Background: Piceatannol is a resveratrol metabolite commonly found in red wine, grapes, and passion fruit seeds. Several studies have investigated the immune-modulating effects of piceatannol on processes related to allergic reactions. However, the relationship between piceatannol and atopic dermatitis (AD) has not yet been reported. Therefore, this study sought to investigate the effects of piceatannol in animal and cell line models. Methods: AD-like symptoms and skin lesions were induced by repeated topical application of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. Piceatannol was topically applied five times per week for four weeks. The molecular mechanism of piceatannol was studied in the TNFα/IFNγ-induced HaCaT cell line. Results: Topical application of piceatannol attenuated DFE-induced AD-like symptoms, as shown by skin thickness, dermatitis score, scratching time, and skin water loss. Histopathological analysis showed that piceatannol suppressed DFE-induced eosinophil and mast cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers, including serum TARC, MDC, and IgE. In addition, piceatannol alleviated Th2 cytokines such as IL-4 and IL-13 in the skin tissue. Piceatannol decreased phosphorylation of JAK-STAT protein in the TNFα/IFNγ-induced HaCaT cell line. A molecular docking study showed that piceatannol strongly interacts with JAK1, suggesting a possible piceatannol mode of action. Conclusions: Piceatannol, a metabolite of resveratrol, has potential therapeutic efficacy in treating AD by targeting JAK1.

Pollinators are in decline thanks to the combined stresses of disease, pesticides, habitat loss, and climate. Honey bees face numerous pests and pathogens but arguably none are as devastating as Deformed wing virus (DWV). Understanding host-pathogen interactions and virulence of DWV in honey bees is slowed by the lack of cost-effective high-throughput screening methods for viral infection. Currently, analysis of virus infection in bees and their colonies is tedious, requiring a well-equipped molecular biology laboratory and the use of hazardous chemicals. Here we describe cDNA clones of DWV tagged with green fluorescent protein (GFP) or nanoluciferase (nLuc), providing high-throughput detection and quantification of virus infections. GFP fluorescence is recorded non-invasively in living bees via commonly available long-wave UV light sources and a smartphone camera or a standard ultraviolet transilluminator gel imaging system. Nonlethal monitoring with GFP allows high-throughput screening and serves as a direct breeding tool for identifying honey bee parents with increased antivirus resistance. Expression using the nLuc reporter strongly correlates with virus infection levels and is especially sensitive. Using multiple reporters, it is also possible to visualize competition, differential virulence, and host tissue targeting by co-occuring pathogens. Finally, it is possible to directly assess the risk of cross-species ‘spillover’ from honey bees to other pollinators and vice versa.

Background: Left pulmonary vein (PV) obstruction can occur due to compression between the left atrium (LA) and the descending aorta (DA). One of the effective solutions for this problem is posterior aortopexy. In this study, we have reported five cases of posterior aortopexy to relieve left PV obstruction between the LA and the DA. Methods: Since August 2012, five patients have undergone posterior aortopexy for compression of the left PV between the LA and the DA. The median age and weight of the patients at the time of operation were 5.5 months (range, 1-131 months) and 5.2 kg (range, 4.2-29.5 kg), respectively. The left PV obstruction was initially diagnosed on echocardiography in four patients and computed tomography angiography in one patient. The median peak pressure gradient across the obstructed left PV was 7.3 mmHg (range, 4-20 mmHg). Concomitant procedures were ventricular septal defect closure in one patient and patent ductus arteriosus ligation in one patient. Results: There was no PV obstruction on echocardiography in any of the patients after the operation except in the case of one patient who had diffuse pulmonary vein stenosis. The median follow-up duration was 34 months (range, 14-89 months), and during follow-up no incidence of the left PV obstruction was observed in any of the surviving patients. Conclusions: The posterior aortopexy technique could be a good surgical option for the left PV obstruction caused by compression between the LA and the anteriorly positioned DA.

