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1.
Osteoarthritis Cartilage ; 31(6): 780-792, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36739939

RESUMO

OBJECTIVE: Blocking the interleukin-1 (IL-1) catabolic cascade following joint trauma can be achieved using its receptor antagonist, IL-1Ra. However, its clinical translation for osteoarthritis therapy has been unsuccessful due to its rapid joint clearance and lack of targeting and penetration into deep cartilage layers at therapeutic concentrations. Here, we target the high negative charge of cartilage aggrecan-glycosaminoglycans (GAGs) by attaching cationic carriers to IL-1Ra. IL-1Ra was conjugated to the cartilage targeting glycoprotein, Avidin, and a short length optimally charged cationic peptide carrier (CPC+14). It is hypothesized that electro-diffusive transport and binding properties of IL-1Ra-Avidin and IL-1Ra-CPC+14 will create intra-cartilage depots of IL-1Ra, resulting in long-term suppression of IL-1 catabolism with only a single administration. DESIGN: IL-1Ra was conjugated to Avidin or CPC+14 using site specific maleimide linkers, and confirmed using gel electrophoresis, high-performance liquid chromatography (HPLC), and mass spectrometry. Intra-cartilage transport and retention of conjugates was compared with native IL-1Ra. Attenuation of IL-1 catabolic signaling with one-time dose of IL-1Ra-CPC+14 and IL-1Ra-Avidin was assessed over 16 days using IL-1α challenged bovine cartilage and compared with unmodified IL-1Ra. RESULTS: Positively charged IL-1Ra penetrated through the full-thickness of cartilage, creating a drug depot. A single dose of unmodified IL-1Ra was not sufficient to attenuate IL-1-induced cartilage deterioration over 16 days. However, when delivered using Avidin, and to a greater extent CPC+14, IL-1Ra significantly suppressed cytokine induced GAG loss and nitrite release while improving cell metabolism and viability. CONCLUSION: Charge-based cartilage targeting drug delivery systems hold promise as they can enable long-term therapeutic benefit with only a single dose.


Assuntos
Avidina , Cartilagem , Animais , Bovinos , Avidina/metabolismo , Avidina/farmacologia , Cartilagem/metabolismo , Peptídeos/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Sistemas de Liberação de Medicamentos , Receptores de Interleucina-1/metabolismo
2.
Cryo Letters ; 44(3): 134-141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883166

RESUMO

BACKGROUND: The recovery of spermatozoa from the cauda epididymis may be the only option to obtain genetic material from elite stallions that had undergone castration or sudden death due to colic or severe injury. OBJECTIVE: To evaluate two different protocols for retrieval of stallion epididymal spermatozoa and to evaluate different cryoprotectants on the freezability of the epididymal spermatozoa. MATERIALS AND METHODS: Six epididymides from three stallions were collected immediately after routine castration under general anesthesia. In the first experiment, each epididymis (of two testes) of the same stallion were processed using different methods for retrieval of the epididymal spermatozoa and were pooled and cryopreserved either using 5% glycerol or 5% dimethyl formamide (DMF) as cryoprotectant. The semen quality parameters viz., progressive motility, HOST, viability and acrosome integrity were evaluated at the fresh, pre-freeze and post-thaw stages. RESULTS: Retrograde method of flushing of epididymis yielded significantly (p < 0.05) higher concentration of the stallion sperm than that of the floating method. The qualitative semen parameters i.e., viability, plasma membrane integrity and acrosome integrity were found to be significantly restored using 5% DMF as cryoprotectant in comparison to when 5% glycerol was used. CONCLUSION: Retrograde flushing method of epididymis yielded significantly higher sperm concentration to that of the floating method, and 5% DMF as cryoprotectant provided acceptable freezability of stallion epididymal spermatozoa. DOI: 10.54680/fr23310110312.


