Land serves as a vital production resource, and therefore, land planning plays an important role in sustainable land-use design. Increasing the global population alters landscapes via land-use and land-cover change across different landscapes, including the drylands. Iran includes large areas of dryland, where the population increased by 60% from 1985 to 2016. Further population increase in Iran would require more land resources to be allocated for human needs. However, the pace and patterns of these changes remain unclear. The aim of this study was to map land-cover change from 1985 to 2016 and predict future land-cover change in the Zayandehrood ecologic sub-basins of Central Iran. By using multiseasonal Landsat imagery, nine thematic classes were mapped with a random forest classifier for 1985, 1998, and 2016 with an overall accuracy of 80% for each period. Classification results revealed that from 1985 to 2016 residential areas doubled and industrial areas increased at the expense of rangelands. Our study also revealed cropland expansion at the expense of rangelands, cropland abandonment and contraction of croplands due to residential and industrial development. Prediction of changes by 2036 with a multi-layer perceptron neural network and Markov chain analysis revealed further expansion of industries and residencies particularly nearby the protected areas such as Ghamashlu Wildlife Refuge. Predicted contraction of some degraded agricultural lands and concomitant agricultural expansion in the agricultural frontier by 2036, underscore the importance of sustainable land management in highly arid areas of Iran and improvement of the strategies for the protection of rangelands.

Objectives: our department was the first in Israel to construct a separate, designated complex for its COVID-19-exposed patients. We aimed to evaluate the effect of the COVID-19 pandemic infection control measures on obstetrical care in the emergency department and delivery unit. Design: cohort study. Setting: tertiary medical center. Population: pregnant women attending the obstetrical emergency department (ED). Methods: February-March 2020 data were collected and compared to a parallel period in 2019. Main outcome measure: rate of referrals, deliveries, mode of delivery, neonatal outcomes. Results: During February-March 2020, 3,897 women were referred to the ED, compared to 4,067 in the previous year. Mean duration of treatment until decision and referral indications did not differ between 2020 and 2019 (207 vs. 220 minutes, p=0.26; urgent referrals: 58.8% vs. 59.2%, p=0.83). Per-week comparison showed a significant reduction in ED referrals only in the last week of the period [337 (2020) vs. 515 (2019), p<0.001]. The proportion of women admitted to the delivery unit in active labor was higher in the last three weeks (39.1% vs. 28.2%, p=0.005), and the rate of discharge was inversely correlated (45.8% vs. 56.7%, p=0.01). Deliveries number and proportions of spontaneous onset of labor, trials of labor, preterm delivery, post-term deliveries, operative vaginal and cesarean deliveries did not differ between February-March of 2020 and 2019. In the per-week comparison, the number of deliveries did not differ between the periods. Conclusion: With timely preparation and proper management, high-level routine obstetrical care during the COVID-19 outbreak can be maintained.

Commentary based on Paniagua Voirol et al. (2020) Plant responses to insect eggs are not induced by egg-associated microbes, but by a secretion attached to the eggs

Bovine tuberculosis is a chronic disease rarely observed in an early age. Our observation of tubercle lesions in the lungs of a three week old calf and confirmation of Mycobacterium bovis strains illustrate that the progression of tuberculosis in neonates can be rapid under natural conditions, contributing to transmission within-herds.

