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The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor-insulator transition that has been explored intensively in graphene electronic devices13-17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm-1, and charge-carrier density, n, at around 1 × 1014 cm-2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on-off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode-electrolyte interfaces.
Assuntos
Grafite , Prótons , Grafite/química , Hidrogenação , CatáliseRESUMO
Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.
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Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.
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BACKGROUND: Interest in developing alternative methods for the treatment of amblyopia has long been a topic of interest among clinicians and researchers, as prescribed occlusion and penalization therapies do not always provide an effective response and are associated with a high risk of recurrence and non-compliance. Here, we present the protocol of a small-scale RCT to evaluate the safety and clinical efficacy of a novel VR-based system designed to provide binocular vision training to children with anisometropic amblyopia. METHODS: We aim to recruit a total of 60 children with anisometropic amblyopia aged 5-17 years with no previous treatment for amblyopia other than refractive correction from the pediatric ophthalmology units of the University Clinical Hospital of Valladolid and the Vithas Medimar International Hospital of Alicante. Children who meet the eligibility criteria and consent to participate will be randomly assigned to a three-month intervention group of 18 half-hour in-office therapy sessions with the NEIVATECH system (group A) or to a parallel group receiving 2 hours of conventional patching per day at home for the same period of time (group B). Assessments of visual function will be carried out before the intervention and at 1, 2 and 3 months, with changes in distance BCVA being the primary outcome measure to be considered. Patient safety, compliance, satisfaction and acceptance to treatment will also be assessed after therapy as other valuable outcome measures. In addition, a rsfMRI scan will be performed on a subgroup of 5 patients from each group at the pre-intervention visit and at the post-intervention visit to test the effects of both therapies on neural plasticity in the visual cortex. DISCUSSION: The NEIVATECH system has been conceived as a serious game designed to provide binocular vision training to anisometropic amblyopic children by complementing the concepts of perceptual learning, dichoptic training and gamification in an immersive VR environment. We hope that this novel approach may lead to greater improvements in vision performance than those provided so far by conventional patching in anisometropic amblyopic children. TRIAL REGISTRATION: This protocol was registered with ClinicalTrials.gov ( NCT04819386 ) on 29 March 2021.
Assuntos
Ambliopia , Jogos de Vídeo , Realidade Virtual , Ambliopia/terapia , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Privação Sensorial , Resultado do Tratamento , Visão Binocular/fisiologia , Acuidade VisualRESUMO
PURPOSE: An efficient framework to identify disease-associated genes is needed to evaluate genomic data for both individuals with an unknown disease etiology and those undergoing genomic screening. Here, we propose a framework for gene selection used in genomic analyses, including applications limited to genes with strong or established evidence levels and applications including genes with less or emerging evidence of disease association. METHODS: We extracted genes with evidence for gene-disease association from the Human Gene Mutation Database, OMIM, and ClinVar to build a comprehensive gene list of 6,145 genes. Next, we applied stringent filters in conjunction with computationally curated evidence (DisGeNET) to create a restrictive list limited to 3,929 genes with stronger disease associations. RESULTS: When compared to manual gene curation efforts, including the Clinical Genome Resource, genes with strong or definitive disease associations are included in both gene lists at high percentages, while genes with limited evidence are largely removed. We further confirmed the utility of this approach in identifying pathogenic and likely pathogenic variants in 45 genomes. CONCLUSION: Our approach efficiently creates highly sensitive gene lists for genomic applications, while remaining dynamic and updatable, enabling time savings in genomic applications.