Assuntos
Análise do Sêmen , Preservação do Sêmen , Masculino , Cavalos , Animais , Congelamento , Sêmen , Glicerol/farmacologia , Epididimo , Criopreservação/veterinária , Criopreservação/métodos , Motilidade dos Espermatozoides , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Espermatozoides , Crioprotetores/farmacologia , Dimetilformamida/farmacologia
3.
J Behav Med ; 45(5): 674-689, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35921055

RESUMO

There is growing interest in offering Internet-delivered cognitive behaviour therapy (ICBT) to individuals with chronic health conditions, with this process often being guided by a single clinician. Due to lack of full time personnel, it is sometimes necessary to have multiple clinicians offer guidance or for no guidance to be offered. In this randomized trial, we compared team-guided ICBT (n = 90) to self-guided ICBT (n = 88). Participants completed measures at pre-, post-, and 3-months post-ICBT. Both groups showed similar rates of treatment completion and large improvements on depression and anxiety at post-treatment and follow-up. Unexpectedly, more participants in the self-guided versus team-guided condition showed clinically significant improvement on depression at post-treatment (76.5% vs 49.2%) and follow-up (70% vs 45.6%). Thus, team-guided ICBT may not provide significant benefits compared to self-guided ICBT. However, it may be an alternative approach to consider among a population of high risk individuals that wants or requires closer monitoring of symptoms.Trail registration TRN: NCT03500237; Date: April 18, 2018.


Assuntos
Terapia Cognitivo-Comportamental , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Doença Crônica , Humanos , Internet , Resultado do Tratamento
4.
Environ Res ; 197: 111142, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33865822

RESUMO

Pollution of water linked to microbial decontamination and extensive use of sodium chlorite (NaClO2) as a disinfectant, especially in the face of the current COVID-19 situation, is a serious water pollution issue that needs to be addressed. In this context, an environmentally friendly and cost-effective method has been developed for the biomimetic synthesis of Ag nanospheres (Ag NSs) using aqueous extract of Piper nigrum for the detection of chlorite (ClO2-) and mercury (Hg2+) ions. The strong antioxidant properties of the biomolecules present in the Piper nigrum extract reduce silver ions (Ag+) to Ag0. After optimization of the formulation parameters, it was observed that 1 mL of piper nigrum extract was sufficient to reduce and stabilize 100 mL of 1.5 mM of Ag+ in 2.5 h at 30 °C. X-ray diffraction (XRD) pattern of Ag NSs revealed their crystalline nature and the characteristic Bragg's diffraction peaks confirmed their face cubic crystal (FCC) lattice. The characteristic reddish-brown color and absorption surface plasmon resonance (SPR) band at 435 nm confirmed the successful fabrication of Ag NSs. Kinetic analysis revealed a three-phase growth pattern involving nucleation, growth and stabilization. Transmission electron microscopy (TEM) and High-resolution transmission electron microscopy (HRTEM) micrograms, showed spherical NSs with narrow polydispersity with particle size ranging from 10 to 30 nm. The synthesized NSs were exposed to various metal ions and anions. The absorption intensity of Ag NSs quenched in the presence of mercury ions (Hg2+) among the cations and Chlorite ions (ClO2-) among the anions. The limit of detection (LOD) of 7.47 µM and 1.11 µM was evaluated from the calibration curve for Hg2+ and ClO2-, respectively. Based on these promising results, it is suggested that the method reported is a low-cost and one step biogenic protocol for the synthesis of Ag NSs and their employment for the detection of Hg2+ and ClO2-ions.


Assuntos
COVID-19 , Mercúrio , Nanopartículas Metálicas , Nanosferas , Cloretos , Humanos , Cinética , SARS-CoV-2 , Prata , Água
5.
BMC Public Health ; 21(1): 2002, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34736425

