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1.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33941687

RESUMO

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.


Assuntos
Dispositivos Lab-On-A-Chip , Modelos Biológicos , Alvéolos Pulmonares/fisiologia , Células Epiteliais Alveolares , Antivirais/farmacologia , Fumar Cigarros/efeitos adversos , Dimetilpolisiloxanos/química , Gelatina/química , Humanos , Hidrogéis/química , Metacrilatos/química , Porosidade , Alvéolos Pulmonares/citologia , Alvéolos Pulmonares/patologia , Respiração , Mucosa Respiratória/citologia , Mucosa Respiratória/fisiologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade
2.
Int J Mol Sci ; 25(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673814

RESUMO

Over the past three decades, the synthesis of new ionic liquids (ILs) and the expansion of their use in newer applications have grown exponentially. From the beginning of this vertiginous period, it was known that many of them were hygroscopic, which in some cases limited their use or altered the value of their measured physical properties with all the problems that this entails. In an earlier article, we addressed the hygroscopic grade achieved by the ILs 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium methyl sulfate, 1-ethyl-3-methylimidazolium ethyl sulfate, 1-ethyl-3-methylpyridinium ethyl sulfate, 1-ethyl-3-methylimidazolium tosylate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-dodecyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylpyridinium tetrafluoroborate, 1-butyl-1-methylpiperidinium bis(trifluoromethyl sulfonyl)imide, 1-methyl-1-propylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, and methyl trioctyl ammonium bis(trifluoromethyl sulfonyl)imide. The objective was to determine the influence of the chemical nature of the compounds, exposed surface area, sample volume, agitation, and temperature. For this purpose, we exposed the samples to abrupt increases in relative humidity from 15 to 100% for days in an atmosphere chamber and then proceeded with the reverse process in a gentle manner. The results show that the sorption of water from the atmosphere depends on the nature of the IL, especially the anion, with the chloride anion being of particular importance (chloride ≫ alkyl sulfates~bromide > tosylate ≫ tetrafluoroborate). It has also been proven for the EMIM-ES and EMIM-BF4 samples that the mechanism of moisture capture is both absorption and adsorption, and that the smaller the exposed surface area, the higher the ratio of the mass of water per unit area.


Assuntos
Ânions , Cátions , Líquidos Iônicos , Líquidos Iônicos/química , Ânions/química , Cátions/química , Imidazóis/química , Molhabilidade , Água/química
3.
J Environ Manage ; 354: 120146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341911

RESUMO

This study deals with energy and agronomic valorisation by anaerobic co-digestion with temperature and microorganism phase separation of sewage sludge, vinasse and poultry manure, with the aim of achieving an integral waste management, obtaining bioenergy and biofertilizer that returns nutrients to the soil in a natural way. The yields obtained were 40 mL H2/gVS and 391 mLCH4/gVS. The resulting effluent showed more than 98 % removal of E. coli and Total Coliforms, as well as total removal of Salmonella. The results obtained in the phytotoxicity tests showed that all the proportions studied had phytostimulant and phytonutrient properties, with 20 % having the highest germination index (GI) with mean values of 145.30 %. Finally, the agronomic trial carried out with strawberry crops (Fragaria sp.) showed that the addition of this biosolid has fertilising properties and can be used as an agronomic amendment, with an increase of 145 % in fresh weight and 102.5 % in dry weight, and fruit production doubled with respect to the control. The ANOVA statistical study corroborated that there were significant differences in crop growth when applying different proportions of biofertilizer in the fertilizer. Therefore, these results show that this technology is promising and would contribute environmentally, socially and economically to the transfer towards a circular economy model.


