Relapsed acute lymphoblastic leukemia (ALL) with high minimal residual disease (MRD) after reinduction has poor prognosis. ALL patients with Down syndrome (DS) have a higher rate of relapse and treatment related mortality. We describe a DS and ALL patient with late bone marrow relapse who was treated per British ALL R3 reinduction chemotherapy. His therapy was discontinued due to severe systemic infections. The patient remained in remission for approximately two years without further treatment. We hypothesize that the sustained remission is attributed to chemotherapy combined with increased cortisol production and cytokine release as a result of systemic stress from infections.

Thrombohemorrhagic disorders are the main cause of morbidities and mortalities of essential thrombocythemia (ET), which are typically observed at age 50–60 years and rarely encountered in adolescence or childhood. Recently, anagrelide, a quinazinolone derivative, has been used as a therapeutic agent for ET. Although it is used to reduce platelet count, its cardiotoxicity has been reported. Here, we present an 18-year-old boy with ET who was treated with anagrelide and developed acute myocardial infarction. This was presumed to be an effect of anagrelide administration and, specifically, damage to the coronary arterial endothelial cell exacerbated by ET.

Climatic variability in the Andean regions of Colombia is high, both spatially and temporally. It should be analyzed in the short and long term, depending on the information available. This type of spatio-temporal analysis generates tools for environmental planning and management in urban areas. Given the high complexity of the meteorological processes that occur in the Andean region and in the tropics, these must be studied, understood and disseminated. This research focuses on a diagnosis of the diurnal cycle, the analysis of the monthly structure of precipitation and rain events, based on information collected from ground stations located in the city of Manizales, Caldas (Colombia), which contributes to the estimation of the city’s design storm. Results show a strong influence of the Intertropical Confluence Zone (ITCZ) on intra-annual city rain behavior: intra-daily, there are significant variations in precipitation across the city; and throughout the day, it rains the least in the morning and the most at night. Recorded rain events are intense, with average durations of 20 minutes, confirming the high spatial-temporal variability. The dimensionless pattern of the observed rainstorms are the basis for the design storm for the city’s hydraulic infrastructures.

SARS-COV-2 infection can be asymptomatic or mildly symptomatic. The effect of chemotherapy on an asymptomatic infected patient is unknown. Three hundred-thirty-four and 56 NFS were performed as screening for SARS-CoV-2 infection in 247 and 34 pediatric patients undergoing chemotherapy and stem cell transplantation, respectively. NFS was positive in 10 patients. All positive patients withdrew from chemotherapy. Nine patients became negative. One patient is still positive after 38 days.The identification of asymptomatic SARS-COV-2 infection is important to reduce the hospital spread of infection. Further studies are needed to define the least risky management of chemotherapy in asymptomatic SARS-CoV-2 patients.

Background: 6-Mercaptopurine (6-MP) is the most frequently used chemotherapy agent in the management of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Skewed drug metabolism can decrease the effectiveness of 6-MP and result in unnecessary toxicities. Current guidelines suggest holding or lowering 6-MP doses with toxicity; however, this approach results in decreased intensity of 6-MP treatment, potentially risking disease relapse. Allopurinol can alter 6-MP metabolism to maximize therapeutic effects while reducing adverse toxicities. Methods: This single institution, retrospective cohort study, quantified the incidence of mercaptopurine related toxicities and the number of mercaptopurine metabolite shunters. For those patients started on allopurinol, we collected clinical follow up information. Results: Of 42 eligible patients, 74% and 88% had at least one episode of hypoglycemia and elevated alanine aminotransferase (ALT), respectively. Mercaptopurine metabolite data were available in 66% of our patients. 6-methylmercaptopurine nucleotide (6-MMPN) levels were >10 000 in 55% of the cohort, suggesting 6-MP shunting. Allopurinol was initiated for metabolite and laboratory derangements in 12 of 23 shunters. All patients who received allopurinol had resolution of toxicities. Discussion: In our population of children and young adults treated for ALL and LL, we found a high incidence of shunters, many with associated toxicities. The patients who received allopurinol in combination with scheduled chemotherapy showed reversal of undesired toxicities, suggesting combination therapy may be beneficial for certain patients. Based on our institutional experience, we propose an algorithm to incorporate allopurinol into chemotherapy regimens for patients with ALL or LL who have inappropriate 6-MP metabolism.