Biochar or pyrogenic carbon, obtained from thermo-chemical conversion of biomass in an anaerobic or oxygen limited environment has been in use in agriculture since long back to Neolithic era. Its unique soil ameliorating properties, render it suitable for environmental remediation as well as sustainable crop production. It improves soil physicochemical properties and plant nutrient availability, facilitates biodiversity, and reduces emission of greenhouse gases, thereby subsiding global warming. Application of biochar reduces soil erosion, improves soil hydrological properties, and soil microbial dynamics. It has synergistic effects on plant growth, disease-pest resistance, and crop yield per unit area and time. Due to its soil ameliorative effects, and soil and water conserving ability, it can very well be used in organic farming, pemaculture, dryland farming, conservation agriculture, and land remediation. Cheaper production cost, simple and easy pyrolytic technologies, easy availability of feedstock and bio-wastes in many developing countries and its long-term effects in soil not only build up soil carbon pool but also help support small and marginal farmers in resource-rich but economically deprived countries for sustainable agriculture and environment. In this review, efforts have been made to elucidate various methods of biochar synthesis, its characteristics and effects on soil properties, and plant growth and development, its role in sustainable agriculture and remediation of the environment.

Comparisons of genomes from recently diverged butterfly populations along a suture zone in central Texas have revealed high levels of divergence on the Z chromosome relative to autosomes, as measured by fixation index, $F_{st}$. The pattern of divergence appears to result from accumulation of incompatible alleles, obstructing introgression on the Z chromosome in hybrids. However, it is unknown whether this mechanism is sufficient to explain the data. Here, we simulate the effects of hybrid incompatibility on interbreeding butterfly populations using a model in which populations accumulate cross–incompatible alleles in allopatry prior to contact. We compute statistics for introgression and population divergence during contact between model butterfly populations and compare them to statistics obtained for 15 pairs of butterfly species interbreeding along the Texas suture zone. For populations that have evolved sufficiently in allopatry, the model exhibits high levels of divergence on the Z chromosome relative to autosomes in populations interbreeding on time scales comparable to periods of interglacial contact between butterfly populations in central Texas.Levels of divergence on the Z chromosome increase when interacting groups of genes are closely linked, consistent with interacting clusters of functionally related genes in butterfly genomes. Results for various periods in allopatry are in qualitative agreement with the pattern of data for butterflies, supporting a picture of speciation in which populations are subjected to cycles of divergence in glacial isolation, and partial fusion during interglacial contact.

Predicting which ecological factors constrain species distributions is a fundamental question in ecology and critical to forecasting geographic responses to global change. Darwin hypothesized that abiotic factors generally impose species’ high-latitude and high-elevation (typically cool) range limits, whereas biotic interactions more often impose species’ low-latitude/low-elevation (typically warm) limits, but empirical support has been mixed. Here, we clarify three predictions arising from Darwin’s hypothesis, and show that previously mixed support is partially due to researchers testing different predictions. Using a comprehensive literature review (886 range limits), we find that biotic interactions, including competition, predation, and parasitism, influenced species’ warm limits more often than species’ cool limits. At cool limits, abiotic factors were consistently more important than biotic interactions, but temperature contributed strongly to cool and warm limits. Our results suggest that most range limits will be sensitive to climate warming, but warm limit responses will depend strongly on biotic interactions.

