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Development and Application of a Validated UHPLC Method for the Determination of Atropine and Its Major Impurities in Antidote Treatment Nerve Agent Auto-Injectors (ATNAA) Stored in the Strategic National Stockpiles

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Pharmacology & Pharmacy 2017年第1期8卷 15-31页

作者： Cheng H.Yen Adil Mohammad Miah Schneider Salwa K.Poole Bryan Lowry Brenda W.Mc Curdy patrick j.faustino Saeed R.Khan Office of Regulatory Affairs Detroit LaboratoryFood and Drug AdministrationDetroitMIUSA Division of Product Quality Research Office of Testing and ResearchOffice of Pharmaceutical QualityCenter for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringMDUSA

The development and implementation of advanced analytical technologies is essential for extending the expiry for complex drug products stored in the Strategic National Stockpiles. Consequently, a novel Ultra High-Performance Liquid Chromatographic (UHPLC) method has been developed for the analysis of atropine and its respective impurities to support the analytical research platform for auto-injectors. This study is part of a larger research effort to improve the efficiency and broaden the applicability of advanced analytical methods for medical counter-measure medications. The current HPLC compendial methodology for atropine sulfate injection requires an analysis time of 40 minutes for atropine. In comparison, the novel gradient UHPLC method required only 8 minutes to evaluate both atropine and its major pharmaceutical impurities. Improved separation was achieved on a Waters Acquity UHPLC BEH C18 1.7 μm, 2.1 × 100 mm column employing gradient elution of mobile phase solvent A (0.1% H3PO4) and solvent B (0.1% H3PO4, 90% ACN, and 10% H2O). The method was validated according to USP Category I requirements for assay. The daily standard calibration curves were linear over a concentration range from 50 μg/mL to 250 μg/mL with a correlation coefficient of >0.999. The detection limit (LOD) and quantitation limit (LOQ) were 3.9 μg/ml and 13.1 μg/ml, respectively. Resolution results indicate that atropine and the following impurities, degradants and a preservative can also be separated and analyzed using this proposed method: noratropine, 4,4’-di-hy-droxydiphenyl ether, 2,4’-dihydroxydiphenyl ether, 4-bromophenol, 4-hydro-xyatropine, tropic acid, apoatropine HCl, atropic acid, hydroquinone, nitroethane, phenol and catechol. The UHPLC method demonstrated enhanced selectivity and significantly reduced the analysis time when compared with the traditional USP compendial HPLC method. The method was successfully applied to the evaluation of atropine in ATNAA auto-injectors lots fro

关键词： Atropine Sulfate Atropine ATNAA SLEP UHPLC Impurities

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Porous Indium Nanocrystals on Conductive Carbon Nanotube Networks for High-Performance CO2-to-Formate Electrocatalytic Conversion

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Energy & Environmental Materials 2024年第4期7卷 413-421页

作者： Liangping Xiao Rusen Zhou Tianqi Zhang Xiaoxiang Wang Renwu Zhou patrick j.Cullen Kostya (Ken) Ostrikov Department of Physics Research Institute for Biomimetics and Soft Matter Fujian Provincial Key Laboratory for Soft Functional Materials Jiujiang Research Institute Xiamen University School of Chemistry and Physics QUT Centre for Materials Science and QUT Centre for a Waste-Free World Queensland University of Technology(QUT) School of Chemical and Biomolecular Engineering University of Sydney

Ever-increasing emissions of anthropogenic carbon dioxide （CO2） cause global environmental and climate *** by biological photosynthesis,developing effective strategies NeuNlto up-cycle CO2into high-value organics is *** CO2reduction reaction （CO2RR） is highly promising to convert CO2into economically viable carbon-based chemicals or fuels under mild process conditions.

