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Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis

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Open Journal of Respiratory Diseases 2024年第2期14卷 39-50页

作者： Myriam Calle rubio Olga de la Serna Blazquez José Luis R. Martin Manuel Ruiz Cuetos Pulmonology Department Hospital Clínico San Carlos Madrid Spain Department of Medicine School of Medicine Universidad Complutense de Madrid Madrid Spain Instituto de Investigacion Sanitaria del Hospital Clínico San Carlos (IdISSC) Madrid Spain Pediatric Pulmonology Unit Pediatrics Department Hospital Universitario La Paz Madrid Spain Simplifying Research Institute Layos Spain Medical department in ITF Research Pharma S.L.U. Alcobendas Spain

Objective: This study aims to systematically examine the existing evidence regarding the clinical benefits of carbocysteine as an adjunctive treatment in acute bronchopulmonary and otorhinological processes. Design: Systematic review and meta-analysis. Data sources: An electronic search was conducted across PubMed, Cochrane Library, ***, and the European Clinical Trial Register, with the search dated to May 2023. Bibliographic references from other literature reviews and meta-analyses were also reviewed. The search was limited to randomized clinical trials published in any language and year. It was completed by cross-checking the references of the located articles. Methods: Inclusion criteria covered studies assessing systemic or inhaled carbocysteine, regardless of dosing regimen. Concomitant medication use was acceptable if balanced between intervention and control groups. Authors independently extracted data, resolving disagreements through consensus. Methodological quality assessment relied on critical reading of each study. Dichotomous variables were analyzed using odds ratio (OR), and a final effect size was calculated. Statistical significance was established when confidence intervals did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified studies, 4 met inclusion criteria. The meta-analysis for poor general condition yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs. 27.2% for placebo. On the seventh day, expectoration rates were 18.37% for carbocysteinevs 33.3% for placebo. Conclusions: The observed clinical benefits align with carbocysteine’s mucoactive and muco-regulatory properties, complemented by anti-inflammatory and antioxidant actions. Carbocysteine stands out among mucolytic agents. In the context of persistent infectious diseases,

关键词： Acute Respiratory Infections Carbocystenine Systematic Review Meta-Analysis

A Systematic Review of Cannabidiol Effects in Coronary Syndromes: Challenges to Clinical Translation

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Journal of Biosciences and Medicines 2024年第4期12卷 246-263页

作者： Mario E. Zuñiga-Ayala Alejandra Meaney-Martínez Alejandro Alcocer-Chauvet Vidal Gonzalez-Coronado Nestor rubio-Infante Gerardo Garcia-Rivas Department of Cardiology Instituto de Seguridad Social and Trabajadores del Estado (ISSSTE) Hospital Regional Primero de Octubre Mexico City Mexico Department of Interventional Cardiology Instituto de Seguridad Social y Trabajadores del Estado (ISSSTE) Hospital Regional Primero de Octubre Mexico City Mexico Instituto Tecnó logico de Monerrey Escuela de Medicina and Ciencias de la Salud C&#225tedra de Cardiolog&#237a and Medicina Vascular Monterrey Mexico

Background: Myocardial ischemia in addition to other several cardiac syndromes represent a pathological proinflammatory state alongside a complex cellular microenvironment that can be modified by using cannabinoids. Cannabidiol (CBD), a non-psychoactive compound of cannabis has been recently proposed as an immudomodulatory and cardioprotective drug. Objectives: In this systematic review we sought to clarify and summarize the clinical and preclinical evidence of potential benefit of the use of CBD in coronary syndromes. Methods: We conducted a systematic search and review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Review of Animal Data from Experimental Studies (CAMARADES) guidelines, in the electronic database from PubMed, Web of Science and Scopus up to April 2022 using predefined search terms. Pre-specified exclusion and inclusion criteria were considered, finally 11 articles were chosen to be included for this peer review. Results: Currently there are no good-quality clinical trials with the use of CBD in acute or chronic coronary syndromes. A total of 11 preclinical studies where prescreened and 5 demonstrated reproducible positive cardiovascular outcomes on in-vivo models treated with CBD. Mechanisms of CBD cardioprotection observed: 1) reduction in oxidative stress and inflammation, 2) activation of adenosine receptors and 3) increased expression of angiotensin type 2-receptor. Experimental models included ischemia/reperfusion injury, myocardial infarction, arrhythmias, and metabolic syndrome-like conditions. Conclusion: No clinical recommendation can be issued with the current evidence, on the use of CBD in acute and chronic coronary syndromes. Based on preclinical evidence, we considered there is enough evidence to propose the development of well-designed clinical trials that include CBD in the management of coronary syndromes.