To the editor,The rapid emergence of COVID-19 pandemics worldwide is of particular concern for fragile populations who are more at risk of acute respiratory distress syndrome and death. Patients treated for malignant hemopathy and solid cancers have a four times higher risk of hospitalization due to influenza infection, and a ten times higher risk of death. This fragility could be due to their age, multiple associated comorbidities, lymphopenia, or the immunosuppressive action of a broad spectrum of anticancer drugs.[1] Therefore, anticancer drugs should be used carefully in this population. Without further safety data, it might be unsafe to treat SARS-CoV-2 positive patients who have COVID-19 symptoms with anticancer drugs known to increase infections or harvesting immunosuppressive properties. We summarized in the table (part A) drug classes that have been reported to increase either neutropenia or infections. Regarding patients tested positive who have recovered from their symptoms, clinical data is missing. It is currently not clear if cancer treatments should be stopped, and if so, the time needed to resume it safely.In any of these settings, clinical trials and incoming standard of care could lead to the prescription of antiviral drugs concomitant to non-immunosuppressive anticancer treatments. Similar to previous works reporting interactions between HIV antiretrovirals and anticancer drugs,[2] these two classes of medications have a narrow therapeutic index and can have pharmacological interactions. Some of them are substrates or interact with hepatic cytochrome P450 cytochrome isoenzymes (CYP), particularly CYP3A4, and pharmacokinetic interactions could lead to supra or infratherapeutic concentrations. For example, enzalutamide, a nonsteroidal antiandrogen prescribed for prostate cancer, is both a CYP3A4 substrate and inducer. Ritonavir, on the other hand, is a pharmacokinetic booster of lopinavir contained in Kaletra, which is explored as a COVID-19 treatment. Ritonavir is a substrate and also a potent inhibitor of CYP3A4. Thus, enzalutamide and ritonavir could interfere with each other’s metabolism, decrease or increase each other’s clearance, and be responsible for severe toxicities or decreased efficacy. Favipiravir, an anti-EBOV drug, also a candidate for the COVID-19 treatment, is an inhibitor of CYP2C8,[3] and therefore may increase anticancer drug metabolized through this pathway, such as dabrafenib and enzalutamide. Furthermore, CYP3A4 induction could lead to sustained CYP3A4 increased activity for up to 1 week after discontinuation. Dabrafenib or enzalutamide, two CYP3A4 inducers, could significantly decrease hydroxychloroquine concentration during the first week of wash-out.Among pharmacodynamic interactions, QT interval prolongation could be of particular interest. Hydroxychloroquine, which is currently widely prescribed as an anti-coronavirus drug, or azithromycin, are two drugs known to prolong QT interval. Concomitant use of QT-prolonging anticancer drugs could lead to Torsade-de-Pointes and be fatal. Caution should be observed in this case, and electrocardiographic monitoring should be implemented to monitor QT interval duration during combination therapy.Similarly, anticancer drugs could potentiate nephrotoxicity and hepatotoxicity of antiviral treatments.The table (part B) summarizes pharmacokinetic and pharmacodynamics interactions between some currently tested drugs against COVID-19 and anticancer drugs.

The potentially lethal COVID-19 infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. There are two major processes that lead to the morbidity and mortality of this disease: initially the viral infection, followed by a host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g. IL-6, IL-8, IL-10, TNFα), developing into a self-targeting toxic “cytokine storm” in which the lungs fill with inflammatory secretions causing critical pulmonary tissue damage. Even though the search for a vaccine and anti-viral agents has already been initiated, the de novo development of a safe, COVID-19 specific solution may take years; regrettably, the need for a therapeutic that is available immediately is growing daily. Therefore, repurposing an already approved drug offers a promising approach to address this urgent need. A truly effective therapeutic, however, should be available not only for the single individual in a developed country, but also for the many people in developing countries. As presented in this review, inhaled furosemide, a small molecule capable of inhibiting IL-6, IL-8 and TNFα within the lung, may be an agent capable of treating the COVID-19 cytokine storm in both resource-rich and developing countries. Furosemide is a “repurpose-able” small molecule therapeutic, that is safe, easily synthesized, handled and stored, and is available in reasonable quantities worldwide.

Introduction: There are few reports of the characteristics, mechanisms, and outcomes of atrial tachycardia (AT) and atrial fibrillation (AF) ablation after cardiac surgery and concomitant Maze procedures. This study investigated the mechanisms and long-term outcomes of AT and AF ablation after various Maze procedures, especially we examined in detail whether the arrhythmia after Maze procedure was due to gap or not. Methods and Results: We analyzed 37 consecutive cases with AT and AF after cardiac surgery and Maze procedure between 2007 and 2019. Fifty-nine atrial arrythmias were induced in 37 consecutive cases, and 49 of those atrial arrythmias were mappable ATs. Forty-two ATs was related to the Maze procedure in the 49 mappable ATs (87.5%). All 37 consecutive cases had residual electrical conductions (gaps) in the Maze lines (88 gaps; 2.4±1.2 gaps/patient). Forty-two of 88 gaps (47.7%) were associated with gap-related ATs. The most common gap-related ATs in this study were peri-mitral atrial flutter in 22 cases. The median follow-up period after ablation was 3.6±3.2 years (median, 2.1 years; interquartile range, 0.89-6.84). The Kaplan-Meier analysis of freedom from recurrent atrial arrhythmia after Maze procedure was 79.9% at 1-year follow up and 69.3% at 4-year follow up. Conclusions: Reentry was the main mechanism of AT after cardiac surgery and concomitant various Maze procedures, and AT were largely related to the gap in the Maze line between mitral valve anulus and pulmonary vein isolation line. Catheter ablation of AT after various Maze procedures seemed to be effective and safe during long-term follow-up.

