Starting from December 2019 the novel SARS-Cov-2 has spread all over the world, being recognized as the causing agent of COVID-19. Since nowadays no specific drug therapies neither vaccines are available for the treatment of COVID-19, drug repositioning may offer a strategy to efficiently control the clinical course of the disease and the spread of the outbreak. In this paper we aim to describe the main pharmacological properties, including data on mechanism of action, safety concerns and drug-drug interactions, of drugs currently administered in patients with COVID-19, focusing on antivirals and drugs with immune-modulatory and/or anti-inflammatory properties. Where available, data from clinical trials involving patients with COVID-19 were reported. A large number of clinical studies have been registered worldwide and several drugs were repurposed to face the new health emergency of COVID-19. For many of these drugs, including lopinavir/ritonavir, remdesivir, favipiravir, chloroquine and tocilizumab, clinical evidence from literature and real life settings support their favorable efficacy and safety profile in improving patients’ clinical conditions. Even though drug repurposing is necessary, it requires caution. Indeed, too many drugs that are currently tested in patients with COVID-19 have peculiar safety profiles. While waiting for the results of clinical studies demonstrating the efficacy of drugs able to reduce symptoms and complications of COVID-19, the best therapeutic path to pursue is the development of an effective vaccine able to prevent this infection.

The mechanisms by which herbivores induce plant defenses are well studied. However, how specialized herbivores suppress plant resistance is still poorly understood. Here, we discovered a rice (Oryza sativa) leucine-rich repeat receptor-like kinase, OsLRR-RLK2, which is induced upon attack by gravid females of a specialist piercing-sucking herbivore, the brown planthopper (BPH, Nilaparvata lugens). Silencing OsLRR-RLK2 decreases the constitutive activity of mitogen-activated protein kinase (OsMPK6) and alters BPH-induced transcript levels of several defense-related WRKY transcription factors. Moreover, silencing OsLRR-RLK2 reduces BPH-induction of jasmonic acid and ethylene but promotes the biosynthesis of both elicited salicylic acid and H2O2; silencing also enhances the production of volatiles emitted from rice plants infested with gravid BPH females. These changes decrease BPH preference and performance in the glasshouse and the field. Our study identifies OsLRR-RLK2 as a major susceptibility factor of rice against BPH. It is likely to be employed by BPH to suppress host plant defenses for its own benefit via signaling crosstalk and/or changing the plant’s defense-related signaling profile.

The occurrence of hepatoblastoma is infrequent in children older than 5 years. Therefore, clinicians need to consider hepatoblastoma even in school-aged children or adolescents.

A 70-year-old male presented with a neglected slow growing anal wart for many years with bleeding.A deep core biopsy of the tumor confirmed a high-grade squamous intraepithelial lesion and carcinoma in situ.

Introduction: Silent cerebral events (SCEs) are related to the potential thromboembolic risk in atrial fibrillation (AF) ablation. Peri-procedural uninterrupted oral anticoagulation (OAC) reportedly reduced the risk of SCEs, but the incidence still remains. Methods and Results: AF patients undergoing catheter ablation were eligible. All patients took non-vitamin K antagonist oral anticoagulants (NOACs, n=248) or vitamin K antagonist (VKA, n=37) for peri-procedural OAC (>4 weeks) without interruption during the procedure. Brain magnetic resonance imaging was performed within 2 days after the procedure to detect SCEs. Clinical characteristics and procedure-related parameters were compared between patients with and without SCEs. SCEs were detected in 66 patients (23.1%, SCE[+]) but were not detected in 219 patients (SCE[-]). Average age was higher in SCE[+] than in SCE[-] (66±10 years vs. 62±12 years, p<0.05). Persistent AF prevalence, CHADS2/CHA2DS2-VASc scores, serum NT-ProBNP levels, left-atrial dimension (LAD), and spontaneous echo contrast prevalence in transesophageal echocardiography significantly increased in SCE[+] vs. SCE[-]. SCE[+] had lower baseline activated clotting time (ACT) before heparin injection and longer time to reach optimal ACT (>300 sec) than SCE [-] (146±27 sec vs. 156±29 sec and 44±30 sec vs. 35±25 sec, p<0.05, respectively). In multivariate analysis, LAD, baseline ACT, and time to reach the optimal ACT were predictors for SCEs. The average values of the ACT parameters were significantly different among NOACs/VKA. Conclusion: LAD and intra-procedural ACT kinetics significantly affect SCEs during AF ablation. Different anticoagulants have different impacts on ACT during the procedure, which should be considered when estimating the risk of SCEs.