RESUMO

BACKGROUND: We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS. METHODS: We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex. Behavioral data were collected via 1:1 or self-administered computerized interviews. Adjusted individual-study, multivariable relative risk regression was used to examine the relationship between CS and SU. We also examined interactions with type of sex and partner HIV status. Pooled effect estimates were calculated using traditional fixed-effects meta-analysis. We analyzed data for recent SU (n = 6781; 82% men, median age = 33 years) and SU before/during sex (n = 2915; 69% men, median age = 40 years). RESULTS: For both exposure classifications, any SU other than cannabis increased the likelihood of CS relative to non-SU (8-16%, p-values< 0.001). In the recent SU group, however, polysubstance use did not increase the likelihood of CS compared to single-substance use. Cannabis use did not increase the likelihood of CS, regardless of frequency of use. Type of sex was associated with CS; those reporting vaginal and anal sex had a higher likelihood of CS compared to vaginal sex only for both exposure classifications (18-21%, p < 0.001). Recent SU increased likelihood of CS among those reporting vaginal sex only (9-10%, p < 0.001); results were similar for those reporting vaginal and anal sex (5-8%, p < 0.01). SU before/during sex increased the likelihood of CS among those reporting vaginal sex only (20%; p < 0.001) and among those reporting vaginal and anal sex (7%; p = 0.002). Single- and poly-SU before/during sex increased the likelihood of CS for those with exclusively HIV-negative partners (7-8%, p ≤ 0.02), and for those reporting HIV-negative and HIV-status unknown partners (9-13%, p ≤ 0.03). CONCLUSION: Except for cannabis, any SU increased the likelihood of CS. CS was associated with having perceived HIV-negative partners and with having had both anal/vaginal sex.


Assuntos
Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Adulto , Preservativos , Feminino , Infecções por HIV/epidemiologia , Heterossexualidade , Homossexualidade Masculina , Humanos , Masculino , Assunção de Riscos , Comportamento Sexual , Parceiros Sexuais , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Sexo sem Proteção
6.
Niger J Clin Pract ; 24(10): 1457-1462, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34657010

RESUMO

AIM: The study aimed to evaluate the effect on condylar guidance values with casts mounted by facebow transfer (Guichet's point as the third point of reference), Bonwill's, and radiographic method. MATERIALS AND METHODS: The dentulous subject's casts were mounted to a semi-adjustable articulator (Artex Type AR) after facebow transfer with Guichet's point as the third point of reference and also by Bonwill's method. Protrusive records made earlier were utilized to program the right and left side condylar guidance value. Two digital lateral cephalograms were made, one in centric relation, and one in protrusion and the condyles were traced and overlapped. The condylar guidance readings obtained by Bonwill's method, facebow transfer, and lateral cephalometric tracings were compared in this study using the SPSS (Version 17.0 Illinois, Chicago, USA) software. RESULTS: The condylar guidance values obtained from Bonwill's and the facebow transfer method (p < 0.001) was lesser than the radiographic method. The values obtained by casts mounted to the Bonwill's method differed significantly (p < 0.001) from the other two methods. CONCLUSION: The values obtained by facebow transfer were closer to the radiographic values whereas the values obtained by Bonwill's method mounting differed markedly.


Assuntos
Articuladores Dentários , Côndilo Mandibular , Cefalometria , Aparelhos de Tração Extrabucal , Humanos , Registro da Relação Maxilomandibular , Côndilo Mandibular/diagnóstico por imagem
7.
Colorectal Dis ; 22(12): 2123-2132, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32940414

RESUMO

AIM: The peritoneal cancer index (PCI) is one of the strongest prognostic factors in patients undergoing cytoreductive surgery (CRS) for colorectal peritoneal metastases. Using pathological evaluation, however, the disease extent differs in a large proportion of patients. Our aim was to study the correlation between the radiological (rPCI), surgical (sPCI) and pathological (pPCI) PCI in order to determine factors affecting the discordance between these indices and their potential therapeutic implications. METHOD: From July 2018 to December 2019, 128 patients were included in this study. The radiological, pathological and surgical findings were compared. A protocol for pathological evaluation was followed at all centres. RESULTS: All patients underwent a CT scan and 102 (79.6%) had a peritoneal MRI. The rPCI was the same as the sPCI in 81 (63.2%) patients and the pPCI in 93 (72.6%). Concordance was significantly lower for moderate-volume (sPCI 13-20) and high-volume (sPCI > 20) disease than for low-volume disease (sPCI 0-12) (P < 0.001 for sPCI; P = 0.001 for pPCI). The accuracy of imaging in predicting presence/absence of disease upon pathological evaluation ranged from 63% to 97% in the different regions of the PCI. The pPCI concurred with the sPCI in 86 (68.8%) patients. Of the nine patients with sPCI > 20, the pPCI was less than 20 in six. CONCLUSION: The rPCI and sPCI both concurred with pPCI in approximately two thirds of patients. Preoperative evaluation should focus on the range in which the sPCI lies and not its absolute value. Radiological evaluation did not overestimate sPCI in any patient with high/moderate-volume disease. The benefit of CRS in patients with a high r/sPCI (> 20) who respond to systemic therapies should be prospectively evaluated.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Neoplasias Colorretais/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/cirurgia , Peritônio/diagnóstico por imagem , Peritônio/cirurgia , Estudos Prospectivos
8.
BMC Public Health ; 20(1): 1908, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317507