关键词： Cannabis Cannabidiol Acute Coronary Syndromes Myocardial Infarction Myocardial Ischemia and Oxidative Stress

Evaluation of Human Impacts on Bartlett Pond Ecosystem, Laredo, Southern Texas, USA, through Empirical Modeling

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Journal of Environmental Protection 2024年第4期15卷 497-526页

作者： Maya P. Bhatt Amede rubio Ganesh B. Malla Cristobal Lopez Virginia Morales Erick Vazquez Cano David Marquez Orlando Berumen Alvarez Alfred Addo-Mensah Department of Biology and Chemistry Texas A&M International University Laredo USA Department of Mathematics Computer Geology and Physics University of Cincinnati-Clermont College Batavia USA

The trace elements chemistry of Bartlett Pond, a small shallow wetland pond in Laredo, Southern Texas, was sampled to evaluate the dynamics of trace elements impacts on water quality and ecosystems ecology of the pond. Two types of fish (bass and tilapia) were also sampled to see the trace element accumulation in different parts of their body. The concentrations of trace elements in water samples were found in the following order: Fe ≫Sb > Pb > As ≫Co > Tl > Cr > Cd within Bartlett Pond. Overall, the water quality of the pond is unacceptable for drinking and any other purposes as trace element concentrations (e.g. As, Cd, Co, Cr, Pb, Fe, Sb and Tl) are exceedingly higher (several fold) than the WHO and US EPA guidelines. Predictive and correlation analysis shows that most trace elements exhibit a strong positive correlation among them indicating the same anthropogenic sources and biogeochemical processes regulate these trace elements within the pond. Distributions of the trace elements in water exhibit different shapes mostly as positively skewed distribution for As, Cd, Co, Cr, and Tl, symmetrical distribution for Fe and almost symmetrical distribution for Pb and Sb. Concentrations of As, Co and Tl accumulated much higher in different parts of the Bass than Tilapia fish. The concentrations of As, Tl, Co, and Sb appeared significantly higher in different parts of the body of both Bass and Tilapia than the maximum SRM certified values. Accumulation of these contaminants in fish tissues pose increased health risks to humans who consume these contaminated fish although fishing is prohibited. Anthropogenic activities in the region primarily degrade the whole pond ecosystem ecology of the Bartlett Pond and waters of this pond to be not recommended for any use. These findings may be useful for the scientific community and concerned authorities to improve understanding about these precious natural resources and conservation of the ecosystem ecology.

关键词： Trace Elements Bartlett Pond Laredo Southern Texas Wetlands Ecosystem Ecology

Complexity of adaptive testing in scenarios defined extensionally

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Frontiers of Computer Science 2023年第3期17卷 11-28页

作者： Ismael RODRÍGUEZ David rubio Fernando rubio Dpto.Sistemas Informáticos y Computación Facultad de InformáticaUniversidad Complutense de MadridMadrid 28040Spain Instituto de Tecnologías del Conocimiento Universidad Complutense de MadridMadrid 28040Spain Instituto de Biomecánica de Valencia.Universitat Politècnica de València València 46022Spain

In this paper,we consider a testing setting where the set of possible definitions of the Implementation Under Test(IUT),as well as the behavior of each of these definitions in all possible interactions,are extensionally defined,i.e.,on an element-by-element and case-by-case *** this setting,the problem of finding the minimum testing strategy such that collected observations will necessarily let us decide whether the IUT is correct or not(i.e.,whether it necessarily belongs to the set of possible correct definitions or not)is studied in four possible problem variants:with or without non-determinism;and with or without more than one possible definition in the sets of possible correct and incorrect *** computational complexity of these variants is studied,and properties such as PSPACE-completeness and Log-APX-hardness are identified.

关键词： formal testing adaptive testing computational complexity PSPACE-completeness approximation hardness

Caving performance through the integration of microseismic activity and numerical modeling at DOZ-PT Freeport,Indonesia

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International Journal of Minerals,Metallurgy and Materials 2009年第1期16卷 1-6页

作者： rubio Enrique Napitupulu Daulat Mining Engineering Department Universidad de Chile Geotechnical Engineering Department PT Freeport IndonesiaTembagapuraIndonesia

This article describes an undergoing research at PT Freeport, Indonesia, in which the main goal is to use the microseismic information recorded as a result of mining to analyze cave propagation and stress performance on the actual production and fixed infrastructure. At the moment, several numerical experiments have been conducted to correlate the mining activity with the microseismic events using the data collected during year 2005 and 2006. As a result of the preliminary analysis a micro- and a macrocracking envelop were proposed on the basis of computation of stress behavior at the location of the events. Stresses have been computed using standard elastic continuous boundary element models. The correlation between the average source radius and the stress performance has provided a method to propose a macrocracking criterion. Several techniques have been tested to nucleate the microseismic activity around different geological features. This last attempt was aimed to look at potential overstresses induced over the undercut and extraction level drifts. A method was devised to integrate the microseismicity into a 3-dimensional ride distribution model. This model has shown to be very effective to quantify the overstress induced as a result of computing volumetric microseismicity density. The volumetric microseismic model showed to induce overstress up to 10 MPa over a period of two months. The future work will concentrate on the calibration of the integrated model with actual damage observations made at the current mining infrastructure.