The nucleotide-binding domain (NBD) and leucine-rich repeat receptors, such as NOD-like receptors (NLRs), have pivotal functions in the innate immune response to various viral infections participating during the recognition of pathogens and activation of signaling pathways. One NLR, NOD2, is a dynamic protein that is activated in the presence of viral genomes and metabolites. However, its participation in combating a dengue virus (DENV) infection remains unclear. The aim of this study was to determine the role of NOD2 in macrophage-like THP-1 cells during an in vitro infection with DENV type 2 (DENV2). The interactions of NOD2 with RIP2 and MAVS was examined in DENV2-infected and agonist-stimulated cells. The effects of downregulating NOD2 expression or signaling on virus loads was also evaluated. The cellular mRNA expression and protein levels of NOD2 on cells under the stimuli were quantified with RT-PCR, Western blot and indirect immunofluorescence. Both the mRNA and protein expression of NOD2 was enhanced in response to DENV-2 infection. Interactions of NOD2 with RIP2 and MAVS, analyzed with confocal microscopy and co-immunoprecipitation assays, were time-dependent and increased in the post-infection period, between 6 and 24 h. After silencing NOD2 expression, DENV2-infected cells displayed greater viral loads and decreased expression of IL-8 and IFN-α (measured in supernatants obtained from the cells), compared to the uninfected (mock control) cells or those transfected with irrelevant-siRNA. Thus, in response to a DENV2 infection, NOD2 was activated in THP-1 human macrophage-like cells, the production of IL-8 and IFN-α was enhanced, and viral replication was limited.

Objective: Evaluation of the efficacy of robotic vasovasostomy post-vasectomy.Patients and methods: We present a retrospective study of four patients aged from 36 to 51 years, who were operated of a vasovasostomy between September 2007 to July 2009. The same surgeon performed a robotic-assisted vasovasostomy, bilateral for three of them and only left unilateral for the last patient who underwent orchidectomy for right testicular seminoma. These patients had a preoperative semen analysis confirmed the absence of sperm after vasectomy. All patients had an outcome of spermatozoa on testicular deferens side in per-operative. The permeability of the distal vas deferens was systematically checked. The success criterion was the presence of spermatozoa in semen control three months. The paternity post vasovasostomy without medically assisted procreation due to father sterility was a secondary endpoint.Results: Four patients had between 0.6 and 27 million sperm per mL in postoperative semen analysis. Three to seventeenth months after the vasovasostomy, the wives of four patients have started a pregnancy between. Conclusion: The robotic vasovasostomy surgery is a technique that enabled this small group of patients having good results in regard to deferential recanalization and to recovery of secondary spontaneous fertility. A larger cohort needs to be evaluated. The medical and economical aspects of this method should be compared to those of usual technics, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

The canga of the Serra dos Carajás, in Eastern Amazon, is home to a unique open plant community, harbouring several endemic and rare species. Although a complete flora survey has been recently published, scarce to no genetic information is available for most plant species of the ironstone outcrops of the Serra dos Carajás. In this scenario, DNA barcoding appears as a fast and effective approach to assess the genetic diversity of the Serra dos Carajás flora, considering the growing need for robust biodiversity conservation planning in such an area with industrial mining activities. Thus, after testing eight different DNA barcode markers (matK, rbcL, rpoB, rpoC1, atpF-atpH, psbK-psbI, trnH-psbA and ITS2), we chose rbcL and ITS2 as the most suitable markers for a broad application in the regional flora. Here we describe DNA barcodes for 1,130 specimens of 538 species, 323 genera and 115 families of vascular plants, with a total of 344 species being barcoded for the first time. In addition, we assessed the potential of using DNA metabarcoding of bulk samples for surveying plant diversity in the canga. Upon achieving the first comprehensive DNA barcoding effort directed to a complete flora in the Brazilian Amazon, we discuss the relevance of our results to guide future conservation measures in the Serra dos Carajás.