RESUMO

BACKGROUND: Addressing non-communicable disease (NCDs) is a global priority in the Sustainable Development Goals, especially for adolescents. However, existing literature on NCD burden, risk factors and determinants, and effective interventions and policies for targeting these diseases in adolescents, is limited. This study develops an evidence-based conceptual framework, and highlights pathways between risk factors and interventions to NCD development during adolescence (ages 10-19 years) and continuing into adulthood. Additionally, the epidemiologic profile of key NCD risk factors and outcomes among adolescents and preventative NCD policies/laws/legislations are examined, and a multivariable analysis is conducted to explore the determinants of NCDs among adolescents and adults. METHODS: We reviewed literature to develop an adolescent-specific conceptual framework for NCDs. Global data repositories were searched from Jan-July 2018 for data on NCD-related risk factors, outcomes, and policy data for 194 countries from 1990 to 2016. Disability-Adjusted Life Years were used to assess disease burden. A hierarchical modeling approach and ordinary least squares regression was used to explore the basic and underlying causes of NCD burden. RESULTS: Mental health disorders are the most common NCDs found in adolescents. Adverse behaviours and lifestyle factors, specifically smoking, alcohol and drug use, poor diet and metabolic syndrome, are key risk factors for NCD development in adolescence. Across countries, laws and policies for preventing NCD-related risk factors exist, however those targeting contraceptive use, drug harm reduction, mental health and nutrition are generally limited. Many effective interventions for NCD prevention exist but must be implemented at scale through multisectoral action utilizing diverse delivery mechanisms. Multivariable analyses showed that structural/macro, community and household factors have significant associations with NCD burden among adolescents and adults. CONCLUSIONS: Multi-sectoral efforts are needed to target NCD risk factors among adolescents to mitigate disease burden and adverse outcomes in adulthood. Findings could guide policy and programming to reduce NCD burden in the sustainable development era.


Assuntos
Doenças não Transmissíveis , Adolescente , Adulto , Criança , Efeitos Psicossociais da Doença , Humanos , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/prevenção & controle , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Desenvolvimento Sustentável , Adulto Jovem
9.
Osteoporos Int ; 30(6): 1317-1320, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30976889

RESUMO

There have been case reports of proximal femur insufficiency fractures in patients who have previously undergone bariatric surgery. We present a follow-up case of a patient who developed bilateral complete proximal femur insufficiency fractures several years after bariatric surgery. Our patient underwent bilateral intramedullary fixation with a satisfactory postoperative outcome. We review and discuss the definition and pathogenesis of atypical femur fractures (AFFs), which may represent a larger category of insufficiency fractures not exclusive to bisphosphonate use, which includes patients with fractures after bariatric surgery.


Assuntos
Derivação Gástrica/efeitos adversos , Fraturas do Quadril/etiologia , Complicações Pós-Operatórias/etiologia , Feminino , Fixação Intramedular de Fraturas , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/cirurgia , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Radiografia , Tomografia Computadorizada por Raios X
10.
Brain Inj ; 33(5): 551-558, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30686042