关键词： microseism underground mining block caving stress distribution microcrack criterion

An ACO-RFD hybrid method to solve NP-complete problems

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Frontiers of Computer Science 2013年第5期7卷 729-744页

作者： Pablo RABANAL Ismael RODRIGUEZ Fernando rubio Dept. Sistemas Inforrnaiticos y Computacion Facultad de Informatica Universidad Complutense de Madrid Madrid 28040 Spain

In this paper we hybridize ant colony optimiza- tion （ACt） and river formation dynamics （RFD）, two related swarm intelligence methods. In ACt, ants form paths （prob- lem solutions） by following each other＇s pheromone trails and reinforcing trails at best paths until eventually a single path is followed. On the other hand, RFD is based on copy- ing how drops form rivers by eroding the ground and de- positing sediments. In a rough sense, RFD can be seen as a gradient-oriented version of ACt. Several previous experi- ments have shown that the gradient orientation of RFD makes this method solve problems in a different way as ACt. In particular, RFD typically performs deeper searches, which in turn makes it find worse solutions than ACt in the first exe- cution steps in general, though RFD solutions surpass ACt solutions after some more time passes. In this paper we try to get the best features of both worlds by hybridizing RFD and ACt. We use a kind of ant-drop hybrid and consider both pheromone trails and altitudes in the environment. We apply the hybrid method, as well as ACt and RFD, to solve two NP-hard problems where ACt and RFD fit in a different manner： the traveling salesman problem （TSP） and the prob- lem of the minimum distances tree in a variable-cost graph （MDV）. We compare the results of each method and we an- alyze the advantages of using the hybrid approach in each case.

关键词： river formation dynamics ant colony optimization heuristic algorithms NP-hard problems

The quest for selective Cs^(+) transport in plants

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Molecular Plant 2021年第4期14卷 552-554页

作者： Manuel Nieves-Cordones Francisco rubio Departamento de Nutricion Vegetal Centro de Edafologia y Biologia Aplicada del Segura-CSICCampus de Espinardo30100 MurciaSpain

Nuclear accidents have led to the release to the environment of radioactive isotopes,mainly radioactive cesium(Cs^(+)),contaminating large areas of soil for very long periods of time(Burger and Lichtscheidl,2018).These contaminated soils contain^(134)Cs^(+)and^(137)Cs^(+)radioisotopes that are readily accumulated into plants and that,through the food chain,are transferred to animals and humans,causing important health problems(Burger and Lichtscheidl,2018).

关键词： readily release transport

Synthesis of glass ceramics from kaolin and dolomite mixture

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International Journal of Minerals,Metallurgy and Materials 2017年第2期24卷 194-201页

作者： Mohamed Reda Boudchicha Fausto rubio Slimane Achour Engineering Mechanics and Materials Laboratory Mechanical Engineering Department Faculty of Technology Universite 20 Aout 1955 de Skikda Skikda 21000 Algeria Ceramics and Glass Institute Consejo Superior de Investigaciones Cientificas Madrid 28049 Spain National Polytechnic School Constantine 25000 Algeria

Cordierite- and anorthite-based binary glass ceramics of the CaO-MgO-Al2O3-SiO2 （CMAS） system were synthesized by mixing local and abundant raw minerals （kaolin and doloma by mass ratio of 82/18）. A kinetics study reveals that the activation energy of crystalli- zation （Ea） calculated by the methods of Kissinger and Marotta are 438 kJ·mol^-1 and 459 kJ·mol^-1, respectively. The Avrami parameter （n） is estimated to be approximately equal to 1, corresponding to the surface crystallization mechanism. X-ray diffraction （XRD） analysis shows that the anorthite and cordierite crystals are precipitated from the parent glass as major phases. Anorthite crystals first form at 850℃, whereas the μ-cordierite phase appears after heat treatment at 950℃. Thereafter, the cordierite allotropically transforms to α-cordierite at 1000℃. Complete densification is achieved at 950℃; however, the density slightly decreases at higher temperatures, reaching a stable value of 2.63 kg·m^-3 between 1000℃ and 1100℃, The highest Vickers hardness of 6 GPa is also obtained at 950℃. However, a substantial decrease in hardness is recorded at 1000℃; at higher sintering temperatures, it slightly increases with increasing temperature as the ct-cordierite crystallizes.

关键词： glass ceramics kaolinite dolomite crystallization activation energy

The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair James Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher Joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK Chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance