Blackcurrant juice (Ribes nigrum L.) was subjected to supercritical carbon dioxide (SCCD) at 10, 30 and 60 MPa for 10 min at 45°C as well as thermally treated at 45°C and 85°C for 10 min to determine the stability, antioxidant capacity (AC) and bioaccessibility (BAc) of vitamin C, total anthocyanins and their individual monomers. An in vitro gastrointestinal digestion model completed with dialysis was used to assess BAc. The use of SCCD at each of the pressures applied improved the stability of vitamin C, total anthocyanins, and AC before in vitro digestion. As a result of digestion, L-ascorbic acid was oxidized to L-dehydroascorbic acid, and finally, the total content of vitamin C, anthocyanins, and AC decreased. SCCD did not significantly improve the BAc of vitamin C and total anthocyanins. The highest BAc of vitamin C was noted in fresh juice (FJ) (40%) and after mild heat treatment at 45°C (T45) (46%). The highest BAc of total anthocyanins was also noted in the FJ (4.4%). The positive effect of the application of SCCD on the BAc of the delphinidin-3-O-glycosides was observed compared to T45 and thermal pasteurization at 85°C (T85). Moreover, cyanidins were generally more bioaccessible than delphinidins in all samples. AC after digestion was higher in SCCD samples compared to thermally treated measured using ABTS+• and DPPH• assays, whereas in dialysate similar trends were observed only for AC measured using the ABTS+• assay. This phenomenon was justified by the formation of individual metabolites detected by UPLC-PDA-MS / MS in the model experiment with delphinidin-3-O-rutinoside. The protocatechuic acid which is well known as a strong antioxidant was detected in the model experiment after digestion. Further research is needed to better understand the metabolic pathway of anthocyanins and the possible uses of SCCD to improve the health properties of fruit products.

Preproenkephalin (PPE) is a precursor molecule for multiple endogenous opioid peptides Leu-enkephalin (ENK) and Met-ENK, which are involved in a wide variety of modulatory functions in the nervous system. Despite the functional importance of ENK in the brain, the effect of brain-derived factor(s) on PPE expression is unknown. We report the dual effect of neural epidermal growth factor (EGF)-like-like 2 (NELL2) on PPE gene expression. In cultured NIH3T3 cells, transfection of NELL2 expression vectors induced an inhibition of PPE transcription intracellularly, in parallel with downregulation of protein kinase C signaling pathways and extracellular signal-regulated kinase. Interestingly, these phenomena were reversed when synthetic NELL2 was administered extracellularly. The in vivo disruption of NELL2 synthesis resulted in an increase in PPE mRNA level in the rat brain, suggesting that the inhibitory action of intracellular NELL2 predominates the activation effect of extracellular NELL2 on PPE gene expression in the brain. Biochemical and molecular studies with mutant NELL2 structures further demonstrated the critical role of EGF-like repeat domains in NELL2 for regulation of PPE transcription. These are the first results to reveal the spatio-specific role of NELL2 in the homeostatic regulation of PPE gene expression.

Although automated Acute Lymphoblastic Leukemia (ALL) detection is essential, it is challenging due to the morphological correlation between malignant and normal cells. The traditional ALL classification strategy is arduous, time-consuming, often suffers inter-observer variations, and necessitates experienced pathologists. This article has automated the ALL detection task, employing deep Convolutional Neural Networks (CNNs). We explore the weighted ensemble of deep CNNs to recommend a better ALL cell classifier. The weights are estimated from ensemble candidates' corresponding metrics, such as accuracy, F1-score, AUC, and kappa values. Various data augmentations and pre-processing are incorporated for achieving a better generalization of the network. We train and evaluate the proposed model utilizing the publicly available C-NMC-2019 ALL dataset. Our proposed weighted ensemble model has outputted a weighted F1-score of 88.6%, a balanced accuracy of 86.2%, and an AUC of 0.941 in the preliminary test set. The qualitative results displaying the gradient class activation maps confirm that the introduced model has a concentrated learned region. In contrast, the ensemble candidate models, such as Xception, VGG-16, DenseNet-121, MobileNet, and InceptionResNet-V2, separately produce coarse and scatter learned areas for most example cases. Since the proposed ensemble yields a better result for the aimed task, it can experiment in other domains of medical diagnostic applications.

ANGPTL3 is an important regulator of lipid metabolism. Its inhibition in people with hypercholesteremia reduces plasma lipid levels dramatically. Genome-wide association studies have associated ANGPTL3 variants with lipid traits. Irisin, an exercise modulated protein, has been associated with lipid metabolism. Intracellular accumulation of lipids impairs insulin action and contributes to metabolic disorders. In this study, we evaluate the impact of ANGPTL3 variants on levels of irisin and markers associated with lipid metabolism and insulin resistance. ANGPTL3 rs1748197 and rs12130333 variants were genotyped in a cohort of 278 Arab individuals from Kuwait. Levels of irisin and other metabolic markers were measured by ELISA. Significance of association signals was assessed using Bonferroni-corrected P-values and empirical P-values. The study variants were significantly associated with low levels of c-peptide and irisin. Levels of c-peptide and irisin were mediated by interaction between carrier genotypes (GA+AA) at rs1748197 and measures of IL13 and TG, respectively. While levels of c-peptide and IL13 were directly correlated in individuals with reference genotype, they were inversely correlated in individuals with carrier genotype. Irisin correlated positively with TG which is strong in individuals with carrier genotypes. These observations illustrate ANGPTL3 as a potential link connecting lipid metabolism, insulin resistance and cardioprotection.

Many neonates undergoing whole body hypothermia (WBH) following moderate to severe perinatal asphyxia suffer from renal impairment. While recent data suggest a WBH-related reno-protection, the differences in serum creatinine (Scr) patterns to reference patterns were not yet reported. We therefore aimed to document Scr trends and patterns in asphyxiated neonates undergoing WBH, and compared these to centiles reference Scr dataset of non-asphyia neonates. Using a systematic review strategy, reports on Scr trends (mean ± SD, or median and range) were collected (day 1-7) in WBH cohorts, and compared to centiles of an earlier reported reference cohort of non-asphyxia cases. Based on 13 papers on asphyxia+WBH cases, a pattern on postnatal Scr trends in asphyxia+WBH cases was constructed. Compared to the reference cohort, mean or median Scr values at birth (>90th centile) and the first two days of WBH (>75th centile) remained clinical relevantly higher in asphyxia+WBH cases, with a subsequent decline to reach at best high or high normal creatinine values (all >50th centile, but mainly >75th centile) from day 4 onwards. Such patterns are valuable to anticipate average changes in renal clearance capacity relevant for pharmacotherapy, but do not yet cover the relevant inter-patient variability observed in WBH cases.

Niemann-Pick type C (NPC) disease is a childhood autosomal recessive inherited rare neuro-degenerative disease, characterized by the accumulation of cholesterol and glycosphingolipids, implicating the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 1,2-diols, exerts beneficial effects in mod-ulating inflammation and autophagy, critical features of the NPC disease. This study aimed to evaluate the effects of UB-EV-52 a sEH inhibitor (sEHi) in the Npc mouse model by administering for 4 weeks (5 mg/kg/day). Behavioral and cognitive assays (open field test (OF), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that treatment produced an improvement in short- and long-term memory as well as in spatial memory. Moreover, the treatment with UB-EV-52 increased body weight and the lifespan by 25% and re-duced gene expression of the inflammatory markers (i.e. Il-1β and Mcp1) and improved oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. Regarding the autophagic markers, we surprisingly found significantly reduced levels of the ratio LC3B-II/LC3B-I and a significant reduction of brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in Npc mice treated group compared to non-treated. Lipid profile analysis showed a significant reduction in lipid storage in the liver and some slight changes in brain tissue in treated Npc mice compared to non-treated groups. Thus, Our results suggest that the pharmacological inhibition of sEH ameliorates most of NPC’s characteristic traits in mice, demonstrating that sEH can be considered a potential therapeutic target for this condition.

Course-based Undergraduate Research Experiences (CUREs) provide the same benefits as individual, mentored faculty research while expanding the availability of research opportunities. One important aspect of CUREs is student’s engagement in collaboration. We developed a partnership with the Caenorhabditis elegans (C. elegans) database, WormBase, in which students submitted annotations of published manuscripts to the website. This activity provided students with a collaborative research activity that benefitted the greater scientific community and enhanced students’ understanding of molecular genetics during the COVID-19 pandemic. WormBase relies on community annotators to read published articles and input phenotypic data. Students submitted a total of nine annotations directly to WormBase, which were curated by WormBase to ensure correctness and to reduce overlap from redundant annotations. Due to the stress on students during this time of crisis, qualitative data were collected in lieu of quantitative pre-post analyses. Students described their learning experiences in terms of interactions with the scientific community and the “real world”, content knowledge and competencies, and changes in perspectives and use of resources. Students also reported that this activity was helpful in their understanding of critical molecular genetics concepts. Most students reported on cognitive processes that represent mid-level Bloom’s categories. The shift to online learning during the COVID-19 pandemic created an immediate need for meaningful, collaborative experiences in CUREs. By partnering with WormBase, students gained insight into the scientific community and contributed as community members. We describe possible modifications for future courses, potential expansion of the WormBase collaboration, and future directions for quantitative analysis.

Emerging pollutants as pharmaceuticals have been focusing international attention for few decades. Ciprofloxacin (CIP) is a common drug widely found in effluents from hospitals, industrial and different wastewater treatment plants, as well as rivers. In this work, the lab-scale 3D-BER system was established, and more than 90% of the antibiotic CIP removal from the Low C/N wastewater. Best results were obtained with current intensity, and different C/N ratio significantly improve the removal of CIP and nitrates, when the ideal conditions were; C/N = 1.5-3.5, pH =7.0-7.5, and I = 60 mA. The highest removal efficiency of CIP = 94.20 %, NO3--N= 95.53 % and total nitrogen (TN) = 84.27 %, respectively. In this novel system, the autotrophic-heterotrophic denitrifying bacteria played vital role for the removal of CIP and enhanced denitrification process. Thus, autotrophic denitrifying bacteria uses CO2 and H2 as carbon sources to reduce nitrates to N2. This system has the assortment and prosperous community revealed at the current intensity of 60 mA, and the analysis of bacterial community structure in effluent samples fluctuates under different condition of C/N ratios. According to the results of LC-MS/MS analysis, the intermediate products were proposed after efficient biodegradation of CIP. Microbial community on biodegrading was mostly found at phylum, and class level was dominantly responsible for the NO3--N and biodegradation of CIP. This work can provide some new insights towards the biodegradation of CIP and the efficient removal of nitrates from low C/N wastewater treatment by the novel 3D-BER system.

This work can be considered as a first step of designing a future competitive data-driven approach for remaining useful life prediction of aircraft engines. The proposed approach is an ensemble of serially connected extreme learning machines. The results of prediction of the first networks are scaled and fed to the next networks as an additive features to the original inputs. This feature mapping allows increasing the correlation of training inputs with their targets by holding new prior knowledge about the probable behavior of the target function. The proposed approach is evaluated under remaining useful estimation using a set of “time-varying” data retrieved from the public dataset C-MAPSS (Commercial Modular Aero Propulsion System Simulation) provided by NASA. The prediction performances are compared to basic extreme learning machine and proved the effectiveness of the proposed methodology.