Nan Ling commodity grain base is a national high-standard farmland demonstration area. Scientific evaluation of soil environmental quality is of important significance to plan land resources rationally to improve the quality and efficiency of agricultural production. This paper try to apply the Radar Chart–a visual graphic data analysis method–to the assessment of soil environmental quality. In the assessment, a new idea was introduced that area and perimeter of radar chart represents the soil environmental quality and the difference between the qualities of the soil environmental quality indicators respectively. Different from the other assessment methods，the Radar Chart method transforms data into graphics and through an intensive analysis of graphics, the data information can be retained and excavated more fully. It was proved through this case study that the application of Radar Chart method to the assessment of soil environmental quality is feasible and it is more intuitive, efficient, comprehensive and fine. The results indicated that the soil environmental quality at depth of 0-60cm in low mountain area of Nan ling commodity grain base is the second grade while that in the hilly and plain area are both the first grade. The indicators of poor soil environmental quality in low mountain area are Cd and As, those in hilly area are Cd、As and Hg, and that in plain area is Cd; The difference between the qualities of the soil environmental indicators in low mountain area is more significant than that in hilly area and plain area.

Globally, temperate grasslands have been significantly altered and subsequently degraded as a result of increased human population, urbanisation, and agriculture. Weeds now dominate most of these ecosystems, resulting in the loss of ecosystem services, reduced carrying capacity for farmers, and loss of habitat for native animals. This paper reviews the literature of temperate grassland restoration efforts from across the globe, and observes what techniques and combinations have been used successfully and unsuccessfully to reduce weed dominance and promote native recruitment and establishment. The findings of this review clarify that weed management should be ongoing in all projects, while optimal revegetation methods and grazing regimes are specific to site location and study scope. There is a need for an increase in long-term monitoring of restoration projects in order to make assumptions with greater confidence.

In habitats with low water availability, a fundamental challenge for plants will be to maximize photosynthetic C-gain whilst minimizing transpirational water-loss. This tradeoff between C-gain and water-loss can in part be achieved through the coordination of leaf-level photosynthetic and hydraulic traits. To test the relationship of photosynthetic C-gain and transpirational water-loss we grew under common growth conditions 18 C4 grasses adapted to habitats with different mean annual precipitation (MAP) and measured leaf-level structural and anatomical traits associated with mesophyll conductance (gm) and leaf hydraulic conductance (Kleaf). The C4 grasses adapted to lower MAP showed greater mesophyll surface area exposed to intercellular air spaces (Smes) and adaxial stomatal density (SDada) which supported greater gm. These grasses also showed greater leaf thickness and vein-to-epidermis distance which may lead to lower Kleaf. Collectively, these leaf traits associated with gm and Kleaf scaled positively with photosynthetic rates (Anet) and leaf-level water-use efficiency (WUE) with low MAP adapted grasses exhibiting greater Anet and WUE. In summary, we identify a suite of leaf-level traits that appear important for adaptation of C4 grasses to habitats with low MAP and may be useful to identify C4 species showing greater Anet and WUE in drier conditions.

