Four adult males died within 18.5 hours due to effect of local liquor consumption in a hilly district of Gandaki province of Nepal. Methanol toxicity due to illicitly produced alcohol consumption should be managed with adequate supportive care and administration of specific antidotes such as ethanol or fomepizole.

This study reports a patient developing TEN after the first dose of (BBIBP-CorV). He developed numerous purpuric and dusky patches with flaccid bullae and areas of epidermal detachment covered more than 30% of the body area within 6 days. After treatment with dexamethasone and cyclosporin, he recovered within 14 days.

Background and Purpose: Myocardial infarction (MI) is an irreversible damage caused by ischemia and hypoxia in coronary arteries accompanied with elevated levels of catecholamine, leading to the accumulation of free radicals. Our previous study discovered coumarin-derived imino sulfonates as a novel class of potential cardioprotective agents possessing strong anti-oxidative effect in cardimyocytes. Therefore, the identification of the compound with the highest cardioprotective activity, 5h, and the mechanism involved was necessary. Experimental Approach: As a kind of catecholamine, isoproterenol induces MI injury mimicking symptoms of MI patients in clinic. Cardiac function, nfarct area, histopathological changes were evaluated. The potential mechanism underlying such action of compound 5h was explored via transfection with adenovirus to downregulate Sirt1 in vitro, and by administration of Ex527, the specific inhibitor for Sirt1, in vivo. Key Results: Compound 5h exhibited strong cardioprotective actions in vivo and in vitro via improving cell survival, cardiac function and decreasing the cellular oxidative stress and cardiac infarct size against MI. Furthermore, compound 5h significantly enhanced cardiac expression of Sirt1, subsequently activating the Nrf2/NQO1 signaling pathway. However, adenovirus induced Sirt1 downregulation or Sirt1 specific inhibitor largely blocked such beneficial effects of 5h in vitro and in vivo, respectively. Conclusions and Implications: Our results demonstrated, for the first time, that the cardioprotective action of 5h against MI was mediated by reducing oxidative stress and apoptosis through the Sirt1/Nrf2 signaling pathway. Our findings proposed novel insights in the development and evaluation of coumarin-derived imino sulfonate compounds as epigenetics-targeted drug therapy for MI.

Background: Topical tacrolimus has been widely used in the treatment of inflammatory and immune dermatoses for its immunosuppression effect. However, a transient irritation like itching, burning induced by tacrolimus is common when initial application, which is similar to pseudo-allergic reaction. MAS-related G protein-coupled receptor-X2 (MRGPRX2) in mast cells (MCs) mediates drug-induced pseudo-allergic reaction and IgE-independent pruritis in chronic skin diseases. Whether MRGPRX2 participates in above tacrolimus adverse reaction should be addressed. Further, immunosuppression mechanism of tacrolimus on MCs is greatly ignored. Methods: Wild-type (WT) mice, kit w-sh/w-sh mice and MrgprB2 deficient (MUT) mice were applied to explore the mechanism of initial irritant reaction and immunosuppression of tacrolimus on the skin MrgprB2 in MCs in vivo. LAD2 cells and MRGPRX2-knockdown LAD2 cells were used to confirm the regulation of MRGPRX2 by tacrolimus in vitro. Results: Tacrolimus could trigger IgE-independent dermatitis when initial application through MrgprB2-related MCs degranulation. Using FK-DNS, a fluorescently labeled tacrolimus, we found tacrolimus could bind to MRGPRX2 directly. Interestingly, after long-term tacrolimus treatment, the initial itching and inflammatory reaction faded away without IgE change. Hence, longstanding treatment with tacrolimus suppressed MRGPRX2/B2 expression and decreased inflammatory cytokines release. Conclusion: Our study provides for the first time a novel target for tacrolimus, demonstrating that short-term tacrolimus treatment induces pseudo-allergic reaction via MRGPRX2/B2 in MCs, while long-term treatment dampens MRGPRX2/B2 expression, leading to decreased inflammatory cytokines release and immune cells recruitment, which may contribute to its potent immunosuppression effect in the treatment of inflammatory and immune skin diseases.

