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Using Pharmacokinetic Modeling and Electronic Health record Data to Predict Clinical and Safety Outcomes after Methylprednisolone Exposure during Cardiopulmonary Bypass in Neonates

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Congenital Heart Disease 2023年第3期18卷 295-313页

作者： Henry P.Foote Huali Wu Stephen J.Balevic Elizabeth J.Thompson Kevin D.Hill Eric M.Graham Christoph P.Hornik karan r.kumar Department of Pediatrics Duke UniversityDurhamUSA Duke Clinical research Institute DurhamUSA Department of Pediatrics Medical University of South CarolinaCharlestonUSA

Background:Infants undergoing cardiac surgery with cardiopulmonary bypass(CPB)frequently receive intraoperative methylprednisolone(MP)to suppress CPB-related inflammation;however,the optimal dosing strategy and efficacy of MP remain ***:We retrospectively analyzed all infants under 90 days-old who received intra-operative MP for cardiac surgery with CPB from 2014–2017 at our *** combined real-world dosing data from the electronic health record(EHr)and two previously developed population pharmacokinetic/pharmacodynamic models to simulate peak concentration(Cmax)and area under the concentration-time curve for 24 h(AUC24)for MP and the inflammatory cytokines interleukin-6(IL-6)and interleukin-10(IL-10).We evaluated the relationships between post-operative,safety,and other clinical outcomes obtained from the EHr with each predicted exposure using non-parametric ***:A total of 142 infants with median post-natal age 8(interquartile range[IQr]:5,37)days received a total dose of 30(19,49)mg/kg of ***(8%)died,37(26%)met the composite post-operative outcome,114(80%)met the composite safety outcome,and 23(16%)had a major *** median Cmax and AUC24 IL-6 exposure was significantly higher for infants meeting the composite post-operative outcome and those with major *** median Cmax and AUC24 MP exposure was significantly higher for infants requiring *** exposure was associated with death or other safety ***:Pro-inflammatory IL-6,but not MP exposure,was associated with post-operative organ dysfunction,suggesting current MP dosing may not adequately suppress IL-6 or increase IL-10 to impact clinical *** study will be required to define the optimal exposure-efficacy and exposure-safety profiles in these infants.

关键词： Neonates cardiopulmonary bypass methylprednisolone exposure

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Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

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Oncology research 2024年第5期32卷 877-897页

作者： karan WADHWA PAYAL CHAUHAN SHOBHIT kumar rAKESH PAHWA rAVINDEr VErMA rAJAT GOYAL GOVIND SINGH ArCHANA SHArMA NEHA rAO DEEPAK KAUSHIK Department of Pharmaceutical Sciences Maharshi Dayanand UniversityRohtak124001India Department of Pharmaceutical Technology Meerut Institute of Engineering and Technology(MIET)NH-58Delhi-Roorkee HighwayMeerut250005India Institute of Pharmaceutical Sciences Kurukshetra UniversityKurukshetra136119India Department of Pharmaceutical Sciences Chaudhary Bansi Lal UniversityBhiwani127021India MM College of Pharmacy Maharishi Markandeshwar(Deemed to be University)Mullana-AmbalaHaryana133207India Delhi Pharmaceutical Sciences and research University(DIPSAr) Delhi Pharmaceutical Sciences and Research UniversityNew Delhi110017India

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive *** high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the ***:recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation ***:relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several ***:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM *** of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

关键词： Glioblastoma Brain tumor Blood-brain barrier Liposomes Metallic nanoparticles Nanocarriers

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Understanding rhabdomyolysis induced acute kidney injury in patients with COVID-19

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World Journal of Virology 2024年第4期13卷 139-142页

作者： Alexander Ikanović karan Varshney School of Medicine Deakin UniversityWaurn PondsVIC 3216Australia School of Public Health and Preventive Medicine Monash UniversityMelbourneVIC 3004Australia