Hundreds of researchers are working to develop a vaccine and are evaluating drugs to mitigate the adverse health and economic consequences of COVID-19 (Coronavirus disease 19) worldwide. If novel compounds are found, geopolitical and economic variables will determine their introduction to communities. Therefore, finding low-cost and widely accessible drugs for prevention or treatment of COVID-19 would be ideal.A recent study found that ivermectin, an FDA-approved anti-parasitic drug, has inhibitory effects on replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1. Ivermectin has broad anti-viral activity through inhibition of viral proteins including importin α/β1 heterodimer and integrase protein2. Caly and colleagues reported that the addition of ivermectin at a concentration of 5 micromolar (μM) (twice the reported IC50) to Vero-hSLAM cells, 2 hours post infection with SARS-CoV-2, resulted in a reduction in the viral RNA load by 99.98% at 48 hours1. The authors suggested that this drug could reduce the viral load in infected patients, with potential effect on disease progression and spread.While the findings by Caly and colleagues provide some promise, there is no evidence that the 5 μM concentration of ivermectin used by Caly and colleagues in their in vitro SARS-CoV-2 experiment, can be achieved in vivo . The pharmacokinetics of ivermectin in humans is well described (Figure 1)3-5, and even with the highest reported dose of approximately 1700 µg/kg (i.e. 8.5 times the FDA-approved dose of 200 μg/kg), the maximum plasma concentration was only 0.28 µM5. This is 18 times lower than the concentration required to reduce viral replication of SARS-CoV-2in vitro . Ivermectin accumulation in tissues is mild and would not be sufficient to achieve the antiviral effect with conventional doses6. Although high doses of ivermectin in adults or children are well tolerated5,7, the clinical effects of ivermectin at a concentration of 5 μM range are unknown and may be associated with toxicity. Consequently, ivermectin has in vitroactivity against SARS-CoV-2 but this effect is unlikely to be observedin vivo using current dosing.Amidst fear of the pandemic, the public and some physicians are now using ivermectin off-label for prophylaxis or as adjuvant therapy for COVID-19. Because ivermectin is only commercially available as a 3 or 6 mg tablets or a 6 mg/ml oral suspension, in order to administer a high dose, some people may experiment with more concentrated veterinary formulations. These actions are not based on clinical trials and have motivated cautionary statements from institutions such as the FDA against the use of pharmaceutical formulations of ivermectin intended for animals as therapeutics in humans 8.Potential avenues for further investigation into repurposing ivermectin for SARS-CoV-2 may be to: (i) develop an inhaled formulation to efficiently deliver a high local concentration in the lung, whilst minimizing systemic exposure; and (ii) evaluate more potent ivermectin analogs (e.g. doramectin) which may also inhibit SARS-CoV-2. These are areas for research – clearly, further studies are needed before ivermectin can be used for the prevention and treatment of COVID-19. As recently discussed in BJCP, this highlights the critical need to consider pharmacological principles to guide in vitro testing when repurposing old drugs for therapeutic use against COVID-199.

Objectives: To analyze the current condition of the urgent neurologic in-hospital consultations, which may help junior doctors to manage diseases related to neurology and carry out emergency consultation. Methods: We conducted a retrospective study of urgent neurologic in-hospital consultations in a large tertiary hospital for four consecutive years (Jan 1, 2014 to Dec 31, 2017). Through the electronic medical record system, the clinical data of patients who received in-patient consultation in emergency neurology department were reviewed and analyzed. Results: A total of 1,437 cases (age range 9 to 103 years old with average age 60.3-year old, Male 54.6%) were included in the study, 57.5% of cases met the urgent consultation criteria. The departments applying for urgent consultation involved 29 clinical departments. The most common reasons of urgent consultation were disturbance of consciousness (36.0%), tic/stiffness (13.6%), limb weakness (8%) and mental disorders (5.6%).Urgent consultation diseases were divided into three categories: neurological diseases (77.8%), non-neurological diseases (10.4%), and unknown diseases (11.8%).Common neurological disorders were urgent cerebrovascular disease (33.6%), epilepsy/status epilepticus (15.8%), and metabolic or infection, toxic encephalopathy (14.9%). Conclusions: Most cases of the urgent neurologic consultation met the urgent neurologic consultation criteria. Non-neurologic junior physicians should clinically enrich their knowledge of neurological diseases.

In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as Tumor Necrosis Factor (TNF). In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature. Keywords: TNF inhibitors, SARS-Cov-2, immunomodulating, infection, hyperinflammatory