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Genômica , Bases de Dados Factuais , Humanos , MutaçãoRESUMO
AIM: As options to treat recalcitrant bacterial infections which are increasingly limited due to multidrug-resistant strains, searching for new, effective antibacterial compounds is necessary. One strategy is to generate treatment alternatives by drug repurposing. METHODS AND RESULTS: In this work, phenotypic microarrays were used for the screening of miscellaneous compounds against the growth and biofilm formation of Acinetobacter baumannii, an important emergent multidrug-resistant opportunistic pathogen. The results showed that the phenothiazine derivatives, such as promethazine, trifluoperazine, thioridazine, and chlorpromazine, inhibited the growth of antibiotic-sensitive and multidrug-resistant strains (showing minimal inhibitory concentrations ranging from 0·05 to 0·6 g l-1 and minimal bactericidal concentrations ranging from 0·1 to 2·5 g l-1 ). All phenothiazine derivatives were active against biofilm cells (with minimal biofilm eradication concentrations ranging from 0·5 to >3 g l-1 ). Chlorpromazine promoted reactive oxigen species (ROS) production, and cell membrane and DNA damage. Chlorpromazine showed synergy with antibiotics such as ceftazidime, meropenem, and colistin and was an effective treatment for experimentally infected Galleria mellonella when combined with ceftazidime. CONCLUSIONS: It was demonstrated that phenothiazine derivatives, especially chlorpromazine, are drugs with attractive antibacterial properties against nosocomial MDR strains of A. baumannii, by generating ROS and cell membrane and DNA damage. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study indicates that repurposing phenothiazine derivatives for treating recalcitrant infections by A. baumannii could be promising.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Fenotiazinas/farmacologiaRESUMO
Diethyldithiophosphate (DEDTP) is a metabolite produced by the degradation of organophosphorus pesticides and a dialkylphosphate that is chemically synthesized with widespread commercial use. DEDTP is a stable compound, and most studies considered it harmless. However, some studies found adverse effects in vitro, including toxicity in different human cell types. However, there are no in vivo studies characterizing the toxicological effects of DEDTP. Therefore, we investigated the genotoxicity and immunotoxicity of DEDTP in a murine model. We used C57BL/6J and Balb/c mice (6-8-weeks-old) exposed to DEDTP i.p. We established that the medium lethal dose (LD50) of DEDTP was 0.537â¯g/kg. DEDTP was genotoxic in vivo because it increased the frequency of micronuclei in polychromatic erythrocytes in peripheral blood at 0.05â¯g/kg. DEDTP showed immunotoxic effects on T and Natural Killer cells and immunomodulatory effects on macrophages, especially M2 type that increased 1000% after 20â¯days of exposure to 0.01â¯g/kg. These effects modified the response to a tumoural challenge. DEDTP exposure increased tumour size and reduced the response of lymphocytes to tumoural antigen stimulation. We conclude that exposure to DEDTP produced genotoxic and immunomodulatory effects at environmentally relevant concentrations, which affected the growth of tumours in vivo. These results suggest that DEDTP might reduce the quality of life in exposed individuals, and it exhibits genotoxicity and immunotoxicity despite its stability.
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Eritrócitos/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Organofosfatos/toxicidade , Organotiofosfatos/toxicidade , Praguicidas/toxicidade , Animais , Biomarcadores/sangue , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Eritrócitos/patologia , Feminino , Sistema Imunitário/metabolismo , Sistema Imunitário/patologia , Dose Letal Mediana , Masculino , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Testes para Micronúcleos , Medição de Risco , Fatores de Tempo , Testes de Toxicidade Aguda , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. TRIAL REGISTRATION: NCT02996630 , on 4th December 2016 (retrospectively registered).
