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Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

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Journal of Pharmaceutical Analysis 2020年第6期10卷 532-545页

作者： Natalia Navas Jesús Hermosilla Anabel Torrente-Lopez Jose Hernandez-Jimenez Jose Cabeza raquel perez-roblesa Antonio Salmeron-García Department of Analytical Chemistry Science Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia Hospitalaria Biomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many countries.Several studies suggest that cytokine storms(interleukins)may play an important role in severe cases of COVID-19.Neutralizing key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality rate.Tocilizumab(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS patients.Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical trials.This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug shortages.Here,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of TCZ.It is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

关键词： COVID-19 Tocilizumab Critical quality attributes IV and SC medicines

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Nutritional epigenetics education improves diet and attitude of parents of children with autism or attention deficit/hyperactivity disorder

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World Journal of Psychiatry 2024年第1期14卷 159-178页

作者： Renee J Dufault Katherine M Adler David O Carpenter Steven G Gilbert raquel A Crider College of Graduate Health Studies A.T.Still UniversityKirksvilleMO 63501United States Department of Research Food Ingredient and Health Research InstituteNaalehuHI 96772United States Department of Health Sciences University of New HavenWest HavenCT 06516United States Institute for Health and the Environment School of Public HealthState University of New YorkAlbanyNY 12222United States Department of Research Institute of Neurotoxicology and Neurological DisordersSeattleWA 98105United States Department of Statistics Food Ingredient and Health Research InstituteNaalehuHI 96772United States

BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIM To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.METHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of

关键词： Epigenomics Parenteral nutrition Autism Attention deficit/hyperactivity disorder Ultra-processed foods Heavy metals

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Sex differences in Alzheimer's disease:an urgent research venue to follow

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Neural Regeneration Research 2024年第12期19卷 2569-2570页

作者： raquel Jiménez-Herrera Ana Contreras Juan D.Navarro-López Lydia Jiménez-Díaz Neurophysiology&Behavior Lab University of Castilla-La ManchaSchool of Medicine of Ciudad RealCiudad RealSpain

Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the year 2050.Among the various forms of dementia.Alzheimer's disease(AD)stands out as the predominant and most prevalent.

关键词： Alzheimer predominant estimates

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Bridging the gap: Predicting brain metastasis in breast cancer

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World Journal of Clinical Oncology 2024年第2期15卷 356-359页

作者： Daniela Gonsalves raquel Ciérvide Felipe Couñago Department of Radiation Oncology GenesisCare MadridMadrid 28043Spain Facultad de Medicina Salud y Deporte Universidad Europea de MadridMadrid 28670Spain Department of Radiation Oncology HM HospitalesMadrid 28050Spain

Chen et al explored clinicopathological features and prognostic factors,revealing advanced tumor stage,lung metastases,HER-2 overexpression,and triple-negative status as key contributors.Recent research connects astrocytes'role in brain metastasis with signaling pathways and the impact of Trastuzumab on HER-2 tumor survival.Factors such as positive HER2 status,lack of estrogen receptor expression,and liver metastasis are identified as additional risk factors.The routine use of magnetic resonance imaging,insights into gene mutations associated with metastasis,and the role of radiotherapy,including prophylaxis possibilities,is controversial in clinical practice.Understanding these risk factors in a multidisciplinary collaboration is precise for local treatments and targeted therapies,particularly for HER2+tumors,impacting directly on longer survival.

关键词： Brain metastases Breast cancer Clinicopathological features High-risk factors

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Efficient removal of the recalcitrant metamizole contaminant from drinking water by using a CaLaCoO_(9) perovskite supported on recycled polyethylene

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Journal of Environmental Sciences 2024年第2期136卷 56-67页

作者： Ernesto Valadez-Renteria Christian perez-Carrasco Dulce Yolotzin Medina-Velazquez Vicente Rodriguez-Gonzalez Jorge Oliva CONACYT-División de Materiales Avanzados Instituto Potosino de Investigación Científica y Tecnológica A.C.San Luis PotosíSLP 78216México División de Ciencias Básicas e Ingeniería Universidad Autónoma Metropolitana AzcapotzalcoCol.Reynosa-TamaulipasC.P.MéxicoDF 02200México

Metamizole(MZ)is a widely used anti-inflammatory drug.Due to its common use,this contaminant is found in sewage and rivers.In order to reduce the contamination produced by the MZ,we fabricated in this work a photocatalytic composite using recycled polyethylene(RPE)and the CaLaCoO_(9)(LCCO)perovskite.Those nanoparticles had a microplate-like morphology and sizes of 1.4–5.5μm according to the analysis of microscopy.The photocatalytic properties of the LCCO powders were evaluated under ultraviolet-visible(UV-Vis)irradiation and found a removal efficiency of 96%.When the RPE+LCCO composite was employed for the photocatalytic degradation of MZ,a maximum degradation of 92.5%was obtained.The influence of the pH on the photocatalytic activity was also studied and found that an initial pH=3 produced a total degradation of MZ after 240 min of UV-Vis irradiation.Moreover,three reuse cycles were carried out for the pure LCCO powders and for the RPE+LCCO composites and found that the maximum loss of degradation was 5%.Furthermore,scavenger experiments demonstrated that the super oxide and hydroxyl radicals are formed during the photocatalytic reaction and were responsible for the degradation of MZ.Additionally,the X-ray photoelectron-spectroscopy and Raman analysis demonstrated the formation of defects(oxygen vacancies),those ones delayed the electron-hole recombination,which in turn,enhanced the degradation of the MZ.Thus,the studies performed in this work proved that composites made with recycled plastics and LCCO perovskites are a low-cost and feasible alternative for the cleaning of water sources polluted with pharmaceutical compounds.

关键词： Photocatalysis Metamizole Pharmaceutical contaminant UV-Vis irradiation Perovskite

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Association of Congenital Heart Defects (CHD) with Factors Related to Maternal Health and Pregnancy in Newborns in Puerto Rico

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Congenital Heart Disease 2024年第1期19卷 19-31页

作者： Yamixa Delgado Caliani Gaytan Naydi perez Eric Miranda Bryan Colón Morales Mónica Santos Biochemistry&Pharmacology Department San Juan Bautista School of MedicineCaguas00726Puerto Rico Hispanic Alliance for Clinical and Translational Research University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico Department of Internal Medicine University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BMI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(CHD)during neonatal development.Methods:Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020.Our assessment encompassed a range of variables,including maternal age,gestational age,BMI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of preeclampsia.Results:A cohort of 673 patients was included in our study.The average maternal age was 26 years,within a range of 22 to 32 years.The mean gestational age measured 39 weeks,with a median span of 38 to 39 weeks.Of the 673 patients,274(41%)mothers gave birth to neonates diagnosed with CHD.Within this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BMI,whereas 126 displayed a normal BMI.Conclusion:We identiﬁed a statistically signiﬁcant correlation between pre-gestational diabetes mellitus and the occurrence of CHD.However,our analysis did not show a statistically signiﬁcant association between maternal BMI and the likelihood of CHD.These results may aid in developing effective strategies to prevent and manage CHD in neonates.

关键词： Congenital heart defects(CHD) obesisty maternal health diabetes body mass index(BMI)

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On-Chip Micro Temperature Controllers Based on Freestanding Thermoelectric Nano Films for Low-Power Electronics

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Nano-Micro Letters 2024年第7期16卷 98-108页

作者： Qun Jin Tianxiao Guo Nicolas perez Nianjun Yang Xin Jiang Kornelius Nielsch Heiko Reith Institute for Metallic Materials Leibniz Institute for Solid State and Materials Research01069 DresdenGermany Institute of Materials Engineering University of Siegen57076 SiegenGermany Institute of Applied Physics Technical University of Dresden01069 DresdenGermany Institute of Materials Science Technical University of Dresden01069 DresdenGermany

