Hydroxychloroquine-azithromycin,doubase C,and QTc prolongation in congolese patients with COVID-19:Myth or reality?

BACKGROUND QTc interval prolongation with an increased risk of torsade de pointes(Tsd)has been described in coronavirus disease 2019(COVID-19)patients treated with hydroxychloroquine(HCQ)and azithromycin(AZI)in Western countries.In the DR Congo,few studies have evaluated the safety of this association or proposed new molecules.AIM To determine the incidence of QTc prolongation and Tsd in COVID-19 patients treated with HCQ-AZIs vs doubase C(new molecule).METHODS In present randomized clinical trial,we have included patients with mild or moderate COVID-19 treated with either HCQ-AZI or doubase C.Electrocardiogram(ECG)changes on day 14 of randomization were determined based on pretreatment tracing.Prolonged QTc was defined as≥500 ms on day 14 or an increase of≥80 ms compared to pretreatment tracing.Patients with cardiac disease,those undergoing other treatments likely to prolong QTc,and those with disturbed ECG tracings were excluded from the study.RESULTS The study included 258 patients(mean age 41±15 years;52%men;3.4%diabetics,11.1%hypertensive).Mild and moderate COVID-19 were found in 93.5%and 6.5%of patients,respectively.At baseline,all patients had normal sinus rhythm,a mean heart rate 78±13/min,mean PR space 170±28 ms,mean QRS 76±13 ms,and mean QTc 405±30 ms.No complaints suggesting cardiac involvement were reported during or after treatment.Only four patients(1.5%)experienced QTc interval prolongation beyond 500 ms.Similarly,only five patients(1.9%)had an increase in the QTc interval of more than 80 ms.QTc prolongation was more significant in younger patients,those with high viral load at baseline,and those receiving HCQ-AZI(P<0.05).None of the patients developed Tsd.CONCLUSION QTc prolongation without Tsd was observed at a lower frequency in patients treated with HCQ-AZI vs doubase C.The absence of comorbidities and concurrent use of other products that are likely to cause arrhythmia may explain our results.

Oriental Reed Warblers do not abandon Common Cuckoo chicks during prolonged nestling periods

The Oriental Reed Warbler(Acrocephalus orientalis)is one of the most commonly used hosts for the parasitic Common Cuckoo(Cuculus canorus).However,as hosts that feed unrelated parasitic nestlings may suffer extra reproductive costs,they may be less willing to care for nestlings that have prolonged nestling periods.To test this hypothesis,the duration of feeding by Oriental Reed Warblers under natural conditions for their own nestlings was compared with the duration of feeding under natural conditions for Common Cuckoo nestlings and for artificially prolonged cuckoo nestlings.The results showed that Oriental Reed Warblers did not starve,drive away,or desert any of the nestlings in the experiment,and neither parent was left alone.Our experimental study indicates that both Oriental Reed Warbler parents were willing to care for nestlings with a prolonged nestling period(up to 30 days,twice the average duration time that the Oriental Reed Warblers fed their own chicks in natural conditions).However,further experiments and observations are required in other host bird species to examine whether both parents or one of the parents may exhibit the behavior of abandoning nestlings with a prolonged nestling period.

Recovering from prolonged cardiac arrest induced by electric shock:A case report

BACKGROUND Cardiac arrest(CA)induced by electric shock is a rare occurrence,particularly in cases of prolonged CA.Currently,there is limited literature on similar incidents,and we present a relevant case report.CASE SUMMARY A 27-year-old Asian male man,experiencing respiratory CA due to electric shock,was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions.In the subsequent stages,the patient received multiple organ function protection measures,leading to a successful recovery and eventual discharge from the hospital.CONCLUSION Prolonging resuscitation time can enhance the chances of survival for patients,this study provide valuable insights into the management of electric shock-induced CA.