Assuntos
Desenvolvimento Infantil , Ensaios Clínicos como Assunto , Cardiopatias Congênitas/complicações , Transtornos do Neurodesenvolvimento/etiologia , Biomarcadores/sangue , Ecocardiografia , Feminino , Idade Gestacional , Cardiopatias Congênitas/sangue , Humanos , Lactente , Imageamento por Ressonância Magnética , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Prognóstico , Estudos ProspectivosRESUMO
Taeniids tapeworms are hermaphroditic helminths that gradually develop testis and ovaries in their reproductive units. The larval stage of the tapeworms named cysticercus is a vesicle that contains the scolex and proliferates asexually in the abdominal cavity of mice. Once in the host, they evaginate, attach to the gut and develop into an adult organism, the tapeworm. We have previously reported reported that T. crassiceps ORF and solium cysticerci transform steroid precursors to androgens and estrogens. Taenia crassiceps WFU cysticerci can also synthesize corticosteroids. The aim of the present work is to investigate the relationship between steroid synthesis ability and the developmental stage of the parasite T. crassiceps WFU. To this purpose, cysticerci were obtained from the abdominal cavity of female mice, manually separated in invaginated (IC) and evaginated parasites (EC) and preincubated for 24â¯h in DMEM plus antibiotics/antimycotics. Next step consisted in incubation for different periods in the fresh media added with tritiated androstenedione (3H-A4) or progesterone (3H-P4) and incubated for different periods. Taenia crassiceps WFU tapeworms were recovered from the intestine of golden hamsters that had been orally infected with cysticerci. The worms were pre-cultured in DMEM plus FBS and antibiotics, and then incubated without FBS for different time periods, in the presence of 3H-A4 or 3H-P4. At the end of the experiments the media from cysticerci and tapeworms were analyzed by thin layer chromatography. Results showed that testosterone synthesis was significantly higher in the evaginated cysticerci and increased with time in culture. The invaginated and evaginated cysticerci also synthesized small quantities of 17ß-estradiol (E2) and estrone. The evaginated cysticerci synthesized twice more 3H-deoxycorticosterone (3H-DOC) than the invaginated parasites, the production increased significantly with time in culture. Taenia crassiceps WFU tapeworms synthesized significant quantities of 3H-testosterone and small amounts of estrone after only 3â¯h of culture in the presence of 3H-A4. The tapeworms also transformed 3H-P4 to 3H-DOC and increased its synthesis after 24â¯h in culture. In summary, our data show the pathways that T. crassiceps WFU cysticerci use to synthesize sexual steroids in both larval developmental stages and reveals the steroidogenic capacity of the tapeworms.
Assuntos
Parasitos/crescimento & desenvolvimento , Esteroides/metabolismo , Androstenodiona/metabolismo , Animais , Cysticercus , Feminino , Camundongos , TaeniaRESUMO
Jacareubin is a xanthone isolated from the heartwood of Calophyllum brasiliense with antibacterial and gastroprotective properties and the intention for clinical use as an anti-cancer treatment (due to the similar chemical structure to other anti-neoplastic drugs) requires an investigation of whether this compound can generate adverse effects on non-transformed cells. Jacareubin (0.5-1000µM in DMSO) was more cytotoxic on phytohemagglutinin (PHA)-stimulated normal human peripheral blood mononuclear cells (PBMCs; IC50 at 72h by MTT: 85.9µM) than on G0 phase-PBMCs (IC50 315.6µM) using trypan blue exclusion and formazan metabolism assays. Jacareubin had lower toxicity on PBMCs than Taxol (1µM). Jacareubin presented cytostatic activity because it inhibited PHA-stimulated PBMCs proliferation (from 2.5µM; CFSE dilution and replication index). Jacareubin induced PBMCs arrest in G0/G1 phase of the cell cycle (from 5µM) as evaluated by DNA content. Moreover, Jacareubin generated genotoxicity by breaking DNA strands selectively in PHA-stimulated PBMCs (from 5µM) rather than on resting PBMCs using the single-cell gel electrophoresis assay and increasing the frequency of micronucleated (MN) PBMCs in vitro (from 5µM) and frequency of hypodiploid cells (from 10µM). When 100mg/kg Jacareubin was injected i.p. into mice (a fifth of the LD50; 0.548g/kg. Approximately to 300µM in vitro), we observe no increase in the MN level in bone marrow cells. Jacareubin can be consider for further anti-tumoural activity due to its preferential genotoxic, cytotoxic and cytostatic actions on proliferating cells rather than on resting cells and the lack of in vivo genotoxicity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Calophyllum/química , Dano ao DNA , Eritrócitos/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Extratos Vegetais/farmacologia , Xantonas/farmacologia , Adulto , Aneuploidia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Eritrócitos/patologia , Humanos , Concentração Inibidora 50 , Leucócitos Mononucleares/patologia , Masculino , Camundongos Endogâmicos BALB C , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Medição de Risco , Fatores de Tempo , Xantonas/isolamento & purificação , Xantonas/toxicidade , Adulto JovemRESUMO