Multidimensional integration and multifunctional com-ponent assembly have been greatly explored in recent years to extend Moore’s Law of modern microelectronics.However,this inevitably exac-erbates the inhomogeneity of temperature distribution in microsystems,making precise temperature control for electronic components extremely challenging.Herein,we report an on-chip micro temperature controller including a pair of thermoelectric legs with a total area of 50×50μm^(2),which are fabricated from dense and flat freestanding Bi2Te3-based ther-moelectric nano films deposited on a newly developed nano graphene oxide membrane substrate.Its tunable equivalent thermal resistance is controlled by electrical currents to achieve energy-efficient temperature control for low-power electronics.A large cooling temperature difference of 44.5 K at 380 K is achieved with a power consumption of only 445μW,resulting in an ultrahigh temperature control capability over 100 K mW^(-1).Moreover,an ultra-fast cooling rate exceeding 2000 K s^(-1) and excellent reliability of up to 1 million cycles are observed.Our proposed on-chip temperature controller is expected to enable further miniaturization and multifunctional integration on a single chip for microelectronics.

关键词： Temperature control Low-power electronics On-chip micro temperature controller Freestanding thermoelectric nano films Temperature-sensitive components

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Portal vein arterialization in 25 liver transplant recipients:A Latin American single-center experience

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World Journal of Transplantation 2024年第2期14卷 135-147页

作者： Nicolas Andres Cortes-Mejia Diana Fernanda Bejarano-Ramirez Juan Jose Guerra-Londono Diego Rymel Trivino-Alvarez raquel Tabares-Mesa Alonso Vera-Torres Division of Anesthesiology Critical Care Medicineand Pain MedicineThe University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Transplant and Hepatobiliary Surgery Department Fundacion Santa Fe de BogotaBogota 110111Colombia General Surgery Department Fundacion Santa Fe de BogotaBogota 110111Colombia

BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.

关键词： Liver transplantation Portal vein arterialization Arteriovenous anastomoses Portal hypertension Portal vein thrombosis Spontaneous portosystemic shunts Vascular steal phenomenon Primary graft dysfunction Early allograft dysfunction

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A new oxidative pathway of nitric oxide production from oximes in plants

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Molecular Plant 2024年第1期17卷 178-198页

作者： Pedro Lopez-Gomez Javier Buezo Marina Urra Alfonso Cornejo raquel Esteban Jorge Fernandez de los Reyes Estibaliz Urarte Estefania Rodriguez-Dobreva Alejandro Chamizo-Ampudia Alejandro Eguaras Sebastian Wolf Daniel Marino Victor Martinez-Merino Jose F.Moran Institute for Multidisciplinary Research in Applied Biology(IMAB) Department of SciencesPublic University of Navarre(UPNA)Avda.de Pamplona 12331192 MutilvaSpain Institute for Advanced Materials and Mathematics(INAMAT2) Department of SciencesPublic University of Navarre(UPNA)Campus de Arosadia31006 PamplonaSpain Department of Plant Biology and Ecology University of the Basque Country(UPV/EHU)Sarriena s/nApdo.64448080 BilbaoSpain Center for Plant Molecular Biology(ZMBP) University of TubingenGeschwister-Scholl-Platz72074 TubingenGermany Institute of Natural Resources and Agrobiology of Salamanca(IRNASA) Department of Plant-Microorganism InteractionsSpanish National Research Council(CSIC)Cordel de Merinas40-5237008SalamancaSpain Department of Biochemistry Area of Molecular BiologyVeterinary FacultyUniversity of LeonCampus de Vegazanas/n.24071 LeonSpain

