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1.
Appl Radiat Isot ; 211: 111408, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38955077

RESUMO

Radiation imaging is extensively applied in nuclear industry for various purposes including fuel characterization. Accurate quantitative evaluation of these radiographic images is difficult by the existing manual process and therefore image analytical methods have been attempted. The method of wavelet transform analysis has been applied on Gamma autoradiography (GAR) images of experimental (U, Pu)O2 mixed oxide (MOX) fuel pins with the objective to investigate the effectiveness of the method for fuel homogeneity characterization. The method was found effective to carry out quantified estimations of size and relative plutonium concentration of the heterogeneous portions in the fuel. The results were validated with theoretically simulated results as practical standards and calibrations are not possible in these samples. The results of wavelet transformation analysis were found to be more accurate with reference to the theoretically simulated values in comparison with conventional pixel analysis applied on the original GAR images.

2.
Ann Oncol ; 35(1): 107-117, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37871702

RESUMO

BACKGROUND: Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti-PD-(L)1-naive patients with mUC. PATIENTS AND METHODS: Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on one prior treatment, and who were anti-PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death. CONCLUSIONS: Erdafitinib and pembrolizumab had similar median OS in this anti-PD-(L)1-naive, FGFR-altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non- FGFR-altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population.


Assuntos
Carcinoma de Células de Transição , Pirazóis , Quinoxalinas , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
Appl Radiat Isot ; 204: 111140, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070360

RESUMO

Double differential neutron fluence distributions were measured in the 7Li(p,n)7Be reaction for proton beam energies 7, 9 and 12 MeV. Seven liquid scintillator based detectors were employed to measure neutron fluence distributions using the Time of Flight technique. Neutron ambient dose equivalents were determined from the measured fluence distribution using ICRP (International Commission on Radiological Protection) recommended fluence to dose equivalent conversion coefficients. Neutron dose equivalents were also measured using a conventional BF3 detector based REM counter. Ambient dose equivalent measured by the REM counter is found to be in agreement with that determined from the neutron fluence spectra within their uncertainties. Angular distributions of the ambient dose equivalents were also determined from the measured fluence distributions at different angles.

4.
Nat Phys ; 19(11): 1630-1635, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970534

RESUMO

Arrays of Josephson junctions are governed by a competition between superconductivity and repulsive Coulomb interactions, and are expected to exhibit diverging low-temperature resistance when interactions exceed a critical level. Here we report a study of the transport and microwave response of Josephson arrays with interactions exceeding this level. Contrary to expectations, we observe that the array resistance drops dramatically as the temperature is decreased-reminiscent of superconducting behaviour-and then saturates at low temperature. Applying a magnetic field, we eventually observe a transition to a highly resistive regime. These observations can be understood within a theoretical picture that accounts for the effect of thermal fluctuations on the insulating phase. On the basis of the agreement between experiment and theory, we suggest that apparent superconductivity in our Josephson arrays arises from melting the zero-temperature insulator.

5.
Chem Rec ; 22(12): e202200172, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36069267

RESUMO

There is growing interest towards the design and synthesis of organic redox-active systems, which exist in ionic form. Multi- redox systems entail life-sustaining processes like photosynthesis and cellular respiration. The significant challenge for material scientists is to rationally design complex molecular materials that can store and transfer multiple electrons at low operational potentials and are stable under ambient conditions. Also, important are the designed ionic π-systems that combine efficient electron and ion transport. Here, we discuss the synthesis of ionic π-systems which exist in the closed-shell form. Firstly, different classes of ionic arylenediimides and viologens with different π-linkers are discussed from the synthetic, structural and redox perspective. These ionic π-systems are based on the electron deficient π-scaffolds, and are shown to accumulate upto six electrons. We then discuss electron-rich ionic arylenediimides which can exist in anionic form or zwitterionic form. The anionic electron donors have absorption extending to the near Infrared (NIR) region and can be stabilized in aqueous solution. We also discuss the effect of the electron accumulation on the aromaticity and non-aromaticity of the naphthalene and the imide rings of the naphthalenediimides. We finally discuss in brief, the applications related to the organic mixed ionic-electronic conductors.