关键词： CO2RR conductive network electrocatalysts formate

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Stand dynamics of old-growth hemlock forests in central Bhutan are shaped by natural disturbances

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Forest Ecosystems 2024年第4期11卷 434-447页

作者： Karma Tenzin Craig R.Nitschke Kathryn j.Allen Raphael Trouve Thiet V.Nguyen patrick j.Baker School of Agriculture Foodand Ecosystem SciencesUniversity of Melbourne500 Yarra BlvdRichmondVictoriaAustralia School of Geography Planningand Spatial SciencesUniversity of TasmaniaSandy BayTasmaniaAustralia Forest Science Institute of South Vietnam 1 Pham Van Hai StreetTan Binh DistrictHo Chi Minh CityViet Nam

Understanding how past disturbances have influenced the development of forests is critical for deciphering their current structure and composition and forecasting future *** this study,dendrochronological methods were applied to uncover the disturbance history of old-growth hemlock-dominated forests in central *** of tree-ring samples from two old-growth hemlock stands,located in two different topographic settings,identified the importance of gap-phase dynamics in facilitating recruitment and growth releases and producing complex,multi-aged structure s over *** site showed evidence of a near stand-replacing disturbance in the late 1700s,while the other showed no evide nce of high-severity disturbance at any time over the last 400 *** both sites low-to medium-severity disturbances,some of which appear to be associated with cyclones originating in the Bay of Bengal,dominated the disturbance *** hemlock stands exhibited a significant positive association between cyclone occurrence and growth release events and between recruitment pulses and growth release *** 1800 to 1970 there was an increase in recruitment of angiosperm tree species at most sites and a corresponding decline in conifer *** the past 50 years there has been little new recruitment;this may be due to light limitation in the understory from shade-tolerant angiosperms and bamboo in the lower strata of these *** variations in disturbance dynamics and recruitment were observed across the study sites,suggesting that other factors,such as topography and climate,may be influencing long-term stand development *** study highlights the complex interplay between historical disturbance regimes and tree recruitment in shaping the age and size structures of old-growth hemlock forests in central *** also provides new insights into the dynamics of these forests that can be used to support effective forest conservation and management i

关键词： Forest structure Hemlock forest Himalaya Natural disturbance

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Inhaled volatile anesthetics in the intensive care unit

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World journal of Critical Care Medicine 2024年第1期13卷 28-39页

作者： Erin D Wieruszewski Mariam ElSaban patrick M Wieruszewski Nathan j Smischney Department of Pharmacy Mayo ClinicRochesterMN 55905United States Anesthesiology and Perioperative Medicine Mayo ClinicRochesterMN 55905United States Department of Anesthesiology&Perioperative Medicine Mayo ClinicRochesterMN 55905United States

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th ***,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care *** the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status *** anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor ***,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation *** the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe *** article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

关键词： Anesthesia Critical care Mechanical ventilation Sedation Volatile anesthetics Sedative

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A novel diagnostic gene region for distinguishing between two pest fruit flies:Bactrocera tryoni(Froggatt)and Bactrocera neohumeralis(Hardy)(Diptera:Tephritidae)

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Insect Science 2024年第4期31卷 1285-1295页

作者： Melissa L.Starkie Elizabeth V.Fowler Alexander M.Piper Xiaocheng Zhu Pauline Wyatt David Gopurenko Matt N.Krosch Francesca Strutt Karen F.Armstrong Hamish patrick Mark K.Schutze Mark j.Blacket Department of Agriculture and Fisheries BiosecurityBrisbaneQueenslandAustralia Agriculture Victoria AgriBioBundooraVictoriaAustralia Department of Primary Industries Wagga Wagga Agricultural InstituteWagga WaggaNew South WalesAustralia Forensic Services Group Queensland Police ServiceBrisbaneQueenslandAustralia Department of Pest-management and Conservation Lincoln UniversityLincolnNew Zealand Better Border Biosecurity(B3 B3nz.org.nz)LincolnNew Zealand

Bactrocera tryoni and Bactrocera neohumeralis are morphologically similar sibling pest fruit fly species that possess different biological attributes,geographic distributions,and host *** need to differentiate between the two species is critical for accurate pest status assessment,management,biosecurity,and maintenance of reference *** morphologically similar,adults may be separated based on subtle characters;however,some characters exhibit intraspecific variability,creating overlap between the two ***,there is currently no single molecular marker or rapid diagnostic assay that can reliably distinguish between *** and ***;therefore,ambiguous samples remain *** we report the first molecular marker that can consistently distinguish between *** and *** diagnostic region consists of two adjacent single nucleotide polymorphisms(SNPs)within the pangolin(pan)gene *** confirmed the genotypes of each species are consistent across their distributional range,then developed a tetra-primer amplification refractory mutation system(ARMS)PCR assay for rapid diagnosis of the *** assay utilizes four primers in multiplex,with two outer universal primers,and two internal primers:one designed to target two adjacent SNPs(AA)present in *** and the other targeting adjacent SNPs present in ***(GG).The assay accurately discriminates between the two species,but their SNP genotypes are shared with other nontarget tephritid fruit fly ***,this assay is most suited to adult diagnostics where species confirmation is necessary in determining ambiguous surveillance trap catches;maintaining pure colony lines;and in Sterile Insect Technique management responses.

