Aim: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has no approved treatment. There are some medications which may be prescribed for COVID-19 patients as investigational treatments. Drug-drug interactions (DDIs) of medications used in treating COVID-19 is an important issue to be studied. Current study aimed to evaluate potential DDIs (pDDIs) and their predictors in hospitalized COVID-19 patients. Methods: A retrospective chart review study was conducted in a tertiary respiratory hospital dedicated for COVID-19 patients. Interacting drug combinations, severity, reliability, mechanism, and clinical management of pDDIs in confirmed COVID-19 cases were identified using the Lexi-Interact database. Logistic regression was applied to assess the correlation between occurrence of severe interactions and probable risk factors. Results: Two hundred and twenty-seven patients’ medical charts were evaluated. About 68% of the patients had at least one comorbidity. The most common comorbidity was hypertension (30.4%), followed by obesity (27.8%) and diabetes (23.8%). At least one major or contraindicated interaction was detected in 37.9% of the patients. Above 50% of the interactions were between lopinavir/ritonavir (protease inhibitor) and commonly prescribed medications (e.g. atorvastatin, alprazolam, salmeterol, and tamsulosin) for management of comorbidities or COVID-19 symptoms. Logistic regression analysis demonstrated that two comorbidities (IHD and CRDs) and ICU admission are significantly associated with occurrence of major or contraindicated pDDIs. Conclusion: The frequency of pDDIs is relatively high in COVID-19 patients. Patients receiving a protease inhibitor and having comorbidity or critical conditions should be monitored carefully in terms of DDIs.

Objective The aim of this study was to investigate relations (or coactions) among maternal mental health measures, clinical and socio-demographic factors and salivary cortisol level of hospitalized mothers and babies. Design A cross-sectional observational and exploratory study at a tertiary referral centre. Setting Maternal and Neonatal Care Ward of the University Hospital of Brasilia, Brazil Population 89 mother-baby dyads at post-delivery period. Methods Dyads were recruited by convenience during the first 48 hours after birth. Main outcome measures The research protocol included maternal sociodemographic and clinical data, screening for maternal depression, self-efficacy and gestational stress, besides salivary cortisol collection from both mother and baby. Results: Exploratory analysis indicated a relation between high gestational stress, high depression symptoms, low self-efficacy perception and high baby’s cortisol level (p < 0.05). Maternal cortisol was positively related to infant cortisol and was indirectly influenced by maternal perception of self-efficacy in reading the baby’s behavior, especially for knowing what the baby likes, or what pleases her/him, maternal situational beliefs (within the concept of parental self-efficacy). Four binary logistic regression models were performed considering maternal mental state variables as factors and clinical and socio-demographic variables as covariates in order to predict the cortisol level of infants. Only two were strong predictors, namely maternal depression and higher gestational stress. Conclusion The findings suggest an important role of maternal mental health in neonatal salivary cortisol levels in the first days of life, which can be considered an early clinical marker for the infant’s reaction to maternal mental status.

Differential diagnoses of patients with multiple bony lesions that are confined to one side of the body should include polyostotic fibrous dysplasia with and without McCune-Albright Syndrome, particularly if there is no history of malignancy. Lesion biopsy ultimately provides the definitive diagnosis.

Nutcracker syndrome refers to symptomatic compression of left renal vein. There are many reasons for that. We report a case that the enlargement of splenic vein has caused to nutcracker syndrome. Results implies that not firm venous structures can be cause of nutcracker syndrome.

Extreme weather events have become a dominant feature of the narrative surrounding changes in global climate. with large impacts on ecosystem stability, functioning and resilience, however, understanding of their risk of co-occurrence at the regional scale is lacking. Based on the UK Met Office's long-term temperature and rainfall records, we present the first evidence demonstrating significant increases in the magnitude, direction of change and spatial co-localization of extreme weather events since 1961. Combining this new understanding with land use datasets allowed us to assess the likely consequences on future agricultural production and conservation priority areas. All land uses are impacted by the increasing risk of at least one extreme event and conservation areas were identified as hotspots of risk for the co-occurrence of multiple event types. Our findings provide a basis to regionally guide land use optimisation, land management practices and regulatory actions preserving ecosystem services against multiple climate threats.