This work comments on an article published in the recent issue of the World Journal of *** is a complex condition with symptoms such as myalgia,changes to urination,and *** the potential for substantial kidney impairment,it has also been shown to be a severe complication of coronavirus disease 2019(COVID-19).To date,various theoretical explanations exist for the development of rhabdomyolysis induced acute kidney injury(rIAKI)in COVID-19 infection,including the accumulation of released striated muscle myoglobin in the urine(myoglobinuria).In their article,they(2024)demonstrate in a retrospective study that rIAKI in COVID-19 patients tended to have elevated levels of C-reactive protein,ferritin,and *** patients also had poorer overall prognoses when compared to COVID-19 patients who have acute kidney injury(AKI)due to other *** is clear from these findings that clinicians must closely monitor and assess for the presence of rhabdomyolysis in COVID-19 patients who have developed ***,additional research is required to further understand the mechanisms behind the development of rIAKI in COVID-19 patients in order to better inform treatment guidelines and protocols.

关键词： COVID-19 rhabdomyolysis Acute kidney injury Mortality Complication

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Finite Deformation, Finite Strain Nonlinear Dynamics and Dynamic Bifurcation in TVE Solids with rheology

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Applied Mathematics 2024年第1期15卷 108-168页

作者： karan S. Surana Sri Sai Charan Mathi Department of Mechanical Engineering University of Kansas Lawrence US

This paper presents a mathematical model consisting of conservation and balance laws (CBL) of classical continuum mechanics (CCM) and ordered rate constitutive theories in Lagrangian description derived using entropy inequality and the representation theorem for thermoviscoelastic solids (TVES) with rheology. The CBL and the constitutive theories take into account finite deformation and finite strain deformation physics and are based on contravariant deviatoric second Piola-Kirchhoff stress tensor and its work conjugate covariant Green’s strain tensor and their material derivatives of up to order m and n respectively. All published works on nonlinear dynamics of TVES with rheology are mostly based on phenomenological mathematical models. In rare instances, some aspects of CBL are used but are incorrectly altered to obtain mass, stiffness and damping matrices using space-time decoupled approaches. In the work presented in this paper, we show that this is not possible using CBL of CCM for TVES with rheology. Thus, the mathematical models used currently in the published works are not the correct description of the physics of nonlinear dynamics of TVES with rheology. The mathematical model used in the present work is strictly based on the CBL of CCM and is thermodynamically and mathematically consistent and the space-time coupled finite element methodology used in this work is unconditionally stable and provides solutions with desired accuracy and is ideally suited for nonlinear dynamics of TVES with memory. The work in this paper is the first presentation of a mathematical model strictly based on CBL of CCM and the solution of the mathematical model is obtained using unconditionally stable space-time coupled computational methodology that provides control over the errors in the evolution. Both space-time coupled and space-time decoupled finite element formulations are considered for obtaining solutions of the IVPs described by the mathematical model and are presented i

关键词： Thermoviscoelasticity rheology Memory Finite Strain Finite Deformation Nonlinear Dynamics Dynamic Bifurcation Ordered rate Theories

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Ameliorative Effects of Paclobutrazol via Physio-Biochemical and Molecular Manifestation in rice under Water Deficit Stress

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rice science 2024年第5期31卷 603-616,I0065页

作者： Chirag MAHESHWArI Nitin kumar GArG Archana SINGH Aruna TYAGI Indian Council of Agricultural research-Indian Agricultural research Institute New Delhi 110012India Sri karan Narendra Agricultural University JobnerRajasthan 303329India