Assuntos
Esterco , Esgotos , Animais , Anaerobiose , Biossólidos , Aves Domésticas , Separação de Fases , Temperatura , Escherichia coli , Digestão , Reatores Biológicos , Biocombustíveis , Metano
4.
Int J Dent Hyg ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394062

RESUMO

INTRODUCTION: Dental caries continues to be a public healthcare problem due to its high prevalence and morbidity. It was proposed to evaluate caries indicators in relation to healthcare access and hygienic-dietary habits in Spanish preschoolers. MATERIALS AND METHODS: A cross-sectional study was carried out on a random sample consisting of 343 patients ranging from 3 to 5 years of age in the primary care setting, the main measurements were: dental care access, hygienic-dietary habits, and caries registration according to WHO criteria. RESULTS: The prevalence of caries was 35.3% and mean ± standard deviation (SD) dft was 1.51 ± 2.93. Preschoolers who had ever visited the dentist had a higher dft occurrence than those who had never attended the dentist. The lower prevalence of caries was significantly associated with the frequency of two daily brushings versus non-daily brushing (p = 0.007; 25.3% vs. 47.1%) and was 10.7% lower in patients who had the habit of night brushing (p = 0.041). The consumption of sugary liquids between meals implied a higher dft index. CONCLUSIONS: The high prevalence of early childhood caries and the dental care access associated with poor oral health suggest the need to implement a multidisciplinary oral healthcare program that involves both healthcare and dental healthcare professionals in Primary Health Care Units without forgetting the participation of the community and local administrations.

5.
J Environ Manage ; 325(Pt A): 116419, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36257226

RESUMO

Anaerobic co-digestion (AcoD) is a mature and consolidated waste management technology that can transform agro-industrial by-products into biogas and digestate. This study conducted a techno-economic assessment of bioenergy and agricultural fertilizer production from AcoD of sewage sludge, wine vinasse, and poultry manure. In this case study, three configurations were investigated: i) Scenario 1, AcoD in thermophilic temperature; ii) Scenario 2, AcoD in mesophilic temperature; and iii) Scenario 3, AcoD in a temperature phase (TPAD) system, where the digestate produced in the first reactor (thermophilic) feeds the second reactor (mesophilic). The process was designed to manage 24,022 m³ wine vinasse y-1, 24,022 m³ sewage sludge y-1, and 480 m³ poultry manure y-1. The major cost was the fixed capital investment for the single-stage (320,981 USD) and TPAD processes (379,698 USD). The TPAD process produced the highest electricity (1058.99 MWh y-1) and heat (4765.47 GJ y-1) with the lowest cost of manufacturing for electricity (84.99 USD MWh-1), heat (0.019 USD MJ-1), and fertilizer (30.91 USD t-1). Regarding the profitability indicators, the highest net present value (509,011 USD) and the lowest payback time (4.24 y) were achieved for Scenario 3. In conclusion, TPAD is a profitable and sustainable waste-to-energy management technology that can be applied in a circular economy framework to recover bioenergy and fertilizer, contributing to decreasing the carbon footprint of the agri-food sector.


Assuntos
Esgotos , Vinho , Animais , Esterco , Anaerobiose , Reatores Biológicos , Aves Domésticas , Temperatura , Fertilizantes , Biocombustíveis , Digestão , Metano
6.
Sensors (Basel) ; 22(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35957324

RESUMO

The complexity of mandibular dynamics encourages constant research as a vehicle to improve oral health. The gold standard motion capture system might help us to understand its functioning and its relation to body position, aiming to perform an exhaustive bibliographic review in the Dentistry field. Six different electronic databases were used (Dentistry & Oral Sciences Source, Scopus, Web of Science, PubMed, CINAHL and SPORTDiscus) in April 2022. The selection criteria includes a biography, critical analysis, and the full text from 1984 to April 2022, based on the odontological gold standard, whether or not in combination with additional devices. Clinical cases, bibliographic reviews or meta-analysis and grey literature were excluded. The checklist of the critical assessment methodology by Joanna Brigs was used (JBI). After choosing scientific articles published in peer-reviewed journals, 23 out of 186 investigations were classified as eligible with a total of 384 participants. The issue being addressed is related to the speech properties, posture and body movement in relation to dento-oro-facial muscle and facial analysis, mandibular kinematics and mandibular dynamics during the mastication process. The markers arrangement depends on the dynamic to be analysed. From a physiologic and pathologic perspective, the applications of the optic system are relevant in Dentistry. The scarcity of literature obtained implies the need for future research.