6.
BMC Infect Dis ; 22(1): 521, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668379

RESUMO

BACKGROUND: Women of reproductive age group have greater predilection to urinary tract infections (UTI). Various risk factors increase the prevalence in women. Emergence of multidrug resistant uropathogens make clinical management of UTI challenging. Here we assess holding of urine as risk factor of UTI in women and reasons for delayed voiding. We also investigate the relationship between frequency of UTIs and overall behavioural features, menstrual hygiene and attitude of women towards their own health issues. METHODS: A questionnaire based cross-sectional study was performed with 816 hostel residents with written consent. Self-reported data was statistically analysed using SPSS software. Urinalysis and urine culture were done for 50 women by random sampling to obtain the information on leading causative agents of UTI in the study population and their antimicrobial resistance profile. RESULTS: The prevalence of UTI among the participants without risk factors was found to be 27.5 (95% CI: 24.4-30.7). Attitude of women towards their own personal health issues and use of public toilets showed a correlation with prevalence of infection. Delay in urination on habitual basis was found to be associated with UTI. Uropathogens isolated by random sampling were resistant to multiple drugs that are generally used to treat UTI. CONCLUSIONS: Holding urine for long time had proven to be an important risk factor and amongst different reasons of holding urine, holding due to poor sanitary condition of public toilets was the most common. Higher frequency of self-reported UTIs is related to holding of urine, behavioural features and attitude of women.


Assuntos
Infecções Urinárias , Micção , Antibacterianos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Higiene , Menstruação , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia
7.
Sci Rep ; 12(1): 6165, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418661

RESUMO

An inhibitory effect of estradiol (E2) on HIV-1 infection was suggested by several reports. We previously identified increased gene expression of actin-binding protein cofilin 1 (CFL1) in endocervix in the E2-dominated proliferative phase of the menstrual cycle. Actin cytoskeleton has an integral role in establishing and spreading HIV-1 infection. Herein, we studied in vitro effects of E2 on HIV-1 infection and on CFL1 expression to gain insight into the mechanism of HIV-1 inhibition by E2. E2 dose-dependently inhibited HIV-1BaL infection in peripheral blood mononuclear cells (PBMCs) and endocervix. In PBMCs and endocervix, E2 increased protein expression of total CFL1 and phosphorylated CFL1 (pCFL1) and pCFL1/CFL1 ratios. LIMKi3, a LIM kinase 1 and 2 inhibitor, abrogated the phenotype and restored infection in both PBMCs and endocervix; inhibited E2-induced expression of total CFL1, pCFL1; and decreased pCFL1/CFL1 ratios. Knockdown of CFL1 in PBMCs also abrogated the phenotype and partially restored infection. Additional analysis of soluble mediators revealed decreased concentrations of pro-inflammatory chemokines CXCL10 and CCL5 in infected tissues incubated with E2. Our results suggest a link between E2-mediated anti-HIV-1 activity and expression of CFL1 in PBMCs and endocervical mucosa. The data support exploration of cytoskeletal signaling pathway targets for the development of prevention strategies against HIV-1.


Assuntos
Cofilina 1 , Estradiol , Infecções por HIV , Soropositividade para HIV , Cofilina 1/metabolismo , Estradiol/farmacologia , Feminino , HIV-1 , Humanos , Leucócitos Mononucleares/metabolismo , Mucosa/metabolismo
8.
Nat Metab ; 4(4): 476-494, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35478031

RESUMO

Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tecido Adiposo/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidases , Fibrose , Inflamação/metabolismo , Resistência à Insulina/genética , Macrófagos/metabolismo , Camundongos , Obesidade/metabolismo
10.
Diabet Med ; 38(4): e14368, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32743838