To comprehensively explore the physio-biochemical and molecular changes of paclobutrazol(PBZ) at the ideal dose under water deficit stress(WDS) conditions, we investigated the effects of 100 mg/kg PBZ applied via drenching on various physio-biochemical and molecular parameters in three rice varieties(N22, Ir64, and Ir64 DTY1.1) under both mild [75%-80% relative water content(rWC)] and severe(60%-65% rWC) WDS conditions. The results showed that PBZ treatment positively influenced the physio-biochemical parameters, significantly increasing dry matter(16.27%-61.91%), rWC(6.48%-16.34%), membrane stability index(4.37%-10.35%), and total chlorophyll content(8.97%-29.09%) in the rice varieties under both mild and severe WDS. Moreover, PBZ treatment reduced drought susceptibility(0.83-0.95) and enhanced drought tolerance efficiency(60.92%-86.78%), indicating its potential as a stress-mitigating agent. Global methylation analysis revealed changes in DNA methylation patterns, indicating the regulatory influence of PBZ on gene expression. The expression analysis of genes involved in the diversification of geranylgeranyl pyrophosphate towards the biosynthesis of abscisic acid, gibberellin acid, and chlorophyll showed alterations in their expression levels, suggesting the involvement of PBZ in the isoprenoid pathway. Overall, this study provides valuable insights into the potential mechanisms by which PBZ modulates physiological and molecular responses in rice plants under WDS. The findings highlight the importance of PBZ as a promising agent for enhancing drought tolerance in rice and offer valuable information for future research in crop stress management.

关键词： rice paclobutrazol drought stress abscisic acid gibberellic acid

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Lean body mass index is a marker of advanced tumor features in patients with hepatocellular carcinoma

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World Journal of Hepatology 2024年第3期16卷 393-404页

作者： Andrew Scott deLemos Jing Zhao Milin Patel Banks Kooken karan Mathur Hieu Minh Nguyen Areej Mazhar Maggie McCarter Heather Burney Carla Kettler Naga Chalasani Samer Gawrieh Department of Medicine Atrium HealthCharlotteNC 28204United States Center for Outcomes research and Evaluation Atrium HealthCharlotteNC 28204United States Department of Medicine Indiana University School of MedicineIndianapolisIN 46202United States Center for Health System Sciences(CHASSIS) Atrium HealthCharlotteNC 28204United States Department of Medicine Northwestern University Feinberg School of MedicineChicagoIL 60611United States Department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisIN 46202United States Department of Gastroenterology and Hepatology Indiana University School of MedicineIndianapolisIN 46202United States

BACKGrOUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its ***,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival *** is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight *** To explore the relationship between BMI and survival in patients with cirrhosis and *** This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical *** and tumor characteristics were extracted manually from medical records of each institutions'cancer *** were stratified according to BMI classes:rweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI *** performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and *** A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as *** three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population *** each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),*** patients with a BMIre included in the lean *** the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were *** three BMI classes did not differ by age,MELD,or Child-Pugh *** hepatitis C was the dominant etiology in lea

关键词： Hepatocellular carcinoma Cirrhosis Obesity Body mass index class Sarcopenia Chronic hepatitis C

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Development of prosthetic arm using body actioned SEMG signals

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Journal of Innovative Optical Health Sciences 2016年第6期9卷 58-65页

作者： karan Veer Tanu Sharma Amod kumar EIED Department Thapar UniversityPatialaIndia CSED Department Global College of EngineeringKhanpur KuiIndia Chief Scientist CSIO-CSIRChandigarhIndia

People's working capability is badly affected when they sufer an amputated *** replacements with prosthetic devices to get a satisfactory level of performance for essential functions with the currently available prosthetic technology are very *** arm prostheses are becoming popular because they are operated by a natural contraction of intact ***,SEMG based artifdal arm was *** system cousists of diferent electronic and mechanical assemblies for operation of hand utilizing microcontroller in order to have minimum signal loss during its *** the hep of relay switching connected to low power DC motor,system is capable of opening and closing of grip according to individual wish.

关键词： SEMG electrodes variable gripping myoelectric controls electronic interface signals processing.