关键词： ARMS-PCR colony molecular diagnostics pangolin tetra-primer

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An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

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Bio-Design and Manufacturing 2024年第3期7卷 240-261页

作者： Seol-Ha jeong jarno Hiemstra patrick V.Blokzijl Rebeca Damian-Ferrara Danilo Martins dos Santos jéssica H.L.da Fonseca Min-Ho Kang jihyun Kim Dilara Yilmaz-Aykut Mei L.L.Cham-Pérez jeroen Leijten Su Ryon Shin Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02139USA Leijten Lab Department of Developmental BioEngineeringFaculty of Science and TechnologyTechnical Medical CentreUniversity of TwenteDrienerlolaan 57522 NB EnschedeThe Netherlands Nanotechnology National Laboratory for Agriculture(LNNA) Embrapa InstrumentaçãoSao CarlosSao Paulo 13560-970Brazil Department of Biomedical-Chemical Engineering The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea Department of Biotechnology The Catholic University of Korea43 Jibong-roBucheon-siGyeonggi-do 14662Republic of Korea

Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural *** in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted *** oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain *** study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with *** report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide ***,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase *** study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release ***,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal *** showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new *** findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated *** work thereby offers a promising avenue for the development of functional tissues with e

关键词： 3D bioprinting Bioink Colloidal gels Extrusion printing Oxygen-generating microparticle

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Multi-Compartment SCFA Quantification in Human

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American journal of Analytical Chemistry 2024年第6期15卷 177-200页

作者： jérémy Monteiro Antoine Lefèvre Diane Dufour-Rainfray Adeline Oury Gabrielle Chicheri Laurent Galineau Hélène Blasco Lydie Nadal-Desbarats patrick Emond Imaging Brain & Neuropsychiatry iBraiN U1253 Universit de Tours INSERM MetaboHub Tours Tours France CHRU de Tours Service de Mdecine Nuclaire in Vitro Tours France Service de Biochimie et Biologie Molculaire CHRU Tours France

Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.

关键词： LC-MS 3-Nitrophenylhydrazine Short-Chain Fatty Acids Human Biological Samples Quantification

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变母线电压的LLC高压电容充电电源设计

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强激光与粒子束 2024年第2期36卷 93-99页

作者：曾宇轩菲华•帕兰斯于克训谢贤飞华中科技大学电气与电子工程学院武汉430074

提出了一种两级式可变母线电压的高压电容充电电源技术方案,该拓扑在半桥LLC谐振电路的基础上增加了一级图腾柱无桥功率因数校正(PFC)电路,通过改变母线电压来解决传统LLC谐振电源在输出更高电压时,工作频率变化范围过大带来的充电效率... 详细信息

提出了一种两级式可变母线电压的高压电容充电电源技术方案,该拓扑在半桥LLC谐振电路的基础上增加了一级图腾柱无桥功率因数校正(PFC)电路,通过改变母线电压来解决传统LLC谐振电源在输出更高电压时,工作频率变化范围过大带来的充电效率下滑的问题。由于图腾柱电路本身具备功率因数校正的功能,该电源设计还拥有能够直接从电网取电而不影响电网电能质量的优势。首先介绍了本电源设计中两部分的电路拓扑和工作原理,采用等效电阻法分析了电容负载下的电源输出特性。针对前级图腾柱电路设计了双环控制器以实现对母线电压和功率因数的控制,针对后级LLC电路提出了比例积分(PI)加低通滤波的恒流控制器以降低高频噪声带来的不利影响。最后通过模型构建与仿真分析,研究了高压电容充电电源3000 V/1 A时的充电特性,验证了本电源技术方案、设计和控制策略的可行性。

关键词：图腾柱无桥功率因数校正变母线电压 LLC谐振变换器双闭环控制恒流控制高压电容充电

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A One Health approach to fight antimicrobial resistance in Uganda: Implementation experience, results, and lessons learned

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Biosafety and Health 2024年第2期6卷 125-132页

作者： Reuben Kiggundu j.P.Waswa Niranjan Konduri Hassan Kasuja Marion Murungi patrick Vudriko Harriet Akello Eric Lugada Cecilia Muiva Esther Were Dinah Tjipura Henry Kajumbula Kate Kikule Emmanuel Nfor Mohan P.joshi USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthArlingtonVA 22203USA College of Veterinary Medicine Animal Resources and BiosecurityMakerere UniversityKampala 256Uganda Ministry of Health Uganda Kampala 256Uganda USAID Strengthening Supply Chain Systems Activity Management Sciences for HealthKampala 256Uganda USAID Medicines Technologiesand Pharmaceutical Services ProgramManagement Sciences for HealthNairobi 254Kenya Department of Microbiology College of Health SciencesMakerere UniversityKampala 256Uganda

Uganda has been implementing the Global Health Security Agenda(GHSA)since 2015 to build its capacity according to World Health Organization(WHO)Benchmarks on International Health Regulations *** country remains prone to outbreaks,with more than 20 disease outbreaks reported in the past five years,including Ebola virus disease,Crimean-Congo haemorrhagic fever,Marburg haemorrhagic fever,measles,yellow fever,coronavirus disease 2019(COVID-19),and *** resistance(AMR)is an ongoing *** scored capacity level 3 on infection prevention and control(IPC)and antimicrobial stewardship(AMS)in the 2017 joint External Evaluation(jEE)*** gaps were being addressed after a self-assessment in *** paper describes the technical assistance approaches provided to Uganda by the Medicines,Technologies,and Pharmaceutical Services Program,funded by the United States(U.S.)Agency for International Development,and implemented by Management Sciences for *** program,through a One Health approach,supported systematic capacity strengthening based on the jEE's capacity advancement framework for global health security,specifically relating to *** program's interventions impacted 32 WHO benchmark actions(7 for AMR multisectoral coordination,16 for IPC,and 9 for AMS),contributing to Uganda's strengthened GHSA *** success built on the AMR platform,the program trained 745 health workers in IPC for the Ebola virus and provided support for simulation exercises by eight district IPC *** program also worked with the Ministry of Health to coordinate IPC for the COVID-19 response in five health regions,covering 45 districts and reaching 5,452 health workers at 858 health facilities.

关键词： One health Antimicrobial resistance Antibiotic resistance jointexternal evaluation Global health security Uganda Africa WHO Benchmarks for International Health Regulations Capacities

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On the Dirichlet form of three-dimensional Brownian motion conditioned to hit the origin

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Science China Mathematics 2019年第8期62卷 1477-1492页

作者： patrick j. Fitzsimmons Liping Li Department of Mathematics University of California at San Diego San Diego CA 92093-0112 USA RCSDS HCMS Academy of Mathematics and Systems Science Chinese Academy of Sciences Beijing 100190 China

Our concern in this paper is the energy form induced by an eigenfunction of a self-adjoint extension of the restriction of the Laplace operator to C_c^∞(R^3\{0}).We will prove that this energy form is a regular Dirichlet form with core C_c^∞(R^3).The associated diffusion X behaves like a 3-dimensional Brownian motion with a mild radial drift when far from 0,subject to an ever-stronger push toward 0 near that *** particular,{0}is not a polar set with respect to *** diffusion X is rotation invariant,and admits a skew-product representation before hitting{0}:its radial part is a diffusion on(0,∞)and its angular part is a time-changed Brownian motion on the sphere S^*** radial part of X is a"reflected"extension of the radial part of X^0(the part process of X before hitting{0}).Moreover,X is the unique reflecting extension of X^0,but X is not a semi-martingale.

关键词： Dirichlet form reflected extension rotationally invariant process Fukushima’s decomposition

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