How soil quality and microbial communities change in conjunction with stand age in plantations is poorly understood. Here, we evaluated soil quality by using an integrated soil quality index (SQI) and traced the paralleled shifts in fungal community composition by high-throughput sequencing in a chronosequence of Chinese fir (Cunninghamia lanceolata) plantations (stand age of 3, 16, 25, 32, >80 years). Soil properties showed pronounced changes with stand age in the top 0-5 cm. The most prominent increase from 3 to >80-year-old stand was for soil organic carbon (SOC, by 2.1-times), total nitrogen (TN, 1.9-times) and available phosphorus (AP, 2.2-times). SQI increased logarithmically with stand age, with sharper change seen in the 0-5 cm layer than in the 5-15 cm layer. Mycorrhizal fungi increased in abundance initially in younger stands, but then they were gradually replaced by saprotrophic fungi in older stands due to the increase in litter input, which sustains saprotrophs. The positive correlation between saprotrophic fungi and the key soil quality indicators, such as TN, AP and NH4+, showed that higher soil quality was tightly linked with the enrichment of decomposers. Mycorrhizal taxa, such as orders Sebacinales, Thelephorales and Russulales, were positively correlated with acid phosphatase mobilizing P from organic matter. This suggests that the establishment of mycorrhizal fungi sustains tree productivity in younger stands under low soil quality. We conclude that the increase in soil quality throughout the development of Chinese fir plantations is closely linked with the observed transition of fungal communities from mycorrhizae to saprotrophs.

Bones, lymph nodes, lungs, or liver, are the common metastatic sites for prostate cancer. However, prostate adenocarcinoma metastasis to the mandible is very rare. In this case report we present a case of a 64-year-old man with poorly differentiated prostate cancer and metastasis to the mandible.

Stab wounds are commonly seen in the emergency room of community hospitals especially in developing countries. The uniqueness of the case to be reported here was that the patient walked in the ER retaining the inflicting weapon in the wound over his back.

Electron Beam Melting (EBM) is one of a few additive manufacturing technologies capable of making full-density functional metallic parts realized from raw materials in the form of powders. The ability of direct fabrications of metallic parts can accelerate product designs and developments in a wide range of metallic-part applications, especially for complex components, which are difficult to make by conventional manufacturing means. To capitalize on these benefits, it must be shown that the mechanical performances of parts produced by EBM can meet design requirements. In this research an intensive mechanical characterization aimed at determining static and fatigue performance of the alloy Ti6Al4V processed by EBM has been performed. The effect of both postprocessing treatments (HIP and surface finish) on the mechanical behavior was evaluated by mechanical testing, microstructural study, computed tomography analysis and fracture surface investigation.

Birds have been observed to have dietary preferences for unsaturated fatty acids (FAs) during migration. Polyunsaturated fatty acids (PUFAs) increase the exercise performance of migrant birds; however, PUFAs are also peroxidation prone and might therefore incur increased costs in terms of enhanced oxidative stress in migratory individuals. To shed light on this potential constraint, we analysed plasma FA composition and estimated the susceptibility to peroxidation of migrants and residents of the partially migratory common blackbird (Turdus merula) at a stop-over site during autumn migration. As predicted, migrant birds had higher relative and absolute levels of PUFAs compared to resident birds. This included the strictly dietary ω-3 PUFA α-linoleic acid, suggesting a dietary preference for these fatty acids in migrants. Interestingly, the FA unsaturation index, which is an index of lipid peroxidation susceptibility, did not differ between migrants and residents. These findings suggest a mechanism where birds alter their levels of metabolic substrate to increase exercise performance without simultaneously increasing the risk of lipid peroxidation and oxidative stress. In summary, our results are in line with the hypothesis of increased exercise performance being constrained by oxidative stress during migration, which is manifested in changes in the composition of key FAs to retain the unsaturation index constant despite the increased levels of peroxidizable PUFAs.

