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Design and redesign journey of a drug for transthyretin amyloidosis

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Neural Regeneration Research 2025年第4期20卷 1096-1097页

作者： Francisca pinheiro Salvador Ventura Institut de Biotecnologia i Biomedicina Departament de Bioquímica i Biologia MolecularUniversitat Autònoma de BarcelonaBellaterraSpain

The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as ***(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic *** systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the *** hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(carroll et al.,2022).

关键词： amyloid aggregation senile

Serological surveillance for SARS-coV-2 antibodies among students,faculty and staff within a large university system during the pandemic

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World Journal of Virology 2025年第1期14卷 99-107页

作者： Marcos G pinheiro Gabriela G O Alves Maria Eduarda R conde Sofia L costa Regina c S Sant’Anna Isa M F Antunes Mônica c carneiro Fabio S Ronzei Julia c Scaffo Felipe R pinheiro Lialyz S Andre Helvecio c Povoa Valéria T Baltar Fabíola Giordani Eduarda S Hemerly Gisele c Alexandre Karla c de Paula Márcio Watanabe Antonio claudio L da Nóbrega Jackeline christiane P Lobato Fabio Aguiar-Alves Laboratory of Molecular Epidemiology and Biotechnology Rodolpho Albino University LaboratoryFluminense Federal UniversityNiterói 24241000Rio de JaneiroBrazil Estácio de SáUniversity Nova Friburgo 28611135Rio de JaneiroBrazil Pathology Program Medicine schoolFluminense Federal UniversityNiterói 24070090Rio de JaneiroBrazil Department of Pharmaceutical Sciences Lloyd L.Gregory School of PharmacyPalm Beach Atlantic UniversityWest Palm BeachFL 33401United States Health Institute of Nova Friburgo Fluminense Federal UniversityNova Friburgo 28613001Rio de JaneiroBrazil Department of Epidemiology and Biostatistics Institute of Collective Health(ISC)Fluminense Federal UniversityNiterói 24033900Rio de JaneiroBrazil Institute of Physical Education Fluminense Federal UniversityNiterói 24020005Rio de JaneiroBrazil Department of Statistics Fluminense Federal UniversityNiterói 24210200Rio de JaneiroBrazil Department of Physiology and Pharmacology Fluminense Federal UniversityNiterói 24210130Rio de JaneiroBrazil

BAcKGROUND At the end of December 2019,the world faced severe acute respiratory syndrome-coronavirus 2(SARS-coV-2),which led to the outbreak of coronavirus disease 2019(cOVID-19),associated with respiratory *** virus has shown significant challenges,especially for senior citizens,patients with other underlying illnesses,or those with a sedentary *** tests conducted early on have helped identify how the virus is transmitted and how to curb its *** study hypothesis was that the rapid serological test for SARS-coV-2 antibodies could indicate the immunoreactive profile during the cOVID-19 pandemic in a university *** To conduct active surveillance for serological expression of anti-SARS-coV-2 antibodies in individuals within a university setting during the cOVID-19 *** This sectional study by convenience sampling was conducted in a large university in Niteroi-RJ,Brazil,from March 2021 to July *** study population consisted of students,faculty,and administrative staff employed by the university.A total of 3433 faculty members,60703 students,and 3812 administrative staff were invited to *** were gathered through rapid serological tests to detect immunoglobulin(Ig)M and IgG against ***χ²or Fisher's exact test was used to conduct statistical analysis.A 0.20 significance level was adopted for variable selection in a multiple logistic regression model to evaluate *** A total of 1648 individuals were enrolled in the *** proportion of cOVID-19 positivity was 164/1648(9.8%).The adjusted logistic model indicate a positive association between the expression of IgM or IgG and age[odds ratio(OR)=1.16,95%cI:1.02-1.31](Pcontact with a cOVID-19-positive case(OR=3.49,95%cI:2.34-5.37)(Pceived the cOVID-19 vaccine(OR=2.33,95%cI:1.61-3.35)(Pcial isolation(OR=0.59,95%cI:0.41-0.84)(P<0.004).The likelihood of sho