We present a combined experimental and theoretical study dedicated to analyzing the structural stability and chemical reactivity of single walled carbon nanotubes (SWCNTs) in the presence of air and nitrogen atmospheres in the temperature interval of 300-1000 K. The temperature dependence of the radial breathing mode (RBM) region of the Raman spectra is irreversible in the presence of air, but it is reversible up to 1000 K in a nitrogen atmosphere. Our density functional theory (DFT) calculations reveal that irreversibility is due to partial degradation of SWCNTs produced by dissociative chemical adsorption of molecular oxygen on intrinsic defects of the nanotube surface. Oxygen partially opens the nanotubes forming semi-tubes with a non-uniform diameter distribution observed by Raman scattering. In contrast, heating CNTs in a nitrogen atmosphere seems to lead to the formation of nitrogen-doped SWCNTs. Our DFT calculations indicate that in general the most common types of nitrogen doping (e.g., pyridinic, pyrrolic, and substitutional) modify the location of the RBM frequency, leading also to frequency shifts and intensity changes of the surrounding modes. However, by performing a systematic comparison between calculated and measured spectra we have been able to infer the possible adsorbed configurations adopted by N species on the nanotube surface. Interestingly, by allowing previously nitrogen-exposed SWCNTs to interact with air at different temperatures (up to 1000 K) we note that the RBM region remains nearly unperturbed, defining thus our nitrogen-pretreated SWCNTs as more appropriate carbon nanostructures for high temperature applications in realistic environments. We believe that we have implemented a post-growth heat-treatment process that improves the stability of carbon nanotubes preserving their diameter and inducing a defect-healing process of the carbon wall.
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The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Assuntos
Rejeição de Enxerto/mortalidade , Aspergilose Pulmonar Invasiva/mortalidade , Falência Renal Crônica/complicações , Transplante de Rim/mortalidade , Complicações Pós-Operatórias/mortalidade , Aspergillus , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Agências Internacionais , Aspergilose Pulmonar Invasiva/etiologia , Aspergilose Pulmonar Invasiva/patologia , Falência Renal Crônica/cirurgia , Testes de Função Renal , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , TransplantadosRESUMO
Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.
Assuntos
Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/etiologia , Aspergilose Pulmonar Invasiva/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Estudos de Casos e Controles , Função Retardada do Enxerto/patologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Aspergilose Pulmonar Invasiva/patologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , TransplantadosRESUMO
Asexually proliferating Taenia crassiceps (Zeder, 1800) metacestodes isolated within past decades have been successfully sub-cultured under experimental conditions using Mus musculus Linnaeus, 1758 mice. However, during their development, morphological irregularities of scolex structures have been reported in two of the three strains of this cestode species maintained in mice - ORF and KBS. The main goal of this work is to describe the abnormalities observed in a sample of 118 cysticerci of the third T. crassiceps strain used at present - WFU. Morphological abnormalities were detected in 39.8% of the evaginated scoleces; they consisted of supernumerary suckers (n= 2), duplicated (n= 2) or absent rostellum (n= 1), as well as absent or aberrant (n= 29) hooks, which were significantly shorter when compared to the large and short hook lengths referred to in the literature.
Assuntos
Adaptação Biológica , Taenia/anatomia & histologia , Taenia/crescimento & desenvolvimento , Animais , Biometria , Cysticercus/anatomia & histologia , Variação Genética , Camundongos , MicroscopiaRESUMO
Evidence suggests the involvement of the cannabinoid system in the pathogenesis of multiple sclerosis (MS). We studied cannabinoid receptor (CB)1 and CB2 receptor gene expression in B, natural killer (NK) and T cells from MS patients before and after 1 year of interferon beta therapy, and compared these levels to those of healthy controls. We also measured the production of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and the gene expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in these cells. Prior to interferon therapy, MS patients showed significantly elevated CB2 expression in B cells, but not in T or NK cells. These levels decreased gradually within 6 months to 1 year of interferon treatment. CB1 expression was elevated in all cell subsets, but only reached statistical significance in T cells; all levels decreased progressively over time. Before treatment, AEA but not 2-AG levels were significantly elevated in the three cell populations; after 1 year of treatment, all values decreased to control levels. The expression of FAAH was unchanged. The different expression of cannabinoid receptor genes and the increased level of AEA in lymphocytes point to a possible role of the cannabinoid system in MS immune response and its modulation by interferon.