Background: The aim of the present study was to investigate the potential predictive significance of pretreatment prognostic nutritional index (PNI) in patients with intravenous immunoglobulin (IVIG) resistant Kawasaki disease (KD). Methods: From June 2013 to May 2020, 1,257 eligible patients with KD were included in the present study. The pretreatment PNI was calculated as albumin level (g/L) +5×total lymphocyte count (109/L). The optimal cut-off values for PNI, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were evaluated via a receiver operating curve analysis. The impact of pretreatment PNI, NLR and PLR for IVIG resistant KD were tested with the Student’s t test or Mann-Whitney U test, and univariate and multivariate analyses. Results: The optimal cut-off values were identified as 49.50 for PNI, 3.58 for NLR and 164.00 for PLR, respectively. Lower pretreatment PNI levels were demonstrated to be associated with lower age, serum sodium levels and platelet counts, and with a higher incidence of IVIG resistance and higher C-reactive protein levels. There was a significantly negative association between the PNI and NLR, and PLR. In the logistic analyses, PNI as independent predictive factors were significantly correlated with IVIG resistance. The discriminatory ability of PNI was not inferior to NLR and PLR for predicting IVIG resistance. Conclusion: Pretreatment PNI could serve as a novel surrogate independent predictor for patients with IVIG resistant KD.

Acute lymphoblastic leukemia (ALL) is the leading cause of cancer related death in children despite recent advances showing improved responses to chemotherapy treatment. Gamma-delta (γδ) T cells are a recent topic of growing interest in the field of adoptive immunotherapy. These cells have also been proven to be an optimal predictor of a favorable outcome in numerous malignancies. We evaluated subgroups of γδ T cells in the peripheral blood of 19 children with newly diagnosed ALL at the time of diagnosis and following chemotherapy induction. Due to the fact that serum HSP90 serves as a ligand for γδ T cells, we also checked the correlation between HSP90 and γδ T cells. As a result, we found, that the number of CD8+ γδ T cells in peripheral blood at disease presentation was almost three times higher in the intermediate risk group compared to patients in high risk group. Furthermore, we observed higher percentages of the subset in younger patients at diagnosis and after induction, but not in healthy controls. We also noticed negative correlations between CD8+ γδ T cells and minimal residual disease (MRD) before chemotherapy and after induction. We showed a positive association between activated CD3+ γδ T cell and serum HSP90 at presentation. In conclusion, our data suggests that CD8+ γδ T cells may be an early marker of favorable prognosis in childhood ALL while serum HSP90 may act as an agent activating CD3+ γδ T effector cells.

Peripheral blood natural killer (pNK) cells can be recruited by the endometrium to participate in the decidualization and be in contact with the villus in the intervillous space during pregnancy. Moreover, pNK cells can exert cytotoxicity to cytotrophoblast, especially in abnormal pregnancy. However, it is still controversial about the association between pNK cytotoxicity and RM so far. In this study, we aim to compare the percentage, immunophenotype and function of pNK cells between patients with RM and fertile controls. The peripheral blood was collected from 49 patients with RM and 11 fertile women in their middle luteal phase of the menstrual cycle. pNK cells were co-cultured with K562 cells at three different cell ratios to measure the cytotoxicity. The percentage of CD3-CD56+ pNK was analyzed by flow cytometry and quantified to evaluate the expression of cytotoxic granules (granzyme B, granulysin, and perforin), and the cell surface receptors related to pNK cell cytotoxicity (NKG2D, NKp30, NKp46, CD158a, CD158b) were also detected. The general linear model analysis showed that pNK cell cytotoxicity in patients with RM was significantly lower than that in fertile controls. The RM group possessed a significantly lower level of granzyme B+ pNK cells and significantly higher level of CD158a+, CD158b+ pNK cells than that in the control group. However, there was no significant difference in the proportion of circulating CD3-CD56+ NK cells expressing the granzyme B, granulysin, perforin, NKG2D, NKp30, NKp46, CD158a, CD158b. Our results suggested that a lower pNK cytotoxicity might be associated with RM.