Objective: The aim of this study was to analyze the culture antibiogram results of samples obtained directly from the middle ear and/or mastoid cells in the operating room, and from the external auditory canal in the outpatient. Methods: This study was conducted between 2016-2018 in Microbiology and Otorhinolaryngology Department. Swab cultures were obtained through the external ear canal preoperatively in outpatients. Middle ear swabs and mastoid granulation tissue were collected intraoperatively, respectively. Demographic datas, bacterial identifications and antibiotic susceptibilities were compared in both groups. Results: Two hundred thirty eight patients with chronic otitis media were enrolled in the study. Out of the 238 cases, 86 patients had negative culture results. P. aeruginosa (n=44), Coagulase Negative Staphylococcus (n=33), S. aureus (n=27), Proteus mirabilis (n=16) and E. coli (n=10) were the most common grown bacteria in both groups. Most common identified groups were Gram-positive bacteria (n=92), non-fermenter Gram-negative bacteria (n=55) and Enterobactericeae (n=42). Gram-positive cocci were higher in outpatient group, whereas Enterobactericeae were higher in intraoperative group (p<0.05). Antibiotic susceptibilities of P. aeruginosa and S. aureus were found to be lower especially in the preoperative group (p <0.05). Conclusion: P. aeruginosa was the most common bacteria in both preoperative and intraoperative cultures and high ciprofloxacin resistance of the isolates were remarkable. Although contamination is an issue in samples collected from the external ear canal of outpatients using cotton swabs, similar microorganisms grew in outpatient and intraoperative cultures

Objective There is no report that anticoagulant or antiplatelet use may lead to abnormal endometrial sonographic findings. This retrospective study reports our first results associated with endometrial sampling in asymptomatic postmenopausal women using anticoagulants or antiplatelet. Materials methods A total of 268 postmenopausal patients who applied to our gynecology outpatient clinic for any reasons except postmenopausal bleeding were included in the study. Patients were divided into three groups according to using drug status: first healty control group (HCG), second anticoagulants agents group (ACG), and third antiplatelet agents group (APG). The effects of anticoagulant and antiplatelet agents on endometrial thickness were compared with histopathological findings. Results The mean endometrial thickness was significantly greater in group ACG (5.2 mm) and APG (4.1 m) than in group HCG (3.3 mm). No significant differences were found in the mean endometrial thickness between groups HCG and APG. However, it is noteworthy that the average endomeric thickness in the ACG group is more than the other two groups and this is statistically significant (p < 0.05). Conclusion If the thickness of the endometrium was > 4 mm. endometrial sampling may be recommended in in asymptomatic postmenopausal women using anticoagulants or antiplatelet agents. Key words: Anticoagulants, antiplatelets, biopsy, endometrial thickness, menopause, ultrasonography

In the wake of the 2020 COVID-19 epidemic, much work has been performed on the development of mathematical models for the simulation of the epidemic, and of disease models generally. Most works follow the susceptible-infected-removed (SIR) compartmental framework, modeling the epidemic with a system of ordinary differential equations. Alternative formulations using a partial differential equation (PDE) to incorporate both spatial and temporal resolution have also been introduced, with their numerical results showing potentially powerful descriptive and predictive capacity. In the present work, we introduce a new variation to such models by using delay differential equations (DDEs). The dynamics of many infectious diseases, including COVID-19, exhibit delays due to incubation periods and related phenomena. Accordingly, DDE models allow for a natural representation of the problem dynamics, in addition to offering advantages in terms of computational time and modeling, as they eliminate the need for additional, difficult-to-estimate, compartments (such as exposed individuals) to incorporate time delays. In the present work, we introduce a DDE epidemic model in both an ordinary- and partial differential equation framework. We present a series of mathematical results assessing the stability of the formulation. We then perform several numerical experiments, validating both the mathematical results and establishing model’s ability to reproduce measured data on realistic problems.