ABC-OCT, Affordable B-scan Camera-based Optical Coherence Tomography, implements Fourier-Domain Optical Coherence Tomography with real-time display using cross-platform C++ and the OpenCV framework. The software can be compiled using current versions of GCC for *nix/Mac and Microsoft^® Visual Studio for Windows. Full functionality of ABC-OCT needs the camera SDK from QHYCCD and a QHYCCD camera to be connected; but the code can be easily modified to support other camera drivers, as is shown by an included demo version which can use any installed webcam. The code is made available under the MIT license. The software is available from GitHub (https://github.com/hn-88/FDOCT).

Background: Cytokines and chemokines are critical regulators of innate and adaptive immunities during viral infection. We examined innate and adaptive immune responses to hepatitis C virus (HCV) and hepatitis B virus (HBV) at baseline and against controls. Methods: Twenty-seven cytokines were evaluated before treatment in 27 patients with chronic hepatitis C(CHC) [genotype1 (n=20), genotype2 (n=7), HCVRNA 5.72IU/ml] and 12 chronic hepatitis B(CHB) [e-antigen (Ag) (+) (n=5), e-Ag (-) (n=7), HBVDNA 6.191.31Logcopies/ml] and against controls(n=5). Results: Th1 and Th2 cytokines were significantly higher (p<0.05) in CHB than in CHC. The levels of IL-IL10 in CHC and CHB, and IL15 in CHC(genotype2) and CHB were significantly lower (p<0.05) than in controls. The levels of CXCL8 in CHC and CHB, IL12 in CHC and CHB [e-Ag (-)] and CXCL10 in CHC and CHB were significantly higher (p<0.05) than in controls. IFN-γwas higher in CHB than in controls. Conclusion: Cytokines levels differed between CHB and CHC before treatment. Innate immune responses were impaired in CHB with HBeAg(-) and CHC, but not in CHB with HBeAg(+) with high viral loads. Adaptive immune responses were impaired in CHB and CHC and appear to reflect the distinct state of virus-host immune interactions between CHB and CHC.

Robotic path planning is a field of research which is gaining traction given the broad domains of interest to which path planning is an important systemic requirement; the aim being to optimise the efficacy of robotic movements in a defined operational environment. For example, robots have been employed in many domains including: cleaning robots (such as vacuum cleaners), automated paint spraying robots, window cleaning robots, forest monitoring robots, agricultural robots (often driven using satellite and geostationary positional satellite data). Additionally, mobile robotic systems have been utilised in disaster areas and locations hazardous to humans (such as war zones in mine clearance). The coverage path planning problem describes an approach which is designed to determine the path that traverses all points in a defined operational environment while avoiding static and dynamic (moving) obstacles. In this paper we present our proposed Smooth-STC model, the aim of the model being to identify an optimal path, avoid all obstacles, prevent (or at least minimise) backtracking, and maximise the coverage in any defined operational environment. The experimental results in a simulation show that, in uncertain environments, our proposed smooth STC method achieves an almost absolute coverage rate and demonstrates improvement when measured against alternative conventional algorithms.

In this study, the fuzzy c- means classifier has been studied with nine other similarity and dissimilarity measures: Manhattan distance, chessboard distance, Bray-Curtis distance, Canberra, Cosine distance, correlation distance, mean absolute difference, median absolute difference and normalised squared Euclidean distance. Both single and composite modes were used with a varying weight constant (m) and also at different α-cuts. The two best single norms obtained were combined to study the effect of composite norms on the datasets used. An image to image accuracy check was conducted to assess the accuracy of the classified images. Fuzzy Error Matrix (FERM) was applied to measure the accuracy assessment outcomes for a Landsat-8 dataset with respect to the Formosat-2 dataset. To conclude FCM classifier with Cosine norm performed better than the conventional Euclidean norm. But, due to the incapability of the FCM classifier to handle noise properly, the classification accuracy was around 75%.

A novel nor-phragmalin-type limonoid, named carapanosin D (1), and two novel mexicanolide-type limonoids, carapanosins E (2) and F (3), were isolated from the seeds oil of Carapa guianensis AUBLET (andiroba), a traditional medicine in Brazil and Latin American countries. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and HRFABMS. Compounds 1—3 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. The NO inhibitory assay suggested that compound 2 may be valuable as potential inhibitors of macrophage activation.

Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both sporadic and hereditary forms and whose pathogenesis is related to RET proto-oncogene alterations. MTCs originate from parafollicular cells, which produce calcitonin that represents the biochemical activity of MTC. Total thyroidectomy is the main treatment for MTC and often cures patients with confined diseases. In cases of metastasis, the approach depends on the rate of progression of disease. We report a case of a 54 years old female with a single, incidentally discovered, thyroid nodule of 1 cm, classified as suspicious MTC after a stimulation test with i.v. calcium. After surgery, we examined the nodule using immunohistochemistry, immunofluorescence and electron microscopy. In addition to calcitonin, we found that it expressed intracellular positivity for the RTK receptors ERBB1 and ERBB2. Consistently with MTC features, ultrastructural examination of the tumor displayed heterogeneous spindle-shaped cells containing two groups of secretory granules. Due to the significant correlation found between high ERBB1/ERBB2 levels in MTCs and extrathyroidal growth, the detection of ERBB1 and ERBB2 expression suggests that the two oncoproteins may possibly be involved in tumor proliferative responses and/or differentiation of C-cells. The biological, prognostic and therapeutic significance of these patterns would merits further investigations.

The mechanistic pathway of TEMPO/I₂-mediated oxidative cyclization of N,N-diaryl amino alcohols 1 is investigated in this study. Based on our direct empirical experiments, three key intermediates (the aminium radical cation 3, the α-aminoalkyl radical 4, and the iminium 5), four kind reactive species (radical TEMPO, cationic TEMPO, TEMPO-I and iodo radical) and three kind pathways (1. SET/PCET mechanism, 2. HAT/1,6-H transfer mechanism, 3. Ionic mechanism) were assumed. Under the assumption, nine free energy diagrams are acquired through DFT calculation. From the comparison of the solution phase free energy, some possibility can be excluded and then the chosen plausible mechanisms are concretized with the more stable intermediate 7.

The goal of the study is to assess the potential correlation between maternal Sars-cov-2 infection , detected three months before the second trimester anomaly scan, and fetal iperecogenicity in order to determine whether or not this could be considered a predictive factor for maternal-fetal complications . The study included 48 pregnant women who did not have any clear maternal or fetal problems. These individuals had an anomaly scan in the second trimester, as well as amniocentesis and fetal cariotyping, and then RT-PCR testing on their placental tissue after birth to rule out transplacental transmission. There have been no reports of fetal abnormalities via amniocentesis or fetal cariotyping. The patients experienced a high rate of spontaneous births (83%). Fetal development problems (2%) and premature delivery (4%) were uncommon, although placental swabs revealed a possibility of viral transmission across the placenta itself. To the best of our knowledge, this is the first observational study to show that detecting isolated intestinal hyperechogenicity during an abnormality scan in fetuses of women infected with Sars-Cov-2 in the previous three months does not appear to be a predictor of poor maternal-fetal outcomes, but may be linked to transplacental virus transmission.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life-cycle, including nuclear importation in case of lentiviruses and integration targeting events, hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase, and interestingly, raltegravir also showed modest antiviral activity against the SARS-CoV-2 Omicron variant in antiviral assays carried out in Vero E6 cells.

Background and Objectives: Cardiovascular events are the leading cause of morbidity and mortal-ity in hemodialysis (HD) patients. Identifying risk factors can help in the effort to reduce cardi-ovascular risk and improve life expectancy. The purpose of this study was to evaluate the ability of CHA2DS2-VASc score [risk index of stroke in atrial fibrillation (AF)] in patients with end stage kidney disease, to predict stroke, major cardiovascular events and mortality. Materials and Meth-ods: CHA2DS2-VASc and HAS-BLED (bleeding risk from use of anticoagulation in AF) scores were calculated in 237 HD patients, [99 women, median age 76 (15) years], at time they com-menced on HD. The scores’ ability to predict long term cardiovascular morbidity and mortality was estimated, both in those with and without AF. Results: CHA2DS2-VASc score was signifi-cantly increased in AF (n=69) compared to non-AF (n=168) patients, 5 (2.5) versus 4 (2), p<0.0001, respectively. Increased CHA2DS2-VASc score was associated with heart failure (p=0.007, p=0.024), stroke (p<0.0001, p<0.0001) and risk of all-cause mortality (p<0.0001, p<0.0001), in both groups, respectively. C statistics indicated that CHA2DS2-VASc score performed modest discrimination in this HD population with and without AF for heart failure, stroke, and all-cause mortality, but for cardiovascular mortality in AF group only. Conclusions: Increased CHA2DS2-VASc score at time starting on HD, can predict stroke, heart failure and all-cause mortality in HD patients in-dependent of the presence of AF. Risk of cardiovascular mortality could be predicted only on patients with AF.

We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the his-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and RBD purification was performed by Ni-chromatography and buffer exchange by membrane filtration. The simplified assay uses single dilutions of sera from finger-pricked native blood samples, purified RBD in 96-well plates, and a chromogenic dye for development. The results of this RBD-ELISA were confirmed to correlate with those of a commercial immunoassay measuring antibodies against the Wuhan strain, as well as direct virus neutralization assays assessing the cellular effects of the Wuhan and the Omicron (BA.5) variants. Here we document the applicability of this ELISA to assess the variant-specific humoral immunity in vaccinated and convalescent patients, as well as to follow the time course of selective vaccination response. This simple and rapid assay, easily modified to detect humoral immunity against emerging SARS-CoV-2 virus variants, may help to assess the level of antiviral protection after vaccination or infection.

Oral diseases remain a major health problem worldwide, with the World Health Organisation reporting that oral health neglect affects almost half of the world’s population. Quorum sensing molecules (QSMs) influence oral biofilms in various ways with knowledge of direct oral QSM-host interaction being limited, and such studies could provide more insight into the cross-kingdom communication occurring during oral disease development. This review aims to explore the literature on oral QSM-host interaction and to highlight areas of advancement in this field. QSM CSP-1 produced by Gram-positive oral bacteria was found to interact with T2R receptors, activating NF-kB signalling and leading to remodeling of the cytoskeleton. AI-2 in the oral cavity was found in various studies to elicit an inflammatory response in specific oral cells. Overall AHL detection methods remain an area for development, through which greater understanding of oral QSMs’ influence on host cells can be achieved. In conclusion, from the current literature it can be inferred that that QSMs are utilised by host cells to detect bacterial presence and in the majority of cases elicit an immune response towards the environmental QSMs. This may provide a base to target QSMs as novel treatment of oral diseases.