Background: Eltrombopag (E-PAG) is being investigated for the treatment of aplastic anemia (AA) by stimulating hematopoietic stem cell (HSC) proliferation. Objective: To evaluate the effectiveness and safety of E-PAG in first-line therapy for pediatric AA. Methods: The present retrospective study reviewed the pediatric patients with newly diagnosed AA in immunosuppressive therapy (IST) therapy with E-PAG at the single center from March to September in 2017. All patients were followed up for >2 years. Results: A total of 14 patients (8 males), aged 86 months, were enrolled in this study. E-PAG was administered with a median time to initiation of 19.5 days after IST, and the median course of treatment was 253 days. The rate of complete response and overall response at 6 months were 64.3% (9/14 case) and 78.6% (11/14 cases) respectively. The survival rate was 100%, and no relapses occurred in responders. E-PAG was well-tolerated; however, the most common adverse events included indirect bilirubin elevation, jaundice, and transient liver-enzyme elevation. By the end of follow-up, bone marrow chromosomes were normal, and no abnormal myelodysplastic syndromes (MDS) -related clones appeared. Conclusions: The addition of E-PAG to IST was associated with the markedly increased complete response with respect to hematology in pediatric patients with SAA than in a historical cohort without the unacceptable side effects.

The defected carbon materials as a metal-free catalyst shown superior stability and catalytic performance in the acetylene hydrochlorination reaction. Through DFT calculation, for the first time several different defected configurations comprising mono, di-vacancies, and Stone Wales defect on single-walled carbon nanotubes (SWCNTs) have been used as a direct catalyst for acetylene hydrochlorination reaction. These defective sites on SWCNTs are the most active site for acetylene hydrochlorination reaction compared to pristine SWCNT. The different configuration of defects have different electronic structure, which specify that mono-vacancy defect, have more states adjecent to the Fermi level. The reactant acetylene (C2H2) adsorbed strongly than hydrogen chloride (HCl) and expected to be the initial step of the reaction Acetylene adsorbed strongly at mono-vacancy defected SWCNT compared to other investigated defects. The reaction pathways analysis revealed that mono- and di-vacancy defected SWCNT has a minimum energy barriers and shows extraordinary performance towards acetylene hydrochlorination. This work suggests the potential of metal-free defected carbon to catalyze acetylene hydrochlorination and provide a solid base for future developments in acetylene hydrochlorination.

Proton pump inhibitors (PPIs) belong to a well-known class of pharmaceutical agents which target the gastric epithelial H+/K+ ATPase. Although the major therapeutic uses of the PPIs are in gastric-acid related diseases, evidences are suggestive of a pleiotropic nature of the compounds. They have been used for the treatment of conditions such as eosinophilic esophagitis and Helicobacter pylori infection, in addition to their conventional use in gastro-oesophageal reflux disease and peptic ulcers. The current pandemic of COVID-19 has put forward a challenge to find treatment options. While multiple studies have been conducted, and many are currently on-going, we have not been able to come up with any specific agent against SARS-CoV-2. PPIs have shown antiviral potencies in various in vivo and in vitro studies. Results from these studies point toward a promising role of PPIs for infections caused by Marburg virus, Influenza virus and Rhinovirus to mention a few. However, neither have they been considered for any clinical trials nor have any guidelines suggested their re-purposing against SARS-CoV-2 till date. In this review, we discuss the probable pathways and cellular machineries via which PPIs could show beneficial therapeutic effects against the novel coronavirus based on the existing evidences.

