Arterial blood gas analysis (ABG) is the gold standard test for carbon dioxide measurement. End-tidal PCO2 (PetCO2) and transcutaneous PCO2 (PtcCO2) are non-invasive alternative methods. Objective: to examine the use of PetCO2 and PtcCO2 as PaCO2surrogates in awake children. Methods: Prospective observational study. Consecutive awake children in stable condition referred to the Sleep Unit of Hospital de Pediatría Prof. Dr. J. P. Garrahan with suspected or confirmed SRRD requiring ABG were included. PetCO2 and PtcCO2 were recorded simultaneously during arterial puncture. PetCO2 and PtCO2 values were compared with PaCO2. Correlation coefficient and Bland-Altman analysis were applied. Sample size was calculated considering a mean difference ≤ 3 mmHg as clinically acceptable. Results: 68 sample sets were obtained from 67 patients. Median age was 9.11 years (0.23-18.76). During 94.1% of the procedures patients breathed spontaneously, 30% needed multiple punctures and 92% resulted in pain. Median (IQR) PaCO2 (mmHg) was 36.3 (31.45; 40.90), PetCO2 33.0 (29;39) and PtcCO2 38.8 (32.95;43.32). Correlation and agreement for PaCO2/PetCO2 and PaCO2/PtcCO2was: r= 0.6 and0.9, and media of bias=2.83(-9.97;15.64) and-1.88 (-9.01;5.24), respectively. Hypercapnia(PaCO2>45.0 mmHg) was present in 8/68 (11.8%) samples. Sensitivity, specificity, positive predictive value and negative predictive value to detect hypercapnia with PetCO2 was 38 %,98%,75% and 92%, respectively, and with PtcCO2, 100%, 90%, 57% and 100%, respectively. Conclusion: PtcCO2 showed better agreement with PaCO2 than PetCO2,.but because of the wide dispersion of values, neither method can replace the gold standard. Transcutaneous CO2might be a good screening tool to detect hypercapnia in awake children.

Appropriate high-dose chemotherapy (HDC) for high-risk neuroblastoma has not yet been established. In Japan, a unique HDC regimen (called double-conditioning regimen) comprising two cycles of total 800 mg/m2 of thiotepa and total 280 mg/m2 of melphalan is widely used. To re-evaluate the safety and the efficacy of this regimen for high-risk neuroblastoma, the medical records of 41 patients with high-risk neuroblastoma who underwent the double-conditioning regimen followed by autologous peripheral blood stem cell rescue between 2002 and 2012 were reviewed. MYCN-amplified high-risk neuroblastomas were observed in 23 patients. All patients underwent intensive multidrug induction chemotherapy, but none underwent anti-GD2 antibody immunotherapy. The primary tumor was resected at the adequate time point. The median follow-up duration for living patients was 9.2 years (range = 5.5–14.0 years). The 5-year event-free survival (EFS) and overall survival (OS) rates from treatment initiation were 41.5% ± 7.7% and 56.1% ± 7.8%, respectively. The 5-year EFS of MYCN-amplified high-risk neuroblastoma patients was 60.9% ± 10.2%, which was significantly superior compared to MYCN-non-amplified high-risk neuroblastoma patients (16.7% ± 8.8%; P < 0.001). MYCN amplification was the most favorable prognostic factor for EFS (hazard ratio = 0.29; 95% confidence interval = 0.12–0.66). Of the 41 patients, 3 died because of regimen-related toxicity (infection, n = 2; microangiopathy, n = 1). The double-conditioning regimen with thiotepa and melphalan is effective for high-risk neuroblastoma, especially in patients with MYCN amplification. However, the double-conditioning regimen is toxic and warrants special attention in clinical practice.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the global pandemic and caused hundreds of thousands of people died in the world, which is in urgent need to develop new drug therapy and pathogen progressive information. Although abundant anti-viral drugs has been directly practiced in some patients, there are no specific drug treatment due to the new SARS-CoV-2 virus, which cause great disaster and panic all over the world. Remdesivir has been recently a strong candidate for the treatment of COVID-19. Recently, due to the support of antiviral experiments in vitro and a case report by compassionate use of the drug, remdesivir has been a promising candidate treatment for the treatment of COVID-19. As a broad-spectrum anti-viral compound targeting the viral RNA dependent RNA polymerase, remdesivir has been shown to suppress the coronavirus, such as SARS-CoV and MERS-CoV. However, is remdesivir really a magic bullet for COVID-19, also a coronavirus? In this article, we first overview the general information about SARS-CoV-2 and its potential suppressing drug remdesivir. Then, we carefully discussed the limitation with the remdesivir antiviral study, including the case report by compassionate use of remdesivir. Finally, from the pharmaceutical perspective we explored the anti-virus capability of remdesivir against different viruses to see whether it’s a magic bullet for COVID-19. Therefore, this paper provides crucial evidence and objective theoretical basis on remdesivir to cure COVID-19 infections.

Combined use of hydroxychloroquine and azithromycin was globally adopted, in part due to paucity and high cost of alternative therapies. However the utility of these medications has been questioned; and thus safety becomes a major concern given clinical equipoise regarding efficacy. Both hydroxychloroquine and azithromycin continue to be administered in US clinical trials examining their potential role in prevention of infection, treatment of mild infection in ambulatory patients, and in combination with other medical regimens in treatment of patients with severe disease. These drugs also continue to be clinically utilized in hospitalized patients around the globe, often without continuous telemetry due to lack of resources. Concern regarding use of hydroxychloroquine without adequate rhythm monitoring in clinical trials has been recently expressed.1 A review of clinicaltrials.gov at the time of submission of this correspondence reveals actively recruiting trials of combined hydroxychloroquine/azithromycin with or without additional COVID-19 therapies, for both ambulatory and hospitalized patients within and outside the US. The potential for hydroxychloroquine and azithromycin to cause QT prolongation is counterbalanced by very low risk of pro-arrhythmia in the general population, and emerging evidence of relatively low risk of Torsades de Pointes (TdP) in COVID-19 patients.2,3,4,5 Thus delineation of the determinants of significant QTc prolongation and pro-arrhythmic risk for hydroxychloroquine/azithromycin is very important, especially given mounting evidence of inefficacy in COVID-19 treatment.

Background: CHEK2 variants are associated with intermediate breast cancer risk among other cancers. We aimed to comprehensively describe CHEK2 variants in a Spanish hereditary cancer (HC) cohort and adjust American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. Methods: First, three CHEK2 frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients. After, the whole CHEK2 coding region was analyzed by next-generation sequencing in 1,848 prospective patients with HC suspicion. We refined ACMGAMP criteria and applied different combinatorial rules to classify CHEK2 variants and define risk alleles. Results: We identified 10 CHEK2 null variants, 6 missense variants with discordant interpretation in ClinVar database, and 35 additional variants of unknown significance. Twelve variants were classified as (likely)-pathogenic; 2 can also be considered “established risk-alleles” and one as “likely risk-allele”. The prevalence of (likely)-pathogenic variants in the HC cohort was 0.8% (1.3% in breast cancer patients and 1.0% in hereditary non-polyposis colorectal cancer patients). Conclusions: Here we provide ACMG adjustment guidelines to classify CHEK2 variants. We hope that this work would be useful for variant classification of other genes with low effect variants

With reference to 1986,1995,2004,2011 and 2016 TM images of the Shengjin Lake National Nature Reserve in Anhui province, this paper used ERDAS and ARCGIS software to collect the different land use information on the experimental, buffer and core areas for more than 30 years. By combining the social and economic data and selecting the index which is about the ecological risk of land use to built the system of land utilization evaluation index on ecological risk . On this basis, the AHP and expert commonly were used to determine the weight of index and establish the assessment model on ecological risk of the land use by using the method of fuzzy mathematics. With reference to the ecological risk index which was calculated, and adopting the interpolation and three regression methods to built a forecasting model .Finally, the computer simulation was used to establish the early warning for ecological risk of the land use.

Molybdenum cofactor deficiency type B (MOCODB, #252160) is a rare autosomal recessive metabolic disorder characterized by intractable seizures of neonatal-onset, muscular spasticity, accompanying with hypouricemia, elevated urinary sulfite levels and craniofacial dysmorphism. Thirty-five patients were reported to date. Our paper aimed to delineate the disease genotype by presenting another patient, in whom novel, inframe variant within the MOCS2 gene was identified. Its clinical significance was supported by the medical history and analysis of the possible mutation consequences on a molecular level with the use of the available crystal structure of the human molybdopterin synthase complex. Moreover, potential pathomechanism resulting from molecular defect was presented, giving original insight into current knowledge on this rare disease, including treatment options.

Hibernation has been selected for increasing survival in harsh climatic environments. Seasonal variability in temperature may push the body temperatures of hibernating animals across boundaries of alternative states between euthermic temperature and torpor temperature, typical of either hibernation or summer dormancy. Nowadays, wearable electronics present a promising avenue to assess the occurrence of criticality in physiological systems, such as body temperature fluctuating between attractors of activity and hibernation. For this purpose, we deployed temperature loggers on two hibernating edible dormice for an entire year and under severe Mediterranean climate conditions. Highly stochastic body temperatures with sudden switches over time allowed us to assess the reliability of statistical leading indicators to anticipate tipping points when approaching a critical transition. Hibernation dynamics showed flickering, a phenomenon occurring when a system rapidly moves back and forth between two alternative attractors preceding the upcoming major shift. Flickering of body temperature increased when the system approached bifurcations, which were also anticipated by several metric- and model-based indicators. Gradual changes in air temperature drove long transient behavior (since flickering began long before bifurcations) and hysteresis. For hibernating animals, hysteresis may increase resilience when ending hibernation earlier than the optimal time, which may occur in regions where temperatures are sharply rising, especially during winter. Temporal changes in early indicators of critical transitions in hibernation dynamics may help to understand the effects of climate on evolutionary life histories and the plasticity of hibernating organisms to cope with shortened hibernation due to global warming.

In this brief report we describe an extraordinary case of a pediatric patient with a history of medulloblastoma who developed an intracranial mass-like lesion during growth hormone treatment. To our knowledge this is the first case report of a mass-like lesion as a consequence of parenchymal fluid leakage adjacent to an intraventricular catheter due to increased intracranial pressure during growth hormone therapy which has been proven by biopsy.

Genetic changes in juvenile myelomonocytic leukemia (JMML) determine distinct subtypes, treatments and outcomes. JMML with germline CBL mutation and somatic NRAS mutation possibly achieves spontaneous remission, but hematopoietic stem cell transplantation is indicated for other subtypes of JMML. We hereby report a child with JMML harboring a germline CBL mutation (c.1111T>C) and an NF1 variant (c.3352A>G) concurrently. After evaluation, we considered the NF1 variant not the major contributor. After one year of observation, this case had no signs of disease progression. This case highlights the importance of combining available evidence and clinical findings in caring patients with unusual genomic variations.

There is controversy over whether the use of montelukast increases neuropsychiatric events (NEs) in patients with asthma and allergic rhinitis. Our objective was to evaluate whether montelukast caused an increase in neuropsychiatric adverse reactions compared with placebo. We conducted a systematic review and meta-analysis to explore the relationship. The main result of the study was the incidence of NEs. Fifteen RCTs were screened and included for meta-analysis to merge statistics. The main results showed no significant increase in NEs compared with the placebo group. Similar results were seen in the occurrence of NEs in patients grouped by age and headache that the most common neuropsychiatric adverse event. Overall, montelukast did not significantly increase NEs in patients with AR and/or asthma compared with placebo.

Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John’s Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, BCG Atlas. Statistical models were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations, experimental studies and public health policies.

Background The aim of the present theoretical essay is to evaluate evidence published on the characteristics of the transcription of SARS-CoV-2 and explain the mechanism of action of ivermectin that may justify its therapeutic use in clinical practice for the treatment of COVID-19. Methods Laboratory studies, narratives, editorials and expert opinions on the subject were identified through a systematic search of the literature in the Medline/PubMed, Cochrane Library, Web of Science and Embase databases. Two blinded, independent reviewers selected studies published up to May 17, 2020 based on the eligibility criteria. Results The search of the databases led to the retrieval of 25 articles. After the different phases of the selection process, eight articles were included in the present review for the extraction of relevant data. The results suggest that ivermectin inhibits the viral replication of SARS-CoV-2 through the action of the hypoxia-inducible factor (HIF-1α) and consequent destabilization of importin α/β1 proteins. Conclusions Ivermectin inhibits the viral replication of SARS-CoV-2. Laboratory and clinical studies are needed to provide more evidence in terms of the best posology and possible associations with other drugs for combatting COVID-19.

Diffuse Large B-Cell Lymphoma is the most common type of Non-Hodgkin’s Lymphoma. The disease exhibits significant clinical and biologic heterogeneity. Treatment with standard first line therapy results in cure in about 60% of patients while 30-40%of patients either are refractory to therapy or relapse. Current prognostic scores and biomarkers are unable to accurately predict patients who would relapse or would have refractory disease. A part of the heterogeneity in the behavior of DLBCL is explained by the cell of origin of the tumor. Germinal center type (GCB) DLBCL which is derived from centroblasts are associated with better prognosis compared with activated B-cell type (ABC), which is derived from a B-cell committed to secretory differentiation. While the gold standard for cell of origin determination is gene expression profiling, immunohistochemical methods are routinely used because of more readily available fixed tissue and expertise. Immunohistochemical methods are however associated with a significant degree of discordance with GEP. Within the ABC and GCB types of DLBCL, subgroups of prognostic significance have been identified using various multiple approaches which do not inure themselves to routine practice partly because of limitation of diagnostic material or expertise. Exosomes are a class of membrane bound extracellular vesicles of endosomal origin, produced by multiple cell types. They are involved in intercellular communication and present in abundance in various bodily fluids. Exosomal cargo which includes nucleic acids and proteins can be analyzed, yielding diagnostic and prognostic information in management of DLBCL.

COVID-19 has been the biggest global health threat since world war II. Up to now, the novel coronavirus pneumonia epidemic has resulted in over 300 thousand deaths. Angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, is also the key modulator of renin-angiotensin-aldosterone system (RAAS) axes, which regulates the inflammatory response to maintain internal environment balance. On the contrary, RAAS axes can also regulate the expression of ACE2 which may influence on the susceptibility of SARS-CoV-2. Furthermore, SARS-CoV-2 binds with ACE2 and subsequently down-regulates ACE2 expression, which may exacerbate the inflammatory response due to RAAS imbalance. In this review, we summarized pathogenesis and clinical characteristics of COVID-19 patients, and discussed the potential link between the RAAS axes imbalance and the susceptibility/progression of organ injury in COVID-19. Therefore, we speculate that rebalance of the RAAS axes is the preventive and therapeutic strategy of COVID-19.

COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed Healthcare Systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could act modulating virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasome, could limit the “cytokine storm” in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improve COVID-19 outcomes.

We analyzed the nationwide hospital discharge records of adolescent inpatients in Italy to map where adolescents with melanoma are treated and identify expert centers. We identified 137 hospitals pointing out a dispersion of these patients that must be addressed to ensure to all adolescents with melanoma adequate treatment and enrolment in clinical studies.

In this blog-post, we present our path and thoughts towards using ultra-cold atom experiments for quantum computation. They are the result of a two month internship where we studied the feasibility of such an undertaking in our group. Many associate only universal devices, especially qubit devices, to be valid quantum computers. We show how we think of our ultra-cold atoms in terms of quantum circuits and implement first steps in the software framework PennyLane.

Main document

We report a case of successful management of short bowel syndrome in a young patient with gangrene of most of intestine following ileocecal knotting. Aggressive resuscitations, timely surgical intervention and use of parenteral nutrition have a good outcome. Key words: knotting, intestinal obstruction, shock, short bowel syndrome

Objectives This review provides an assessment of recent published or presented trends of perioperative healthcare of COVID-19 which is hitting the world, to provide refer for the frontline medical staff during the outbreak of epidemic, especially for surgeons and anesthesiologists. Methods Searching and reviewing recent published or presented articles about the COVID-19 from PubMed, COVID-19 center of ScienceDirect, Medline, JAMA, The LANCET, MedRxiv, some main Chinese journals and so on. Results The coronavirus disease 2019 has heightened infectious probability and has caused hundreds of thousands death. How to recognize, treat, and overcome this disease is a problem that all medical staff and all humans need to face. First, we should correctly identify suspicious and diagnosed patients and take protection levels according to the type of patients. Surgery and endoscopy are a serious issue during the epidemic, unless emergency condition. Once COVID-19 patients have to accept surgery, more detailed issues should be considered. Besides, special management methods should be implemented for special COVID-19 patients. Conclusion Safety for patients and healthcare providers is very important, we should do what we can do to cut off the spread of the virus in hospital and reduce the risk of infection.

The patient was a 78 year old man who had undergone thrombolysis and angioplasty LAD.. After 45 days, he returned to the clinic with icterus, after detailed work up,suspecting clopidogrel induced liver injury, the clopidogrel was substituted with ticagrelor. icterus and laboratory abnormality was relieved in 2 weeks.

Hybridization between species is likely to be associated with a new ecological impact. However, in termites, reports of hybridization mostly focus on hybrid zones caused by species invasion or the development of initial-stage colonies. In this study, we combined microsatellite genotyping with mitochondrial DNA sequencing to investigate the hybridization and adaptive introgression between two sympatric, long-differentiated related termite species, Reticulitermes flaviceps and R. chinensis, in nature. Similar levels of mitochondrial and nuclear genetic diversity were found in R. flaviceps and R. chinensis. Asymmetric interspecific genetic differentiation was observed between mitochondrial and nuclear genes, with high genetic divergence found in mitochondrial DNA but low genetic divergence in nuclear genes. Our results indicated a lack of mitochondrial gene exchange in R. flaviceps and R. chinensis but unconstrained nuclear introgression between them. This asymmetric genetic differentiation between nuclear and cytoplasmic material strongly suggests that there is interspecific hybridization between R. flaviceps and R. chinensis in nature, which provides new insight into the dynamics of hybridization and its potential consequences for speciation in termites.

Centrifugal fan blades of high-speed train ventilation and cooling system are subjected to cyclic loading which will shorten the life of fan blades. It could cause an accident of high-speed-train in service. In this study, a modified method based on nominal stress method was proposed and developed for the fatigue life prediction of centrifugal fan blades. The finite element model was firstly introduced to analyze the mode and stress of fan blades based on physical material property. The fatigue life was predicted based on S-N curve, using the Miner's cumulative damage rule to calculate total damage. In order to verify the effectiveness of this method, the experimental tests based on fatigue bench system were conducted on fan blades, which were typical structure of the ventilation cooling system of high-speed-train. The damage mechanism of blades was deduced from the fracture fractographs. Relatively good correlation was achieved between the prediction model and actual experimental results, testifying the practicability and effectiveness of this proposed method. Thus, the research result could reduce the probability of accidents caused by fan blade damage and improve the reliability of ventilation cooling system of high-speed train.