More than 3 years have passed since the emergence of COVID-19. On May 8, 2023, COVID-19 in Japan was downgraded to Category 5 by the Infectious Disease Control Law. In Japan, at the beginning of the COVID-19 pandemic in 2020, cases of infection and deaths from severe disease were few compared with those of Western countries. However, in the medical field, screening for COVID-19 was given top priority, resulting in confusion and proving disadvantageous for many patients, also the overreaction to COVID-19 as the most important issue in society can be attributed largely to statements by infectious disease experts. In addition, the mRNA vaccine emerged in 2021, and most of the population was vaccinated up to two times within a short period of less than 1 year because infectious disease experts strongly promoted vaccination. After 2022, when vaccination progressed, and the Omicron strain, which is an attenuated strain, became the mainstay of the SARS-CoV-2, the number of severe cases of COVID-19 decreased significantly; however, the number of infected people increased dramatically instead. A significant portion of the population is thought to have hybrid immunity due to vaccination plus natural infection and maintains high antibody titers. Henceforth, additional vaccination should be given preferentially to those who will benefit most from it. Conversely, measures against COVID-19 caused serious damage to the economy and society. Policies that not only address countermeasures against infection, but also those that encompass the economy and society as a whole are necessary.

Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and anti-viral activity, which may limit sexual transmission of infectious diseases during intercourse. We have recently discovered that PDC-109 inhibits the membrane fusion activity of influenza virus particles and significantly impairs viral infections at micromolar concentrations. Here we investigated whether the antiviral activity of PDC-109 is restricted to Influenza or if other mammalian viruses are similarly affected. We focused on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 19 (COVID-19), thoroughly assessing PDC-109 inhibition with SARS-CoV-2 Spike (S)-pseudotyped reporter virus particles, but also live-virus infections. Consistent with our previous publications we found significant virus inhibition, albeit accompanied by substantial cytotoxicity. Using time-of-addition experiments however, we discovered treatment regimen that enable virus suppression without affecting cell viability. We furthermore demonstrated that PDC-109 is also able to impair infections mediated by the VSV glycoprotein (VSVg) thus indicating a broad pan-antiviral activity against multiple virus species and families.

The COVID-19 pandemic had profound negative effects on millions of couples affected by infertility and in need to resort to assisted reproductive technologies. There is no consensus over the optimal way and moment of screening triage-negative asymptomatic patients and staff. We present SARS-CoV-2 antibodies’ (IgM, IgG) seroprevalence in 516 triage-negative patients and 30 fertility care providers. The sampling for SARS-CoV-2 serological assays took place from the lockdown release throughout the second half of 2020 (17.05 - 01.12.2020). It revealed an increased seroprevalence of antibodies that closely followed the local epidemiology of COVID-19, with the highest rate of seropositivity coincident with the peak of the second wave. From 546 triage-negative individuals whose blood samples were assessed for SARS-CoV-2 antibodies, 6% yielded positive results. The overall seroconversion rate was 2.8% for IgG and 5.1% for IgM. In the group with positive IgM, we observed a negative predictive value for IgM of 98.36% (95% CI: 88.79 – 99.78%), which is clinically meaningful. Serological testing of triage-negative patients up to seven days prior to the actual fertility procedure might avoid the more expensive and not more sensitive molecular testing currently being used for patient screening in most fertility units.

Covid-19 pandemic has captivated scientists to investigate if this new disease can affect the central nervous system (CNS). The most challenging symptoms of Covid-19 are related to respiratory distress, and most patients admitted in intensive care units cannot breathe by their own. Therefore, a crucial question is if respiratory distress can be partially explained by the CNS affection. SARS-Cov-2 is a beta-coronavirus that shares high similarities with SARS-CoV. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Those coronaviruses have been able to invade the brainstem via a synapse‐connected route to the medullary respiratory center, where the infected regions included the nucleus of the solitary tract and nucleus ambiguous. The vagal afferent nerves from receptors in the lung communicate with the medulla and pons respiratory control centers to coordinate inspiration and expiration. This suggests that neuroinvasion of SARS‐CoV‐2 might play a role in the acute respiratory failure of Covid-19. Therefore, acute respiratory distress in Covid-19 can be partially explained by brainstem dysfunction, suggesting the needs of more specific and aggressive treatments with the direct participation of neurologists and neurointensivists.

SARS-CoV-2 causes severe pneumonia epidemics and probably originated in horseshoe bats, but the intermediate host is unknown. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from different species including cats, chimpanzees, dogs, cattles. Our results show, domestic cats (Felis catusc) and dogs (Canis lupus familiaris) are more susceptible to infection by SARS-CoV-2 and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

Clathrate hydrate-based technologies have been considered as promising and sustainable alternatives for the effective management of the climate change risks related to emissions of carbon dioxide, produced by human activities. This work presents a combined experimental and computational investigation of the effects of the operational procedures and characteristics of the experimental configuration, on the phase diagrams of CO2-H2O systems and CO2 hydrates formation, growth and dissociation conditions. The operational modes involved (i) the incremental (step-wise) temperature cycling and (ii) the continuous temperature cycling processes, in the framework of an isochoric pressure search method. Also, two different high pressure PVT configurations were used, of which one encompassed a stirred tank reactor and the other incorporated an autoclave of constant volume with magnetic agitation. The experimental results implied a dependence of the subcooling, (P, T) conditions for hydrate formation and dissociation and thermal stability of the hydrate phase on the applied temperature cycling mode, and the technical features of the utilized PVT configuration. The experimental findings were complemented by a thermodynamic simulation model and other calculation approaches, with the aim to resolve the phase diagrams including the CO2 dissolution over the entire range of the applied (P, T) conditions.

Fiber-rich green river Aonori alga is mass-cultivated in Japan; it has been reported to reduce inflammation and improve metabolic health in humans. Peroxisome proliferation-activated receptor (PPARs) are associated with metabolic disorders such as obesity and type 2 diabetes (T2DM). We evaluated the effects of supplementation with NBF2, a formula made of algal and junos citrus biomaterials, on metabolic markers in obese and diabetic rats. An experimental study was performed using 18 obese and hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats randomly assigned to high dose NBF2 (20mg/kg; n=6), low dose (10mg/kg; n=6) NBF2 drink for 6 weeks, whereas OLETF control rats received similar amount of tap water (vehicle; n=6). LETO rats were used as normal controls (n=8). Biospecimens were taken for ELISA and real-time PCR. Both high dose and low dose NBF2 increased brown adipose tissue (BAT) mass and adiponectin (APN), improved insulin sensitivity, and significantly improved glycemic and lipid (TG, LDL-c) profiles in NBF2-supplemented OLETF rats after a 6-week supplementation with NBF2 (vs. OLETF controls), as well as LDL-c (p<0.05). During the glucose tolerance test (OGTT), both NBF2 groups and LETO rats had normal glycemia by 90-minute time-point (vs. OLETF controls; p<0.01). Furthermore, intake of NBF2 up-regulated PPARa/g-mRNA and Sirt2-mRNA gene expressions in BAT, and improved blood pressure profile in OLETF rats. Findings from this research suggest that intake of NBF2 formula induces dual PPAR-a/g and Sirt2 activation, providing insights on beneficial prophylactic and therapeutic effects of this NB2 formula on dyslipidemia and hyperglycemia in T2DM.

(1) Background: SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms in children. However, the multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here we compare the humoral and cellular immune responses elicited in children (n=15) aged 5-11 years vaccinated with RBD-based vaccines combined in a heterologous scheme of SOBERANA® 02 and SOBERANA® Plus with those from children (n=10) aged 4-11 years who recovered from mild symptomatic COVID-19. (2) Methods: Blood samples were taken 14 days after last dose for vaccinated and 45-60 days after the infection diagnosis for COVID-19 recovered children. Anti-RBD IgG and ACE2-RBD inhibition were assessed by ELISA; IgA, cytokine and cytotoxic related proteins profile were determined by multiplex assays. Total B and T cell subpopulations and IFN-γ release were measured by multiparametric flow cytometry using a large panel of antibodies after in vitro stimulation with S1 peptides. (3) Results: Significant higher levels of specific anti-RBD IgG and IgA and ACE2-RBD inhibition capacity were found in vaccinated children in comparison to COVID-19 recovered children. Th1-like and Th2-like CD4+ T cells were also significantly higher in vaccinated subjects. IFN-γ secretion were higher in central memory CD4+ T cells of COVID-19 recovered children, but no differences between both groups were found in CD4+ and CD8+ T cells effector, terminal and naïve T cell subpopulations. High levels of IL-2, IL-6, IFN-γ and IL-10 in contrast to low levels of IL-4 suggesting a predominant Th1 cell polarization. Cytotoxic-related proteins granzyme A and B, perforin and granulin were also found in the supernatant after S1 stimulation in both vaccinated and recovered children. (4) Conclusions: Vaccination with the heterologous scheme of SOBERANA® 02/ SOBERANA® Plus induces strong antibody and cellular immune response compared to natural infections of young children.

β-cyclodextrin (CD) derivatives containing aromatic triazole ring were studied as potential carriers of drugs containing an anthraquinone moiety in the structure: anthraquinone-2-sulfonic acid (AQ2S), anthraquinone-2-carboxylic acid (AQ2CA) and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and stability constants of the complexes formed and revealed the unique properties of the chosen CDs as effective pH dependent drug complexing agents. The stability constants of the drug complexes with the CDs containing triazole: βCDLip and βCDGAL were significantly larger than with the native βCD. The AQ2CA and AQ2S drugs are ill-soluble and their solubilities increased as the result of complex formation with βCDLip and βCDGAL ligands. AQ2CA, AQ2S were negatively charged at pH 7.4 and therefore they were less prone to form inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when they were protonated. βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at acidic pH (pH 5.5) than in the neutral medium (pH 7.4) when the drug dissociates to the neutral, uncharged form. This pH dependence is favorable for anti-tumor applications.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

The role of the Renin-Angiotensin-Aldosterone System (RAAS) in Corona Virus Disease 2019 (COVID-19) infection has become a controversial topic of discussion. RAAS inhibitors, such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs), which are used to treat cardiovascular diseases, have been implicated in potentially increasing cell surface levels of ACE2. ACE2 is the host receptor for COVID-19 that was discovered in Wuhan, China in December 2019. Since December, COVID-19 has transmitted rapidly across the world and has become a global pandemic. COVID-19 is similar to the Middle East respiratory syndrome coronavirus (MERS-CoV) with the first case reported in Saudi Arabia in September 2012. COVID-19, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is also similar to SARS-CoV, which first infected humans in the Guangdong province of southern China in 2002, and caused an epidemic between November 2002 and July 2003. Both SARS-CoV and COVID-19 use ACE2 to enter host cells. ACE2 is primarily expressed in the mouth, lung, heart, esophagus, kidney, bladder, and intestines, and is a component of RAAS, which serves to maintain vascular tone and blood volume. Inhibition or activation of other components of RAAS has been shown to directly increase or decrease the expression and/or activity of ACE2. Furthermore, RAAS-targeting therapeutics, such as ACE inhibitors and ARBs, have also been shown to regulate the expression and/or activity of ACE2, albeit in animal models. Although these changes in ACE2 have been demonstrated only in animal models, there is no evidence that administration of RAAS-targeting therapeutics to humans for the treatment of hypertension, diabetes, and other cardiovascular diseases (e.g., myocardial infarction and heart failure) causes changes in ACE2 expression. Nor is there clinical evidence that RAAS-targeting therapeutics augment COVID-19 infection, morbidity, or mortality. However, clinical evidence does suggest that ACE2 expression may protect against respiratory distress caused by a variety of noxious agents. This review attempts to provide a balanced overview of the potential role of RAAS in regulating ACE2, and the role of ACE2 during COVID-19 infection. Evidence is provided to show that the expression of ACE2 may mediate both positive and negative outcomes, depending on the timing of ACE2 expression.

