outcomes. We aim to evaluate if vacuum erection devices (VED) treatment before pe-nile curvature surgery is able to improve the post-operative surgical outcomes. Methods: All enrolled patients were assigned to the following groups: a) treatment group, VED treatment (3 times per week) starting 3 months before surgery and (3 times per week) one months after surgery and b) control group, VED treatment (3 times per week) one months after surgery. Follow-up urologic visits were scheduled at 3 and 6 months after surgery and the two groups were compared. Results: Thirty-eight patients have been enrolled (median age 67 years, 57-74, IQR), 20 in the treatment group and 18 in the control group. At the follow-up visits, the two groups are different in terms of IIEF-5 (26 vs 24; p=0.02), ‘yes’ to SEP2 and 3 (85% vs 55%; p<0.001, 85% vs 50%; p<0.001, respectively) and PDQ (-16 vs -11; p=0.03). Complete correction of penile curvature was achieved in 36 patients (94.7%). In the treatment group, no hourglass deformity has been reported, while in the control group 1 patient reported a mild hourglass deformity. In the treatment group, we obtained a longer total penile length (median +1.5 cm). The overall satisfaction rate was 98% in the treatment group and 96% in the control group. Conclusions: The VED treatment before penile curvature surgery in patients affected by PD is able to improve the post-operative surgery.

Physical activity (PA) is a modifiable factor that may have an influence on the course of Parkinson’s disease (PD). This study aimed to apply a simple behavioral intervention to encourage PD sufferers to increase their everyday physical activity and assess which parameters of motor functions will be improved. The research covered 50 PD patients (28 men and 22 women) aged 40-81 years (65.38 ± 9.23), with a duration of the disease 2-4 years, in stages 1-3 on the Hoehn and Yahr scale. The patients were randomly divided into two groups: the experimental group with behavioral therapy, and the control group without intervention. During 12 weeks the patients from the experimental group had five phone conversations. Each conversation lasted 15 minutes and was an interview about the subjects’ physical activity in the last month. The results were assessed by the Timed Up and Go test (TUG), Unified Parkinson's Disease Rating Scale (UPDRS) – part III, FIR (Functional Index “Repty” – own modification of Functional Independence Measure (FIM)), Functional Ambulation Category (FAC) and International Physical Activity Questionnaire (IPAQ). The results showed that spontaneous physical activity increased in the experimental group and motor functions improved. Physical activity improvement depended on age, body mass index, and gender.

Due to the complex and variable anatomy of the left atrial appendage, percutaneous left atrial appendage closure (LAAC) can be challenging. In this study, we investigated the impact of fusion imaging (FI) on the LAAC learning curve of 2 interventionalists. The first interventionalist (IC 1) was initially trained without FI and continued his training with FI. The second interventionalist (IC 2) performed all procedures with FI. We compared the first 36 procedures without FI of IC 1 (group 1) with his next 36 interventions with FI (group 2). Furthermore, group 1 was compared to 36 procedures of IC 2 who directly started his training with FI (group 3). Group 1 demonstrated that the learning curve without FI has a flat course with weak correlations for fluoroscopy time, contrast volume, and procedure time, but not for dose area product. Group 2 with FI showed improvement with a steep course and strong correlations for all 4 parameters. In group 3 we also saw a steep progression with strong correlations. Furthermore, the mean measurements of the procedural parameters in the groups with FI decreased significantly as indicator for procedural efficacy. We demonstrated that FI may improve the learning curve of experienced and non-experienced ICs.

While biologic originators’ patents are expiring, biosimilars are emerging to take their place, offering significant cost savings to healthcare systems. Many challenges still need to be addressed in the clinical practice of inflammatory bowel disease (IBD). A global survey was organized to highlight physicians’ current knowledge and beliefs and to gain insight about their practical management and remaining concerns and obstacles associated with starting a biosimilar, switching from an originator to a biosimilar, or switching from one biosimilar to another (multiple switches and reverse switching). Fifteen physicians with expertise in the field of IBD from 13 countries attended a virtual international consensus meeting to develop practical guidance regarding biosimilar adoption worldwide, considering the survey results. Consensus was reached on 10 statements regarding biosimilar effectiveness, safety, indications and rationale, multiple switches, therapeutic drug monitoring of biosimilars, non-medical switching and future perspectives.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been associated with poor cardiovascular disease (CVD) outcomes, supporting its role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1 release or interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs), but the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from a inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3β, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3β overexpression in control ECs increased ADAM10/17 and VCAM1. A GSK3β inhibitor reduced active GSK3β and VCAM1 ectodomain shedding. These findings suggest that diabetic ECs with elevated GSK3β activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3β inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease particularly in diabetes, holds significant therapeutic potential.

Background The prognostic value of estimated pulse wave velocity (ePWV) has been infrequently explored in high-risk patient groups. Our study aimed to evaluate the prognostic significance of ePWV among patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods A total of 4,119 consecutive subjects who underwent PCI with DES (mean age, 67.1 ± 11.6 years and 33.1% were female) were retrospectively analyzed. ePWV was calculated based on the patient’s age and mean blood pressure. Major adverse cardiovascular event (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke, were evaluated. Reults During a median follow-up duration of 3.51 years (interquartile range, 1.35 ~ 6.37 years), there were 746 MACE (18.1%). Multivariable analysis showed that higher ePWV was associated with higher MACE incidence (middle tertile vs. the lowest tertile: hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.81-3.42; P < 0.001; the highest tertile vs. the lowest tertile: HR, 6.18; 95% CI, 4.33-8.80; P < 0.001) The inclusion of ePWV data significantly increased the global chi-square values when added to the clinical information (from 96 to 128; P < 0.001). Conclusion ePWV demonstrated a significant association with MACE in patients who underwent DES implantation. Given its relative simplicity to calculate, ePWV could potentially serve as a valuable instrument for stratifying cardiovascular risk within this high-risk patient population.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