In the 21st century, human civilization, has witnessed three major epidemics caused by Coronaviruses namely severe acute respiratory syndrome coronavirus (SARS‑CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS‑CoV) in 2012 and 2019‑novel coronavirus (2019‑nCoV) or coronavirus disease (COVID‑19) in 2019. Among these, COVID-19 has greater transmission and mortality rate.  2019‑nCoV belongs to a large family of positive sense single-stranded RNA viruses (+ssRNA) that can be isolated in different animal species. The most communal symptoms of COVID-19 include fever, cough, and shortness of breath during the incubation period (2-14 days) of infection. COVID-19 transmission is occurring from infected humans to close contact with one another through respiratory droplets, coughs, and sneezes of infected person. Moreover, the virus containing surfaces may also transmit the infection. Diagnosis is being carried out by collecting a nasopharyngeal swab or sputum specimen for detection of SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction (RT-PCR). Rapid diagnosing methods are also under development which can diagnose COVID 19 in few minutes to hours. Currently, there is no specific cure or preventive therapeutics available. Hence, based upon limited in-vitro and anecdotal data, Chloroquine, or Hydroxychloroquine, Remdesivir, Lopinavir and Ritonavir are being employed in the management. Search for new specific anti-viral drugs from natural/synthetic origins is under full swing and many of them are currently used as chemotherapeutic drugs under clinical investigation. Yet, there is a strong need for development of vaccine, which may take several months to few years for the development.

SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population, causing over 2.8 million confirmed cases worldwide. As COVID-19 has posed a global threat with significant human casualties and severe economic losses, there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus. Although there are no specific antiviral therapies that have proven effective in randomized clinical trials, currently, the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission. Besides, global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19. Herein, the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.

Experimental Approach: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and in women. It’s expected to cause about 53,200 deaths during 2020. An effective drug for therapy and prognosis after surgery still does not exist. Therefore, the search for new lead structures and chemical entities for the development of new effective anticancer agents is an increasingly important task in medicinal chemistry. This trend of global research includes work on the use of 1,2,4-triazine scaffold as a source for the design of biologically relevant molecules with well-known broad biological applications. A series of new pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine sulfonamides were designed, synthesized, and assessed as anticancer activity agents. Experimental Approach: The impact of two selected compounds, MM-128, and MM-129 (MMs), were evaluated against human colon cancer in in vitro and in zebrafish embryo xenograft model. Key Results: Our results show that the new synthesized compounds effectively inhibit cell survival and DNA synthesis in both DLD-1 and HT-29 cell lines. Their effectiveness is much higher as compared with the standard chemotherapy used for colorectal cancer, i.e. 5-fluorouracil. Flow cytometry analysis after annexin V-FITC and propidium iodide staining revealed that apoptosis was the main response of colorectal cancer cells to MMs treatment. We also found that MM-129 effectively inhibits tumor development in both DLD-1 and HT-29 zebrafish xenografts. Conclusion and Implications: New pyrazolo[4,3-e]tetrazolo[4,5-b][1,2,4]triazine sulfonamides may be new candidates for further evaluation as chemotherapeutic agents against colorectal cancer.

Objective: To assess the correlations between clinical and hormonal parameters and comorbidity burden in Caucasian women presenting for fertility treatment. Design: Cross-sectional study. Setting: Single academic reproductive medicine center. Patient: Cohort of 3163 single-ethnicity women seeking medical help for fertility treatment, who underwent centralized lab testing for fertility-related hormonal assessment. Intervention: Complete clinical and laboratory data from the entire cohort of patients were retrospectively analysed. Main outcome measures: Assessment of i) the comorbidity burden scored via the Charlson Comorbidity Index (CCI; categorized as 0 vs. 1 vs. >2); and, ii) the potential associations between CCI and clinical and hormonal parameters. Results: Descriptive statistics and regression models tested the associations between clinical and laboratory parameters and CCI. Of 3163, CCI=0, CCI=1 and CCI>2 were found in 2977 (94.1%), 113 (3.6%) and 73 (2.3%) patients, respectively. Age, gravidity, Anti-Müllerian hormone (AMH) and thyroid stimulating hormone (TSH) values were found to be significantly different among CCI groups (all p≤ 0.01). At regression models, age at presentation and AMH emerged as independent predictors of CCI>1. Age at presentation <36 years (OR=1.742, 95% CI [1.284; 2.364]) and an AMH level <2.3 ng/ml (OR=1.864, 95% CI [1.29; 2.69]) were the most informative cutoff values for CCI >1. Conclusions: A younger age at presentation and lower AMH levels are significant predictors of decreased general health in women requiring clinical evaluation for fertility treatment. As observed for sperm parameters in men, AMH might serve as a proxy of women’s general health status. Key words: AMH, comorbidities, health, infertility