Flower-visiting insects in agroecosystems forage on field-edge weeds often exposed to agrochemicals that may compromise the quality of their floral resources. We conducted complementary field and greenhouse experiments to evaluate the: 1) effect of low concentrations of agrochemical exposure on nectar and pollen quality and 2) relationship between floral resource quality and insect visitation. We found pollen amino acid concentrations were negatively affected by herbicide exposure, and pollen fatty acid concentrations were negatively affected by fertilizer exposure, while nectar sugar concentrations were positively affected by both fertilizer and herbicide exposure. These variations found in the greenhouse helped explain insect visitation in the field study. The insect visitation rate correlated with floral resource quality. An interaction between pollen protein and floral display suggested pollen protein drove insect abundance for larger display sizes. We show that flower-visiting insects can detect and respond to changes in floral resource quality mediated by agrochemicals.

This study aimed to investigate epidemiological, clinical, and laboratory features of children with COVID-19 to identify predictors for pulmonary involvement. We conducted a retrospective, single-center study of pediatric COVID-19 at a tertiary care hospital in Turkey between December 2020 and June 2021. A total of 126 children (70 males, 55.6%) were examined during the study period. Their mean age was 74.73 ± 81.11 months (range, 1–216 months). The most frequent COVID-19 symptoms were fever (65.9%), cough (52.4%), and shortness of breath (18.3%). Ten patients required noninvasive mechanical ventilation. Sixty-nine patients (54.8%) had pneumonia. Longer duration of fever and the presence of cough were significantly associated with pulmonary involvement. In children with pneumonia, the C-reactive protein (CRP), procalcitonin levels, erythrocyte sedimentation rate (ESR), and viral load were significantly higher and lymphocyte and thrombocyte counts were significantly lower than in children without pneumonia. The cutoff viral load, CRP, and procalcitonin values for predicting pulmonary involvement were 26.5 cycle threshold (Ct; 95% confidence interval [CI], 0.54–0.74; sensitivity, 0.65; specificity, 0.56; area under curve [AUC]: 0.647, p = 0.005), 7.85 mg/L (95% CI, 0.56–0.75; sensitivity, 0.66; specificity, 0.64; AUC = 0.656; p = 0.003) and 0.105 ng/mL (95% CI, 0.52–0.72; sensitivity, 0.55; specificity, 0.58; AUC = 0.626; p = 0.02), respectively. High CRP, procalcitonin levels, ESR, and viral load and low lymphocyte and thrombocyte counts can predict pulmonary involvement in children with COVID-19, so better management may be provided for good prognosis.

The rustrela virus (RusV) was recently described as a novel pathogen in a circumscribed area of northern Germany close to the Baltic Sea. Up to now, the virus has been detected in cases of fatal non-suppurative meningoencephalitis in zoo animals of different species and a single wild carnivore as well as in apparently healthy yellow-necked field mice ( Apodemus flavicollis). Data regarding the background of this previously undiscovered pathogen, including clinical presentation of the disease, host range, and distribution of the virus, are still limited. Here, three euthanized red-necked wallabies ( Macropus rufogriseus) from zoos of different areas in northeastern Germany were submitted for necropsy after presenting with apathy and therapeutically unresponsive neurological symptoms. A moderate to severe, non-suppurative meningoencephalitis was diagnosed in all three cases. RusV was consistently detected via RT-qPCR and RNA in situ hybridization in the brains of all wallabies. Other, commonly known neuropathogens could not be detected. Overall, red-necked wallabies appear to be highly susceptible to RusV as novel neuropathogen, which is broader distributed in northeastern Germany.