Nitric oxide(NO)is an essential reactive oxygen species and a signal molecule in plants.Although several studies have proposed the occurrence of oxidative NO production,only reductive routes for NO production,such as the nitrate(NO_(3)^(-))-upper-reductase pathway,have been evidenced to date in land plants.However,plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO3−,evidencing the existence of a metabolic pathway for oxidative production of NO.We hypothesized that oximes,such as indole-3-acetaldoxime(IAOx),a precursor to indole-3-acetic acid,are intermediate oxidation products in NO synthesis.We detected the production of NO from IAOx and other oximes catalyzed by peroxidase(POD)enzyme using both 4-amino-5-methylamino-2′,7′-difluorescein fluorescence and chemiluminescence.Flavins stimulated the reaction,while superoxide dismutase inhibited it.Interestingly,mouse NO synthase can also use IAOx to produce NO at a lower rate than POD.We provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory calculations.We showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO,while in vivo supplementation of IAOx and other oximes increased the number of lateral roots,as shown for NO donors,and a more than 10-fold increase in IAOx dehydratase expression.Furthermore,we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants,while prx33-34 mutant plants,defective in POD33-34,had reduced production.Our data show that the release of NO by IAOx,as well as its auxinic effect,explain the superroot phenotype.Collectively,our study reveals that plants produce NO utilizing diverse molecules such as oximes,POD,and flavins,which are widely distributed in the plant kingdom,thus introducing a long-awaited oxidative pathway to NO production in plants.This knowledge has essential implications for und

关键词： ammonium oxidation auxin nitric oxide oxime peroxidase root phenotype

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Quality-adjusted life years and surgical waiting list:Systematic review of the literature

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1155-1164页

作者： Roberto de la Plaza Llamas Lorena Ortega Azor Marina Hernández Yuste Ludovica Gorini raquel Aránzazu Latorre-Fragua Daniel Alejandro Díaz Candelas Farah Al Shwely Abduljabar Ignacio Antonio Gemio del Rey Department of General and Digestive Surgery Hospital Universitario de GuadalajaraGuadalajara 19002Spain Department of Surgery Medical and Social SciencesFaculty of Medicine and Health SciencesUniversity of AlcaláAlcaláde Henares 28871MadridSpain

BACKGROUND The quality-adjusted life year(QALY)is a metric that is increasingly used today in the field of health economics to evaluate the value of different medical treatments and procedures.Surgical waiting lists(SWLs)represent a pressing problem in public healthcare.The QALY measure has rarely been used in the context of surgery.It would be interesting to know how many QALYs are lost by patients on SWLs.AIM To investigate the relationship between QALYs and SWLs in a systematic review of the scientific literature.METHODS The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.An unlimited search was carried out in PubMed,updated on January 19,2024.Data on the following variables were investigated and analyzed:Specialty,country of study,procedure under study,scale used to measure QALYs,the use of a theoretical or real-life model,objectives of the study and items measured,the economic value assigned to the QALY in the country in question,and the results and conclusions published.RESULTS Forty-eight articles were selected for the study.No data were found regarding QALYs lost on SWLs.The specialties in which QALYs were studied the most in relation to the waiting list were urology and general surgery,with 15 articles each.The country in which the most studies of QALYs were carried out was the United States(n=21),followed by the United Kingdom(n=9)and Canada(n=7).The most studied procedure was organ transplantation(n=39),including 15 kidney,14 liver,5 heart,4 lung,and 1 intestinal.Arthroplasty(n=4),cataract surgery(n=2),bariatric surgery(n=1),mosaicplasty(n=1),and septoplasty(n=1)completed the surgical interventions included.Thirty-nine of the models used were theoretical(the most frequently applied being the Markov model,n=34),and nine were real-life.The survey used to measure quality of life in 11 articles was the European Quality of Life-5 dimensions,but in 32 articles the survey was not specified.The willingness-to-pay per QALY gained ranged fro

关键词： Quality-adjusted life year Waitlist Quality of life Surgery Systematic review

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