Background & Purpose: The constitutive androstane receptor (CAR) belongs to nuclear receptor superfamily. The administration of CAR agonist TCPOBOP to mice leads to hepatomegaly but the mechanism is unclear. Yes-associated protein (YAP) is a downstream factor of Hippo signaling pathway, which is a potent regulator of organ size and tissue homeostasis. This study examined the role of YAP in CAR-promoted hepatomegaly and liver regeneration. Experimental Approach: The effect of CAR on liver enlargement and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. KI67 and CTNNB1 staining were performed to evaluate the proliferation response and hepatocytes size. The protein levels of YAP and its downstream targets were measured and Co-IP was conducted to explore the protein-protein interaction between CAR and YAP. Key Results: The results suggested TCPOBOP increases the liver/body weight ratio in WT mice and PHx mice. Hepatocytes enlargement occurred around the central vein area, while the number of KI67+ cells increased around portal vein area. The translocation of YAP was induced and its downstream targets were upregulated after CAR activation via TCPOBOP. Co-IP results revealed a potential protein-protein interaction between CAR and YAP. However, CAR-induced hepatomegaly was still observed in Yap-/- mice. Conclusion and Implications: CAR activation promotes hepatomegaly and liver regeneration in part by inducing nuclear translocation of YAP and interaction with YAP pathway, which provides new insights for understanding the physiological functions of CAR, and suggests the potential for manipulation of liver size.

Background and Purpose: Pudilan (PDL), a four-herb prescription with the traditional function of heat-clearing and detoxifying, has been used for anti-SARS-CoV-2 infection, anti-inflammation effect, and clear infection. PDL is one of the therapeutic potentials for COVID-19 while the underlying mechanisms remain to be clarified. Experimental Approach: We used network pharmacology analysis, and selected 68 co-targeted genes/proteins as targets of both PDL and COVID-19. These co-targeted genes/proteins were predicted by SwissDock Server for their high-precision docking simulation, and analyzed by STRING for proteins to protein interaction (PPI), pathway and GO (gene ontology) enrichment. WebGestalt (WEB-based Gene SeT AnaLysis Toolkit) was used for gene set enrichment analysis (GSEA) for functions and pathways enrichment. The therapeutic effect for PDL treatment on COVID-19 was validated by the TCMATCOV (TCM Anti COVID-19) platform. Key Results: PDL may prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2). It may inhibit the cytokine storm by affecting C-reactive protein (CRP), interferon-γ (IFN-γ), interleukin- 6 (IL-6), interleukin- 10 (IL-10), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), C-C Motif Chemokine Ligand 5 (CCL5), transforming growth factor-β1 (TGFβ1), and other proteins. PDL may moderate immune system to shorten the course of the disease, delay disease progression and reduce the mortality rate. Conclusion and Implications: We showed the molecular mechanism of PDL treatment for COVID-19. Based on previous studies, PDL was proven to be useful in the treatment of COVID-19 via different levels studies including clinical practice, animal experiments, cell testing, and network pharmacology.

The aromaticity of boron-nitrogen clusters has been revisited through a systematic analysis using magnetic criteria. The results obtained through Ring Current Strength (RCS) measurements indicate that B2N2 has a strongly antiaromatic character, even the bond pattern analysis reveals that this system is doubly antiaromatic presenting two σ- and two π-orbitals of 4c-2e, according to the Adaptive Natural Density Partitioning bond pattern analysis (AdNDP) and z-component of the dissected Nucleus Independent Chemical Shift (NICSzz) isolines. B4N4 and B6N6 are marginally antiaromatic according to RCS and the bond pattern suggest four and six 8c-2e and 12c-2e delocalized π-orbitals respectively. B3N3 and B5N5 are slightly aromatic, with a bond pattern of three and five 6c-2e and 10c-2e π-orbitals respectively. All rest of the systems (x = 7 – 11) are non-aromatic. The results show some discrepancies with results based on the classical nucleus independent chemical shift, which can be attributed to tensor in-plane and core electron contributions. Finally, presented results reveal the need to be careful with the interpretations given by this index, so it will be necessary the use of 1D, 2D or 3D derived methodologies for a complete and correct analysis of (anti)aromaticity.