Objectives: The aim of this study was to investigate whether the prevalence of group 2 innate lymphoid cells (ILC2s) in sinonasal tissues or in peripheral blood is associated with the postoperative outcome in chronic rhinosinusitis (CRS) patients. Design: A cross-sectional study of CRS patients undergoing endoscopic sinus surgery (ESS). Setting: The Department of Otorhinolaryngology-Head and Neck Surgery at Shiga University of Medical Science Hospital. Participants: Eleven patients with eosinophilic CRS (eCRS) and ten patients with non-eCRS were recruited. Main outcome measures: We examined the ILC2 prevalence in sinonasal tissues and in peripheral blood before and after ESS. Lund-Mackay computed tomography (LMK-CT) scores were used to evaluate the postoperative outcomes; cases with more than 50% improvement were categorized into the good outcome group, and cases with less than 50% improvement were categorized into the poor outcome group. Results: The ILC2 prevalence in sinonasal tissues was correlated with that in preoperative blood in the eCRS and non-eCRS patients. The ILC2 prevalence in sinonasal tissues and in preoperative blood was not correlated with the pre- or postoperative LMK-CT scores. Postoperatively, the ILC2 prevalence in blood was decreased in the eCRS and non-eCRS patients, and the decrease was associated with the good outcome group, but not the poor outcome group. Conclusion: The decreased ILC2 prevalence in blood may be related to good postoperative outcomes after ESS in eCRS and non-eCRS patients.

Giant cell arteritis (GCA) is a chronic vasculitis of large- and medium-sized vessels that can lead to acute aortic adverse events. We describe a 74-year-old female patient who presented with acute-on-chronic aortic dissection. Her pathology was significant for aortitis in the setting of giant cell arteritis. The patient ultimately underwent successful repair of her dissection and was discharged home.

The measurement of biodiversity is an integral aspect of life science research. With the establishment of second- and third-generation sequencing technologies, an increasing amount of metabarcoding data is being generated as we seek to describe the extent and patterns of biodiversity in multiple contexts. The reliability and accuracy of taxonomically assigning metabarcoding sequencing data has been shown to be critically influenced by the quality and completeness of reference databases. Custom, curated, eukaryotic reference databases, however, are scarce, as are the software programs for generating them. Here, we present CRABS (Creating Reference databases for Amplicon-Based Sequencing), a software package to create custom reference databases for metabarcoding studies. CRABS includes tools to download sequences from multiple online repositories (i.e., NCBI, BOLD, EMBL, MitoFish), retrieve amplicon regions through in silico PCR analysis and pairwise global alignments, curate the database through multiple filtering parameters (e.g., dereplication, sequence length, sequence quality, unresolved taxonomy), export the reference database in multiple formats for the immediate use in taxonomy assignment software, and investigate the reference database through implemented visualizations for diversity, primer efficiency, reference sequence length, and taxonomic resolution. CRABS is a versatile tool for generating curated reference databases of user-specified genetic markers to aid taxonomy assignment from metabarcoding sequencing data. CRABS is available for download as a conda package and via GitHub (https://github.com/gjeunen/reference_database_creator).

1. Coral growth rate is one of the common measurements used as an indicator of coral reef health. The traditional approach is by directly measuring the linear extension rate. Yet, this method is a one-dimensional measurement where it underestimated actual coral growth due to coral morphotypes. Therefore, a multidimensional measurement would provide a better understanding on coral dynamic growth. Moreover, current practices are either invasive or needs a sample to be sacrificed therefore unfeasible for repeated sampling. This study aims to evaluate the accuracy of 3D-photogrammetry by comparing with standardised stainless steel gauge blocks of known dimensions. Also, aluminium foil wrap methods were compared with 3D photogrammetry to examine coral surface area of different morphotypes. 2. To explore the application of 3D-photogrammetry, 10 coral nubbins (approximately 3cm) of Acropora digitifera were taken from Pulau Bidong and transported back to the mesocosm system. Three different approaches were tested, they are (1) Photo-geometry linear extension (LE) rate using ImageJ software, (2) buoyant weight (BW), and (3) surface area (SA) estimation via 3D-photogrammetry modelling using Agisoft Photoscan software. Coral growth rates were measured every 14 days. 3. The coral growth was significantly reduced at week-8 as showed by the reduction in LE rate and BW values, while SA values increased exponentially. This was believed due to energy shift to form thin calcified layer at the base of the nubbins for stabilisation. 4. This finding suggests corals prioritise in establishment of a base for stability over linear growth after the asexual fragmentation. 3D photogrammetry allows a better understanding of corals’ life history strategy by recreating fairly accurate estimates of real objects (irregular coral) without sacrificing and removing it from water. In conclusion, this method further contributes to understanding coral performances after it is transplanted and for future in-situ long term coral monitoring purposes.