Chagas disease, caused by Trypanosoma cruzi, leads to severe complications in 30% of infected individuals, including acute myocarditis and chronic fibrosing cardiomyopathy. Despite the significant burden of the disease, there is currently no licensed vaccine available to prevent it. This study aimed to evaluate the mucosal and systemic immunogenicity as well as the prophylactic efficacy of a mucosal vaccine and its impact on both acute and chronic cardiomyopathy. The results showed that nasal administration of Trans-sialidase (TS) plus c-di-AMP (TS+A). TS+A vaccine elicited NALT expression of IFN-γ, IL-17a, and IL-4 mRNA, and nasal-specific IgA production. Ex vivo challenge with TS also triggered enhanced proliferation of lymphocyte from the NALT, sentinel cervical lymph node and spleen. TS+A immunization increased plasma levels of Th1/Th2/Th17 cytokines and an evident cellular response to judge enhanced delayed-type hypersensitivity responses following TS footpad challenge. After oral infection, TS+A-vaccinated mice showed significantly reduced parasitemia and parasite load in heart, muscle and intestine, while markers of hepatic and muscle damage as well as clinical manifestations of acute infection are strongly diminished. TS+A also attenuated acute myocarditis and heart expression of inflammatory markers. The protection conferred by TS+A extended into the chronic phase, where it resulted in a clear reduction in chronic myocarditis, fibrosis, and functional electrocardiographic abnormalities, associated with decreased expression of the pro-fibrotic TGF-β. These results revealed that it is possible to develop a mucosal vaccine against T. cruzi based on TS and c-di-AMP, capable to reduce the development of Chagas cardiomyopathy, the hallmark of Chagas disease.

Background: miRNA-122 has been reported to be a useful tool for monitoring ACR after LT. IL-28B SNP rs8099917 genotype is known to contribute to the control of HCV infection. We sought to investigate the relationship between IL-28B SNP rs8099917 genotype and miRNA-122 expression and immune mechanism of ACR after LT using hepatitis C antibody calibration. Patients and Methods: A total of 45 patients with chronic hepatitis C received LDLT. IL-28B SNP rs8099917 genotyping was used to divide TT and GT groups. The relative expression levels of miRNA-122 were calculated by quantitative PCR as 2[(Ct of miR-122) (Ct of U6)] normalized to a reference gene and compared to a control sample, and the anti-HCV titers before and after LT were tracked to observe the relationship with ACR. Results: In the genotype of rs8099917, TT was significantly more associated with higher serum miRNA-122 levels than GT (p = 0.029). The ACR was significantly higher in genotype TT than in GT (p = 0.002). TT was significantly associated with low levels of pre-LT anti-HCV compared with GT (p = 0.022). Multivariate analysis with 95% confidence intervals showed a significant association between rs8099917 genotype TT, lower pre-LT and higher post-LT anti-HCV and ACR. Conclusion: Based on our current data, IL-28B SNP rs8099917 genotype TT may express higher miRNA-122 and correlate with lower Pre-LT and higher Post-LT anti-HCV titers, and may correlate to the pathogenesis of ACR after LT.

We studied yeast hand carriage of 260 students from medicine (78), nursing (89), and medical laboratory scientist (93). We isolated yeasts in 27 students (10.4%), with no differences between careers or gender. A significant lower prevalence of carriage was shown in the clinical cycle (2.7%) compared to the basic cycle (13.5%) (p=0.022) and the preclinical cycle (13.5%) (p=0.014).Increased handwashing frequency and alcohol gel use decreased yeast carriage. Students who applied moisturizing hand cream two or more times a day had a lower frequency of yeast carriage (3.4%) compared to those who did not use it or used it only once a day (16.5%), showing a significant difference (p=0.016). The most prevalent species was C. parapsilosis sensu stricto (81.5%), followed by Meyerozyma guilliermondii (C. guillermondii) (7.4%), Trichosporon mucoides (7.4%), and R. mucilagenosa (3.7%). And one case showed mixed carriage of C. parapsilosis and C. albicans. All strains were sensitive to voriconazole, caspofungin, and anidulafungin. This study shows the yeast carriage on the hands of health students, especially of C. parapsilosis, and its reduction with the frequent use of infection control measures and moisturizing hand cream.

Capsaicin, vitamin C, carotenoids and phenolic compounds from cumari-do-Pará peppers (Capsicum chinense Jacq.) harvested from two different locations from Pará, Brazil, and at different ripening stages were extracted employing ultrasonic-assisted extraction (UAE). Edible vegetable oils from soybean (Glycine max), Brazilian nuts (Bertholettia excelsa H.B.), and palm olein were used as the extraction solvent, as an alternative to organic solvents combined with UAE. The proximate composition of the pepper extracts and vitamin C were determined through AOAC methods, while total phenolic compounds and carotenoids were assessed by UV/Vis spectrophotometry, and capsaicin, by high-performance liquid chromatography. The antioxidant activities of cumari-do-Pará extracts were evaluated by the ABTS radical scavenging and β-carotene/linoleic acid system assays. Bioactive compounds and antioxidant activity varied with harvesting location and pepper ripening stage. Soybean oil was the most effective in extracting hydrophobic molecules particularly linoleic acid, corresponding to about 60% of the total fatty acid. Carotenoids were extracted whith highest yields by all oil extracts . Oily cumari-do-Pará extracts can be used as spices in foodstuffs and as additives in pharmaceuticals and nutraceuticals. Edible vegetable oils combined with UAE are, thus, efficient for bioactive compound extraction, also comprising an environmentally friendly, safe, low-cost, and fast alternative.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

In Southeast Asia, the incidence of Leukemia, a malignant blood cancer originating from hema-topoietic progenitor cells, is on the rise, marked by a concerning 54% mortality rate. This study focuses on enhancing early-stage prediction to improve patient recovery prospects significantly. Leveraging Machine Learning and Data Science, we employ protein sequential data from frequently mutated genes such as BCL2, HSP90, PARP, and RB to predict Chronic Myeloid Leukemia (CML). Our approach relies on robust feature extraction techniques, namely Di-peptide Composition (DPC), Amino Acid Composition (AAC), and Pseudo amino acid composition (Pse-AAC), with prior attention to addressing outliers and validating feature selection through the Pearson Corre-lation Coefficient. Data augmentation ensures a well-rounded dataset for analysis. Employing a range of Machine Learning models, including Support Vector Machine (SVM), XGBoost, Random Forest (RF), K Nearest Neighbor (KNN), Decision Tree (DT), and Logistic Regression (LR), we achieve accuracy rates spanning from 66% to 94%. These classifiers undergo comprehensive as-sessment using performance metrics such as accuracy, sensitivity, specificity, F1-score, and the confusion matrix. Our proposed solution, encompassing a user-friendly web application dashboard, presents an invaluable tool for early CML diagnosis with profound implications for practitioners, offering a deploy-able asset within healthcare institutions and hospitals.

Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse aspects. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

Let $n \geq 2$ be a fixed integer and $\mathcal{A}$ be a $C^*$-algebra. A permuting $ n $-linear map $ \mathcal{G} : \mathcal{A} ^{n} \rightarrow \mathcal{A} $ is known to be symmetric generalized $n$-derivation if there exists a symmetric $n$-derivation $ \mathfrak{D} : \mathcal{A} ^{n} \rightarrow \mathcal{A} $ such that $ \mathcal{G} \left(x_{1}, x_{2}, \ldots, x_{i} x_{i}^{\prime}, \ldots, x_{n}\right)= \mathcal{G} \left(x_{1}, x_{2}, \ldots, x_{i}, \ldots, x_{n}\right) x_{i}^{\prime}+x_{i} \mathfrak{D} (x_{1}, x_{2},\ldots, x_{i}^{\prime}, \ldots, x_{n})$ holds for all $x_{i}, x_{i}^{\prime} \in \mathcal{A} $. In this paper, we investigate the structure of $C^*$-algebras involving generalized linear $n$-derivations. Moreover, we describe the forms of traces of linear $n$-derivations satisfying certain functional identity.

Study design: Technical note. Objectives: To present a new technique of treatment for a patient with thoracolumbar focal kyphosis due to osteoporotic verte-bral fracture (OVFs). Background : OVFs are common among the elderly population. Following a severe wedged fracture, patients often experience low back pain and disruptions in activities of daily living. Reconstruction surgeries, such as corpectomy, are among the treatment options for this condition. However, corpectomy requires longer surgical times and involves a significant amount of blood loss. Materials and Methods : An 80-year-old woman presented to our hospital with severe low back pain and gait disturbance. She had experienced an L2 OVF six years prior. Although she had no neurological deficit, she could not walk more than 200m due to pain. Preoperative spinal radiographs revealed severe sagittal malalignment, with the L2 vertebra collapsed and focal kyphosis of L1-3 measuring 34 degrees. Results: The patient underwent anterior and posterior surgery in the right decubitus position using a C-arm free technique. The surgical time was 133 minutes with an estimated blood loss of 100 ml. Hyperlordotic cages were inserted in the upper and lower disc space via a lateral approach, while percutaneous pedicle screws (PPS) were inserted from a posterior approach. These procedures were performed simultaneously under navigation guidance only. Post-operative images showed excellent spinal alignment, with local kyphosis reduced from 34 to 14 degrees, and no major or severe complications occurred. At one-year follow-up, the patient was able to walk smoothly, with her visual analogue scale for low back pain improving from 73mm to 13mm, and her Oswestry Disability Index improving from 53.3% to 13.3%. Conclusions/Level of Evidence : The simultaneous use of hyperlordotic cages and PPS is an effective and innovative navigation technique that yields promising outcomes for thoracolumbar focal kyphosis resulting from OVFs. This approach not only reduces surgical time but also minimizes intraoperative blood loss. Level V.

: Cardiac surgery (CS) with extracorporeal circulation (ECC), induces oxidative stress and systemic inflammatory response, which may seriously affect postoperative lung function. We aimed to test if high parenteral (200mg/kg/24h) perioperative (48h) doses of Vitamin C (VitC) may reduce the incidence and severity of postoperative pulmonary complications (PPC) in selected CS patients. Single centered, prospective, randomized, single-blinded, interventional study included 150 patients, assigned to control group A (n=75) and interventional group B (n=75). Group B intraoperatively received 1/4 of the planned daily Vit C dose (200mg/kg/24h), diluted in 10 ml of normal saline, divided into three parts, while Group A received an equal volume of normal saline at the same time frames. After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 200 mg/kg/24h - 30 min i.v. infusion of VitC in 50 ml of normal saline, every 6h, for the next 48h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 hours, for the next 48h. Modified Kroenke’s score was used to determine the incidence and severity of PPC. The overall incidence of PPC was 36.7% and was significantly lower in Group B (13.3% v.s. 60.0%, p&lt;0.001). The severity of PPC was also significantly lower in Group B [1(1) v.s. 3(2), p&lt;0.001]. Besides, patients from Group B had significantly less damaged lungs and better postoperative renal function, shorter ICU stay, fewer ICU re-admissions, and lower hospital mortality. High parenteral daily VitC doses (200mg/kg/24h) given to selected CS patients for 48h after CS are safe and effective in reducing the incidence and severity of PPC. Further multicenter RCT is needed to confirm these results.