RESUMO

OBJECTIVE: To assess the psychometric properties of the available assessment questionnaires for substance abuse studied within a brain injury population. METHODS: A literature search was conducted on MEDLINE, PsycINFO, CINAHL, and Embase databases. Articles published in English from inception through March 2018 on the screening questionnaires used to identify substance abuse post brain injury were reviewed. Eligible primary studies had to include: adults (participants ≥18 years old) post brain injury; and report measures of diagnostic accuracy (e.g., sensitivity, specificity, and diagnostic odds ratio). RESULTS: Six screening questionnaires were included: Alcohol Use Disorders Identification Test, Brief Michigan Alcohol Screening Test, CAGE, Drug Abuse Screening Test, Substance Abuse Screening Inventory and the Short Michigan Alcohol Screening Test (SMAST). All questionnaires, except the SMAST, used the Diagnostic and Statistical Manual of Mental Disorders as the criterion measure. While report measures of diagnostic accuracy were reported and summarized, none of the studies provided reliability information or subgroup analysis among those with brain injury. CONCLUSIONS: Concerns of social desirability, population demographics, responsiveness to treatment effects, and administrative burden are important when selecting a questionnaire. Research examining the reliability of substance abuse screening questionnaires in the brain injury population is lacking and future research is warranted.


Assuntos
Lesões Encefálicas/complicações , Programas de Rastreamento/normas , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Inquéritos e Questionários/normas , Humanos , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Transtornos Relacionados ao Uso de Substâncias/etiologia
11.
Br J Biomed Sci ; 76(1): 29-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30379116

RESUMO

OBJECTIVE: An imbalance in oxidant-antioxidant status may impact the severity of sepsis. We hypothesised links between nitrosative stress and pro-inflammatory cytokines and their correlation with the severity of sepsis and associated organ dysfunction. METHODS: The hypothesis was tested in 110 patients with sepsis (in whom a disease severity score (APACHE II) and assessment of organ failure score (SOFA) were determined) and 55 healthy volunteers. Neutrophil inducible nitric oxide synthase (iNOS) expressions at mRNA and protein levels were estimated by real-time PCR and immuno-precipitation followed by Western blotting, respectively. Nitric oxide (NO) content was assessed in neutrophils by confocal microscopy, plasma nitrite by the Griess reaction and inflammatory cytokines (TNF-α, IFN-γ and IL-8) by ELISA (in plasma) and real-time PCR (in neutrophils). Serum bilirubin and creatinine were determined by routine methods and lung function by the PaO2/FiO2 ratio. RESULTS: Increased neutrophil iNOS expression and NO content, plasma total nitrite content and pro-inflammatory cytokines were present in sepsis patients (all P < 0.001). Plasma nitrite correlated with cytokines, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.63-0.85, P < 0.001). Cytokines correlated with nitrite, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.35-0.85, P < 0.001). CONCLUSION: Neutrophils iNOS expression, NO content, plasma nitrite and cytokines have a role in the assessment of the severity of sepsis and organ toxicity.


Assuntos
Interferon gama/sangue , Interleucina-8/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Estresse Nitrosativo , Sepse/diagnóstico , Fator de Necrose Tumoral alfa/sangue , APACHE , Adulto , Idoso , Bilirrubina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Sepse/sangue , Sepse/fisiopatologia
12.
J Viral Hepat ; 25(3): 220-227, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29316030

RESUMO

The availability of effective, simple, well-tolerated oral direct-acting antiviral (DAA) hepatitis C regimens has raised optimism for hepatitis C virus (HCV) elimination at the population level. HCV reinfection in key populations such as people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM) however threatens the achievement of this goal from a patient, provider and population perspective. The goal of this review was to synthesize our current understanding of estimated rates and factors associated with HCV reinfection. This review also proposes interventions to aid understanding of and reduce hepatitis C reinfection among PWID and HIV-infected MSM in the oral direct-acting antiviral era.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Administração Oral , Homossexualidade Masculina , Humanos , Incidência , Masculino , Recidiva , Fatores de Risco , Abuso de Substâncias por Via Intravenosa
13.
J Viral Hepat ; 25(1): 37-46, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28719029