RESUMO

AIM: This prospective observational study evaluated the role of infrared (IR) dermal thermometry in the management of diabetic foot ulcers. METHODS: Thirty participants with unilateral neuropathic diabetic foot ulcers of University of Texas grade 1 or 2 (stage A) were followed up monthly for 1 year. At each visit, skin temperatures were measured with an IR dermal thermometer at corresponding sites on both feet, using the contralateral feet without ulcers as controls. RESULTS: Average temperature and ulcer temperature in affected feet were significantly higher than in unaffected feet, with a mean difference of 1.2 °C [95% confidence interval (CI) 0.7 to 1.7] and 3.1 °C (95% CI 2.3 to 3.9), respectively. Although the gradient between average temperature of affected foot and that of unaffected foot normalized (mean difference 0.2 °C, 95% CI -0.2 to 0.7) at healing, the temperature gradient between the ulcer and a corresponding site on the unaffected foot decreased but did not normalize (mean difference 2.1 °C, 95% CI 1.2 to 3.1) even at healing, as documented by skin closure, and persisted for up to 1 month after skin closure. A gradient of ≥1 °C between average temperature of affected foot and that of unaffected foot at initial presentation or at any time during ulcer healing was found to predict impaired healing and should alert clinicians to ulcers requiring more attention. An incremental trend in temperature gradient (median difference 2.2 °C; range 0.1-6.3 °C) at a site on the foot was predictive of a recurrent ulcer involving the same site. CONCLUSIONS: IR dermal thermometry may have a role in predicting diabetic foot ulcer healing, in determining the completeness of healing and in guiding the duration of offloading. Serial monitoring of the temperature gradient may predict the development of recurrent diabetic foot ulcers.


Assuntos
Pé Diabético/terapia , Raios Infravermelhos/uso terapêutico , Termometria/métodos , Adulto , Temperatura Corporal , Estudos de Casos e Controles , Pé Diabético/diagnóstico , Pé Diabético/patologia , Pé Diabético/fisiopatologia , Progressão da Doença , Feminino , Pé/fisiopatologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Prognóstico , Cicatrização/fisiologia
11.
West Indian med. j ; West Indian med. j;69(3): 168-170, 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1341889

RESUMO

ABSTRACT Rhinoscleroma (more appropriately 'scleroma') is a chronic, disfiguring inflammatory lesion that is rarely encountered in the present-day otolaryngology practice. The diagnosis often becomes difficult especially when it recurs and presents late with complications. This report illustrates the clinical and histologic features of rhinoscleroma in a defaulter patient who represents advanced-stage disease with orbital and intracranial extensions. Special emphasis has been provided on the computed tomography impressions such that the evolution of scleroma with time can be studied.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Rinoscleroma/patologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Rinoscleroma/diagnóstico por imagem
12.
J Phys Condens Matter ; 32(33): 334002, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289754

RESUMO

We report investigation of phonons and oxygen diffusion in Bi2O3 and (Bi0.7Y0.3)2O3. The phonon spectra have been measured in Bi2O3 at high temperatures up to 1083 K using inelastic neutron scattering. Ab initio calculations have been used to compute the individual contributions of the constituent atoms in Bi2O3 and (Bi0.7Y0.3)2O3 to the total phonon density of states. Our computed results indicate that as temperature is increased, there is a complete loss of sharp peak structure in the vibrational density of states. Ab initio molecular dynamics simulations show that even at 1000 K in δ-phase Bi2O3, Bi-Bi correlations remain ordered in the crystalline lattice while the correlations between O-O show liquid like disordered behavior. In the case of (Bi0.7Y0.3)2O3, the O-O correlations broadened at around 500 K indicating that oxygen conductivity is possible at such low temperatures in (Bi0.7Y0.3)2O3 although the conductivity is much less than that observed in the undoped high temperature δ-phase of Bi2O3. This result is consistent with the calculated diffusion coefficients of oxygen and observation by quasielastic neutron scattering experiments. Our ab initio molecular dynamics calculations predict that macroscopic diffusion is attainable in (Bi0.7Y0.3)2O3 at much lower temperatures, which is more suited for technological applications. Our studies elucidate the easy directions of diffusion in δ-Bi2O3 and (Bi0.7Y0.3)2O3.