关键词： Serological surveillance SARS-coV-2 antibodies cOVID-19 Serological rapid test Risk factors for cOVID-19

Structural optimization of patient-specific temporomandibular joint replacement implants for additive manufacturing:novel metrics for safety evaluation and biomechanical performance

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Bio-Design and Manufacturing 2022年第2期5卷 333-347页

作者： Manuel pinheiro Anouar Krairi Robin Willaert Maria c.costa Wim Van Paepegem Mechanics of Materials and Structures(MMS) Ghent UniversityGhentBelgium Materials Innovation Institute(M2i) DelftThe Netherlands Department of Oral and Maxillofacial Surgery University Hospitals Leuven LeuvenBelgium 4 Department of Head and Neck SurgeryGhent University HospitalGhentBelgium

Total temporomandibular joint(TMJ)replacement is recommended only when there is irreversible damage to the joint and no conservative treatment can provide functional *** stock and custom-made TMJ implants have been made available;however,retrospective and comparative studies were unable to find significant differences between the two types of *** introduction of additive manufacturing(AM)techniques in medical practice allows for a greater freedom of design and a higher degree of device *** combination of AM with structural optimisation may streamline development and provide the key for fabricating biomechanic ally enhanced TMJ *** this study,structural optimis ation techniques were applied to develop and numerically validate a patient-specific TMJ *** biomechanical behaviour of each intermediate TMJ design was assessed under four different nominal and maximum biting tasks using finite element *** addition,a new set of metrics were proposed to compare each design regarding biomechanical performance and implant *** results suggest that 55-82%of the natural/intact strain patterns can be recovered with the finally selected TMJ *** represents an increase of 15%in biomechanical performance for incisor biting,15%for right molar biting,17%for left molar biting and a decrease of 2%for left group biting compared with the initial *** results also suggest that load transfer at the proximal ramus reduces the implant’s impact on the mandible’s strain ***,structural optimisation allows for a volume reduction of up to 44%with a minimum loss of implant safety and biomechanical performance.

关键词： Temporomandibular joint Additive manufacturing Implant safety Biomechanical performance Finite element analysis

Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?

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Neural Regeneration Research 2019年第11期14卷 1897-1898页

作者： Francisca pinheiro Salvador Ventura Institut de Biotecnologia i Biomedicina Universitat Autonoma de BarcelonaBellaterraSpainDepartament de Bioquimica i Biologia MolecularUniversitat Autonoma de BarcelonaBellaterraSpain

Proteins might misfold during translation and folding or even once they are in their native states, due to stochastic fluctuations, destabilizing mutations or cellular stress. Aberrant protein species are usually detected and either refolded or cleared by the protein quality control machinery (ciechanover and Kwon, 2015). When misfolded protein conformers cannot be degraded, they tend to self-assemble to form aggregates, a characteristic of many neurodegenerative diseases.

关键词： inhibitingα-synuclein aggregation native states protein quality control machinery

Accuracy details in realistic cFD modeling of an industrial centrifugal pump in direct and reverse modes

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Journal of Thermal Science 2010年第6期19卷 491-499页

作者： J.c. Páscoa F. J. Silva J.S. pinheiro D.J. Martins Department of Electromechanical Engineering Center for Aerospace Sciences and Technology University of Beira Interior EFAFLU Bombas e Ventiladores S.A. R. S. Brás 269 Apartado 23 4494-909 Póvoa do Varzim Portugal

Numerical computation of the flowfield inside a pump is herein used as a numerical laboratory, subject to the limitations of modeling assumptions and to experimental verification. A numerical computation of the flow inside a real industrial centrifugal pump is performed that includes a very sophisticated geometry. conversely to other computations, in this test case no simplification of the geometry was introduced. Numerical computations are obtained using Spalart-Allmaras turbulence model. A detailed analysis of the turbulent flowstructure is performed for the design point and two off design conditions. Additional computations were performed in order to compare the numerical and experimental pump characteristics; these were obtained under normalized testing conditions. Further computations are presented for the pump working in reverse turbine mode (PAT). Detailed analyses of the flow allow a comparison of the internal flow losses when the pump is operating in direct and reverse mode. This is also useful to help in the selection of an adequate pump geometry that can work in both modes with best efficiency.