Dirac relativistic partial wave analysis has been employed to analyze the angular distributions and critical minima along with maximum spin polarization for the elastic scattering of electrons from copper atoms over the energy range 1 - 2000 eV. Integrated elastic, inelastic, total and momentum transfer cross sections have also been calculated. This work uses a complex electron-atom optical potential that includes static, exchange, correlation-polarization and absorption potentials. Comparison of our calculations with the available experimental data and other theoretical calculations show a satisfactory agreement. As far as we are concern, critical minima and corresponding maximum spin polarization points have not yet been reported in literature.

Raspberry Pi (RPi) is a well known single-board computer natively equipped with a Linux-based operating system, Raspbian, and a powerful programming language, Python. In this work, we propose an integrated project on physics and computer science exploiting RPi and Python: a set of lab activities, coding, and discussion related to the study of charging and discharging phases of a capacitor in an RC circuit. In our simple experiments, entirely computer-controlled, the RPi and Python scripts are used to: (i) apply a known constant voltage to the circuit at a desired time; (ii) measure the voltage on selected circuit elements as a function of time; (iii) evaluate and analyze experimental data. This approach is based on inexpensive hardware and open source software. It allows a hands-on experience with electric circuits and with dedicated examples of Python coding. The codes involve Python modules such as Numpy, Scipy, and Matplotlib that prove to be easy to use and efficient for our goals, supporting the choice of Python language for further study or research tasks.  

SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.

In this paper, we use the Hirota bilinear method to nd the N-soliton solution of a (3+1)-dimensional generalized Kadovtsev-Petviashvili equation. Then, we obtain the T-order breathers of the equation, and combine the long-wave limit method to give the M-order lumps. Resorting to the extended homoclinic test technique, we obtain the breather-kink solutions for the equation. Last, the interaction solution composed of the K-soliton solution, T-breathers and M-lumps for the (3+1)-dimensional generalized KP equation is constructed.

In this paper, we show a regularity criteria for three dimensional nematic liquid crystal flows. More precisely, we prove that the strong solution $(u,d)$ can be extended beyond $T$, provided $\nabla u_{3}\in{L^{p}(0,T; L^{q}(\mathbb{R}^{3}))}$, $\frac{2}{p}+\frac{3}{q}\leq{\frac{19}{12}+\frac{1}{2q}}(\frac{30}{19}3)$ with some conditions about the orientation field $\nabla_{h}d\in{L^{\alpha}(0,T; L^{\beta}(\mathbb{R}^{3}))}$, $\frac{2}{\alpha}+\frac{3}{\beta}\leq{\frac{3}{4}+\frac{1}{2\beta}}(\beta>{\frac{10}{3}})$.

The spatiotemporal dynamics for general reaction-diffusion systems of Brusselator type under the homogeneous Neumann boundary condition is considered. It is shown that the reaction-diffusion system has a unique steady state solution. For some suitable ranges of the parameters, we prove that the steady state solution can be a codimension-2 Turing-Hopf point. To understand the spatiotemporal dynamics in the vicinity of the Turing-Hopf bifurcation point, we calculate and analyze the normal form on the center manifold by analytical methods. A wealth of complex spatiotemporal dynamics near the degenerate point are obtained. It is proved that the system undergoes a codimension-2 Turing-Hopf bifurcation. Moreover, several numerical simulations are carried out to illustrate the validity of our theoretical results.

La cattiva gestione delle attività antropiche è una fra le  principali cause della contaminazione delle matrici ambientali. Negli ultimi anni, Il crescente interesse per l’ambiente e per la sostenibilità ha portato alla necessità di adottare nuovi approcci e favorire la bonifica delle matrici ambientali. Tra i processi disponibili, trova applicazione la bioremediation  ed in particolare il biosparging che, tramite processi di natura biologica,  permette la degradazione dei composti indesiderati nell’ambiente. Il biosparging è particolarmente adatto per la rimozione degli idrocarburi. Il presente studio riporta l'analisi di un caso studio di un sito contaminato da idrocarburi policiclici aromatici (IPA) e idrocarburi di petrolio (TPHs), in cui, grazie all’utilizzo combinato di aria e specifici bioattivatori e nutrienti, si sono ottenute alte efficienze di abbattimento sia nel terreno che in falda.  

The article investigates the efficacy of gemini surfactant/polymer/nanoparticle flooding on chemical EOR. Initially, physicochemical behavior of aqueous chemical fluids were investigated via interfacial tension reduction, wettability alteration, adsorption, viscosity moderation and oil displacement experiments. During compositional analysis, Cartesian model with specified grid properties, injection flow-rate, well pattern, and rock-fluid characteristics was developed using CMG-STARS tool. Contour map analyses showed that oil saturation decreased from ~80% (initial) to 31.96%, 30.68% and 29.30% after {14-6-14 GS + chase water}, {14-6-14 GS + PHPA + chase water} and {14-6-14 GS + PHPA + SiO2 chase water} flooding respectively. Tertiary recoveries of 15-19% were achieved, depending on injected fluid composition. Experimental data were history matched via CMOST tool to achieve good matching of simulated results. The CMG flooding simulator provides a holistic approach to investigate oil displacement profiles, assess flooding recovery capabilities with near-accuracy and predict the feasibility of proposed chemical EOR projects.