Assuntos
Lista de Checagem , Mastigação , Fenômenos Biomecânicos , Humanos , Músculos
7.
Molecules ; 27(19)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36234823

RESUMO

The detection of analytes in complex organic matrices requires a series of analytical steps to obtain a reliable analysis. Sample preparation can be the most time-consuming, prolonged, and error-prone step, reducing the reliability of the investigation. This review aims to discuss the advantages and limitations of extracting bioactive compounds, sample preparation techniques, automation, and coupling with on-line detection. This review also evaluates all publications on this topic through a longitudinal bibliometric analysis, applying statistical and mathematical methods to analyze the trends, perspectives, and hot topics of this research area. Furthermore, state-of-the-art green extraction techniques for complex samples from vegetable matrices coupled with analysis systems are presented. Among the extraction techniques for liquid samples, solid-phase extraction was the most common for combined systems in the scientific literature. In contrast, for on-line extraction systems applied for solid samples, supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, and pressurized liquid extraction were the most frequent green extraction techniques.


Assuntos
Cromatografia com Fluido Supercrítico , Verduras , Micro-Ondas , Reprodutibilidade dos Testes , Extração em Fase Sólida
8.
N Engl J Med ; 379(23): 2209-2219, 2018 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-30345907

RESUMO

BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7×10-17). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10-35) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10-49). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10-5), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10-6). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).


Assuntos
Artrite Reumatoide/genética , Mutação com Ganho de Função , Doenças Pulmonares Intersticiais/genética , Mucina-5B/genética , Idoso , Artrite Reumatoide/complicações , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Fibrose Pulmonar Idiopática/genética , Pulmão/química , Pulmão/patologia , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade , Mucina-5B/análise , Razão de Chances , Regiões Promotoras Genéticas
9.
Eur Respir J ; 57(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32646919

RESUMO

QUESTION ADDRESSED BY THE STUDY: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD. METHODS: Through a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. RESULTS: Analysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Pulmonares Intersticiais , Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Estudos de Casos e Controles , Humanos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/tratamento farmacológico , Metotrexato/efeitos adversos
10.
Rheumatology (Oxford) ; 60(11): 5028-5041, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33580257

RESUMO

OBJECTIVE: To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD). METHODS: (1) Analysis of SSc patients from the EUSTAR database: 144 anti-PM/Scl+ without SSc-specific autoantibodies were compared with 7202 anti-PM/Scl-, and then to 155 anti-Pm/Scl+ with SSc-specific antibodies. (2) Case-control study: additional data were collected for 165 anti-PM/Scl+ SSc patients (85 from the EUSTAR registry) and compared with 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration and age at SSc onset. RESULTS: Patients with isolated anti-PM/Scl+, as compared with anti-Pm/Scl-, had higher frequency of muscle involvement, ILD, calcinosis and cutaneous signs of DM, but similar frequency of SRC and malignancies (either synchronous with SSc onset or not). The presence of muscle involvement was associated with a more severe disease phenotype. Although very frequent, ILD had a better functional outcome in cases than in controls. In patients with both anti-PM/Scl and SSc-specific antibodies, a higher frequency of typical SSc features than in those with isolated anti-PM/Scl was observed. CONCLUSION: The analysis of the largest series of anti-PM/Scl+ SSc patients so far reported helps to delineate a specific clinical subset with muscle involvement, cutaneous DM, calcinosis and ILD characterized by a good functional outcome. SRC and malignancies do not seem to be part of this syndrome.