关键词： centrifugal pump impeller turbulence modeling Spalart-Allmaras PAT

colon and rectal cancer:An emergent public health problem

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World Journal of Gastroenterology 2024年第7期30卷 644-651页

作者： Marina pinheiro David Nascimento Moreira Michele Ghidini LAQV REQUIMTEDepartment of ChemistryFaculty of PharmacyUniversity of Porto4050-313 PortoPortugal Unidade de Saúde Pública Unidade Local de Saúde Barcelos/EsposendeBarcelinhos 4755-069BragaPortugal Medical Oncology Unit Fondazione IRCCS Ca’Granda Ospedale Maggiore PoliclinicoMilan 20122Italy

colorectal cancer ranks third globally,with a high mortality *** the United States,and different countries in Europe,organized population screenings exist and include people between 50 and 74 years of *** screenings have allowed an early diagnosis and consequently an improvement in health *** and rectal cancer(cRc)is a disease of particular interest due to the high global burden associated with it and the role attributed to prevention and early diagnosis in reducing morbidity and *** study is a review of cRc pathology and includes the most recent scientific evidence regarding this pathology,as well as a diagnosis of the epidemiological situation of ***,the recommendation from a public health perspective will be discussed in detail taking into account the context and the most current recommendations.

关键词： colon and rectal neoplasia colon and rectal tumor Mortality Morbidity

In vitro toxicity of particulate matter emissions from residential pellet combustion

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Journal of Environmental Sciences 2022年第5期34卷 215-226页

作者： Estela D.Vicente Daniela Figueiredo catia Goncalves Isabel Lopes Helena Oliveira Nora Kovats Teresa pinheiro celia A.Alves Department of Environment and Planning and cESAM-centre for Environmental and Marine Studies University of Aveiro3810-193 AveiroPortugal Department of Biology and cESAM-centre for Environmental and Marine Studies University of Aveiro3810-193 AveiroPortugal centre of Natural Environmental Sciences University of PannoniaEgyetem str.108200 VeszpremHungary Instituto de Bioengenharia e Biociencias Departamento de Engenharia e Ciencias NuclearesInstituto Superior TecnicoUniversidade de LisboaAv.Rovisco Pais 11049-001 LisboaPortugal

Particulate matter emissions(PM10)from the combustion,in a residential stove,of two com-mercial brands of certified(ENplus A1)pellets,a non-certified brand and laboratory made pellets of acacia were tested for their ability to induce ecotoxic,cytotoxic,and mutagenic re-sponses in unicellular organisms and a human cell *** was evaluated through the Vibrio fischeri bioluminescence inhibition ***,cytotoxicity was assessed at two time points(24-and 48-hr)through two complementary techniques in order to evaluate the cellular metabolic activity and membrane integrity of human lung epithelial cells *** Ames test using two Salmonella typhimurium strains(TA100 and TA98)was employed to assess the mutagenic potential of the polycyclic aromatic hydrocarbon fraction extracted from the PM10 *** obtained with the bioluminescent bacteria indicated that only particles from the combustion of acacia pellets were *** samples induced im-pairment on the A549 cells metabolic activity,while no significant release of lactate dehy-drogenase was ***10 emissions from acacia pellets were the most cytotoxic,while samples from both certified pellets evoked significant cytotoxicity at lower ***-icity time-dependency was only observed for PM10 from the combustion of acacia pellets and one of the brands of certified *** activity was not detected in both *** murium *** study emphasises the role of the raw material for pellet manu-facturing on the toxicological profile of PM *** raw materials should be deeply investigated before their use in pelletisation and combustion in residential appli-ances.