13.
Virology ; 542: 63-70, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32056669

RESUMO

Sindbis virus (SINV) produces the small membrane protein TF from the 6K gene via a (-1) programmed ribosomal frameshifting. While several groups have shown that TF-deficient virus exhibits reduced virulence, the mechanism(s) by which this occurs remain unknown. Here, we demonstrate a role for TF in antagonizing the host interferon response. Using wild-type and type 1 interferon receptor-deficient mice and primary cells derived from these animals, we show that TF controls the induction of the host interferon response at early times during infection. Loss of TF production leads to elevated interferon and a concurrent reduction in viral loads with a loss of pathogenicity. Palmitoylation of TF has been shown to be important for particle assembly and morphology. We find that palmitoylation of TF also contributes to the ability of TF to antagonize host interferon responses as dysregulated palmitoylation of TF reduces virulence in a manner similar to loss of TF.


Assuntos
Interferon Tipo I/biossíntese , Sindbis virus/imunologia , Sindbis virus/metabolismo , Proteínas Virais/imunologia , Proteínas Virais/metabolismo , Infecções por Alphavirus/genética , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/virologia , Animais , Feminino , Genes Virais , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Lipoilação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/imunologia , Sindbis virus/genética , Proteínas Virais/genética , Virulência/genética , Virulência/imunologia , Virulência/fisiologia
14.
BJS Open ; 3(5): 722-732, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31592517

RESUMO

Background: Emergency and essential surgical, obstetric and anaesthesia (SOA) care are now recognized components of universal health coverage, necessary for a functional health system. To improve surgical care at a national level, strategic planning addressing the six domains of a surgical system is needed. This paper details a process for development of a national surgical, obstetric and anaesthesia plan (NSOAP) based on the experiences of frontline providers, Ministry of Health officials, WHO leaders, and consultants. Methods: Development of a NSOAP involves eight key steps: Ministry support and ownership; situation analysis and baseline assessments; stakeholder engagement and priority setting; drafting and validation; monitoring and evaluation; costing; governance; and implementation. Drafting a NSOAP involves defining the current gaps in care, synthesizing and prioritizing solutions, and providing an implementation and monitoring plan with a projected cost for the six domains of a surgical system: infrastructure, service delivery, workforce, information management, finance and governance. Results: To date, four countries have completed NSOAPs and 23 more have committed to development. Lessons learned from these previous NSOAP processes are described in detail. Conclusion: There is global movement to address the burden of surgical disease, improving quality and access to SOA care. The development of a strategic plan to address gaps across the SOA system systematically is a critical first step to ensuring countrywide scale-up of surgical system-strengthening activities.


Antecedentes: En la actualidad, se reconoce que la atención quirúrgica, obstétrica y anestésica urgente y esencial (surgical, obstetric, and anaesthesia, SOA) es uno de los componentes de la cobertura sanitaria universal y un elemento necesario para el funcionamiento de un sistema de salud. Para mejorar la atención quirúrgica a nivel nacional, se necesita una planificación estratégica que aborde los seis dominios de un sistema quirúrgico. En este artículo, se detalla el proceso para el desarrollo de un plan nacional de cirugía, obstetricia y anestesia (national surgical, obstetric, and anaesthesia plan, NSOAP) basado en las experiencias de los principales proveedores, los funcionarios del Ministerio de Salud, los líderes de la Organización Mundial de la Salud y consultores. Métodos: El desarrollo de un NSOAP incluye ocho pasos clave: (1) apoyo y dependencia del ministerio, (2) análisis de la situación y evaluaciones de referencia, (3) compromiso de los agentes implicados y establecimiento de prioridades, (4) redacción y validación, (5) seguimiento y evaluación, (6) análisis de costes, (7) gobernanza y (8) implementación. Redactar un NSOAP implica definir los déficits actuales en la atención, sintetizar y priorizar soluciones, y proporcionar un plan de implementación y seguimiento con unos costes proyectados para los seis dominios de un sistema quirúrgico: infraestructura, prestación de servicios, personal, gestión de la información, finanzas y gobernanza. Resultados: Hasta la fecha, cuatro países han completado un NSOAP y 23 más se han comprometido con su desarrollo. Las lecciones aprendidas de estos procesos previos de NSOAP se describen con detalle. Conclusiones: Existe un movimiento global para abordar la carga de las enfermedades que precisan cirugía, mejorar la calidad y el acceso a la atención SOA. El desarrollo de un plan estratégico para la aproximación sistemáticamente los déficits en todo el sistema SOA es un primer paso crítico para garantizar la ampliación a nivel nacional de las actividades de fortalecimiento del sistema quirúrgico.