Background and Purpose: Emerging evidence has shown that pinocembrin protects myocardial from ischemic injury in animals. However, it is unknown whether it has cardioprotection when given at the onset of reperfusion. Also, mechanisms mediating the cardioprotective actions of pinocembrin were largely unknown. Thus, this study aimed to investigate the effects of pinocembrin postconditioning on ischemia-reperfusion (I/R) injury and the underlying mechanisms. Experimental Approach: In vivo mouse model of myocardial I/R injury, ex vivo isolated rat heart with global I/R and in vitro hypoxia/reoxygenation (H/R) injury model for primary cardiomyocytes were used. Key Results: We found that pinocembrin postconditioning significantly reduced the infarct size and improved cardiac contractile function after acute myocardial I/R. Mechanically, in primary cardiomyocytes we found that pinocembrin may confer protection in part via direct stimulation of cardiac glycolysis via promoting the expression of glycolytic enzyme, PFKFB3. Besides, PFKFB3 inhibition abolished pinocembrin-induced glycolysis and protection in cardiomyocytes. More importantly, PFKFB3 knockdown via cardiotropic adeno-associated virus (AAV) abrogated cardioprotective effects of pinocembrin. Conclusions and Implications: In conclusion, these results established that the acute cardioprotective benefits of pinocembrin are mediated in part via glycolytic stimulation through PFKFB3, which may provide a new therapeutic target to impede the progression of myocardial I/R injury.

KEYWORDSBROKER, INTERNET OF THINGS (IOT), MQTT, PROTOCOL

COVID-19 PANDEMIC: A CHALLENGE TO A CHILD WITH CANCER Dear Editor,People of all ages can be infected by the new coronavirus (2019-nCoV). Older people, and people with pre-existing medical conditions (such as asthma, diabetes, heart disease) are more vulnerable to becoming severely ill with the virus. There is a widespread anxiety among families of children with cancer due to risk of exposure to SARS-CoV-2, either in the hospital or community setting. [1]Recently Ogimi et al [2] reported that infants and younger children (i.e., ≤5 years) are more likely to develop severe clinical manifestations than older children, maybe due to immaturity of the immune system. Sullivan et al [3] reported that the COVID-19 pandemic was one of the most serious global challenge to delivering affordable and equitable treatment to children with cancer. They have provided some practical advice for adapting diagnostic and treatment protocols for children with cancer during the pandemic, the measures to be taken to contain it (e.g. extreme social distancing) and how to prepare for the anticipated recovery period.The Government and administrative measures such as lockdown has further compounded these challenges. Lack of state transport, closure of district borders, non-availability of medications has put these children at risk of rapid growth of disease, delay in treatment and poor outcome. A four and half year-old child, a known case of synchronous bilateral Wilms tumour, having undergone bilateral nephron sparing surgery was on adjuvant chemotherapy. The COVID-19 pandemic brought about an interruption in his chemotherapy schedule in January 2020. When he presented in early May, he had a small swelling of 1.5 cm diameter below the left subcostal margin (Figure 1a). Ultra sonography revealed a hypoechoic lesion below the skin measuring 1.5 cm in diameter (Figure 1b). Fine needle aspiration cytology was done which revealed sheets of cells with high nuclear/cytoplasm ratio (Figure 1c). The features were highly suspicious of a malignant lesion. The lesion was excised and histo-pathological examination revealed a metastasis from WILMS tumour (Figure 1d). The child has been resumed on further chemotherapy.Most childhood cancers behave aggressively and need immediate treatment, often requiring prolonged periods of intensive multiagent chemotherapy. Postponement of treatment such as surgery, radiation and chemotherapy is not a safe option in children. There is an urgent need amongst health professionals and families for informed guidance on the range of reasonable and safe adaptations to their services and cancer treatment during the pandemic.Conflict of Interest: None.Compliance with Ethical Standards.