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients

BACKGROUND Dexmedetomidine and propofol are two sedatives used for long-term sedation.It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation.AIM To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury.METHODS Patients who underwent mechanical ventilation for>72 h were randomly assigned to receive sedation with dexmedetomidine or propofol.The Richmond Agitation and Sedation Scale(RASS)was used to evaluate sedation effects,with a target range of-3 to 0.The primary outcomes were serum levels of S100-βand neuron-specific enolase(NSE)every 24 h.The secondary outcomes were remifentanil dosage,the proportion of patients requiring rescue sedation,and the time and frequency of RASS scores within the target range.RESULTS A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group,respectively.Baseline data were comparable between groups.No significant differences were identified between groups within the median duration of study drug infusion[52.0(IQR:36.0-73.5)h vs 53.0(IQR:37.0-72.0)h,P=0.958],the median dose of remifentanil[4.5(IQR:4.0-5.0)μg/kg/h vs 4.6(IQR:4.0-5.0)μg/kg/h,P=0.395],the median percentage of time in the target RASS range without rescue sedation[85.6%(IQR:65.8%-96.6%)vs 86.7%(IQR:72.3%-95.3),P=0.592],and the median frequency within the target RASS range without rescue sedation[72.2%(60.8%-91.7%)vs 73.3%(60.0%-100.0%),P=0.880].The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance(69.2%vs 50.8%,P=0.045).Serum S100-βand NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation,respectively(all P<0.05).CONCLUSION Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Predicting prolonged postoperative ileus in gastric cancer patients based on bowel sounds using intelligent auscultation and machine learning

BACKGROUND Prolonged postoperative ileus(PPOI)delays the postoperative recovery of gastrointestinal function in patients with gastric cancer(GC),leading to longer hospitalization and higher healthcare expenditure.However,effective monitoring of gastrointestinal recovery in patients with GC remains challenging because of AIM To explore the risk factors for delayed postoperative bowel function recovery and evaluate bowel sound indicators collected via an intelligent auscultation system to guide clinical practice.METHODS This study included data from 120 patients diagnosed with GC who had undergone surgical treatment and postoperative bowel sound monitoring in the Department of General Surgery II at Shaanxi Provincial People's Hospital between January 2019 and January 2021.Among them,PPOI was reported in 33 cases.The patients were randomly divided into the training and validation cohorts.Significant variables from the training cohort were identified using univariate and multivariable analyses and were included in the model.RESULTS The analysis identified six potential variables associated with PPOI among the included participants.The incidence rate of PPOI was 27.5%.Age≥70 years,cTNM stage(Ⅰ and Ⅳ),preoperative hypoproteinemia,recovery time of bowel sounds(RTBS),number of bowel sounds(NBS),and frequency of bowel sounds(FBS)were independent risk factors for PPOI.The Bayesian model demonstrated good performance with internal validation:Training cohort[area under the curve(AUC)=0.880,accuracy=0.823,Brier score=0.139]and validation cohort(AUC=0.747,accuracy=0.690,Brier score=0.215).The model showed a good fit and calibration in the decision curve analysis,indicating a significant net benefit.CONCLUSION PPOI is a common complication following gastrectomy in patients with GC and is associated with age,cTNM stage,preoperative hypoproteinemia,and specific bowel sound-related indices(RTBS,NBS,and FBS).To facilitate early intervention and improve patient outcomes,clinicians should consider these factors,optimize preoperative nutritional status,and implement routine postoperative bowel sound monitoring.This study introduces an accessible machine learning model for predicting PPOI in patients with GC.

超对称Bullough-Dodd模型的prolongation分析

在扭曲仿射代数 A(2 )2 上建立了超对称的 Bullough-Dodd模型 .Prolongation方法的研究表明 ,该模型承认一个 Lax pair,从 Lax意义上证明该模型可积 .另外 ,当该超对称模型的所有费米量为零时 ,该系统就定义了一个新奇的由单标量玻色场指数相互作用构成的可积模型 .这个发现还打破了长久以来的一种认识 :只有 sinh-Gordon和标准Bullough-Dodd模型是 Liouville模型 .

Prolongation Structure of Semi-discrete Nonlinear Evolution Equations

Based on noncommutative differential calculus, we present a theory of prolongation structure for semidiscrete non/inear evolution equations. As an illustrative example, a semi-discrete model of the non/inear SchrSdinger equation is discussed in terms of this theory and the corresponding Lax pairs are also given.