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Effect of transverse compression on the residual tensile strength of ultrahigh molecular weight polyethylene(Dyneema~? SK-76) yarns

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Defence Technology（防务技术） 2020年第1期16卷 35-42页

作者： karan Shah Subramani Sockalingam McNAIr Center for Aerospace Innovation and research University of South CarolinaSCUSA Department of Mechanical Engineering University of South CarolinaSCUSA

Ballistic impact induces complex stress states on fiber-based armor *** impact fibers undergo multiaxial loading which includes axial tension,axial compression,transverse compression,and transverse *** co mpression induced by the projectile leads to permanent defo rmation and fibrillation of fibers resulting in degradation of material tensile *** work(Sockalingam et *** res.J 2018) has shown a reduction of 20% in the tensile strength of Dyneema~? SK76 single fibers subjectet to 77% nominal transverse compressive *** investigation of quasistatic transverse compression on Dyneema~? SK-76 yarns,unconstrained in the lateral direction,indicate an average of 4% reduction in tensile strength of yarns compressed to 77% nominal *** this work we use finite element modeling techniques to understand the difference in residual tensile strength between single fibers and yarns observed in laterally unconstrained transverse compression *** element study of the transverse compression response of single fibers and yarns indicate that local strains developed in fibers within the yarn are much lower than the local strains developed in single fibers subjected to a given nominal strain and may explain the less reduction in strength observed in yarns.

关键词： Polymer fibers Compression Tensile strength

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Spectral and mathematical evaluation of electromyography signals for clinical use

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International Journal of Biomathematics 2016年第6期9卷 263-272页

作者： karan Veer Electrical and Instrumentation Engineering Department Thapar University Patiala 174001 India

The surface electromyography （SEMG） is a complicated biomedical signal, generated during voluntary or involuntary muscle activities and these muscle activities are always controlled by the nervous system. In this paper, the processing and analysis of SEMG signals at multiple muscle points for different operations were carried out. Myoelectric signals were detected using designed acquisition setup which consists of an instrumenta- tion amplifier, filter circuit, an amplifier with gain adjustment. Fhrther, Labview^-based data programming code was used to record SEMG signals for independent activities. The whole system consists of bipolar noninvasive electrodes, signal acquisition protocols and signal conditioning at different levels. This work uses recorded SEMG signals generated by biceps and triceps muscles for four different arm activities. Feature extraction was done on the recorded signal for investigating the voluntary muscular contraction relationship for exercising statistic measured index method to evaluate distance between two independent groups by directly addressing the quality of signal in separability class for different arm movements. Thereafter repeated factorial analysis of variance technique was implemented to evaluate the effectiveness of processed signal. From these results, it demonstrates that the proposed method can be used as SEMG feature evaluation index.

关键词： Electromyogram muscle movements ANOVA noninvasive electrode statis-tics upper arm.

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Fresh or aged:Short time anodization of titanium to understand the influence of electrolyte aging on titania nanopores

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Journal of Materials Science & Technology 2022年第24期119卷 245-256页

作者： Tianqi Guo Saso Ivanovski karan Gulati The University of Queensland School of DentistryHerston QLD 4006Australia

Electrochemical anodization(EA)is a simple and cost-effective technique to fabricate controlled nanostructures on Ti substrates,such as TiO_(2)nanotubes and *** aging of organic EA electrolytes(repeated EA using non-target Ti before EA of target Ti)is recognized to influence the characteristics of the anodized ***,there is limited information about how surface topography and electrolyte aging dictate the formation and characteristics of the anodized *** the current study,short-time EA(starting at 10 s)of micro-machined Ti substrates was performed with electrolytes of various ages(fresh/unused,15 h aged and 30 h aged),followed by evaluation of the TiO_(2)nanopores(TNPs)characteristics in terms of topography,chemistry,stability and protein *** results showed that aligned TNPs were obtained earlier(120 s)with fresh electrolyte as compared to the aged electrolyte EA(600 s).Interestingly,TNPs fabricated using fresh electrolyte(at lower EA times)showed favorable wettability,protein adhesion capacity and mechanical properties compared with aged electrolyte *** findings of the study demonstrate how nanopore formation differs between fresh and aged electrolytes when performing EA of micro-machined Ti,which provides an improved understanding of electrolyte aging and its influence on anodized nanostructures.

关键词： Titanium Titania nanopores Electrochemical anodization Electrolyte aging Surface modification

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