Objective: To establish reference ranges of adrenal artery Doppler indices for the the inferior adrenal artery (IAA) and middle adrenal artery (MAA). Design: longitudinal observational study Setting:China Population or sample: 168 low-risk singleton pregnant women and their fetuses (85 male and 83 female) with 843 observations Methods: The pulsatility index (PI), resistance index (RI), and systolic:diastolic ratio (S/D) of the IAA and MAA were obtained serially at 4-week intervals. Gestational age-associated reference ranges were established by multilevel modeling. Differences in Doppler indices between the IAA and MAA were assessed. Main outcome measures: fetal adrenal artery Doppler Results: Longitudinally established percentiles of Doppler indices show that the IAA had a reduction around 35 weeks of gestation and that the MAA remained unchanged throughout the second half of pregnancy. The IAA had a higher detection rate than the MAA (100% vs 89.2%, p<0.05). Lower PI, RI and S/D were observed in the MAA than in the IAA (p<0.05) from 752 paired measurements. Conclusion: Reference ranges for adrenal artery Doppler indices that are based on longitudinal observations appear to be more appropriate for serial evaluation of fetal hemodynamics. There is a zonal difference in blood supply in favor of the fetal zone, which may correspond to its unique function, i.e., androgen secretion to help produce estrogens and maintain pregnancy. Funding: This study was supported by the State Natural Sciences Foundation of China (nos. 81871372,81501497). Keywords:fetal; adrenal; doppler; pulsatility index

Objective: To determine the combined effects of maternal and paternal preconception overweight and obesity on infant birthweight. Design: Retrospective data analysis, fresh cycles (2009-2017), Repromed, South Australia. Setting: Assisted Reproductive Technology. Population: Couples undergoing either in vitro fertilisation or intracytoplasmic sperm injection with their own gametes and transfer of a single blastocyst (N=1479). Methods: Maternal and paternal BMI were recorded prior to cycle initiation. Infant birthweight was recorded at delivery. The impact of paternal and maternal overweight and obesity and their interaction on infant birthweight was assessed using quantile regressions constructed at 5th, 10th, 50th, 90th and 95th birthweight percentiles based on Australian standards. Main Outcome Measures: First, singleton, term birth (≥ 37 weeks’ gestation) birthweight. Results: There was weak evidence for an interaction between parental BMI for median birth weight (β=-0.98; 95%CI=[-1.90, -0.05], p=0.04) with infants having increasing birth weight with increasing parental BMI, when one parent has normal weight. When either parent is overweight or obese, although birth weights are higher (maternal β=15.9; 95%CI=[1.63, 30.1], p=0.03; paternal β=7.33; 95%CI=[0.297, 14.4] p=0.04), they are not associated with increasing BMI of the other parent. Conclusions: Both maternal and paternal overweight and obesity at conception independently increase median infant birthweight. These findings necessitate the need for a family centered approach for preconception counselling on healthy BMI prior to pregnancy. Further studies are warranted in other ART or general population cohorts to support or refute our findings. Funding: NOM is the recipient of an NHMRC Early Career Fellowship.

Objective The aim of this study was to compare the outcomes of with laparotomy or laparoscopy in the treatment of high-risk CSP and evalute the optimal treatment measure about it. Design A retrospective study. Setting Tongji Hospital. Population 278 patients with caesarean scar pregnancy between 2013 and 2018. Methods We compared and analysed the characteristics of the laparoscopic and open surgeries in the treatment of high-risk CSP and the advantages and disadvantages of different methods of vascular pretreatment. We also systematically evaluated CSP patients undergoing laparoscopic or laparotomic surgery. Results Intraoperative bleeding, transfusion rate, total days of hospitalization and postoperative hospital stay were better in laparoscopy than in laparotomy (p<0.05). There was no difference in the factors (β-HCG decrease, reoperation and tissue residues) closely related to the success of the surgery in the two groups. Furthermore, we pretreated blood vessels differently before the operation. Tissue residue, reoperation and intraoperative blood transfusion rates in patients with temporary vascular occlusion were better than in patients with permanent vascular occlusion. As of the latest English literature, the systematic review results showed that most of the current studies on CSP are case reports and retrospective analyses (67.74% and 29.03%, respectively), and the sample sizes of these retrospective studies are very small. Conclusions This study revealed that laparoscopic surgery is superior to laparotomic surgery in the treatment of high-risk CSP. Patients benefited from temporary arterial occlusion in both groups. Temporary arterial occlusion under laparoscopic surgery may be the best treatment for high-risk CSP.