EP RoundsA 24-year-old male with no past medical history presents to an urgent care center with palpitations. Four days prior he noticed that his heart rate was elevated and sometimes irregular which he recorded on his fitness watch. He had associated intermittent diaphoresis and dyspnea with exertion. Initial ECG obtained is shown in Figure 1A. He was instructed to follow up with a cardiologist. Transthoracic echocardiogram (TTE) obtained in the office demonstrated global left ventricular (LV) dysfunction with an ejection fraction (EF) of 35%. After being sent to the hospital, administration of intravenous amiodarone terminated the patient’s tachycardia and a subsequent ECG was obtained (Figure 1B). Repeat TTE showed normalization of the EF to 55% and cardiac magnetic resonance imaging (cMRI) demonstrated a normal LV without evidence of myocardial pathology. What is the most likely diagnosis of the tachycardia? What is the etiology of the abnormalities seen in the patient’s ECG as shown in Figure 1A? What is the appropriate management for this patient?

Cardiac leiomyosarcoma is an extremely rare tumor with a poor prognosis. We reported an 18- year-old girl with a left atrial leiomyosarcoma extending to right lower pulmonary veins. We performed complete tumor excision by the right anterolateral mini-thoracotomy approach using minimally invasive techniques. After pathological confirmation of the tumor, right lower lobectomy was performed with the same incision one week later to prevent a recurrence. Although no tumor remnant was found in the lobectomy specimen, adjuvant chemotherapy was started. No recurrence was detected during the 12-month follow-up.

Predation can take unexpected turns. For instance, various invertebrate species - most commonly spiders - may prey on tetrapods. Here, we report observations of spiders (Sparassidae, Olios sp.) preying on amphibians (Hyperoliidae, Heterixalus andrakata) in north-eastern Madagascar. To do so, the spiders built highly-specialized traps by weaving two leaves together. Four cases by different individuals of the same species show that spiders hide at the rear end of the trap. One case reports the feeding on a small frog caught inside the trap. Previous reports on amphibian predation by spiders describe opportunistic and indiscriminate predation behaviour by generalist ground-dwelling or aquatic spiders. The only more targeted cases concern large orb-weaver spiders building large webs that may serve as an effective trap for small vertebrates, but those only make up a small percentage of prey compared to insects. In contrast, the novel traps type reported here seems to be solely targeted at catching amphibians seeking shelter during the daytime. We thus report systematic trapping of amphibian by spiders, a newly recorded behaviour.

Background: Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. Objective: To study the role of IL-17A, CXCL13 and lymphotoxin (LT) in eLT formation in NPs. Methods: The expression of CXCL13 and LT as well as their receptors, and the phenotypes of stromal cells in NPs were studied by flow cytometry, immunostaining, and RT-PCR. Purified nasal stromal cells and polyp B cells were cultured and a murine model with nasal type 17 inflammation was established for the mechanistic study. Results: Excessive CXCL13 production was found in NPs and correlated with enhanced IL-17A expression. Stromal cells, with an expansion of CD31-Pdpn+ fibroblastic reticular cell (FRC) type, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1β2 in NPs with eLTs. CXCL13 upregulated LTα1β2 expression on polyp B cells, which in turn promoted CXCL13 production from polyp B cells and nasal stromal cells. LTα1β2 induced expansion of FRCs and CD31+Pdpn+ lymphoid endothelial cells, corresponding to the phenotypic characteristic of stromal cells in NPs with eLTs. IL-17A gene knockout, and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model. Conclusion: We identified an important role of IL-17A-induced stromal cell remodeling in the initiation, and crosstalk between B and stromal cells via CXCL13 and LTα1β2 in the enlargement of eLTs in NPs.

Reaction-diffusion equations are often used in epidemiological models. In this paper, we generalize the algorithm of Meerschaert and Tadjeran for fractional advection-dispersion flow equations to a coupled system of fractional reaction-diffusion like an equation that arises from vector bourne disease modeling.