Recently, the Third Generation Partnership Project (3GPP) introduced the New Radio (NR) technology for Vehicle-to-everything (V2X) communication to enable delay-sensitive and bandwidth-hungry applications in vehicular communication. The NR system is strategically crafted to complement the existing Long Term Evolution (LTE) Cellular-Vehicle-to-Everything (C-V2X) infrastructure, particularly to support advanced services such as the operation of automated vehicles. It is widely anticipated that the 5th generation (5G) NR system will surpass LTE C-V2X in terms of achieving superior performance in scenarios characterized by high throughput, low latency, and enhanced reliability, especially in the context of congested traffic conditions and a diverse range of vehicular applications. This article will provide a comprehensive literature review on vehicular communications from Dedicated Short Range Communication (DSRC) to NR V2X. Subsequently, it delves into a detailed examination of the challenges and opportunities inherent in NR V2X technology. Finally, we proceed to elucidate the process of creating and analyzing an open-source 5G NR V2X module in network simulation-3 (ns-3) and then demonstrate the NR V2X performance in terms of different key performance indicators implemented through diverse operational scenarios.

Analytics have become increasingly popular among sports in recent years, providing valuable information regarding physical and mental health. Many athletes have found that analytics during training can help to improve their performance, reduce the risk of injury, and enhance their overall well-being. This paper aims to improve the results of handball players by applying a method for measuring the influence of different trials on aggregate performance calculated per each athlete in order to qualify for the Olympic Games. By separating the isolated action of each trial, the result is an additional influence caused by the interaction of factors or the simultaneous action. That might explain why the neuromuscular feedback loop is utterly necessary to perform handball motor actions. Further on, the ML analysis can help identify areas for improvement, optimize training programs, and enhance overall team performance.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Transition metal alloys have emerged as promising electrocatalysts due to their ability to modulate key parameters such as d-band electron filling, Fermi level energy, and interatomic spacing, thereby influencing their affinity towards reaction intermediates. However, the structural stability of alloy electrocatalysts during alkaline hydrogen evolution reaction (HER) remains a subject of debate. In this study, we systematically investigate the structural evolution and catalytic activity of the c-Co/Co3Mo electrocatalyst under alkaline HER conditions. We reveal that the instability of the Co3Mo alloy and H0.9MoO3 during alkaline HER leads to the destruction of the crystal structure, resulting in the formation of hexagonal cobalt (h-Co) from hexagonal Co(OH)2 as an intermediate species. Furthermore, we explore the re-adsorption and surface coordination of the Mo element, which enhances the catalytic activity for alkaline HER. This work provides valuable insights into the dynamic behavior of alloy-based electrocatalysts, shedding light on their structural stability and catalytic activity during electrochemical reduction processes

Background. In the last decade, it was concluded that glaucomatous optic neuropathy is part of the neurodegenerative diseases in which destructive neuronal lesions are located not only in the structure of the retina, but they are also present at the level of the central visual and nervous pathways. Patients with Primitive Open Angle Glaucoma may have experienced changes such as sensorineural hearing loss as well as balance changes. The purpose of this study is to evaluate the degree of involvement of the auditory system in patients with glaucoma, the structural changes in the optic nerve and, to establish correlation between the hearing loss and structural changes in the optic nerve. The subjects included in the study are grouped as follows: a group of patients with glaucoma that will be compared to a group of patients without glaucoma only as well as identi-fy-ing the evolution of structural changes in optic nerve to patients with glaucoma and to normal patients. Material and methods. It is a prospective, cross-sectional study on 32 eyes of 16 subjects with Primitive Open Angle Glaucoma in a study group and 24 eyes of 12 healthy subjects in con-trol group with a mean age of 62 years in both groups. Both groups underwent ophthalmo-logical, audiological and radio imaging evaluation: Pure-tone audiometry (PTA) were recorded, oph-thalmologic evaluations according to a standardized protocol and MRI cerebral examination was performed. Results: In the Study group patients, compared to the Control group, the average lev-els of the left PTA, the cup/disc (C/D) area in both eyes, the C/D ratio in both eyes are in-creased. The mean level of Retinal nerve fiber layer (RNFL) mean thickness was slightly lower in patients with glaucoma. Multivariate analysis demonstrates that gender can be a good predictor of C/D area, gender and age can be good predictors of PTA both eyes and C/D ratio in the right eye, and gender, age and background can be good predictors of disc area in the left eye. Conclu-sions: Pa-tients with Primitive Open Angle Glaucoma show changes in audiometry test in correla-tion with ophthalmological parameters demonstrating that the auditory system can be affected in Primitive Open Angle Glaucoma. This study emphasizes the problem of interdisciplinarity in medicine with the aim of ensuring the quality of life of patients with glaucoma. A good collabora-tion between ophthalmologist and otolaryngologist will be very useful for these patients.

This study investigates the stress corrosion cracking (SCC) behavior of type 316L stainless steel (SS316L) produced with sinter-based material extrusion additive manufacturing (AM). This technology has been shown to produce SS316L with microstructures and mechanical properties comparable to its wrought counterpart in the annealed condition. However, despite plenty of research on SCC of SS316L, little is known about SCC in sinter-based AM SS316L. This study focuses on the influence of sintered microstructures on susceptibility to SCC initiation and crack-branching. Custom-made C-rings were exposed to different stress levels in acidic chloride solutions at various temperatures. To better understand the SCC behavior of SS316L, solution-annealed (SA) and cold-drawn (CD) wrought SS316L were tested for comparison. Results showed that sinter-based AM SS316L was more susceptible to SCC initiation than SA wrought SS316L but more resistant than CD wrought SS316L. Moreover, sinter-based AM SS316L showed noticeably better resistance to crack-branching than both wrought SS316L counterparts. The investigation was supported by comprehensive pre- and post-test microanalysis using light optical microscopy (LOM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and micro-computed tomography (micro-CT)

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

Cellular Vehicle-to-Everything (C-V2X) is a communication technology that supports various safety, mobility, and environmental applications given its higher reliability properties compared to other communication technologies. The performance of these C-V2X-enabled Intelligent Transportation System (ITS) applications is affected by the performance of the C-V2X communication technology (mainly packet loss). Similarly, the performance of the C-V2X communication is dependent on the vehicular traffic density which is affected by the traffic mobility patterns, and vehicle routing strategies. Consequently, it is critical to develop a tool that can simulate, analyze, and evaluate the mutual interactions of the transportation and communication systems at the application level and to the evaluate the benefits of the C-V2X enabled ITS applications. In this paper, we demonstrate the benefits gained when using C-V2X Vehicle-to-Infrastructure (V2I) communication technology in an energy-efficient dynamic routing application. Specifically, we develop a Connected Energy-Efficient Dynamic Routing (C-EEDR) application using C-V2X as a communication medium in an integrated vehicular traffic and communication simulator (INTEGRATION). The results demonstrate that the C-EEDR application achieves fuel savings of up to 16.6% and 14.7% in the IDEAL and C-V2X communication cases, respectively for a peak hour demand on the downtown Los Angeles network considering a 50% level of market penetration of connected vehicles. The results demonstrate that the fuel savings increase with increasing levels of market penetration at lower traffic demand levels (25% and 50% the peak demand). At higher traffic demand levels (75% and 100%) the fuel savings increase with increasing levels of market penetration with maximum benefits at a 50% market penetration rate. Although the communication system is affected by the high density of vehicles at the high traffic demand levels (75% and 100% the peak demand), the C-EEDR application manages to perform reliably producing system-wide fuel consumption savings.The C-EEDR application achieves fuel savings of 15.2% and 11.7% for the IDEAL communication and 14% and 9% for the C-V2X communication at the 75% and 100% market penetration rates, respectively. Finally, the paper demonstrates that the C-V2X communication constraints only affect the performance of the C-EEDR application at the full demand level when the market penetration of connected vehicles exceeds 25%. This degradation, however is minimal (less than a 2.5% reduction in fuel savings).

Background: Acute pancreatitis is a common emergency. Morbidity control requires early detection of disease severity. METHODS: A total of 131 AP patients were analyzed retrospectively. Patients were divided into two groups mild AP (MAP: Ranson score <3) and severe AP (SAP: Ranson score ≥3), according to Ranson’s criteria. Demographic data, hospitalization duration, PNI, CRP, and RDW levels were compared. Any p-value below 0.05 (p<0.05) was accepted as statistically significant. RESULTS: Study included 67 (51.15%) males and 64 (48.85%) females. The age average was 59.74 (19-90) years. 95 (72.52%) patients had MAP, and 36 (27.48%) patients had SAP. Mean hospitalization time, PNI, and CRP differed significantly between the two groups (p=0.010, p<0.05, p<0.05, respectively). The RDW (p=0.380) level difference was insignificant. For SAP prediction; the sensitivity, specificity and cut-off value according to Ranson code cut-off point for PNI were determined as 80.0% (95% CI:54.8-85.8), %72.2 (95% CI:70.5-87.5) and ≤45.6 (gr/L) + (mm3), respectively, and 94.7% (95% CI:57.8-87.9), %75.0 (95% CI:88.1-98.3) and >105,1 mg/L, respectively for CRP. CONCLUSION: PNI and CRP values (but not RDW values) were compatible with the disease severity determined by the Ranson criteria.

It is shown that the representation theory of some finitely presented groups thanks to their $SL_2(\mathbb{C})$ character variety is related to algebraic surfaces. We make use of the Enriques-Kodaira classification of algebraic surfaces and the related topological tools to make such surfaces explicit. We study the connection of $SL_2(\mathbb{C})$ character varieties to topological quantum computing (TQC) as an alternative to the concept of anyons. The Hopf link $H$, whose character variety is a Del Pezzo surface $f_H$ (the trace of the commutator), is the kernel of our view of TQC. Qutrit and two-qubit magic state computing, derived from the trefoil knot in our previous work, may be seen as TQC from the Hopf link. The character variety of some two-generator Bianchi groups as well as that of the fundamental group for the singular fibers $\tilde{E}_6$ and $\tilde{D}_4$ contain $f_H$. A surface birationally equivalent to a $K_3$ surface is another compound of their character varieties.

Background: The demand in the development of cancer nanomedicine has increased due to various limitations in conventional cancer therapy. This study assessed the mRNA transcriptomic profiling of human HepG2 cells exposed to C. roseus-AgNPs. Methods: The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with C. roseus‑AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, DEG analysis, GO analysis, and pathway analysis. Results: The mean IC₅₀ values of C. roseus‑AgNPs on HepG2 was 4.38±1.59 µg/mL while on THLE3 cells was 800±1.55 µg/mL. Transciptomic profiling revealed an alteration of 296 genes. C. roseus‑AgNPs induced the expression of stress-associated genes such as MT, HSP and HMOX-1. Cellular signaling pathways were potentially activated through MAPK, TNF and TGF pathways that responsible for apoptosis and cell cycle arrest. The alteration of ARF6, EHD2, FGFR3, RhoA, EEA1, VPS28, VPS25, TSG101 indicated the uptake of C. roseus-AgNPs via both clathrin-dependent and clathrin-independent endocytosis. Conclusions: This study provides the new insights on gene expression study of biosynthesized AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicates the C. roseus‑AgNPs as an ideal anticancer candidate.

Understanding of the decisive role of the interaction mechanism and kinetics in the combustion processes is highly relevant for the elaboration of optimal conditions for obtaining Mo-Cu composite powders. From this perspective, the efficient delivery of the reduction mechanism of copper and molybdenum oxides with combined Mg + C reducing agents at high heating rates is crucial to develop a valuable approach for the combustion synthesis of Mo-Cu composite powders. Herein, we shed light on the mechanism of the reactions in all the studied binary, ternary and quaternary systems contemporaneously demonstrating the effect of the heating rate on the conversion degree. The combination of two highly exothermic and speedy reactions (MoO3+3Mg and CuO+Mg vs MoO3+CuO+4Mg) led to a slow interaction with weak self-heating (dysynergistic effect) due to a change in the reaction mechanism. On the other hand, it has been shown that during the simultaneous utilization of the Mg and C reducing agents, the process begins exclusively with carbothermic reduction, and at relatively high temperatures it continues with magnesiothermic one. The effective activation energy values of the magnesiothermic stages of the studied reactions were determined by Kissinger isoconversional method.

Host ribosome-associated scaffold protein Receptor for Activated C Kinase 1 (RACK1) is utilized by a diverse group of human viruses for Internal Ribosomal Entry Sites (IRES) – mediated translation of viral mRNAs. We recently reported inhibition of herpes virus by small molecules targeting the RACK1 functional site. Here, we tested these molecules against HIV-1 and HCV, as HIV-1 contains two potential IRES sites and HCV translation occurs exclusively through IRES. Compounds significantly downregulated activities of HIV-1- and HCV-related dicistronic reporter constructs in transfected HEK293T cells. The compounds also strongly downregulated production of the HIV-1 capsid protein p24 in HIV-infected cells, as well as production of HIV-1 Gag precursor p55 and p55-derived proteins p24 and p17 in cells infected with the HIV-1 virus. Hepatitis C virus (HCV) IRES activities were also significantly inhibited by RACK1 inhibitor compounds. Since a number of human and plant pathogenic viruses are reported to use IRES, the RACK1 compounds can be established as broad host-targeted antivirals.

Pd-Pt catalysts supported on carbon preheated to 1600°C have been reinvestigated in CHFCl2 hydrodechlorination. An additionally adopted catalyst oxidation at 350-400°C produced an order of magnitude increase in the catalytic activity of Pd/C. This increase is not caused by changes in metal dispersion or possible decontamination of the Pd surface from superficial carbon, but rather by unlocking the active surface, originally inaccessible in metal particles tightly packed in the pores of carbon. Burning carbon from the pore walls attached to the metal changes the pore structure, providing easier access for the reactants to the entire palladium surface. As upon calcination the performance of the rest of the Pd-Pt/C catalysts changes less than for Pd/C, the relation between the turnover frequency and alloy composition does not confirm the Pd-Pt synergy invoked in our previous work. The use of even higher-preheated carbon (1800°C), completely free of micropores, results in a Pd/C catalyst that does not need to be oxidized to achieve high activity and excellent selectivity up to CH2F2 (>90%).

Biochar application to the soil can improve soil quality and nutrient leaching loss. Recent studies have reported that surficial application of biochar to stored swine manure can reduce emissions of odorous compounds and reduce the volatilization loss of ammonia. Our working hypothesis was that the biochar-treated manure application to the soil would decrease nutrient leaching from manure and increase plant-available nutrients. The study objectives were to evaluate the impact of biochar-treated swine manure on soil total C, N, and other major and minor nutrients. Three biochars (i) neutral pH red-oak (RO), (ii) highly alkaline autothermal corn (Zea mays) stover (HAP), and (iii) mild acidic Fe-treated autothermal corn stover (HAPE) were incubated with swine manure for a month. The biochar-manure mixture was applied in triplicate to soil columns with application rate determined by the P₂O₅-P content in manure or manure-biochar mixtures after the incubation. The ammonium (NH₄⁺), nitrate (NO₃^-), and reactive P concentrations in soil column leachates were recorded for eight leaching events. Soil properties and plant-available nutrients were compared between treatments and control manure & soil. Manure-(HAP&HAPE) biochar treatments significantly increased soil organic matter (OM) and increased soil total C, N, and improved soil bulk density. Concentrations of KCl-extractable NH₄⁺ and NO₃^- significantly increased in HAPE column leachates during this 4-week study and in the soil after the experiment. A significant reduction in soil Mehlich3 Cu was also observed for the manure-HAPE mixture compared with the control. Overall, the manure-biochar incubation enabled biochar to sorb nutrients from manure, and the subsequent manure-biochar mixture application to soil improved soil quality and plant nutrient availability in comparison to conventional manure application to soil. This proof-of-the-concept study suggests that biochars could be used to solve both environmental and agronomic challenges and further improve the sustainability of animal and crop production agriculture.

In this paper, 6063 aluminum alloy for common building profiles is used as the research object. By adding a new Al-Ti-C-La composite alloy, the effect of 6063 aluminum alloy on the microstructure and properties of 6063 aluminum alloy is studied. The results show that Al-Ti-C-La composite alloy has obvious effect on grain refinement of 6063 aluminum alloy. With the addition of Al-Ti-C-La composite alloy, the grain size decreased significantly. When the addition amount of Al-Ti-C-La composite alloy is 1%, the grain size is reduced from 482 μm to 121 μm. Rare earth La is mainly distributed near the Mg2Si phase and β-AlFeSi, and complex compounds such as AlFeSiMgLa are formed. After aging for 270 days on the basis of T6 heat treatment, the tensile strength and elongation of 6063 aluminum alloy augmented with the addition of Al-Ti-C-La composite alloy, and the Vickers hardness gradually diminished. When the addition amount of Al-Ti-C-La composite alloy is 1%, the tensile strength, elongation and Vickers hardness of 6063 aluminum alloy reach 177.2 MPa, 17.8% and 60.9 HV, respectively, and the tensile strength is increased by 16.3%. The elongation is increased by 50.8%, the Vickers hardness is reduced by 15.4%, and the fracture of the alloy is mainly ductile fracture.

In this paper, the forecast horizon and solar variability influences on MHFM model based on multiscale decomposition, AR and NN models, are studied. This article follows the works published in [1] showing the performance of the MHFM using 3 multiscale decomposition methods and a forecast horizon equal to 1 hour. Several forecast horizon strategies and his influence on the MHFM performances are investigated. We show that the best strategy for a rRMSE variying from $4.43\%$ to $10.24\%$ is obtained for forecast horizons from $5$ minutes to $6$ hours. In a second part, the solar variability influence on the MHFM is studied. A classification based on a shows that the best performance of MHFM is obtained for clear sky days with a rRMSE of $2.91\%$ and worst for cloudy sky days with a rRMSE of $6.73\%$.

Sumudu transform of the Dixon elliptic function with non zero modulus a ≠ 0 for arbitrary powers sm^N(x,a) ; N ≥ 1 ; sm^N(x,a)cm(x,a) ; N ≥ 0 and sm^N(x,a)cm²(x,a) ; N ≥ 0 is given by product of Quasi C fractions. Next by assuming denominators of Quasi C fraction to 1 and hence applying Heliermann correspondance relating formal power series (Maclaurin series of Dixon elliptic functions) and regular C fraction, Hankel determinants are calculated and showed by taking a = 0 gives the Hankel determinants of regular C fraction. The derived results were back tracked to the Laplace transform of sm(x,a) ; cm(x,a) and sm(x,a)cm(x,a).

A convenient and efficient strategy for the preparation of 2-sulfonylindoles has been achieved through iodophor/H2O2-mediated 2-sulfonylation of indoles with readily available sulfonyl hydrazides in aqueous phase. Iodophor is commercially available and serves as the green catalyst and aqueous phase. A series of 2-sulfonylated products from indoles and N-methylpyrrole were synthesized in moderate yields in only 10 min. Control experiments were also conducted to reveal the mechanism. This method is environment friendly, easy to operate and suitable for a wide range of substrates.

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

Accurate fuel mapping plays a crucial role in fire detection and management strategies. This paper presents a method for discriminating between wildfire fuel types by exploiting together remote sensing data and Convolutional Neural Networks (CNN). Specially, a CNN-based classification approach that leverages Sentinel-2 imagery is exploited to accurately classify fuel types into seven preliminary main classes (conifers, broadleaf, shrubs, grass, bare soil, urban areas, and water bodies) with an high accuracy of 0.99$\%$. To further refine the fuel mapping results, subclasses were generated from the seven principals by using biomass and bioclimatic maps. These additional maps provide complementary information about vegetation density and climatic conditions, respectively. By incorporating this information, we align our fuel type classification with the widely used Scott/Burgan fuel classification system. This refinement step allows for a more detailed and comprehensive assessment of fuel types, enhancing the accuracy and effectiveness of fire management efforts, which can be utilized by fire management agencies, policymakers, and researchers for improved fire behavior prediction and mitigation practices. The proposed approach presents a valuable tool for enhancing fire management, contributing to more effective wildfire prevention and mitigation efforts.

A large population has been infected by COVID-19 (Coronavirus disease-19) and it has been necessary a rapid and simple diagnostic method to detect the SARS-CoV-2and control its spread. We developed a colorimetric reverse transcription-loop-mediated isothermal amplification (RT-LAMP) kit that allow the detection of SARS-CoV-2 from nasopharyngeal swab samples without the need of RNA extraction. The kit utilizes three sets of LAMP primers targeting two regions of ORF1ab and one region in the E gene. The results are reported using colorimetric change of hydroxynaphthol blue, enabling visual interpretation without the need for expensive instrument. The kit demonstrated sensitivity to detect between 50 and 100 copies of the viral genome per reaction. The kit was authorized by the National Administration of Drugs, Food and Technology (ANMAT) of Argentina after validation using samples previously analyzed by gold standard RT-qPCR. The results showed sensitivity of 90,6 % and specificity of 100%, consistent with conventional RT-qPCR. In silico analysis confirmed the recognition of SARS-CoV-2 Variants of Concern (VOCs) B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427, B.1.429and lineages of variant Omicron (B.1.1.529) with 100% homology. This rapid, simple, and sensitive RT-LAMP method paves a way for a large screening strategy to be carried out at locations lacking sophisticated-instrumental and trained-staff, as particularly happen at regional hospitals and medical centers from rural areas.

We provide a summary of various epidemiological parameters related to COVID-19 such as incubation period, serial interval and other parameters. Understanding these parameters is important for developing prevention strategies. SARS-CoV-2 can be transmitted by droplets and close contact, but there is evidence of airborne transmission. Aerosol-generating procedures have been identified as one of the specific risk factors for healthcare workers. Super-spreading events refer to situations where a small number of individuals cause the majority of infections. The basic reproductive number (R0) and the spread parameter (k) are used to characterise the transmissibility of the disease. Estimated values for R0 range from 2 to 3 and the estimated value for k is 0.1.The duration of infectiousness depends on viral load and shedding. Viral load varies according to factors such as clinical spectrum, type of variant and vaccination status. The relationship between viral load and infectivity is not fully understood.With regard to the frequency of symptoms and signs of COVID-19, fever, cough, fatigue and dyspnoea are common. The prevalence of olfactory and gustatory dysfunction (OGD) varies between studies and countries. Age and comorbidities are factors associated with olfactory dysfunction.Estimates of the proportion of asymptomatic patients range from 6% to 96%. Asymptomatic transmission is considered likely and is important for control measures.We reviewed the quantitative semiology of COVID-19 is reported on sensitivity, specificity and likelihood ratios of signs.Finally, we also review risk factors for COVID-19 (including health care workers), co-infections, and epidemiology of variants..

SARS-CoV-2 pandemic caused an increase in Intensive Care Unit (ICU) hospitalizations with rise in morbidity and mortality; nevertheless, there is still little evidence of pandemic impact on antibiotic resistance in ICU. Retrospective monocentric epidemiological study. All microorganisms isolated from all patients admitted to E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. Aim of the study was to describe and analyze the impact of SARS-CoV-2 pandemic on ICU microorganisms resistance patterns. 1,771 microorganisms identified, 221 (12.47%) had resistant pattern (Resistant Organisms; ROs) isolated from 1,679 patients during 12,030 hospitalization days. The majority of ROs were Gram-negative (79.66% 2018, 77.29% 2019, 61.83% 2020, 62.56% 2021, 60.75% 2022), but increase of Gram-positive microorganisms was observed (20.34% to 39.25% between 2018-2022). Prevalence of AR was: 19.44% 2018, 11.54% 2019, 38.04% 2020, 34.15% 2021, 39.29% 2022 for Gram-positives; 19.86%, 13.56%, 18.12%, 12.41%, 12.31% for Gram-negatives. Incidence of Ros showed COVID-related rise in 2020-2021, followed by a lowering trend since 2021, with new rise in 2022. Possible explanations are antibiotic overtreatment and drop of containing measures. Interesting finding is the cumulative lowering trend of carbapenem resistant K. pneumoniae and P. aeruginosa probably due to different patient features.

Introduction SARS-CoV-2 infection normally damages respiratory system but may likewise impair endocrine organs’ function. Thyroid dysfunction and hyperglycemia are common endocrine complications of SARS-CoV-2 infection. Onset of T1D and associated complications including DKA, hospitalization and death, are thought to be increased during the COVID-19 pandemic. The aim of this study is to review the available data about the incidence rate of T1D and accompanying complications since the beginning of the COVID-19 pandemic. Methods: A systematic review was conducted using electronic databases PubMed and Google Scholar. The keywords “T1D, T1DM, Type 1 DM or Type 1 Diabetes”, “Coronavirus, SARS-CoV-2 or COVID-19” were used to search these databases. Titles and abstracts were screened for selection, and then relevant studies were reviewed in full text. Result: we selected 21 manuscripts out of 296 identified studies. Data about the incidence rate of T1D, hospitalization and death are not consistent across countries, but DKA incidence and severity seem to be higher during the COVID-19 pandemic. Conclusion: Our data collection demonstrated that COVID-19 may or may not increase the incidence of type 1 diabetes. Nevertheless, it is associated with higher incidence and severity of DKA in T1D patients. Antivirals are not fully protective against endocrine complications of SARS-CoV-2 infection. Combining medications that reduce SARS-CoV-2 entry into the cells and modulate the immune response to infection is an alternative practical approach to treating COVID-19.

The recent global emergence of the SARS-CoV-2 pandemic has accelerated research in several areas of science whose valuable outputs and findings can help to address future health challenges in the event of emerging infectious agents. We performed a multifocus shotgun analysis to compare differences in bacterial spectrum and viral presence through culture-independent RNA sequencing. We compared the microbiome of healthy people versus those with varying degrees of COVID-19 severity. We observed a significant increase in the diversity of microbial species in patients with COVID-19 regardless of disease severity. Some bacterial phyla, such as Actinobacteria, are significantly more abundant in healthy people than in infected people, whereas Bacteroides are less abundant in the latter. Infected people, regardless of severity and symptoms, have the same proportional representation of Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteriales the same. In addition to SARS-CoV-2 and numerous phage groups, we identified sequences of clinically significant viruses such as Human Herpes Virus 1, Human Mastadenovirus D, Molluscum Contagiosum Virus, and Rhinovirus A in several samples. Analyses were performed retrospectively, therefore, in the case of SARS-CoV-2 various WHO variants such as Alpha (B.1.1.7), Delta (B.1.617.2), Omicron (B.1.1.529), and 20C strains are represented. Additionally, the presence of specific virus strains has a certain effect on the distribution of individual microbial taxa.

The Mont-Saint-Michel is known worldwide for its unique combination of the natural site and the Medieval abbey at the top of the rocky islet. But the Mont is also located within an estuarine complex, which is considerably silting up. For two decades, large-scale works were planned to prevent the Mont from being surrounded by the expanding salt meadows. The construction of a new dam over the Couesnon River, the digging of two new channels, and the destruction of the causeway were the main operations carried out between 2007 and 2015. The remote sensing approach is fully suitable for evaluating the real impact of the engineering project in both time and space, particularly the expected large-scale hydrosedimentary effects, for reestablishing the maritime landscape around the Mont. Sentinel-2 satellite data have been used for the period from 2015 to 2023. Aster data were used for the previous period covering 2000 to 2017. Aerial photographs and an ALOS scene have been also used. The remote sensing approach is based on time-series images. It allows identifying local or regional consequences and temporary or permanent effects. The migration of the different channels (especially for the new west and east Couesnon river courses) and the erosion-progradation balance of the vegetation through space and time are the main features to study. Between 2007 and 2023, the erosion of the salt meadows is significant to the south-west of the Mont (− 150 ha) but more limited to the south-east (− 65 ha). The erosion effect is limited to the immediate environment because the vegetation fringe of the uppermost tidal flat along the main dike is slightly increasing (+ 35 ha) to the west and to the east (+ 40 ha). During the same period, the sedimentation considerably increased to the north-east of the Bay, between the Bec d’Andaine, the Grouin du Sud and Tombelaine islet, which seems now facing the same silting-up problem. At this stage, the remote-sensing survey indicates mixed results for the engineering project.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

The COVID-19 pandemic has had a major impact on health systems around the globe and Romania is no exception. The impact on healthcare expense for pregnant women has been considerable, especially in COVID-only tertiary centers, where specialized care is being provided .The aim of this study is to analyze the impact of SARS-CoV-2 infection on healthcare costs, in particular by managing cases in COVID-only maternity. Material and Methods: The objective of the study was to analyze if the model adopted by the health system consisting in complete separation of delivering obstetrical care for covid and non-covid patients was efficient. We conducted an observational study in which we compared a group of pregnant women infected with SARS-CoV-2 (study group) with a control group in which we included uninfected pregnant women. The patients were recruited from Bucur Maternity Hospital, declared a COVID-only center in march 2020. We compared the two groups in terms of expenses over the entire period of hospitalization, i.e. expense on hospitalization, medicines, medical supplies, and medical investigations.

The COVID-19 pandemic has been challenging for society, especially for those residing in long-term care facilities (LTCF). This study aimed to describe rates of infection, hospitalization, and death due to COVID-19 among older people and staff of LTCF in a state of Southeastern Brazil and identify strategies to prevent and control the disease spread. This cross-sectional study was conducted with 164 LTCF (6,017 older people). Among the studied LTCF, 48.7% confirmed COVID-19 infection in older people, resulting in 39.6% hospitalization and 32.3% death among infected. Moreover, 68.9% of LTCF confirmed COVID-19 infection in the staff, with 7.3% hospitalization and 1.2% death. Preventive measures were identified and classified as organizational, infrastructure, hygiene items and personal protective equipment, and staff training against COVID-19. These measures showed strategies and barriers experienced in the daily routine of LTCF during the pandemic. LTCF in Brazil experienced challenges similar to observed worldwide.

Patients with COVID-19 demonstrate higher rates of cardiovascular complications, including thromboses and thromboembolism. One may suppose that the action of SARS-CoV-2 transforms stable atherosclerotic plaques into unstable status. Cardiovascular complications in COVID-19 may be caused by progressive viral alteration the blood vessels, including vasa vasorum. A lethal case of ischemic brain disease caused by cerebral atherosclerosis and exacerbated with a stroke during COVID-19 infection is briefly described. The results of autopsy showed perivascular lymphocytic infiltration and signs of vasa vasorum vasculitis with thrombi of adventitial microvasculature. The data discussed in the article are interpreted in context of the concept giving the important role in atherogenesis to vasa vasorum.

Background: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. Methods: A retrospective cohort study was conducted and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate factors associated with symptomatic SARS-CoV-2 infections. Results: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person-months. In multiple model, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03 - 1.06]) and those with a severe first illness episode (vs mild disease, RR = 1.05 [1.01 - 1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97 - 0.99]). Conclusions: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults and they seem to be determined, partially, by vaccination status and age.

The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

Viral variant analysis is a bedrock of the disease surveillance. When combined with temporospatial analysis variant analysis can further the knowledge of disease spread in a study area. This paper suggests a method to perform the analysis in an operational setting which will allow for real-time surveillance of viral variants and allow local public health professionals to rapidly respond to changes in the evolution of the disease. This method includes three main subprocesses: preprocessing, analysis, and rendering. This method can be performed across multiple software platforms. A use case is given in which it was found that this method helped a hospital system understand the spread of SARS-CoV-2 in Northeast, Ohio.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), etiological agent of the novel coronavirus disease 2019 (COVID-19), has spread since December 2019, resulting in massive health and economic crisis worldwide. While efforts to stop the pandemic are crucial, collecting epidemiological data to help manage current and future pandemics will be important. In addition to humans, serological and molecular based studies have demonstrated SARS CoV-2 exposure in several wild, domestic and farmed animals. For examples Shriner and the team showed serologically an exposure of 40% to the white deer living in close proximity to urban centers. Additional reports have also emerged of susceptibility of animal’s species like cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters to SARS-CoV-2 infection.. It’s worth emphasizing that these reports are based on experimental data mostly derived from Europe, USA, South America and parts of Asia. In limited instances natural infections of SARS-CoV-2 have been reported in pet dogs, cats, tigers, lions, snow leopards, pumas, gorillas at zoos and farmed mink and ferrets. The presence of the virus in animal species and an understanding of whether these are natural or recent human to animal transmissions is important. It’s possible that such transmission could passage the virus or subject the virus to a different immunological pressure thereby helping with the development of viral variants in addition to being a host for future reservoirs of the virus. In Kenya SARS-CoV-2 was first detected on March 12th 2020 from imported human cases of persons who had travelled from the United States. This was followed by detection of imported cases majorly from China, Sweden and United Kingdom. Later infections were confirmed in Nairobi and Mombasa suggesting further cases of disease importations through the major ports of entry. However, no comparable data on animal exposure have hitherto been generated in Kenya. To address this key concern, we focused on three objectives; 1) development of a robust antibody ELISA based on crude SARS-CoV-2 lysate. 2) SARS-CoV-2 serology of domestic animals in Kenya. 3) Corroboration of the crude lysate based seroprevalence data and a commercial ELISA kit based on the Spike receptor binding domain (RBD) antigen. Our sample set included camel sera (both pre- & post outbreak sera), as well as sera from cats and dogs collected at the peak of the pandemic. Our results using the ELISA based on crude SARS-CoV-2 lysate indicated SARS-CoV-2 antibodies in camels (71%, N=145), cats 11% (N=16) and dogs (81%, N=36) with varying titer levels. These findings were comparable to those obtained using the commercial ELISA kit based on the spike RBD antigens. In summary, the data warrants two key conclusions: (i) we have demonstrated that the crude lysate ELISA allows for SARS-CoV-2 antibody detection, and given its potential to offer robust detection could be applied for initial mass screening (ii) although the current study cannot disentangle the relative contributions of antigenic cross-reactivity, pre-pandemic exposure to SARS-CoV-2 or human-animal transmission, it nonetheless demonstrates for the first time the prevalence of SARS-CoV-2 like antibodies in domestic and wild animals in Kenya. Our findings set the scene for further research into the prevalence of SARS-CoV-2 in domestic and wild animals to understand their potential epidemiological implications.