Abstract: Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion and sterile inflammation. Oral l-glutamine administration has been shown to reduce the frequency of pain crisis in SCD patients, however, the long-term effect of l-glutamine in SCD remains to be determined. To understand the long-term effect of l-glutamine administration in SCD liver we used quantitative liver intravital microscopy and biochemical analysis in humanized SCD mice. We here show that chronic l-glutamine administration reduces hepatic hemoglobin-heme-iron level, but fails to ameliorate ischemic liver injury. Remarkably, we find that this failure in resolution of hepatobiliary injury and persistent liver fibrosis is associated with reduced expression of hepatic Kupffer cells post l-glutamine treatment. These findings establish the importance to investigate the long-term effects of l-glutamine therapy on liver pathophysiology in SCD patients.

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

Non-alcoholic fatty liver disease (NAFLD) has gained attention in the last few years due to its increasing prevalence worldwide becoming a global epidemic. This review aims to discuss the latest recommendations regarding diagnosis and treatment of NAFLD-associated HCC and the remaining challenges. Thus, there is a high amount of data derived from basic and clinical studies that revealed the molecular pathways which drive NAFLD-associated hepatocellular carcinoma (HCC). Based on these findings, new prevention, surveillance and treatment strategies are emerging. However, current data on treatment modalities in NAFLD-associated HCC are still scarce, but based on subgroup analysis results from non-NAFLD HCC studies are promising and could provide a basis for future research agenda to address NAFLD/NASH patients. Conclusion: Due to the pandemic proportions that NAFLD gained in the last few years, there is a high amount of data derived from basic and clinical studies that revealed the molecular path-ways which drive NAFLD-associated HCC. Based on these findings, new prevention, surveillance and treatment strategies could be developed at an individual level.

The discovery of microRNAs and their role in disease today represents a substantial breakthrough that has inspired and propagating research on microRNAs as targets for diagnosis and therapy. Cardiovascular disease is an area where the limitations of early diagnosis and conventional pharmacotherapy are evident and deserve attention. Thus microRNA-based drugs have substantial potential for development. Research and its application can progress considerably as witnessed in preclinical and clinical trials. The use of miRNAs remains experimental at the time of writing but has a promising role in the diagnosis and prognosis of a variety of acute coronary syndrome presentations. Its use, alone or in combination with currently available biomarkers, could be adopted soon, especially if diagnostic ambiguity exists. In this review, we explore the current state of knowledge about microRNAs as potential targets for diagnosis and therapy in the cardiovascular system. We report recent improvements in the acknowledgment and characterization of microRNAs focusing on clinical translation. The new dares and outlooks toward clinical application are discussed.

Gaucher Disease's (GD) pathophysiology generates anesthetic concerns in Total Hip joint Arthroplasty (THA), and due to its rareness, data on perioperative risks is scarce. This 22-year study at a large reference center addresses anesthetic management and perioperative outcomes in GD. This retrospective-cohort study assessed anesthetic success and safety in 30 THA patients, comparing them with a control-matched group. Data on clinical characteristics, perioperative events, and outcomes were collected. The primary outcome was difficult anesthesia-initiation incidence. Secondary outcomes were difficult intraoperative course and hemodynamic management, and the development of postoperative-complications. The age, sex, weight, body mass index, primary-to-revision hip arthroplasty ratio were similar in both groups. The mean age was 48±13 years. Ten arthroplasties were revision while twenty were primary. There was no significant difference at all-type anesthesia first initiation attempt success. No particular preference by staff anesthetists for general anesthesia or neuraxial procedures was observed. The GD group showed significantly higher mean intraoperative packed red blood cell units administered (0.73 vs 0.18);(p= 0.038)), higher intraoperative and postoperative platelet transfusion incidence (5/30 [16.7%] vs. 0/56 [0.00%];p=0.004) and (3/30 [10%] vs 0/56 [0%];p=0.040) and longer mean recovery-room length-of-stay (426±412 vs 175±140;p=0.004). Postoperative complications were not significantly different.

Background: The presence of single nucleotide polymorphisms in the gene encoding key en-zyme in the folate pathway methyltetrahydrofolate reductase (MTHFR), causes methylation disorders associated with CAD development. Methods: Study group: 42 patients with CAD con-firmed by coronary angiography. Controls: 16 patients without CAD symptoms or significant coronary artery stenosis, based on invasive coronary angiography or multislice computed to-mography with coronary artery calcification scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined by LC-MS. Results: c.[1286A>C];[1286A>C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to (CAD-) cohort and to the European population. The con-centration of 5-MTHF and folic acid in the subgroups of patients with methylation disorders di-vided by genotypes and (CAD+) was lower compared to (CAD-). Conclusions: The homozygous c.1286 A>C MTHFR variant can be considered as CAD genetic marker. In the subjects with the c.1286 A>C heterozygous and homozygous genotypes, lower concentrations of methyltetrahy-drofolate (5-MTHF) were observed. 5-MTHF can be considered as a biomarker of CAD. Identifi-cation of people at high risk of CAD using genetic tests can contribute to personalized therapy using active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymor-phisms.

Plant roots host various microorganisms around and inside their roots, known as the root microbiome. To become healthy and productive, plants should keep under surveillance niches around the roots to recognize disease-causing microbes and similarly exploit the services of beneficial microorganisms in nutrient acquisition, stress mitigation and growth promotion. Here we presented the communication strategies between plant roots and root-associated microbes in improving plant growth and yield. Understanding how plant root and root-associated microbes communicate is vital in designing ecofriendly strategies for targeted disease suppression and improved plant growth that will help in sustainable agriculture.