Background and Purpose Airway hyperresponsiveness (AHR) is a central abnormality in asthma. Interleukin-5 (IL-5) may modulate AHR in animal models of asthma, but inconsistent data are available on the impact of targeting IL-5 pathway against AHR. The difference between targeting IL-5 or IL-5Rα in modulating AHR remains to be understood in human airways. The aim of this study was to compare the role of the anti-IL-5Rα benralizumab and the anti-IL-5 mepolizumab against AHR, and to assess whether these agents influence the levels of cyclic adenosine monophosphate (cAMP). Experimental Approach Passively sensitized human airways were treated with benralizumab and mepolizumab. The primary endpoint was the inhibition of AHR to histamine; the secondary endpoints were the protective effect against AHR to parasympathetic activation and mechanical stress, and the tissue modulation of cAMP. Key Results Benralizumab and mepolizumab significantly (P<0.001 vs. positive control) prevented the AHR to histamine (maximal effect -134.14±14.93% and -108.29±32.16%, respectively), with benralizumab being 0.73±0.10 logarithm significantly (P<0.05) more potent than mepolizumab. Benralizumab and mepolizumab significantly (P<0.001 vs. positive control) inhibited the AHR to transmural stimulation and mechanical stress. Benralizumab was 0.45±0.16 logarithm significantly (P<0.05) more potent than mepolizumab against AHR to parasympathetic activation. The effect of these agents was significantly correlated (P<0.001) with increased levels of cAMP. Conclusion Targeting the IL-5/IL-5Rα axis is an effective strategy to prevent the AHR. Benralizumab resulted more potent than the mepolizumab and the concentration dependent beneficial effects of both these agents were related with improved levels of cAMP in hyperresponsive airways.

Background: The use of immunotherapy to treat recurrent/metastatic squamous cell carcinoma of the head and neck has become a popular research topic in recent years, and many clinical trials have been carried out. Objectives: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent/metastatic head and neck squamous cell carcinoma. Methods: We searched PubMed, Embase, Cochrane Library and other databases up to 1 November 2019 for publications reporting the use of PD-1/PD-L1 inhibitors in the treatment of squamous cell carcinoma of the head and neck. Revman 5.0 was used for combination analysis, and the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events were determined. Results: Five articles were included. Compared with other treatment methods, this meta-analysis showed that treatment with PD-1/PD-L1 inhibitors can significantly improve OS (P < 0.0001), but there was no significant improvement in PFS or ORR. The risk of anaemia and nausea was significantly reduced by treatment with PD-1/PD-L1 inhibitors. Conclusions and Significance: Treatment with PD-1/PD-L1 inhibitors alone can improve the overall survival rate for recurrent/metastatic squamous cell carcinoma of the head and neck but there is no obvious advantage in other aspects and adverse events.

Background: Increasing the use of tobacco by the younger generation has increased in oral cavity tumours. Surgical treatment is radical and results in severe functional morbidity. Using computer-aided designing technology, surgical and rehabilitative planning can be better. We present here our concept of a biomechanical 3D tongue model and its clinical utility in the management of tongue tumours. Methods: Patients diagnosed with Carcinoma of Tongue were included. These patients underwent a pre-operative Magnetic Resonance Imaging (MRI) of the head and neck region at our center. These patients were informed about the use of a 3D biomechanical patient-specific model for treatment planning and execution. Using Materialise Mimics Innovation Suite 19 DICOM data was imported, visualized, edited and segmented. Flashforge ‘Creator-pro’3D Printer was used for 3D Printing. Fused Deposition Modeling (FDM) technology was used to print the tumour and uninvolved tongue in two different colors for easy identification. These patients underwent surgery with the 3D model serving as a guide for margins. Results: Two patients with stage III squamous cell carcinoma of tongue underwent the surgery based on the plan evolved from the 3D model. All the surgical margins were clear. The model helped address the discordance between patient expectations and surgical outcomes. We found that the model aided the reconstructive surgeon to plan the flap volume better and this translated into better rehabilitative outcomes. Discussion and Conclusion: The 3D biomechanical tongue model is a novel concept and may aid in improving our overall treatment outcomes.

The use of ultrasound enhancing agents (UEA) help optimize visualization in technically difficult studies, with improved left ventricular opacification and endocardial border definition. The use of these agents may often unveil critical data that drastically alter clinical management. Despite the clinical benefit of using UEA, it is sometimes not used routinely in emergency situations with an unstable patient for many reasons. Herein, we demonstrate a challenging case of late presentation myocardial infarction complicated with cardiogenic shock and pseudoaneurysm formation that was not observed in non-contrast images emblematically demonstrating how the use of ultrasound enhancing agents can drastically impact clinical decision-making.