Species living in a changing environment are capable of adapting to alterations of various factors. Physiological acclimatization may be significantly influenced by the heterozygosity, especially with regards to allele variance and its specific expression (ASE) under different conditions. Data from RNA-seq experiments can be used to identify and quantify the alleles expressed, in order to detect and characterize ASE and regulation of gene expression. However, the allele matching the reference genome creates a mapping bias that prevents a reliable estimation of the allele depth unless the haplotype of the experimental individuals is provided. We developed a pipeline that allows the identification of the alleles corresponding to an RNA-seq dataset and their unbiased quantification. This pipeline does not require the sequencing of the DNA nor the previous knowledge of the haplotype. The identified SNPs are further substituted in the reference genome, thus creating two pseudogenomes with the alternative alleles on two independent samples of the experiment. The SNPs are further called against each pseudogenome thus providing with two SNP datasets that are averaged for calculation of the allele depth. The final SNP calling file contains the coordinates of the SNPs and also the ID of genes containing the SNPs, the expressed genotypes, the unbiased allele depth and the statistical tests for identifying ASE according to the experimental design and correlated with differentially expressed genes. Therefore, the pipeline presented here can calculate ASE in non-model organisms and can be applied to previous RNA-seq datasets for expanding studies in gene expression regulation.

Despite recent advances in high-throughput DNA sequencing technologies, a lack of locally relevant DNA reference databases may limit the potential for DNA-based monitoring of biodiversity for conservation and biosecurity applications. Museums and national collections represent a compelling source of authoritatively identified genetic material for DNA database development yet obtaining DNA barcodes from long-stored specimens may be difficult due to sample degradation. We demonstrate a sensitive and efficient laboratory and bioinformatic process for generating DNA barcodes from hundreds of invertebrate specimens simultaneously via the Illumina MiSeq system. Using this process, we recovered full-length (334) or partial (105) COI barcodes from 439 of 450 (98 %) national collection-held invertebrate specimens. This included full-length barcodes from 146 specimens which produced low-yield DNA and no visible PCR bands, and which produced as little as a single sequence per specimen, demonstrating high sensitivity of the process. In many cases, the identity of the most abundant sequences per specimen were not the correct barcodes, necessitating the development of a taxonomy-informed process for identifying correct sequences among the sequencing output. The recovery of only partial barcodes for some taxa indicates a need to refine certain PCR primers. Nonetheless, our approach represents a highly sensitive, accurate, and efficient method for targeted reference database generation, providing a foundation for DNA-based assessments and monitoring of biodiversity.

Microbe associated molecular pattern (MAMP) triggered immunity research has traditionally centred around signal transduction pathways originating from activated membrane localised pattern recognition receptors (PRRs), culminating in nuclear transcription and post translational modifications. More recently, chloroplasts have emerged as key immune signalling hubs. Chloroplasts play a central role in integrating environmental signals. Notably MAMP recognition induces chloroplastic ROS (cROS) which is suppressed by pathogens effectors, which also modify the balance of defence hormone precursors, jasmonic acid (JA), salicylic acid (SA) and abscisic acid (ABA), whose precursors are chloroplast synthesised. This study focuses on how well characterised PRRs and co-receptors modulate chloroplast physiology, examining whether diverse signalling pathways converge to similarly modulate chloroplast function. Pre-treatment of receptor mutant plants with MAMP and D(Damage)AMP peptides usually protect against effector modulation of chlorophyll fluorescence and prevent Pseudomonas syringae effector mediated quenching of cROS and suppression of Fv/Fm. The MAMP-triggered immunity (MTI) co-receptor double mutant, bak1-5/bkk1-1, exhibits a remarkable decrease in Fv/Fm compared to control plants during infection, underlining the importance of MTI mediated signalling in chloroplast immunity. Further probing the role of the chloroplast in immunity we unexpectedly found that high light uncouples plant immune signalling.

Dittrichia viscosa (L.) Greuter is gaining attention for its high genetic plasticity and ability to adapt to adverse environmental conditions including heavy metals and metalloids pollution. Uptake and translocation of cadmium, copper, iron, nickel, lead, and zinc to the shoots have been characterized but its performance with arsenic is less known and sometimes contradictory. Tolerance to As is not related to a reduced uptake but the null mutation of the aquaporin Nip1.1 gene in Arabidopsis, makes the plant completely resistant to the metalloid. This aquaporin, localized in the Endoplasmic Reticulum is responsible for arsenite and antimony (Sb) membrane permeation but the uptake of arsenite occurs also in the null mutant, suggesting a more sophisticated action mechanism than direct uptake. The DvNIP1 gene homologue is here cloned and its expression profile in roots and shoots is characterized in different arsenic stress conditions. The use of clonal lines allowed to evidence that DvNip1.1 expression level is influenced by arsenic stress. The proportion of gene expression in roots and shoots can be used to generate an index that appears to be a promising putative selection marker to predict arsenic-resistant lines of Dittrichia viscosa plants.

Background: Sternal dehiscence is a serious complication of cardiac surgery that has been a clinically intractable problem. The study aimed to explore the advantages of new rigid sternal plates (NRSP) compared with wire cerclage (WC) in the cardiac surgery of high- risk patients with sternal dehiscence and summarize the application experience. Methods: A retrospective analysis was performed on high-risk patients for sternal dehiscence who underwent cardiac surgery operation in the Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. All cases were identified and divided into WC (n=276) and NRSP (n=291). Risk factors for sternal complications, postoperative outcomes and cost associated with surgery and subsequent treatment were analyzed. Results: There was no significant difference in demographics and preoperative comorbidities compared to patients with WC(p＞0.05), those with NRSP had longer sternal closure time(p＜0.001). However, there are shorter hospital length of stay(p＜0.001), less postoperative drainage volume of 24h (p＜0.001), and lower total costs at 6 months(p=0.043) and 12 months(p＜0.001) in NRSP patients. After multivariate logistic regression analysis, the remaining five independent risk factors for the development of sternal dehiscence were used to compose the nomogram. The area under the receiver operating characteristic curve (AUC) of the model was 0.865 (95% confidence interval [CI], 0.802–0.927), and the calibration curve was good by the Hosmer–Lemeshow test. Conclusions: NRSP can enhance the stability of sternal fixation in high-risk patients after cardiac surgery and reduce the risk of sternal complications. Moreover, the nomogram comprised of age, body mass index (BMI)＞30kg/m 2, diabetes mellitus(DM), chronic obstructive pulmonary disease (COPD) and sternal closure method may predict the risk of sternal dehiscence.

Here we describe the case of a caucasian man referred to our Center for a suspicion of Multiple Myeloma which comprehensive work-up ruled out the presence of plasma cells neoplasm and allowed us to perform a diagnosis of brown tumor (BT).

Abstract text is in the manuscript due to problem with words limit

Orogastric and nasogastric tube are common methods of enteral feeding. While simple, these methods are not free of complications. A rare complication of these feeding methods is the fracture of the tube. This report describes a fracture of an orogastric tube in a 58-year-old stroke patient.

The potential benefit of concomitant surgical revascularization represents a controversial topic of the surgical treatment of post-infarction ventricular septal rupture (VSR). Beliaev and colleagues presented a case series interestingly focusing on this issue and showed how the possibility to perform coronary artery bypass grafting at time of VSR repair was associatd with better early and late mortality and improved cardiac function. However, a few more aspects deserve further comments in this controversial topic, especially considering late survival and postoperative cardiac function, although it seems reasonable to conclude that the presence of coronary artery disease not amenable to revascularization represents a strong negative prognostic factor in surgically treated VSR patients.

Here we show that substituting the ten protons in the dianion of a bispentalene derivative (C18H102-) by six Si2+ dications produces a minimum energy structure with two planar tetracoordinate carbons (ptC). In Si6C18, the ptCs are embedded in the terminal C5 pentagonal rings and participate in a three-center, two-electron (3c-2e) Si-ptC-Si σ-bond. Our exploration of the potential energy surface identifies a triphenylene derivative as the putative global minimum. But robustness to Born-Oppenheimer molecular dynamics (BOMD) simulations at 900 and 1500 K supports bispentalene derivative kinetic stability. Chemical bonding analysis reveals ten delocalized π-bonds, which, according to Hückel’s 4n+2 π-electron rule, would classify it as an aromatic system. Magnetically induced current density analysis reveals the presence of intense local paratropic currents and a weakly global diatropic current, the latter agreeing with the possible global aromatic character of this specie.