Assuntos
Exorribonucleases/imunologia , Complexo Multienzimático de Ribonucleases do Exossomo/imunologia , Sistema de Registros , Escleroderma Sistêmico/imunologia , Adulto , Autoanticorpos , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia
11.
J Tissue Viability ; 29(4): 310-318, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32912759

RESUMO

AIMS: To evaluate a prevention strategy implemented to reduce incidence and severity of positioning related pressure injuries affecting pediatric patients in a pediatric critical care unit. Secondary objective was to evaluate compliance with preventive recommendations. BACKGROUND: The skin in infants or children has important physiological and anatomical differences compared with adults. Further, factors such as the immaturity of the skin and limited activity and mobility in pediatric critical care unit, along with the pressure exerted by medical devices, increases the risk of pressure ulcers in infants and children. The most effective preventive measures specific to this intensive care population need to be evaluated. MATERIAL AND METHODS: Quasi-experimental before-after study with consecutive sampling. The effectiveness of the care bundle implementation was evaluated based on the latest evidence (intervention group) versus the application of non-standardized care (control group). Pediatric patients up to 14 years old at risk of suffering from pressure injuries and who were admitted more than 48 h in a pediatric intensive care unit (level III) participated. For the collection of data, two computer programs and the hospital clinical records of each participant were consulted. The data collection period was 6 months per group (pre and post intervention). RESULTS: A sample of 110 patients was obtained (50 control group and 60 intervention group). The cumulative incidence in pediatric patients exposed to the risk of pressure injuries was reduced from 16% to 13.3%; and in the subgroup of patients with prolonged stay (≥28 days), the incidence was reduced from 55.55% to 20%. In the intervention group, category III and IV pressure ulcers were completely reduced. In addition, the total number of pressure injuries decreased by 21.43%. The care bandle recommendations with the highest level of adhesion recorded were: skin inspection, application of hyperoxygenated fatty acids and use of a special support surface. The main risk factor found during the study was the prone position (p < 0.05). CONCLUSIONS: The application of a care bundle for prevention can be an effective solution to reduce the number and severity of LPPs in an intensive care unit. The most vulnerable subgroup of patients may benefit from the application of these resources.


Assuntos
Úlcera por Pressão/prevenção & controle , Adolescente , Criança , Pré-Escolar , Estado Terminal/terapia , Feminino , Humanos , Incidência , Lactente , Unidades de Terapia Intensiva Pediátrica/organização & administração , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Posicionamento do Paciente/efeitos adversos , Posicionamento do Paciente/métodos , Pediatria/métodos , Úlcera por Pressão/fisiopatologia , Fatores de Risco , Higiene da Pele/métodos
12.
J Hepatol ; 71(1): 45-51, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30853642

RESUMO

BACKGROUND & AIMS: People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. METHODS: The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. RESULTS: Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%-96%) never injectors, 673 (92%, 95% CI 89%-93%) PWID not on OAT and 177 (89%, 95% CI 83%-92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p <0.001). Among ongoing drug users, 15 (17%) were lost-to-follow-up, and 3 (3.5%) became reinfected. In the per protocol analysis, 97% never injectors, 95% PWID not on OAT and 95% PWID on OAT achieved SVR12 (p = 0.246). After adjustment, ongoing drug use was associated with SVR12 (intention-to-treat) and OAT use was not. CONCLUSIONS: HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. LAY SUMMARY: Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.


Assuntos
Antivirais , Infecções por HIV , Hepacivirus , Hepatite C Crônica , Transtornos Relacionados ao Uso de Opioides , Abuso de Substâncias por Via Intravenosa , Adulto , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/etiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Adesão à Medicação , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/terapia , Transtornos Relacionados ao Uso de Opioides/virologia , Abuso de Substâncias por Via Intravenosa/terapia , Abuso de Substâncias por Via Intravenosa/virologia , Resposta Viral Sustentada , Resultado do Tratamento
13.
J Viral Hepat ; 26(1): 16-24, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30141222