RESUMO

We assessed the feasibility of field-based directly observed therapy (DOT) with minimal monitoring to deliver HCV treatment to people with a history of drug use in Chennai, India. Fifty participants were randomized 1:1 to sofosbuvir+peginterferon alfa 2a+ribavirin (SOF+PR) for 12 weeks (Arm 1) vs sofosbuvir+ribavirin (SOF+R) for 24 weeks (Arm 2). SOF+R was delivered daily at participant chosen venues and weekly peginterferon injections at the study clinic. HCV RNA testing was performed to confirm active HCV infection and sustained virologic response 12 weeks after treatment completion (SVR12). No baseline genotyping or on-treatment viral loads were performed. Median age was 46 years. All were male and 20% had significant fibrosis/cirrhosis. All self-reported history of injection drug use, 18% recent noninjection drug use and 38% alcohol dependence. Six discontinued treatment (88% completed treatment in each arm). Of 22 who completed SOF+PR, all achieved SVR12 (22/25=88%); 15 of 22 who completed SOF+R achieved SVR12 (15/25=60%; P=.05). Among those completing SOF+R, SVR12 was significantly less common in participants reporting ongoing substance use (36% vs 100%) and missed doses. Active substance use and missed doses did not impact SVR with SOF+PR. Field-based DOT of HCV therapy without real-time HCV RNA monitoring was feasible; however, achieving 100% adherence was challenging. SOF+PR appeared superior to SOF+R in achieving SVR12, even when doses were missed with no discontinuations due to side effects. Further exploration of short duration treatment with peginterferon plus direct-acting antivirals is warranted.


Assuntos
Antivirais/administração & dosagem , Terapia Diretamente Observada , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Sofosbuvir/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento , Carga Viral , Adulto Jovem
14.
Scand J Immunol ; 87(4): e12653, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29484685

RESUMO

Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P < .001) in the sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis.


Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo/fisiologia , Sepse/patologia , Adulto , Catalase/sangue , Estudos Transversais , Feminino , Humanos , Interferon gama/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Peroxidase/sangue , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
15.
Epidemiol Infect ; 146(14): 1845-1853, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30070187

RESUMO

Mixing matrices quantify how people with similar or different characteristics make contact with each other, creating potential for disease transmission. Little empirical data on mixing patterns among persons who inject drugs (PWID) are available to inform models of blood-borne disease such as HIV and hepatitis C virus. Egocentric drug network data provided by PWID in Baltimore, Maryland between 2005 and 2007 were used to characterise drug equipment-sharing patterns according to age, race and gender. Black PWID and PWID who were single (i.e. no stable sexual partner) self-reported larger equipment-sharing networks than their white and non-single counterparts. We also found evidence of assortative mixing according to age, gender and race, though to a slightly lesser degree in the case of gender. Highly assortative mixing according to race and gender highlights the existence of demographically isolated clusters, for whom generalised treatment interventions may have limited benefits unless targeted directly. These findings provide novel insights into mixing patterns of PWID for which little empirical data are available. The age-specific assortativity we observed is also significant in light of its role as a key driver of transmission for other pathogens such as influenza and tuberculosis.


Assuntos
Uso Comum de Agulhas e Seringas/estatística & dados numéricos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adulto , Fatores Etários , Baltimore/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
16.
Epidemiol Infect ; 146(9): 1079-1088, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29745351

RESUMO

Community-led total sanitation (CLTS) is an intervention that strives to end the practice of open defaecation. This study measured the effectiveness of CLTS in Nyando District by examining the association between community open defaecation-free (ODF) status and childhood diarrhoeal illness. A cross-sectional study design was used among households with children ⩽5 years old to ascertain information on acute diarrhoea in the past year (outcome), sanitation and health behaviours. Water testing was conducted to determine Escherichia coli and turbidity levels for 55 water sources. Data were obtained from 210 parents or caregivers from an ODF community and 216 parents or caregivers in a non-ODF community. The non-ODF participants reported a non-significant 16% increased risk of diarrhoea compared with the participants from the ODF community. Children's HIV positivity (adjusted prevalence ratio (aPR) = 2.29; 95% CI 2.07-2.53), unsafe child stool disposal (aPR = 1.92; 95% CI 1.74-2.12) and low household income (aPR = 1.93; 95% CI 1.46-2.56) were associated with diarrhoea, in the non-ODF community. The ODF location had a higher percentage of E. coli in the drinking water compared with the non-ODF location (76.7% vs. 60%). Diarrhoeal disease rates in children ⩽5 years old did not differ by whether a latrine intervention was implemented. Water sampling findings suggest water safety may have decreased the effectiveness of the CLTS' improvement of childhood diarrhoea. Improved water treatment practices, safe stool disposal and education may improve the CLTS intervention in ODF communities and therefore reduced the risk of childhood diarrhoea.