Coronavirus disease 2019 (COVID-19) is a remarkably challenging health issue that provoked all the health-care providers to contemplate some measures about the situation. All the health-care workers frontline (esp. emergency service, pulmonologists, infection disease specialist and anesthesiologist) have produced recommendations on prevention and taking care of COVID-19 patient (1,2). Whereas, at the second line another important issue is the ongoing healthcare for the continual disease situations.There are two main critical issues on cardiovascular surgery in this pandemic. Firstly, to delay the elective surgeries is essential to sustain the health-care service. Elective case triage is trickier for cardiovascular procedures which are relatively progressive conditions. Definitive decision to defer a procedure should be made regarding firstly to the capacity of health-care system, and then availability of surgical/anesthesia staff, intensive care unit beds, need for isolation beds, ventilators, cardiopulmonary bypass machine, extracorporeal membrane oxygenator, supplies such as sutures, grafts, valves and blood and blood product availability. The patient status should be taken into account to defer or to perform the procedure, as well. Therefore, we developed “Level of Priority” (LoP) statement for cardiovascular procedures (3). Elective cases are defined as LoP I that may be postponed as much as possible. LoP II to IV cases should be reconsidered by individual basis by “Heart Team”. The situations that can be managed by percutaneous coronary intervention, endovascular procedures and etc. may be handled by non-operative manners.The second one is the personal protection equipment and infection measures while dealing with a suspected / confirmed COVID-19 patient. It is obvious that a suspected / confirmed COVID-19 patient ought to be assessed with specific measures for any medical or surgical intervention. Personal protection equipment (PPE) is the most crucial measure during the pandemic. It is recognized that many centers are facing PPE shortages and there are recommendations to re-sterile the masks to be effective for reuse.(4) More measures should be taken into consideration for sterile environment such as surgical procedures. Some added measures such as face shield may be recommended for surgical procedures. The surgical team who scrubbed in, must wear extra equipment such as surgical coat and double gloves. It may be recommended to fix the long-sleeve gloves to the surgical coat by adhesive drapes (3). It is obvious that this kind of working environment with all this equipment is challenging, sometimes irritating and disquieting. One other big problem is the fraught feeling of health-care providers to be diseased or to be contagious for their family. Therefore, health-care providers may need enormous support for burnouts during the pandemic.The other measures such as preparation of the operating room (OR), anesthesiologic management, transportation of patients and disinfection of OR were discussed in the referring article (3).In conclusion, it is important to assess the “Level of Priority” for surgical procedures to support the service of health-care facility. More than that, whole surgical team should be protected by adequate PPE and should take the time to get full protected.

Naso-pharyngeal discharge as the first symptom of COVID-19 infection is presented in two cases . Appropriate diagnosis and isolation of the patients who may be at risk for covid-19 such as these cases help reduce further transmission.

Objective. To externally validate the M6 risk model and the two-step triage strategy (2ST) to triage pregnancies of unknown location (PUL), and compare performance with the M4 model and beta human chorionic gonadotropin (BhCG) ratio cut-offs. Design. Model validation study. Setting. Eight UK hospitals with early pregnancy assessment units. Population. Women presenting with a PUL and BhCG >25 IU/L. Methods. Women were managed using the 2ST protocol: step 1 classifies PUL as low risk of ectopic pregnancy (EP) if presenting progesterone ≤2 nmol/L, M6 is used as step 2 in the remaining cases. We validated 2ST and M6 alone (with and without progesterone as a predictor: M6P and M6NP). M6 and M4 require the BhCG ratio over two days. Based on these models, we classified PUL as high risk for EP when the risk was ≥5%. We meta-analysed centre-specific results. Main outcome measures. Discrimination, calibration and clinical utility (decision curve analysis) for predicting EP. Results. Of 2899 eligible women, the main analysis excluded 297 (10%) women that were lost to follow-up. 16% (95% confidence interval 12-20) of women had presenting progesterone ≤2 nmol/L. The area under the ROC curve for EP was 0.88 (0.86-0.90) for 2ST and 0.89 (0.86-0.91) for M6P. Sensitivity for EP was 94% (89%-97%) for 2ST and 96% (91%-98%) for M6P. Both approaches had good overall calibration, with modest variability between centres. M4 and BhCG ratio cut-offs had inferior performance and lower clinical utility. Conclusions. The 2ST and M6P alone are the best approaches to triage PUL.