Assuntos
Anestesia/métodos , Serviços Médicos de Emergência/normas , Obstetrícia/organização & administração , Procedimentos Cirúrgicos Operatórios/métodos , Anestesia/economia , Anestesia/normas , Atenção à Saúde/economia , Atenção à Saúde/organização & administração , Feminino , Implementação de Plano de Saúde/métodos , Mão de Obra em Saúde/organização & administração , Humanos , Gestão da Informação , Liderança , Programas Nacionais de Saúde/organização & administração , Obstetrícia/economia , Obstetrícia/normas , Participação dos Interessados , Procedimentos Cirúrgicos Operatórios/economia , Procedimentos Cirúrgicos Operatórios/normas , Assistência de Saúde Universal , Organização Mundial da Saúde/economia , Organização Mundial da Saúde/organização & administração
15.
Sci Rep ; 9(1): 13494, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530865

RESUMO

Despite extensive studies suggesting increased susceptibility to HIV during the secretory phase of the menstrual cycle, the molecular mechanisms involved remain unclear. Our goal was to analyze transcriptomes of the endocervix and ectocervix during the proliferative and secretory phases using RNA sequencing to explore potential molecular signatures of susceptibility to HIV. We identified 202 differentially expressed genes (DEGs) between the proliferative and secretory phases of the cycle in the endocervix (adjusted p < 0.05). The biofunctions and pathways analysis of DEGs revealed that cellular assembly and epithelial barrier function in the proliferative phase and inflammatory response/cellular movement in the secretory phase were among the top biofunctions and pathways. The gene set enrichment analysis of ranked DEGs (score = log fold change/p value) in the endocervix and ectocervix revealed that (i) unstimulated/not activated immune cells gene sets positively correlated with the proliferative phase and negatively correlated with the secretory phase in both tissues, (ii) IFNγ and IFNα response gene sets positively correlated with the proliferative phase in the ectocervix, (iii) HIV restrictive Wnt/ß-catenin signaling pathway negatively correlated with the secretory phase in the endocervix. Our data show menstrual cycle phase-associated changes in both endocervix and ectocervix, which may modulate susceptibility to HIV.


Assuntos
Colo do Útero/metabolismo , Fase Folicular/genética , Perfilação da Expressão Gênica , Fase Luteal/genética , Transcriptoma , Biologia Computacional/métodos , Endométrio/metabolismo , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Transdução de Sinais
16.
Clin Exp Immunol ; 198(2): 251-260, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31260079