关键词： Ecotoxicity cytotoxicity Mutagenicity Fuel quality Pellet combustion PM10 emissions

Lithic soils in the semi-arid region of Brazil:edaphic characterization and susceptibility to erosion

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Journal of Arid Land 2022年第1期14卷 56-69页

作者： carlos R pinheiro JUNIOR conan A SALVADOR Tiago R TAVARES Marcel c ABREU Hugo S FAGUNDES Wilk S ALMEIDA Eduardo c SILVA NETO Lúcia H c ANJOS Marcos G PEREIRA Federal Rural University of Rio de Janeiro(UFRRJ) Department of SoilsSeropédicaRio de Janeiro 23890Brazil center for Nuclear Energy in Agriculture(cENA) University of São Paulo(USP)PiracicabaSão Paulo 13416Brazil Federal Institute of Education Science and Technology of Rondônia(IFRO)Rural ZoneAriquemesRondônia 78930Brazil

Soils(Leptosols or Epileptic Regosols)with lithic contact at a depth of 50 cm occupy almost 20%of the Brazilian semi-arid *** lithic soils are susceptible to erosion due to faster saturation of water-holding capacity during rainfall,which accelerates the beginning of ***,erosion traits of lithic soils in the semi-arid region of Brazil are less *** aim of this study was to characterize the soil and landscape attributes in areas with Neossolos Litólicos(Entisols)in the caatinga biome to identify region of high susceptibility to *** showed that the soils were characterized by a sandy texture,soil structure with poor development and low content of organic *** attributes increase susceptibility to erosion and reduce water storage capacity,especially in the states of cearáand *** these states,the content of rock fragments in the soil reaches 790 g/*** contents of silt and fine sand,high silt/clay ratio,predominance of Leptosols and strong rainfall erosivity were observed in Piauíand northwestern ceará.A very high degree of water erosion was observed in the states of Pernambuco and Paraí*** the low degree of erosion observed in the state of Bahia,it is highly susceptible to erosion due to the predominance of very shallow soils,rugged relief and high values of rainfall *** vulnerability was observed in the state of Alagoas because of its more smoothed relief,greater effective soil depth,thicker A horizon of soil and lower rainfall *** general,the characteristics that intensify the susceptibility to erosion in the caatinga biome are those soil structures with poor development or without aggregation,low contents of organic carbon,high contents of silt and fine sand,high values of silt/clay ratio and rugged relief in some *** study collected information contributing to a better characterization of soils with lithic contact in the semi-arid region of *** addition,regions with

关键词： caatinga biome drylands erosive processes leptosols soil degradation

Stabilisation of estuarine sediments with an alkali-activated cement for deep soil mixing applications

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第4期16卷 1398-1410页

作者： claver pinheiro Sara Rios António Viana da Fonseca Nuno cristelo centre of Physics of Minho and Porto Universities (cF-UM-UP) Azurém CampusUniversity of MinhoGuimarães4800-058Portugal cONSTRUcT-GEO Faculty of EngineeringUniversity of PortoRua Dr.Roberto FriasPortos/n 4200-465Portugal cQ-VR School of Science and TechnologyUniversity of Trás-os-Montes e Alto DouroVila Real5000-801Portugal

In this work,an alternative alkali-activated cement(AAc)made of ladle slag precursor mixed with sodium hydroxide and sodium silicate has been developed to enhance the bearing capacity of estuarine soils in coastal conditions via deep soil mixing(DSM).The AAc was optimized to use a low reactivity precursor(ladle slag)and to deal with a contaminated high-water content natural sediment cured under *** material performance was analysed by comparison to a mixture made with Portland cement and cured in the same *** and unconfined compressive strength tests as well as seismic waves measurements after 3-,7-,14-and 28-d curing were performed to obtain a relationship between elastic stiffness and strength with curing time for both ***,the AAc mix demonstrated superior strength results,exhibiting almost double flexural and compressive strengths after 28 d compared to the Portland cement *** AAc mix also showed a higher rate of stiffness increase than the Portland cement mix,which has a higher initial stiffness at young ages but lower stiffness *** analysis confirmed that the proposed AAc could effectively immobilise any contaminants from soil or *** effect of curing under stress was analysed in triaxial compression tests and found to be insignificant,indicating that laboratory data obtained without stress curing can represent the material's behaviour in a DSM column,which will cure under the weight of the column.

关键词： Alkaline-activation Steel slag Submerged curing Seismic wave measurements Leachate analysis curing under stress