COVID-19 in a child with severe aplastic anemiaYunus Murat Akçabelen1, Ayça Koca Yozgat1, Aslı Nur Parlakay2, Nese Yarali11 Department of Pediatric Hematology, Ankara City Hospital Children’s Hospital, Turkiye2 Department of Pediatric Infectious Disease, Ankara City Hospital Children’s Hospital, TurkiyeArticle type: Letter to the editörRunning Title: COVID-19 in pediatric aplastic anemiaKey words: COVID-19, children, aplastic anemiaDisclosures: noneWord counts: 625

A document by Vladimir Giménez Rivera. Click on the document to view its contents.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 (COVID-19). It has fatality rate that floats from 5 to 15% and the symtoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. Thus, we propose to pharmacologically block the kallicrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.

A novel bat coronavirus (2019-nCoV) caused an outbreak of infectious pneumonia termed COVID-19 in the world. This reminds us of another notorious bat coronavirus, SARS-CoV, which mysteriously broke out in China 17 years ago and killed nearly 800 people worldwide. A key to its efficient human attack is adopting angiotensin-converting enzyme 2 (ACE2) as the receptor. The relationship between 2019-nCoV and SARS-CoV has aroused much public concern. To our surprise, we found that the two CoV lineages may frequently exchange their genetic materials through homologous recombination. Particularly 2019-nCoV might thereby acquire the receptor-binding domain from the SARS-CoV clade, enabling it to make use of ACE2 as well and thus spread rapidly in humans. Our findings suggest the accomplice role of a virus of SARS-CoV clade in COVID-19 and warn of the possible emergence of more mosaic CoVs capable of launching severe epidemic.

Background and Purpose: The emergence of new synthetic cathinones continues to be a matter of public health concern. In fact, they are quickly replaced by new structurally related alternatives. The main goal of the present study was to characterize the pharmacological profile, the psychostimulant and rewarding properties of novel synthetic cathinones differing in its amino terminal substitution. Experimental Approach: Rat brain synaptosomes were used for [3H]dopamine uptake experiments. HEK293 transfected cells (hDAT, hSERT, hOCT; human dopamine, serotonin and organic cation transporter, respectively) were also used for [3H]monoamine uptake and transporter binding assays. Molecular docking allowed to investigate the effect of the amino substitutions on the biological activity. Locomotor activity experiments and conditioned place preference paradigm were used in order to study the psychostimulant and rewarding effects in mice. Key Results: All compounds tested are potent inhibitors of DAT with very low affinity for SERT, hOCT-2 and -3, and their potency inhibiting DAT increased when the amino-substituent expanded from a methyl- to either an ethyl-, a pyrrolidine- or a piperidine-ring. Regarding the in vivo results, all the compounds induced an increase in locomotor activity and possess rewarding properties. Results also showed a significant correlation between predicted binding affinities by molecular docking and affinity constants (Ki) for hDAT. Conclusions and Implications: Our study demonstrated the role of the amino-substituent in the pharmacological profile of novel synthetic cathinones and provides the first evidence that some of them are potent DAT inhibitors and able to induce psychostimulant and rewarding effects in mice.

Abstract The objective of this study was to describe early respiratory outcomes of asymptomatic COVID-19 patients after cardiac surgery. In this retrospective clinical study (case series) we reviewed and analyzed patient clinical data of 25 covid-19 asymptomatic patients that underwent urgent or emergent cardiac surgery between February 29 and April 10, 2020 in Tehran Heart Center Hospital. Median of age was 63 years (IQR, 52-67), Euro SCORE 7.50 (IQR, 6.5-8.5) and body mass index 26.3 (IQR, 22.5-28.6). 68% of patients had one or more comorbidities. Hypertension (56%) was the most common followed by Diabetes type 2 (40%). Off-pump cardiac surgery was done in 4 patients and on-pump on 21 patients with median CPB time of 85 minutes (IQR, 50-147.50). Median anesthesia time was 4.5 hours (IQR, 4-5). Median oxygen index and Fio2 on ventilator were 10 cmH20 (IQR, 9.5-10.5) and 0.64(IQR, 0.60-0.64) respectively. Median pao2/Fio2 was 231(IQR, 184-261). There was one case of extubation failure. The Median intubation time and length of ICU stay were 13 hours (IQR, 9.5-18) and 3 days (IQR, 2-4) respectively. Overall mortality was 16%. Readmission rate to ICU was 16% with. In this group respiratory outcome was worse with median Pao2/Fio2 84.5 (75-122), oxygen index of 4.38(IQR, 3.77-5.1) and morality rate of 75%. Conclusion: Based on the results of this study, very early post-cardiac surgery respiratory outcomes in asymptomatic COVID-19 patients are apparently smooth; nonetheless, readmission to the ICU is high. Overall respiratory outcomes are poor especially for those who readmitted to ICU.