Assuntos
Endocanabinoides/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interferon beta/farmacologia , Subpopulações de Linfócitos/metabolismo , Esclerose Múltipla/genética , Esclerose Múltipla/metabolismo , Receptores de Canabinoides/genética , Adolescente , Adulto , Amidoidrolases/genética , Amidoidrolases/metabolismo , Feminino , Humanos , Interferon beta/uso terapêutico , Estudos Longitudinais , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/metabolismo , RNA Mensageiro/genética , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Adulto JovemRESUMO
Intercellular adhesion modulated by cadherin molecules plays an important role in diverse cellular functions including tissue morphogenesis, regeneration, and pathogenesis. However, it is a challenging task to decipher the effects of cell-cell adhesion in vitro because of difficulty in controlling the extent and numbers of cell-cell contacts. In this study, we hypothesize that tethering recombinant extracellular domains of neural cadherin with a C-terminal immunoglobulin Fc domain (N-Cad-Fc) to a substrate with an immobilized anti-Fc antibody (Fc-antibody) and a bifunctional polymer, which is reactive to both protein and substrate, would allow us to recapitulate cell-cell adhesion, independent of the number of cells plated on the substrate. To examine this hypothesis, we first immobilized Fc-antibody to a polyacrylamide hydrogel and a methacrylate-substituted glass using poly(amino-2-hydroxyethyl-co-2-methacryloxyethyl aspartamide)-g-poly(ethylene glycol)-N-hydroxysuccinimide ester (PHMAA-g-PEGNHS) and then incubated the gel in medium containing defined concentrations of the recombinant N-Cad-Fc. The resulting N-Cad-conjugated substrate enabled us to modulate adhesion of bone marrow stromal cells to the gel surface by varying the surface density of N-Cad-Fc. In contrast, direct chemical conjugation of N-Cad-Fc to the gel surface did not support cell adhesion. Additionally, the glass substrate biologically tethered with N-Cad-Fc promoted neuronal adhesion significantly more than substrates coated with poly-l-lysine. We suggest that this novel biological tethering method could be broadly applicable for modifying substrates with a variety of classical cadherins to enable the systematic study of the effects of cadherin-modulated cell-cell adhesion on cellular activities.
Assuntos
Antígenos CD/metabolismo , Células da Medula Óssea/metabolismo , Caderinas/metabolismo , Adesão Celular/fisiologia , Animais , Antígenos CD/química , Caderinas/química , Células Cultivadas , Células HEK293 , Humanos , Camundongos , Especificidade por Substrato/fisiologiaRESUMO
Reports of renal neoplasia are rare in neotropical wildcats. Ocelots (Leopardus pardalis) are medium-sized wildcats living in America's tropical forests. A 12-year-old captive ocelot was diagnosed with a renal mass occupying approximately 25% of the total right kidney volume. The tissue was stained with routine hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). Immunohistochemistry with the following markers was performed: cytokeratin (CK) AE1/AE3, CK19, CK 7, CD10, vimentin, Melan A, HMB45, Pax-8, and Wilms' tumor 1 (WT1). Histopathology revealed a well-differentiated epithelial tubular neoplasia with less than one mitotic figure per 2.37mm2 field. Vimentin and Pax-8 were the only positive markers. Immunohistochemically, neoplasia was diagnosed as a renal adenoma. Renal adenomas are seldom reported in neotropical wildcats. Reports on wild species are valuable for properly establishing a clinical prognosis for captive species. To the best of our knowledge, this is the first report that provides detailed microscopic and immunohistochemical descriptions of renal adenoma in a captive ocelot.