Background: This study was planned and carried out to determine the influence of nutrition situations and physical activity levels of individuals working as academicians at the university on their anthropometric measurements, blood glucose, and blood lipid. Materials and Methods: 47 volunteers participated in the research, and their height, waist circumference (WC), and weight was measured. The blood samples of the volunteers was taken after 12 hours of fasting, their preprandial blood glucose (PrBG), postprandial blood glucose (PoBG), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol levels were measured. Nutritional consumption measurements were taken with 24-hour recall method, and, after having the volunteer subjects make nutritional changes, daily consumption quantities were determined. Results: The body mass index (BMI) was 24.34±4.73kg/m2 in the women and 27.90±3.97 kg/m2 in men. The mean WC was 84.15±15.89 cm for women and 98.18±10.89 for men. A statistically significant difference was found between the BMI of the women and their WC, total cholesterol level, HDL-cholesterol, LDL-cholesterol, and triglyceride averages. According to the BMI of the men, a statistically significant difference was found with their WC, PoBG, and triglyceride averages. In both women and men, it was observed that as their physical activity increased, their levels of BMI, WC, PoBG level, and triglyceride level were reduced. Conclusions: We conclude from this study that academicians who are overweight and who suffer from impaired glucose intolerance and dyslipidemia have balanced nutrition and to do physical activities to become healthy.

Climate impacts are not always easily discerned in wild populations as climate change occurs in the context of natural variability. Furthermore, species responses to climate change and variability differ among life histories. The time of emergence (ToE) identifies when the signal of anthropogenic climate change can be quantitatively distinguished from noise associated with natural variability. This concept has been applied extensively in the climate sciences, but has not yet formally been explored in the context of population dynamics. Here, we present a theoretical assessment of the ToE of climate-driven signals in population dynamics (ToEpop) to detect climate signals in populations. We identify the dependence of ToEpop on the magnitude of climate trends and variability and explore the demographic controls on ToEpop. We demonstrate that different life histories (fast species vs. slow species), demographic processes (survival, reproduction) and functional relationships between climate and demographic rates, yield population dynamics that filter trends and variability in climate differently. We illustrate empirically how to detect the point in time when anthropogenic signals in populations emerge from the envelope of natural variability for a species threatened by climate change: the emperor penguin. Finally, we propose six testable hypotheses and a road map for future research.

Pancreatic ductal adenocarcinoma (PDAC) cells are Gln-metabolism dependence, which can preferentially utilize glutamic oxaloacetate transaminase 1 (GOT1) to maintain the redox homeostasis of cancer cells. Therefore, small molecule inhibitors targeting GOT1 can be used as a new strategy for developing cancer therapies. Here, we identified a cyclobutyrolactone lignan, Aspulvinone H (AH), showing significant GOT1 inhibitory activity in vitro. The complex crystal structure of GOT1-AH elucidated the molecular mechanism, which AH and the cofactor pyrido-aldehyde 5-phosphate (PLP) competitively bound to the active sites of GOT1. Structure-activity relationship (SAR) analysis exhibited that the π-π stacking and isopentenyl side chain of aspulvinone were related to the inhibition of GOT1 activity. Further biological study indicated that AH could suppress glutamine metabolism, which made PDAC cells sensitive to oxidative stress and inhibited cell proliferation. Besides, AH exhibited potent in vivo antitumor activity in the SW1990 cell-induced xenograft model. These findings suggest that AH could be considered as a promising lead molecule for the development of PDAC anticancer agents.

Abstract. An econometric analysis of consumer research data which hit newspaper headlines in the Netherlands illustrates almost everything that can go wrong when standard statistical models are fit to the superficial characteristics of a data-set with no attention paid to the data generation mechanism.Author: Richard D. Gill, Mathematical Institute, Leiden University, The Netherlands; email address: gill@math.leidenuniv.nl.

In this work, the advantage of two-dimensional population balance modeling (2D PBM) for a needle-shaped API is highlighted by comparing the one-dimensional population balance model (1D PBM) developed for an antisolvent crystallization with the 2D PBM. The API utilized for this work had extremely slow desupersaturation, and was not able to achieve solubility concentration despite a ~50 h seed bed age. While the 1D PBM is useful in optimizing the crystallization process to enhance desupersaturation, it is unable to match the particle size quantiles well. 2D PBM was necessary to probe the impact of crystallization process parameters on particle aspect ratio (AR). Simulations utilizing the 2D PBM indicated that regardless of antisolvent addition rate or seed morphology, the final material would still be high aspect ratio. This knowledge saved the investment of much time and efforts in trying to minimize particle AR with changes in crystallization processing parameters alone.