Rationale: Coronavirus disease 2019 (COVID-19) leads to hospitalization and death, especially in elderly and those with comorbidities. There are evidences showing that sitagliptin and spironolactone can potentially improve the clinical outcomes of COVID-19 cases. Objective: In this observational study on acutely symptomatic outpatient COVID-19 cases, we investigated the effects of spironolactone and sitagliptin on the outcomes of the disease. Methods: This prospective cohort study was conducted at Shiraz University of Medical Sciences Clinics during the fifth wave of the COVID-19 pandemic between July 2021 and September 2021. We followed mild to moderate symptomatic COVID-19 patients, who were treated with either combination (spironolactone 100 mg daily and sitagliptin 100 mg daily) or standard (steroid, antiviral and/or supportive care) therapy up to 30 days. Our primary outcome was hospitalization rate. The secondary outcomes included ER visit, duration of disease, and complications, such as hypoglycemia, low blood pressure or altered mental status. Results: Of the 206 patients referred to clinics, 103 received standard therapy and 103 treated with combination therapy. There were no significant differences in baseline characteristics, except for slightly higher clinical score in control group (6.92 ± 4.01 control, 4.87 ± 2.92 combination; P <0.0001). Treatment with combination therapy was associated with lower admission rate (5.8% combination, 22.3% control; P = 0.0011), ER visits (7.8% combination, 23.3% control; P = 0.0021) and average duration of symptoms (6.67 ± 2.30 days combination, 18.71 ± 6.49 days control; P =<0.0001). Conclusion: In this prospective cohort study of acutely ill outpatients with COVID-19, the combination of sitagliptin and spironolactone reduced duration of COVID infection and hospital visits better than standard therapeutic approaches. The effects of combination of sitagliptin and spironolactone in COVID-19 patients should be further verified in a double blind, randomized, placebo-controlled trial. Iranian Registry of Clinical Trials: IRCT registration number: IRCT20201003048904N2, Registration date: December 10, 2020.

Vampire bat-transmitted rabies has recently become the leading cause of rabies mortality in both humans and livestock in Latin America. Evaluating risk of transmission from bats to other animal species has thus become a priority in the region. An integrated bat-rabies dynamic modeling framework quantifying spillover risk to cattle farms was developed. The model is spatially explicit, and is calibrated to the state of São Paulo, using real roost and farm locations. Roosts and farms characteristics, as well as environmental data through ecological niche model, are used to modulate rabies transmission. Interventions in roosts (such as culling or vaccination) and in farms (vaccination) where considered as control strategies implemented to reduce risk. Both interventions significantly reduce the number of outbreaks in farms and disease spread (based on distance from source), with control in roosts being a significantly better intervention. High risk areas where also identified, which can support ongoing programs, leading to more effective control interventions.

Multi-parameters of physiological metabolism, environmental state, cell morphology, and manipulated variable, have mutual influences and constraints on coenzyme Q 10 (CoQ 10) biosynthesis of Rhodobater sphaeroides. In this work, a multi-parameter fusional correlation-analysis were applied to illuminate and optimize the crucial metabolism on CoQ 10 biosynthesis. The quantitative response model for accurate living cells concentration, morphological deformation, specific oxygen consumption rate (Q O2), and specific product biosynthesis rate were established, the results revealed that maintain the optimal electrical conductivity(Cond.) and Q O2 at 9.0±0.5 mS/cm and 0.06-0.08±0.01×10 -7mmol/cell/h, respectively, by adjusting the nutrient feeding and oxygen transfer rate, the cell’s morphology and oxygen uptake rate were strengthened. CoQ 10 production in 50L bioreactors was successfully improved by 35% to 3384mg/L than that of control, which would be more powerful and effective for scale up in the large-scale production of CoQ 10.