RESUMO
Engagement in physical activity, across various sports, promotes a diverse microbiota in active individuals. This study examines the gut microbiota of Colombian athletes, specifically weightlifters (n = 16) and road cyclists (n = 13), compared to non-athletes (n = 15). Using Kruskal-Wallis tests, the physical activity level of a group of non-athletic individuals and the sports experience of a group of professional athletes is analyzed. The median age of participants is 24 years, comprising 25 men and 19 women. The microbiota is collected using fecal samples. Participants provided these samples during their pre-competitive stage, specifically during the concentration phase occurring two weeks prior to national competitions. This timing is chosen to capture the microbial composition during a period of heightened physical preparation. Questionnaire responses and microbial composition assessments identify disparities among groups. Microbial composition analysis explores core microbiome, abundance, and taxonomy using Pavian, MicrobiomeAnalyst 2.0, and GraPhlAn. ANCOM-BC2 reveals differentially abundant species. Road cyclists exhibit decreased Bacteria and increased Archaea abundance. Phylum-level variations included Planctomycetes, Acidobacteria, and Proteobacteria, while Bacteroidetes prevailed. Key families influencing gut microbiota are Bacteroidaceae, Muribaculaceae, and Selenomonadaceae. Weightlifters exhibit unique viral and archaeal community connections, while cyclists showed specialized microbial interplay influenced by endurance exercise. Correlation network analysis emphasizes distinctive microbial interactions within athlete groups, shedding light on the impact of physical activities on gut microbiota and athlete health.
Assuntos
Archaea , Atletas , Bactérias , Ciclismo , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Colômbia , Adulto , Atletas/estatística & dados numéricos , Archaea/isolamento & purificação , Adulto Jovem , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Levantamento de Peso/fisiologia , Fezes/microbiologiaRESUMO
The present work investigates the quality and the chemical effects of dehydration, using a novel dehydration system based on an electromagnetic induction and low pressures technique, comparing it with the thermo-solar drying system. High oleic sunflower seeds, which are an important oil seed crop, were used due to the fact that they have a special place in the food industry. The seed samples were exposed to electromagnetic induction and low pressures by 0.5 and 1 h, then several chemical characterizations were carried out, in the electrophoresis study, it was found that most proteins in the hull were degraded or denatured, some of them were lost during the time in the thermosolar dryer while in kernel keeps 94.9% of the concentration in control proteins. Otherwise, the electromagnetic induction dryer did not lose the most of proteins in the kernel keeping 99.1% in 0.5 h and 98.4% in 1 h, just degrading its concentration. Germination viability results did not show changes after 0.5 h in the electromagnetic fields, but they decreased in 1 h from 66 to 40% until the thermosolar method fell to 24% in 4 h, both analysis results change proportionally with the treatment time and moisture content and the amount of the oxygen.
Assuntos
Germinação , Helianthus , Sementes , Helianthus/química , Sementes/química , Germinação/efeitos dos fármacos , Proteínas de Plantas , Dessecação/métodos , Água/química , DesidrataçãoRESUMO
AIM: The aim of the study was to assess the safety and feasibility of laparoscopic surgery for transverse colon cancer and to compare the clinicopathological outcome with that of conventional open surgery. METHOD: From March 1998 to December 2009, 1253 patients with colorectal tumours were operated on, 564 laparoscopically. There were 154 cases of transverse colon cancer, 86 of which were included in the study. Details were collected on age, sex, body mass index (BMI), operation time, blood loss, time to first flatus, time to resume a liquid diet, postoperative length of hospital stay, complications, TNM stage, tumour size, distal resection margin, proximal resection margin, number of nodes harvested and surgical procedure. Laparoscopic and open surgical removal was compared. RESULTS: No significant differences were found between laparoscopic and conventional groups in age, sex, BMI, operation time or postoperative length of hospital stay. The mean blood loss during the operations was significantly less in the laparoscopic group (105.9 ± 140.9 ml vs 305.7 ± 325.3 ml; P = 0.05). The time to the first flatus was shorter (2.1 ± 0.3 days vs 3.8 ± 3.0 days; P = 0.043) and diet was started earlier (3.1 ± 1.4 days vs 3.4 ± 1.5 days) in the laparoscopic group. No significant differences in tumour size, proximal resection margin or number of lymph nodes were observed. The mean distal resection margin was not statistically different (10.3 ± 4.5 cm vs 8.8 ± 4.9 cm). At a mean follow up of 33 ± 2.3 months, nonport-site metastases occurred in eight patients and locoregional recurrence occurred in three, with no significant difference between the groups. The 3-year cumulative overall survival rate was 78%, and the disease-free survival rate was 69%. CONCLUSION: There was no difference in the outcome of laparoscopic and open surgery for transverse colon cancer, including the cancer-specific outcome.