QT prolongation is associated with increased mortality in end stage liver disease

AIM To determine the prevalence of QT prolongation in a large series of end stage liver disease(ESLD) patients and its association to clinical variables and mortality.METHODS The QT interval was measured and corrected for heart rate for each patient,with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females.Multiple clinical variables were evaluated including sex,age,serum sodium,international normalized ratio,creatinine,total bilirubin,beta-blocker use,Model for EndStage Liver Disease(MELD),MELD-Na,and etiology of liver disease. RESULTS Among 406 ESLD patients analyzed,207(51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender(OR = 3.04,95%CI:2.01-4.60,P < 0.001). During the study period,187patients(46.1%) died. QT prolongation was a significant independent predictor of mortality(OR = 1.69,95%CI:1.03-2.77,P = 0.039). In addition,mortality was also associated with viral etiology of ESLD,elevated MELD score and its components(P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation. CONCLUSION QT prolongation was commonly encountered in an ESLD population,especially in males,and served as a strong independent marker for increased mortality in ESLD patients.

Prolongation structure for nonlinear integrable couplings of a KdV soliton hierarchy

In this paper, a new nonlinear integrable coupling system of the soliton hierarchy is presented. Prom the Lax pairs, the coupled KdV equations are constructed successfully. Based on the prolongation method of Wahlquist and Estabrook, we study the prolongation structure of the nonlinear integrable couplings of the KdV equation.

Covariant Prolongation Structure of Konno-Asai-Kakuhata Equation

Based upon the covariant prolongation structures theory, we construct the sl（2, R）×R（p） prolongation structure for Konno-Asai-Kakuhata equation. By taking two and one-dimensional prolongation spaces, we obtain the inverse scattering equations given by Konno et al. and the corresponding Riccati equation. The Baecklund transformations are also presented.

THE PROLONGATION STRUCTURES AND NONLOCAL SYMMETRIES FOR MODIFIED BOUSSINESQ SYSTEM

The Wahlquist-Estabrook （WE） prolongation structures of modified Boussi-nesq （MB） system are studied from the coverings point of view. The realizations and classifications of one-dimensional coverings of this system are obtained completely. More-over the sufficient and necessary conditions for a vector field to be a nonlocal symmetry of this system are also demonstrated in the WE prolongation structures.

Prolongation structure of the variable coefficient KdV equation

The prolongation structure methodologies of Wahlquist-Estabrook [Wahlquist H D and Estabrook F B 1975 J. Math. Phys. 16 1] for nonlinear differential equations are applied to a variable-coefficient KdV equation. Based on the obtained prolongation structure, a Lie algebra with five parameters is constructed. Under certain conditions, a Lie algebra representation and three kinds of Lax pairs for the variable coefficient KdV equation are derived.

Antipsychotic Medication and Risk of QTc Prolongation: Focus on Multiple Medication and Role of Cytochrome P450 Isoforms

Objective: To identify the effects of antipsychotics on QTc prolongation in light of age, gender, antipsychotic combination pattern, antipsychotic doses and cytochrome P450 (CYP) mediation, using large database describing the antipsychotic treatment of patients with schizophrenia in Japan. Methods: Using database of 4176 patients with schizophrenia discharged between April 2004 and March 2005 and receiving outpatient treatment from 526 psychiatric hospitals in Japan. Of the patients, 1437 were included for the analysis. These patients were classified into three groups according to the antipsychotic CPZ-equivalent doses that they received (low, 1 - 299 mg;middle, 300 - 999 mg;and high, ≥1000 mg). QTc intervals ≥ 440 msec were considered prolonged. We reviewed all the package inserts of the antipsychotics used from the website of Pharmaceuticals and Medical Devices Agency. Results: The mean QTc interval of the total patient group was 410.4 ± 23.3 msec. The females had significantly higher QTc values than the males (414.5 ± 24.0 vs. 406.8 ± 22.2 msec, respectively;p 0.05). Logistic regression analysis revealed that female gender (odds ratio [OR] = 1.83;95% CI: 1.28 - 2.56), CYP3A4-metabolized drugs (OR 1.56;95% CI: 1.05 - 2.30) were associated with an increased risk of QTc prolongation. Conclusion: The co-prescription of CYP3A4-mediated antipsychotic drugs should be carefully considered in females due to potential risk of QTc prolongation. Further studies of the cardiovascular safety of antipsychotics are warranted in patients receiving multiple medications.