Background: The isoflurane minimum alveolar concentration (MAC) was measured in rats chronically treated with WIN 55,212-2. Methods: The isoflurane MAC was determined in 24 male rats from the end expiratory samples at time of tail clamping under the following conditions: without treatment (MACISO), in rats treated for 21 days with WIN 55,212-2 (MACISO+WIN55) and other group 8 days after stopping treatment for 21 days with WIN 55,212-2 (MACISO+WIN55+8D). Results: The MACISO was 1.32 ± 0.06. In the MACISO+WIN55 group the MAC increase to 1.69 ± 0.09 (28%). After 8 days stopping treatment, MAC did not decrease significantly 1.67 ± 0.07 (26%). Conclusions: The administration for 21 days of WIN 55,212-2 increases the MAC of isoflurane in rats; this effect does not disappear after 8 days of discontinuing treatment with the synthetic cannabinoid.

Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..

Prevention practices have been extensively used to contain the spread of the SARS-CoV-2 virus. These include social distancing, wearing masks, disinfection of hands, and sanitization of contact surfaces. However, the excessive usage of chemical disinfectants pose long term adverse effects to human health and the environment. Development of effective and environmentally friendly biocides, or virucidal agents, will help mitigate the ill effects of chemical disinfectants. Enzymes are potential candidates for the preparation of biocides against bacteria and viruses. Exploration of the virucidal activity of commercial enzymes, will highlight prospective, readily available sources for research on enzyme based biocides. In this study, the virucidal effect of some com-mercial enzyme preparations has been investigated against the SARS-CoV-2 virus. Vida Defense (2000 µg/ml), Excellacor (1500 µg/ml), and SEBkinase (3000 µg/ml) reduced SARS-CoV-2 viral ti-ters by ≥1 log CCID50 (≥90%). ImmunoSEB (6000µg/ml) and Peptizyme SP (500µg/ml) reduced the SARS-CoV-2 viral titers by 0.8 log CCID50 (84.2%). The study indicates that enzyme prepara-tions offer the potential to be explored further for an anti-viral biocide against SARS‐CoV‐2 for reducing the risk of COVID‐19 transmission. However, further studies are mandated to improve efficacy and establish safety.

Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P &lt; .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.

The Coronavirus disease 2019 (COVID-19) pandemic is clearly taking a firmer grip on South Africa and more podiatrists will face the potential transmission of SARS-CoV-2. Government response was swift with the implementation of a travel ban, strict national lockdown as well as social distancing and hygiene protocols in line with international health regulations. Co-morbidities such as tuberculosis and HIV/AIDS, endemic to South Africa, are considered a dangerous combination with COVID-19, making many South Africans vulnerable to contracting the COVID-19. Patients with diabetes as well as the aged are vulnerable, both in terms of potential combined complications and challenges in continuity in foot care. The demands of the pandemic may outstrip the ability of the health systems to cope. Should this time arrive, all healthcare practitioners, including podiatrists, would have to step in and take on a role beyond their scope of practice in order to ensure that the healthcare system does not get overwhelmed. It is important for podiatrists to keep abreast with the developments around the COVID-19, in order that they may institute appropriate clinical practice which will ensure maximum protection for themselves, staff and patients as well as providing quality foot health care.

In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13^th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

COVID-19 pandemic has caused a large-scale havoc in almost every country across the globe, putting major challenges for the healthcare system in many parts of the world. Several of the laboratories are running in the race with undying efforts for developing potential vaccine, drugs or therapeutics to treat or prevent the infection. However, with the limited time window and high rate of infection, the task is very big for humanity to find a cure. With hundreds of genomic data of SARS-CoV-2 virus isolates from humans are being submitted almost every day, it is coming into knowledge that virus is mutating, slower in countries with sporadic cases, but higher in countries experiencing large outbreak. These types of mutations in virus may bring challenges in vaccine or therapeutic development for use in each and every country, as each hotspot region may have their own pattern of mutations in virus with ongoing outbreak. In our current study, we retrieved non-synonymous mutation data of around 12,225 SARS-CoV-2 virus samples isolated from humans globally, and discovered all mutations that are collectively happening in antibody epitope regions of the virus country-wise. We found a few numbers of epitope regions in SARS-CoV-2 that are highly conserved collectively in all variants and may be used for epitope-based vaccine development for whole world. We also found epitope regions that are conserved collectively in SARS-CoV-2 variants country-wise and can be used for customized epitope-based vaccine development in each different country.

“Severe acute respiratory syndrome” (SARS) due to Coronavirus (SARS-CoV) infection is a known cause of death. Sometimes demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flue-like symptoms. In this dobtfull cases the forensic pathologist could be requested to define cause of death occurred outside hospital. In this report the authors describe two thorough autopsied cases of SARS-CoV-2 related deaths occurred suddenly at home and not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.

The regulation of apoptosis depends upon the Bcl-2 protein family. The process of cell death and survival is highly complicated and regulated by various types of extrinsic as well as intrinsic network of biological system. Several enzymes and regulators play crucial role in cell death and survival cycle not only in healthy but also in pathological state particularly in cancer. In cancerous cells, various proto-oncogenes and anti-apoptotic proteins are activated and responsible for the cell survival and longevity. The mechanism of activation and inactivation of various proteins in cell survival is regulated by the process of phosphorylation (kinases) and dephosphorylation (phosphatases). The current review will summarize the dynamics of Bcl-2 phosphorylation and its role in apoptosis and cell survival.

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2 or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce an increase in a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines including interleukins IL-1, IL-6, CCL2 protein and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes four unconventional but commercially accessible immunomodulatory agents that could be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: Low-dose oral interferon-alpha, microdose DNA, low-dose thimerosal and phytocannabinoids.

The emergence of SARS-CoV-2 is a challenge in the actual medical scenario. Besides the classical lung and respiratory disease, patients infected with the virus can present with cardiac injury, and pathogenic mechanisms point to a direct infection of the heart.

OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2.MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the keywords “severe acute respiratory syndrome coronavirus”, “2019-nCoV”, “COVID-19, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection.RESULTS: The global cases of COVID-19 as of April 2, 2020 have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness.Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from a underlying chronic medical condition like hypertension, diabetes, cancer, respiratory illness or cardiovascular diseases.CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.

Covid-19 has now become a public health concern worldwide. The infection primarily involves the respiratory tract. Hitherto, some Covid-19 pneumonia patients carry the viral nucleic acids, and the active virus was detected in stool specimens. The virus discharged with feces is a potential contagious source. In the present study, three Covid-19 respiratory tract infection patients showed no gastrointestinal symptoms, and two were positive for viral nucleic acids in anal swab specimens remained positive 6 and at least 14 days after virus turned negative in the respiratory tract, respectively (details of the patients were listed in Fig 1). Thus, for Covid-19-infected patients with or without gastrointestinal symptoms, viral nucleic acids in stool specimens or anal swab specimens should be focused on for testing in order to decide the isolation duration of the patient.

Rice is an essential crop for national food security in Egypt. Increasing the population calls for regular increases in rice production. At the same time, cultivated rice crop areas should be decreased because of the gradual scarcity of irrigation water. This means more rice production should be gained from less rice area. This situation calls for the annual accurate system for rice monitoring and yield estimation. Therefore, it is necessary to apply a remotely sensed based system for rice cultivation assessment using satellite imagery parallel with field measurements of some biophysical parameters. Multi-temporal normalized difference vegetation index (NDVI) extracted from twelve sentinel-2 imagery cover the whole summer season with variance and maximum value assessed by ground control points (GCPs), were used to isolate uncultivated areas, then to isolate rice areas and other vegetation covers. object-based classification methods with kappa co-efficient 0.9261 and overall accuracy 94.92% was generated to discriminate rice crop area and other summer crops on the study area. Leaf area index (LAI) for the experiment the l site was calculated using the surface energy balance algorithm for Land (SEBAL) model and then tested versus measured (LAI). NDVI and LAI were used to generate an empirical ran rice yield prediction model. Then, this model was used to produce rice to yield a map. The study was carried out in an experimental site in Kafr Elsheikh governorate with a total area of 5040 Hectare. Produced cultivated land use map showed 95% overall accuracy. High similarity was observed between measured and calculated (LAI) with high accuracy of R2 = 0.94. of Rice, yield map showed expected to yield more to than a month before harvest. The generated yield map was tested using a correlation coefficient between actual yield and estimated yield with high accuracy R2 = 0.9. This method is applicable to estimate the acreage and productivity of rice in the northern Nile delta in adequate time before harvest.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.

Introduction: Type 2 diabetes (T2D) is a major driver of health care costs, thus treatments enabling T2D reversal may reduce expenditures. We examined the impact of a T2D continuous care intervention (CCI) on health care utilization. Previous research documented that CCI, including individualized nutrition supported by remote care, simultaneously reduced hemoglobin A1c and medication use and improved cardiovascular status after two years; however, the impact on utilization is unknown. Methods: This study used four years of data (two years pre-intervention, two years post-intervention) from the Indiana Network for Patient Care (INPC) health record. Two methods estimated the impact of CCI on utilization. First, an interrupted time series (ITS) including only CCI participants (n=193) compared post-intervention utilization to expected utilization had the pre-intervention trend persisted. Deviation from the trend was estimated non-parametrically for each 6-month interval after the implementation of CCI . Second, a 1:3 matched comparator group (n=579) was constructed and used for a difference-in-differences (DiD) analysis. The primary outcome was annualized outpatient encounters. Secondary outcomes included emergency encounters and hospitalizations. Results: In two years prior to intervention, CCI participants had a mean of 5.77 annualized encounters (5.62 outpatient, 0.04 hospitalizations, 0.11 emergency). The CCI group showed a reduction in outpatient utilization after intervention. In ITS analysis, 1.6 to 1.9 fewer annualized outpatient encounters occurred in each 6-month interval post-intervention relative to expected utilization based on pre-intervention trends (p<0.01 each 6-month period; 28-33% reduction). The DiD analysis suggested a larger reduction; 5 fewer annualized outpatient encounters in the quarter after intervention, diminishing to 2.5 fewer after 2 years (p<0.01 each quarter). The study was underpowered to draw conclusions about hospitalization and emergency encounters due to the limited number of CCI patients and the rarity of encounters. Conclusions: Outpatient encounters were significantly reduced for a T2D patient population up to 2 years after receiving an individualized intervention supporting nutrition and behavior change through remote care.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.