A bio-ceramic coating was prepared on the surface of ZK60 magnesium alloys by micro-arc oxidation (MAO) method. The substrate (BM) and coated (MAO) specimens were pre-corroded in a simulated body fluid (SBF) for 12 h. Strain-controlled and stress-controlled loading modes were used to conduct fatigue tests for the two specimens, respectively. The cyclic deformation behavior of the two specimens with non-corroded and pre-corroded was studied. The mechanism of cyclic deformation under different loading conditions is related to twinning and slip. At the same test conditions, the fatigue life of the non-corroded BM specimen is higher than that of the non-corroded MAO specimen, while the fatigue life of the pre-corroded MAO specimen is higher than that of the pre-corroded BM specimen. A modified total strain energy model is proposed and the precision of life prediction is higher than that of traditional fatigue model.

An increased basal cholinergic tone, induced by psychological health impairment, could be a likely link between psychological/psychiatric disorders and severe bronchial asthma in children, as well as in adolescents and adults. This link can explain the high rate of anxiety in asthmatics in comparison to non-asthmatics of all ages.

Metagenomic analysis of the conjunctival bacterial and fungal microbiome in vernal keratoconjunctivitisShort title: Microbiome in VKCText Word Count: 597To the Editor,there is increasing interest in the role of conjunctival microbiome in the healthy ocular surface (1) and in different ocular diseases. There is also enough evidence that dysregulation of resident microbial communities (dysbiosis) might be associated with allergy risk(2). Vernal keratoconjunctivitis (VKC) is a severe form of ocular allergy affecting mostly male children and young adults with typical seasonal recurrences and potentially visual impairment. We recently found and overexpression of multiple pattern recognition receptors (PRRs) in VKC suggesting the role of host-microbe interaction in VKC pathogenesis(3). To investigate the VKC-associated ocular microbiome, we applied 16S and ITS2 amplicon sequencing (online supplementary MM) in conjunctival swabs obtained from 22 VKC patients and 20 age, sex and ethnicity-matched healthy controls (HC) (Table 1S). Written informed consent was obtained from all parent/subjects enrolled. Type of VKC, allergen sensitization, disease-specific ongoing treatment and results of the Quality of Life in Children with VKC (QUICK) questionnaire were recorded. A 10-items questionnaire investigating the presence of the principal factors related to allergy development was administered to all included subjects.16S rRNA amplification was successfully carried out in 12/22 VKC and 4/20 HC samples. High-throughput amplicon sequencing produced a total of 734.157 high-quality reads (average of 45.885 reads/sample), which were clustered into 1.241 OTUs (97% sequence identity) and classified according to the Greengenes database. Compared with HC, α-diversity was significantly higher in all VKC (p=0.05), in IgE-negative patients (p=0.03), in tarsal VKC (p=0.03), in formula-fed versus breastfed children (p=0.03) and in children with history of atopic dermatitis (AD) (p=0.01). β-diversity highlighted differences in microbiota composition (Figure 1S) suggesting clusters of subjects with different conjunctival microbiomes. At the phylum level, conjunctival microbiome was dominated by Proteobacteria , Firmicutes , Actinobacteria andBacteriodetes that accounted for >90% of all reads (Figure 1). Of the 132 observed families, Moraxellaceae (W=15) showed a higher abundance in VKC than HC (Figure 2S). At the genus level, Pseudomonas , Staphylococcus , Streptococcus ,Acinetobacter , Neisseria , Haemophilus ,Prevotella , Corynebacterium , Propionibacterium andRothia accounted for >70% of sequences (Figure 3S). In VKC, Bacteroidetes and Fusobacteria met the core microbiome’s definition criteria (Table 2S), which includes different species of gram-negative bacteria able to potentially induce an LPS-driven inflammatory response as shown in experimental models(4).For the fungal microbiome, 10/22 VKC samples produced a detectable ITS2 amplicon. A total of 677,115 high-quality reads (average of 48,365 reads/sample) were clustered into 933 OTUs and taxonomically classified against the UNITE ver. 7.0 database. At the family level,Saccharomycetaceae , Malasseziaceae , Pleosporaceaeand Cladosporiaceae accounted for the majority of sequences (Figure 2). OTUs referred to Malasseziaceae were significantly increased in VKC compared with HC (W=42). Malassezia have been associated with AD inducing a mixed Th2/Th17 response(5) interacting with several PRRs and activating multiple signaling pathways. Since multiple PRRs are over-expressed in VKC(3), we suggest that glycan, phospholipid carbohydrate residues of allergens and microbes may engage innate receptors on conjunctival cells priming a type-2 response in VKC.14/22 VKC children were under topical treatments at the time of swabbing, creating a potential bias (Table 1S). However, only 5/10 patients whose swabs were not sequenced because of absence of amplicons, were under topical medication. In addition, β-diversity didn’t show differences in microbial communities considering the use and type of medications suggesting that factors other than topical eyedrops may alter the conjunctival microbiota. The main limitation was the higher difficulty to obtain amplicon products from HC, which has been already described and attributed to the physiological antimicrobial activity and to the lower microbial load of healthy subjects(6).In conclusion, the described dysbiosis in VKC highlights the role of the host-microbes interaction in VKC pathogenesis.Andrea Leonardi1Rocco Luigi Modugno1Fabiano Cavarzeran1Umberto Rosani21 Department of Neuroscience, Ophthalmology Unit, University of Padova, Padova, Italy2 Department of Biology, University of Padova, Padova, ItalyKeywords: ocular surface microbiome, vernal keratoconjunctivitis, 16S rRNA gene amplicon sequencing, ITS2 rRNA gene amplicon sequencing, core microbiomeCorresponding author:Andrea Leonardi, MDDepartment of Neuroscience, Ophthalmology Unit, University of Paduavia Giustiniani 235128 Padua, ItalyFax: +39-049-875 5168Email: andrea.leonardi@unipd.itAcknowledgmentsa. Funding/Support: Supported by MIUR DOR1952345/19 and DOR2092417/20 from Italian Institute of Health.b. Conflicts of Interest:Andrea Leonardi: No Conflicts of Interest.Rocco Luigi Modugno: No Conflicts of InterestFabiano Cavarzeran: No Conflicts of InterestUmberto Rosani: No Conflicts of Interestc. Contributions to Authors in each of these areas: Andrea Leonardi (AL), Rocco Luigi Modugno (RLM), Fabiano Cavarzeran (FC), Umberto Rosani (UR)Conception and Design: AL, URAnalysis and interpretation: AL, RLM, URWriting the article: AL, RLMCritical revision of the article: URFinal approval of the article: AL, RLM, URData Collection: RLM, UR, FCProvision of materials, patients, or resources: AL, URStatistical expertise: FCObtaining funding: ALLiterature search: RLM, AL, URAdministrative, technical or logistic support: AL, FCd. Statement about Conformity with Author Information: nonee. Other Acknowledgments: none