The Prolongation Structures for the System of the Reaction-Diffusion Type

Equations of the reaction-diffusion type are very well known and have been extensively studied in many research areas. In this paper, the prolongation structures for the system of the reaction-diffusion type are investigated from theory of coverings. The realizations and the classifications of the one-dimensional coverings of the system are researched. And the corresponding conservation law of the one-dimensional Abelian coverings is concluded, which is closely connected with the symmetry of the system by Noether theorem.

Use of Human Embryonic Stem Cell-Derived Cardiomyocyte Clusters to Assess Potential for Chronic Treatment with Compounds to Cause QT Prolongation

Drug-induced QT prolongation is a serious clinical issue in developing novel drug candidates and marketing drugs. A major cause of QT prolongation is direct inhibition of human ether-à-go-go-related gene (hERG) channels. Reduction in repolarization-related channel expression levels on plasma membranes is another mechanism that induces QT prolongation. Recently, we established a system for assessing the risk of QT prolongation by using human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indicator of drug-induced QT interval prolongation. Here, we examined whether this system was able to detect FPDc prolongation caused by pentamidine or probucol, both of which can induce QT prolongation after long-term treatment. hES-CMCs were treated with pentamidine or probucol, and the FPDc of the same clusters was measured 10 min, 4 h, and 24 h after the start of treatment. Concentration-dependent FPDc prolongation was observed at 24 h, but not at 10 min, with pentamidine or probucol treatment. These results suggest that the hES-CMC-based assessment system can be used to detect both acute (at 10 min) and delayed (at 24 h) QT prolongation risk on the same platform by simple alteration of the extended culture period.

Covariant Prolongation Structure, Conservation Laws and Soliton Solutions of the Gross-Pitaevskii Equation in the Bose-Einstein Condensate

In this paper, we investigate the Gross-Pitaevskii (GP) equation which describes the propagation of an electron plasma wave packet with a large wavelength and small amplitude in a medium with a parabolic density and constant interactional damping by the Covariant Prolongation Structure Theory. As a result, we obtain general forms of Lax-Pair representations. In addition, some hidden structural symmetries that govern the dynamics of the GP equation such as SL(2,R), SL(2,C), Virasoro algebra, SU(1,1) and SU(2) are unearthed. Using the Riccati form of the linear eigenvalue problem, infinite number of conservation laws of the GP equation is explicitly constructed and the exact analytical soliton solutions are obtained by employing the simple and straightforward Hirota’s bilinear method.

Effect of natural prolongation with geological features on maritime delimitation

The United Nations Convention on the Law of the Sea entitled the coastal States to naturally extend the continental shelf, which has caused more drastic disputes of maritime delimitation. This paper devotes to clarifying the significant concept of natural prolongation through an effect method combing the legal principles and technical analysis. Firstly, the classic samples with respect of the development of geological features are traced. Based on these samples, the classification with a model is proposed in order to affirm the concept＇s significance under certain geomorphologic situations. Lastly, scientific analysis is used to present two potential prolongation situations and emphasize that all the technical analysis on maritime delimitation should be complied with international law and protect the common interest of all the mankind.

Covariant Prolongation Structure of Coupled Inhomogeneous Nonlinear Schrodinger Equation

We investigate the coupled inhomogeneous nonlinear Schrodinger equation by the covariant prolongationstructure theory, and obtain its Lax's representation. Moreover, we present the corresponding Riccati equations, Backlundtransformation, and one-soliton solution.

Fermionic Covariant Prolongation Structure for a Super Nonlinear Evolution Equation in 2+1 Dimensions

The integrability of a （2＋1）-dimensional super nonlinear evolution equation is analyzed in the framework of the fermionie covariant prolongation structure theory. We construct the prolongation structure of the multidimen- sional super integrable equation and investigate its Lax representation. Furthermore, the Backlund transformation is presented and we derive a solution to the super integrable equation.