The incidence of mechanical complications of acute coronary syndromes (ACS) needing cardiac surgery has reduced significantly in the last years due to early diagnosis and treatments. Covid-19 pandemic, however, would generate in the patients a sense of fear regarding access to the ERs so they probably underestimate symptoms such as chest pain or angina equivalents until situation does not became critical. In this way, this behaviour could create a vast pool of patients who will enter the hospital in much more critical situations and with mechanical complications of an evolving ACS needing cardiac surgery treatment.

A global coronavirus (COVID-19) pandemic occurred at the start of 2020 and is already responsible for more than 74,000 deaths worldwide, just over 100 years after the influenza pandemic of 1918. At the center of the crisis is the highly infectious and deadly SARS-CoV-2, which has altered everything from individual daily lives to the global economy and our collective consciousness. Aside from the pulmonary manifestations of disease, there are likely to be several electrophysiologic (EP) sequelae of COVID-19 infection and its treatment, due to consequences of myocarditis and the use of QT-prolonging drugs. Most crucially, the surge in COVID-19 positive patients that have already overwhelmed the New York City hospital system requires conservation of hospital resources including personal protective equipment (PPE), reassignment of personnel, and reorganization of institutions, including the EP laboratory. In this proposal, we detail the specific protocol changes that our EP department has adopted during the COVID-19 pandemic, including performance of only urgent/emergent procedures, afterhours/7-day per week laboratory operation, single attending-only cases to preserve PPE, appropriate use of PPE, telemedicine and video chat follow-up appointments, and daily conferences to collectively manage the clinical and ethical dilemmas to come. We discuss also discuss how we perform EP procedures on presumed COVID positive and COVID tested positive patients in order to highlight issues that others in the EP community may soon face in their own institution as the virus continues to spread nationally and internationally.

Mini-commentary on BJOG-20-0093.R1: The impact of age and high risk human papillomavirus (hrHPV) status on the prevalence of high grade cervical intra-epithelial neoplasia (CIN2+) in women with persistent hrHPV positive, cytology negative screening samples: a prospective cohort study.

NK cells are an important arm of the innate immune system, and they constitutively express the NKp30 receptor. NKp30-mediated responses are triggered by the binding of specific ligands, such as tumour cell-derived B7-H6, and involve the secretion of cytotoxic mediators TNF-α, IFN-γ, perforins and granzymes. The latter two constitute a target cell-directed response that is critical in the process of immunosurveillance. The structure of NKp30 is presented, focusing on the ligand-binding site, on the ligand-induced structural changes, and on the experimental data available correlating structure and binding affinity. The translation of NKp30 structural changes to disease progression is also reviewed. NKp30 role in immunotherapy has been explored in chimeric antigen receptor T-cell (CAR-T) therapy. However, antibodies or small ligands targeting NKp30 have not yet been developed. The data reviewed unveils the key structural aspects that must be considered for drug design in order to develop novel immunotherapy approaches.

The manuscript describes a computational study that provides molecular-level insight into shale gas adsorption and transport in shale rocks, which are composed of organic and inorganic matter. Atomistic simulations were used to generate realistic models of the organic matter structures with both micro- and mesoporosity, and correspond to mature and overmature type-II kerogens. These porous material models are unique to most other previous kerogen models since they contain other components (asphaltene/resin, hydrocarbons and carbon dioxide/water fractions) that are typically not modeled. The inclusion of these additional components significantly influences the resulting porous structure characteristics. The adsorption and diffusion behavior of methane (as a shale gas proxy) and methane/carbon dioxide mixtures were simulated in the model structures. Several key industrial-relevant findings are described in the manuscript.