RESUMO

Among patients with cirrhosis, recovery of liver function after SVR to all-oral direct-acting antivirals (DAA) in HIV/HCV coinfection could be different to that in HCV monoinfection. Because of this, we compared the changes in several markers of liver function between HCV-monoinfected and HIV/HCV-coinfected patients with cirrhosis who achieved SVR12 to DAA combinations. In this retrospective cohort study, cirrhotics included in the HEPAVIR-DAA and GEHEP-MONO cohorts were selected if they had SVR12 to all-oral DAAs. Patients treated with atazanavir were excluded. Liver function improvement was defined as Child-Pugh-Turcotte (CPT) decrease ≥1 and/or MELD decrease ≥2 between baseline and SVR12. Liver function worsening was defined as a CPT increase ≥1 and/or MELD increase ≥2 and/or decompensations between baseline and SVR12. We included 490 patients, 270 (55%) of them with HIV coinfection. Liver function improved in 50 (56%) HCV-infected individuals and in 82 (57%) HIV/HCV-coinfected patients (P = 0.835). Liver function worsened in 33 (15%) HCV-monoinfected patients and in 33 (13%) HIV/HCV-coinfected patients (P = 0.370). Factors independently related with liver function improvement were male gender [adjusted OR (AOR) 2.1 (95% confidence interval, 95% CI: 1.03-4.2), P = 0.040], bilirubin < 1.2 mg/dL (AOR 1.8 [95% CI: 1.004-3.3], P = 0.49), and INR < 1.3 (AOR 2.4 [95% CI: 1.2-5.0], P = 0.019) at baseline. After multivariate analysis, albumin < 3.5 g/dL was associated with liver function worsening (AOR 6.1 [95% CI: 3-12.5], P < 0.001). Liver function worsening and improvement rates after responding to DAA are similar among HCV-monoinfected and HIV/HCV-coinfected cirrhotics. Gender, INR, bilirubin, and albumin levels were associated with liver function changes after response to DAAs.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Cirrose Hepática/virologia , Fígado/fisiologia , Administração Oral , Feminino , Infecções por HIV/virologia , Hepatite C/complicações , Hepatite C/virologia , Humanos , Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores Sexuais
14.
J Antimicrob Chemother ; 73(9): 2435-2443, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982683

RESUMO

Objectives: To assess the impact of all-oral direct-acting antiviral agent (DAA) regimens on the risk of hepatocellular carcinoma (HCC) in HIV/HCV-coinfected patients with cirrhosis. Methods: This was a multicentre prospective cohort study recruiting HIV/HCV-coinfected patients with a new diagnosis of compensated cirrhosis. Patients were followed up until HCC, death or the censoring date (March 2017). The primary endpoint was the emergence of HCC. The incidence rate (IR) (95% CI) of HCC in different groups was computed. Time-to-event analyses were performed to identify predictors of HCC emergence. Results: The study included 495 HIV/HCV-coinfected patients with cirrhosis. After a median (IQR) follow-up of 59 (27-84) months, 22 (4.4%; 95% CI 2.6-6.3) patients developed an HCC. The IR (95% CI) of HCC was 0.93 (0.06-1.42) per 100 person-years (PY). Three hundred and three (61%) patients achieved sustained virological response (SVR) during follow-up, 79 after interferon (IFN)-based regimens and 224 after an all-oral DAA regimen. The IR (95% CI) of HCC after all-oral DAA was 0.35 (0.14-0.85) per 100 PY whereas it was 1.79 (1.11-2.88) per 100 PY in the remaining cohort (P = 0.0005). When only patients with SVR were considered, the IR (95% CI) of HCC after all-oral DAA was 0.32 (0.12-0.86) whereas it was 0 per 100 PY among those with SVR after IFN-based therapies (P = 0.27). Achieving SVR with an all-oral DAA regimen during follow-up was independently associated with a lower risk of HCC emergence (subhazard ratio 0.264; 95% CI 0.070-0.991; P = 0.049). Conclusions: SVR with all-oral DAA regimens reduces the risk of HCC in HIV/HCV-coinfected patients with compensated cirrhosis.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Adulto , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Resposta Viral Sustentada
15.
J Am Acad Dermatol ; 78(2 Suppl 1): S1-S23.e1, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29127053

RESUMO

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.