Methods The study included 59 patients with normal fetal heart structure, blood flow, and heart rhythm (fetal abnormality-negative group) and 50 patients with abnormal fetal heart structure, blood flow, and/or heart rhythm (fetal abnormality-positive group). aCMQ was performed in both groups to obtain left and right ventricular endocardial global longitudinal strain (GLSendo), mid-myocardial global longitudinal strain (GLSmid), and epicardial global longitudinal strain (GLSepi). Parameters between the two groups were compared and correlation analyses performed. A deformation analysis was performed by two trained observers, and reproducibility was assessed. Results The fetal left ventricular and right ventricular global longitudinal strain (LV-GLS and RV-GLS, respectively) decreased in a gradient from the endocardium to the epicardium. LV-GLS and RV-GLS of all myocardial layers were lower in the fetal abnormality-positive than -negative group (all P<0.05). Correlation analysis showed that neither LV-GLS nor RV-GLS was significantly correlated with gestational age in the fetal abnormality-negative group (all P>0.05), whereas left ventricular GLSendo, GLSmid, and GLSepi were negatively correlated with gestational age in the fetal abnormality-positive group (r=−0.39 to −0.44, all P<0.05). Repeatability testing showed that the inter-observer and intra-observer intraclass correlation coefficients for LV-GLS and RV-GLS in each myocardial layer were >0.75 (all P<0.001). Conclusions As a new speckle tracking echocardiography tool, aCMQ has feasibility and repeatability in evaluating myocardial deformation of the fetal ventricle. This technique might provide helpful information on ventricular myocardial deformation in fetal hearts with abnormal structure or rhythm for clinical guidance in pregnancy.

Since the start of the novel coronavirus SARS-Cov-2 pandemic, a disease that has become one of the world’s greatest global health challenges, the role of the immune system has been at the forefront of scientific studies. The pathophysiology of COVID-19 is complex, which is evident by those at higher risk for poor outcome. Multiple systems contribute to thrombosis and inflammation seen in COVID-19 patients, including neutrophil dysfunction, platelet activation, endothelial cell activation. Understanding how the immune system functions in different patient cohorts (particularly given recent emerging events with the Oxford/AstraZeneca vaccine) is vital to understanding the pathophysiology of this devastating disease and for subsequent development of novel therapeutic targets and expedite possible drug repurposing strategies that could benefit society on a global scale.

Although the majority of microalgal species reproduce asexually for large parts of the growth season, most population genetic studies have rarely found clones in microalgal blooms. Instead, population genetic studies have identified large intraspecific diversity in most microalgal species. This paradox of frequent asexual reproduction but low number of clones creates challenges when interpreting the proportion of clones and distinct genotypes in natural microalgal populations. To estimate the proportion of clones and genotype richness, we created a computer model that simulates the composition of microalgal populations after a defined period of exponential growth. We simulated the probability of picking clones of the same genotype from this population as a function of initial genotype diversity, intraspecific differences in growth rates and sample size. This model was applied to five microalgal species for which high-resolution population genetic data and population growth rates based on monitoring data were available. The number of distinct genotypes in each population was extrapolated from the model outputs and the observed proportion of clones in the respective population genetic studies. The estimates from our simulation suggested that the genotype richness in most blooms exceeds several thousand distinct genotypes with very high variability among microalgal species. The highest numbers of distinct genotypes (500,000 and 2,000,000 genotypes) were estimated for species with very low numbers of observed clones in population genetic studies (< 5%), but genotype richness was also strongly impacted by intraspecific variability in growth rates. Furthermore, the probability of finding clones and presumably sampling a representative fraction of genotypes increased significantly with higher sample sizes, challenging the detection of differences in genotype diversity between sub-samples with few isolates.

Pyroptosis, is a specialized form of inflammatory cell death which aids the defensive response against invading pathogens. Its tight regulation is lost during infection by the severe acute respiratory coronavirus 2 (SARS-CoV-2) and thus uncontrolled pyroptosis disrupts the immune system and the integrity of organs defining the critical conditions in patients with high viral load. Molecular pathways engaged downstream to the formation and stabilization of the inflammasome -required to execute the process- have been uncovered and drugs are available for their regulation. On the contrary, pharmacological inferring of the upstream events -which are critical to sense and interpret the initial damage by the pathogen- is far from being elucidated. This limits our capacity to identify early markers and targets to ameliorate SARS-CoV-2 linked pyroptosis. Here we aim to raise attention on mitochondria and pathways leading to its dysfunction with the goal to inform early steps of inflammasome and devise tools to interpret and counteract diseases by the SARS-CoV-2.