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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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.

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.