Assuntos
Acne Vulgar/tratamento farmacológico , Dermatologistas/normas , Gerenciamento Clínico , Guias de Prática Clínica como Assunto , Acne Vulgar/diagnóstico , Administração Oral , Administração Tópica , Antibacterianos/administração & dosagem , Consenso , Quimioterapia Combinada , Feminino , Humanos , Internacionalidade , Masculino , Melhoria de Qualidade , Retinoides/uso terapêutico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
16.
Phys Chem Chem Phys ; 20(13): 8724-8736, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29536993

RESUMO

This paper extends the study of the induced temperature change in the mesostructure and in the physical properties occurring in aqueous mixtures of the ionic liquid 1-ethyl-3-methyl imidazolium octyl-sulfate [EMIm][OSO4]. For some compositions, these mixtures undergo a phase transition between the liquid (isotropic in the mesoscale) and the mesomorphic state (lyotropic liquid crystalline) at about room temperature. The behavior of mixtures doped with a divalent metal sulfate was investigated in order to observe their applicability as electrolytes. Calcium sulfate salt is almost insoluble even in the 20 wt% water mixture. The magnesium salt, in contrast, can be dissolved up to concentrations of 730 ppm in the same mixture and it has a profound impact on its properties. Six aqueous mixtures (with water content from 10 wt% to 33 wt%) of [EMIm][OSO4] were saturated with magnesium sulfate salt, producing the ternary mixture [EMIm][OSO4] + H2O + MgSO4. Viscosity, density and ionic conductivity for these samples were measured from 10 °C to 90 °C. In addition, SAXS, FTIR, diffussion NMR and Raman spectroscopy of the most interesting samples have been performed, and structural data indicate a transition between a hexagonal lyotropic liquid crystalline phase below and an isotropic solution phase above room temperature. The octyl sulfate anions of the cylindrical micelles in the hexagonal phase are coordinated with water molecules through H-bonds (about four per sulfate anion), while the [EMIm] cations seem to be poorly coordinated and so free to move. Inorganic salt addition reinforces that network, increasing the phase transition temperature.

17.
Acta Odontol Scand ; 76(8): 545-552, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29536787

RESUMO

AIM: To analyse differences in the eruption of primary teeth between both sexes. MATERIALS AND METHODS: A cross-sectional study was performed in a sample of 1250 children aged between 3 and 42 months. The clinical emergence of teeth was taken to estimate average ages for primary teeth eruption. The t-test was used to analyse gender and arch differences. RESULTS: Eruption of primary teeth began at the same time in girls as in boys; although the eruptive process was longer in girls. It was observed that almost all deciduous teeth emerged earlier in boys, except for the first molar (upper and lower) and the maxillary central incisors. The differences were statistically significant for almost all the primary teeth except for the central incisors, both upper and lower. CONCLUSIONS: By comparing the timing of the eruption of primary teeth in both sexes, it was found that eruption of almost all primary teeth took place earlier in boys than in girls and that the eruption process was shorter for boys than for girls. Most of the deciduous teeth erupted earlier in the right side in both sexes. No differences were found in the sequence of eruption of primary teeth between genders.


Assuntos
Desenvolvimento Infantil/fisiologia , Erupção Dentária/fisiologia , Dente Decíduo/crescimento & desenvolvimento , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Incisivo/crescimento & desenvolvimento , Lactente , Masculino , Dente Molar/crescimento & desenvolvimento , Caracteres Sexuais , Espanha
18.
Clin Infect Dis ; 65(6): 1012-1019, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28903510

RESUMO

BACKGROUND: Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. METHODS: HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. RESULTS: Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029). CONCLUSIONS: After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. CLINICAL TRIALS REGISTRATION: NCT01900015.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Raltegravir Potássico/efeitos adversos , Alcinos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Ciclopropanos , Didesoxinucleosídeos/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada , Técnicas de Imagem por Elasticidade , Emtricitabina/uso terapêutico , Feminino , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/uso terapêutico , Tenofovir/uso terapêutico , Triglicerídeos/sangue , Relação Cintura-Quadril
19.
Hepatology ; 61(5): 1503-11, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25545020