Assuntos
Diarreia/prevenção & controle , Banheiros , Pré-Escolar , Estudos Transversais , Diarreia/epidemiologia , Diarreia/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Masculino , Distribuição de Poisson , Avaliação de Programas e Projetos de Saúde , Fatores de Risco , Saúde da População Rural/estatística & dados numéricos
17.
Br J Anaesth ; 120(4): 725-733, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29576113

RESUMO

BACKGROUND: The contribution of thrombosis to the aetiology of perioperative myocardial infarction (MI) is uncertain. We used optical coherence tomography (OCT) to determine the presence of thrombus and plaque morphology in patients experiencing a perioperative MI and matched patients experiencing a non-operative MI using OCT. METHODS: We conducted a single-centre, prospective, cohort study. Thirty patients experiencing a perioperative MI and 30 matched patients experiencing a non-operative MI, without ST elevation, underwent OCT to determine the presence of thrombus and culprit lesion plaque morphology. Angiography and OCT were performed a mean of 1.93(1.09) days and 1.53(0.68) days after the onset of perioperative and non-operative MI, respectively. OCT images were evaluated by an independent core laboratory without knowledge of whether the patient had suffered a perioperative or non-operative MI. RESULTS: We identified thrombus at the culprit lesion in four of 30 patients (13.3%) who experienced a perioperative MI and in 20 of 30 patients (66.7%) who experienced a non-operative MI, P<0.01. The only non-culprit lesion with thrombus was in a perioperative MI patient who also had a culprit lesion thrombus. Perioperative and non-operative MI culprit lesions demonstrated fibroatheroma in 18 patients (60.0%) us 20 patients (66.7%), respectively (P=0.52) and thin cap fibroatheroma in one patient (3.3%) us five patients (16.7%), respectively (P=0.11). One perioperative MI patient (3.3%) suffered a cardiac death and no non-operative MI patient died during the 30-day follow-up. CONCLUSIONS: Thrombosis was less common in perioperative than non-operative MI, despite similar underlying plaque morphology.


Assuntos
Infarto do Miocárdio/epidemiologia , Período Perioperatório , Trombose Venosa/epidemiologia , Idoso , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , Tomografia de Coerência Óptica , Trombose Venosa/diagnóstico por imagem
18.
J Nanosci Nanotechnol ; 18(5): 3218-3229, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442822

RESUMO

This manuscript represents the synthesis of silica nanoparticles modified with four different types of cationic surfactants. The surfactant capped nanoparticles have better control over the size of silica nanoparticles. The as formed as model nanomaterials were used for the removal of naphthalene, a simple white crystalline polycyclic aromatic hydrocarbon (PAH) from aqueous media. The obtained materials were characterized by various microscopic and spectroscopic techniques. The average particle size of nanoparticles was approximately between 50 and 75 nm. The removal kinetic and adsorption studies were also conducted on silica nanoparticles with different contact time, initial concentrations of silica and naphthalene to achieve the optimum adsorption conditions. CPB functionalized nanoparticles have displayed higher removal efficiency of more than 85% as compared to 75 to 80% in case of CTAB, CTAC and CPC functionalized silica nanoparticles. The effects of various parameters like pH, adsorbent doses, naphthalene concentration and addition of salt have also been investigated for better understanding of the removal efficacy of prepared nanoparticles.

20.
Genes Immun ; 18(2): 82-87, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28300059

RESUMO

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r2=0.98-1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml-1 of IL-18 after adjusting for covariates (rs80011693; rs111311302 ß=-0.06, P-value=2.7 × 10-4). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections.


Assuntos
Coinfecção/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Hepatite C Crônica/imunologia , Interleucina-18/sangue , Interleucina-18/genética , Adulto , Dioxigenases/genética , Feminino , Infecções por HIV/sangue , Hepatite C Crônica/sangue , Humanos , Inflamassomos/imunologia , Masculino , Polimorfismo de Nucleotídeo Único
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