Large osteochondroma arising from chest wall and sternum is uncommon and presentation with airway compression is further uncommon. Here we present a case of large chest wall osteochondroma as a part of Hereditary multiple exostoses in a 9 years old boy presented with a history of stridor and shortness of breath. The bony mass of the right chest wall was extending up to a suprasternal notch and compressing the trachea. The case was successfully managed by initial femoro-femoral cardiopulmonary bypass under local anesthesia prior to the induction of anesthesia to prevent respiratory collapse, followed by debulking surgery was done.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date it has resulted in ~5.6 million confirmed cases and caused 353,334 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socio-economic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a “cytokine storm” leading to acute respiratory distress syndrome, endothelitis, thrombo-embolic complications and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19 and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development and epidemiology. Over 140 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

Tricuspid and pulmonary valve replacement in patients with carcinoid heart disease (CaHD) reduces right heart failure and improves prognosis. The surgical literature is limited concerning technical aspects of valve replacement in CaHD. Although dedicated multidisciplinary care is required, optimization of surgical details is important and may lead to better postoperative outcomes in these frail patients.

Background: This retrospective analysis aims to identify differences in surgical outcomes between pancreas and/or kidney transplant recipients compared to the general population undergoing CABG. Methods: Using NIS data from 2005 to 2014, patients who underwent CABG were stratified by either no history of transplant, or history of pancreas and/or kidney transplant. Multivariate analysis was used to calculate odds ratio (OR) to evaluate in-hospital mortality, morbidity, length of stay (LOS), and total hospital charge in all centers. Results: Overall, 2,678 KTx, 184 PTx, 254 KPTx, and 1,796,186 Non-Tx met inclusion criteria. KPTx experienced higher complication rates compared to Non-Tx (78.3% vs. 47.8%, p<0.01). Those with PTx incurred greater total hospital charge and LOS. On weighted multivariate analysis, KPTx was associated with an increased risk for developing any complication following CABG (OR 3.512, p<0.01) and emergency CABG (3.707, p<0.01). This risk was even higher at transplant centers (CABG OR 4.302, p<0.01; emergency CABG OR 10.072, p<0.001). KTx was associated with increased in-hospital mortality following emergency CABG, while PTx and KPTx had no mortality to analyze. Conclusion: KPTx experienced a significantly higher risk of complications compared to the general population after undergoing CABG, in both transplant and non-transplant centers. These outcomes should be considered when providing perioperative care.

The present work analyses the behaviour of aqueous solutions of N,N-dimethylethylenediamine as chemical solvent for carbon dioxide separation by gas-liquid absorption. The interest of this molecule is centred on the presence of different types of amino centres that confer the capability to act as typical solvent based on mixtures of amines taking into account the suitable behaviour of some mixtures. For this reason a comparison between diamine and amine blend solvents has been carried out in order to understand the differences between these solvents using absorption and NMR studies. This experimental work analyses the influence of amine type, concentration and ratio between different amines. Also, the effect of gas flow rate used in the bubble column reactor upon the absorption kinetics has been analysed.

The main problem during the fermentation process is competition between microorganisms and provision of favorable conditions for archaea. The elements like magnesium, sodium and calcium play an important role during the anaerobic digestion, due to its capability to maintain normal life activities. Besides magnesium can work like effective catalyst during the fermentation process. Therefore, this work reports the influence of the mentioned elements on methane production. Moreover, mathematical model for biogas production for anaerobic digester was presented, which based on a continuous technology. This high-activity and cost-effective mathematical model could improve biogas production efficiency as a tool support for understanding fermentation process.

All tested patients were classified into two groups, Group A (patients who were tested positive) and Group B (patients who were tested negative). A total of 28 patients were evaluated. The primary diagnosis of patients in Group A was B-Cell ALL and Thalassemia Major (50% each), whereas, in Group B, the primary diagnosis was B-Cell ALL (46.1%) and AML. The most prevalent symptoms warranting testing in Group A were fever (100%) and cough (50%); Group B the most common symptoms were fever (53.8%), cough (26.9%), and neutropenia (15.4%). No mortality or significant morbidity was reported in either of the cohorts.