RESUMO

UNLABELLED: Liver fibrosis is used to make decisions about the timing of therapy against hepatitis C virus (HCV) in routine clinical practice, which should be based on the short-term likelihood of liver decompensations. Thus, we aimed at evaluating the risk of decompensations and death among human immunodeficiency virus (HIV)/HCV-coinfected individuals according to their baseline fibrosis classified by either liver biopsy or liver stiffness measurement (LSM). Patients coinfected with HIV/HCV, naive or without sustained virological response to HCV therapy, were included in this cohort. Fibrosis was classified by biopsy in 683 patients and by LSM in 1046 individuals. Reference categories were fibrosis stage 0 and LSM <6 kPa. For patients with biopsy, the adjusted subhazard ratio for decompensations and 95% confidence interval (95% CI) by fibrosis stage were as follows: stage 1, 2.3 (0.27-20.3), P = 0.443; stage 2, 2.8 (0.33-24), P = 0.345; stage 3, 4.91 (0.60-41), P = 0.137; stage 4, 9.89 (1.25-79.5), P = 0.030. For patients with LSM, the adjusted subhazard ratio and 95% CI by LSM category were as follows: 6-9.4 kPa, 1.89 (0.18-20.3), P = 0.599; 9.5-14.5 kPa, 6.59 (0.73-59.2), P = 0.092; ≥14.6 kPa, 59.5 (8.3-427), P < 0.0001. Regarding the risk of death, the adjusted hazard ratio and 95% CI for death by fibrosis stage were as follows: stage 1, 1.3 (0.4-4.11), P = 0.677; stage 2, 2.68 (0.86-8.36), P = 0.090; stage 3, 2.58 (0.82-8.15), P = 0.106; stage 4, 4.35 (1.43-13.3), P = 0.010. For patients with LSM, the adjusted hazard ratio and 95% CI for death by LSM were as follows: 6-9.4 kPa, 1.7 (0.63-4.79), P = 0.288; 9.5-14.5 kPa, 3.38 (1.2-9.5), P = 0.021; ≥14.6 kPa, 12.7 (4.9-33.6), P < 0.0001. CONCLUSION: Patients coinfected with HIV/HCV without advanced fibrosis are at very low risk of decompensations in the short term; deferral of HCV therapy for a few years and monitoring fibrosis progression is a safe option until cheaper, more effective, and more convenient HCV treatment becomes widely available.


Assuntos
Coinfecção/complicações , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Hepatite C Crônica/complicações , Hepatite C Crônica/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Falência Hepática/etiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Fatores de Tempo
20.
Blood ; 124(12): 1887-93, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25102853

RESUMO

Melphalan (M), in combination with prednisone (MP), has been the backbone of new combinations, including bortezomib plus MP (VMP). However, new alkylator-free schemes, such as lenalidomide plus low-dose dexamethasone, are challenging the role of alkylators in myeloma treatment of elderly patients. Here we have updated, after a long follow-up (median 6 years), the results of the GEM2005 study that addressed this question by comparing VMP with bortezomib plus thalidomide and prednisone (VTP) as induction. Between April 2005 and October 2008, 260 patients were randomized to receive 6 cycles of VMP or VTP as induction. The median progression-free survival was 32 months for the VMP and 23 months for the VTP arms (P 5 .09). VMP significantly prolonged the overall survival (OS) compared with VTP (median of 63 and 43 months, respectively; hazard ratio [HR]: 0.67, P 5 .01). Achieving immunophenotypic complete response was associated with a significantly longer OS, especially in the VMP arm (66%remain alive after 8 years). Melphalan, plus bortezomib, should be maintained as standard care for the treatment of elderly multiple myeloma patients. This trial was registered at www.clinicaltrials.gov as #NCT00443235.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Idoso , Ácidos Borônicos/administração & dosagem , Bortezomib , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Melfalan/administração & dosagem , Prednisona/administração & dosagem , Pirazinas/administração & dosagem , Talidomida/administração & dosagem
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