RESUMO

Global incidence of dengue has drastically increased in the last few years. Despite the global morbidity and mortality associated with dengue infection, mechanisms of immune control and viral pathogenesis are poorly explored. Pancytopenias, along with increased oxidative stress, are salient clinical findings in severe dengue patients. Previously, we demonstrated significant differences of circulating immune complexes (CICs) among severe and non-severe dengue patients. Accordingly, here we sought to determine the contributory role of affinity-purified antibody-bound CICs in dengue severity. To characterize intracellular oxidative stress induced by antibody-bound CICs, 5-(and-6)-chloromethyl-2'-7'-dichlorodihydrofluorescein diacetate (DCFDA) was measured by flow cytometry. At the same time, CICs sensitized healthy red blood cells (RBC) and patients' RBC morphology was determined by scanning electron microscopy and flow cytometry analysis. Erythrophagocytosis and ferritin levels were further determined in severe and non-severe dengue patients. Our results showed that the severe patients had high titres of immunoglobulin (Ig)M-bound CICs (P < 0·0001) in their sera, increased intracellular oxidative stress (P < 0·0001), high ferritin levels (P < 0·0001), altered morphology of RBC and finally enhanced erythrophagocytosis. This study shows for the first time that RBC morphology is altered in severe dengue patients. Taken together, this study suggests that the enhanced IgM-bound CICs could contribute to the increased oxidative stress and act directly on RBC destruction of severe dengue patients, and is an important pathophysiological determinant. Hence, IgM-bound CICs can serve as an important laboratory parameter to monitor dengue infection progression.


Assuntos
Complexo Antígeno-Anticorpo , Eritrócitos , Imunoglobulina M , Estresse Oxidativo/imunologia , Dengue Grave , Adulto , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/imunologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Eritrócitos/patologia , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Dengue Grave/sangue , Dengue Grave/imunologia , Dengue Grave/patologia , Índice de Gravidade de Doença
17.
Br J Surg ; 106(2): e81-e90, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30620064

RESUMO

BACKGROUND: Surgery is among the most neglected parts of healthcare systems in low- and middle-income countries. Ethiopia has launched a national strategic plan to address challenges in the surgical system. This study aimed to assess surgical capacity in two Ethiopian regions to inform priority areas for improvement. METHODS: A mixed-methods study was conducted using two tools adapted from the Lancet Commission's Surgical Assessment Tools: a quantitative Hospital Assessment Tool and a qualitative semistructured interview tool. Fifteen hospitals selected by the Federal Ministry of Health were surveyed in the Tigray and Amhara regions to assess the surgical system across five domains: service delivery, infrastructure, workforce, information management and financing. RESULTS: Service delivery was low across hospitals with a mean(s.d.) of 5(6) surgical cases per week and a narrow range of procedures performed. Hospitals reported varying availability of basic infrastructure, including constant availability of electricity (9 of 15) and running water (5 of 15). Unavailable or broken diagnostic equipment was also common. The majority of surgical and anaesthesia services were provided by non-physician clinicians, with little continuing education available. All hospitals tracked patient-level data regularly and eight of 15 hospitals reported surgical volume data during the assessment, but research activities were limited. Hospital financing specified for surgery was rare and the majority of patients must pay out of pocket for care. CONCLUSION: Results from this study will inform programmes to simultaneously improve each of the health system domains in Ethiopia; this is required if better access to and quality of surgery, anaesthesia and obstetric services are to be achieved.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Cirurgia Geral/estatística & dados numéricos , Recursos em Saúde/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Etiópia , Inquéritos Epidemiológicos , Humanos
18.
Br J Dermatol ; 179(3): 717-723, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29851030

RESUMO

BACKGROUND: Eczema and asthma are chronic diseases with onset usually before the age of 5 years. More than 50% of individuals with eczema will develop asthma and/or other allergic diseases. Several loss-of-function mutations in filaggrin (FLG) have been identified in patients with eczema. However, the association of FLG with healthcare use is unknown. OBJECTIVES: To determine whether FLG mutations are associated with increased prescribing for eczema and asthma and whether increased prescribing is associated with increased healthcare costs. METHODS: A secondary analysis of BREATHE, a cross-sectional study of gene-environment associations with asthma severity, was undertaken. BREATHE data was collected for 1100 participants with asthma, in Tayside and Fife, Scotland during the period 2003-2005. Through collaboration with the Health Informatics Centre in Dundee, BREATHE was linked to accident and emergency, community prescribing and Scottish morbidity records. The data linkage allowed longitudinal exploration of associations between genetic variation and prescribing. RESULTS: An association was found between FLG mutations and increased prescribing for mild and moderate eczema, asthma-reliever medicine and asthma exacerbations. A strong association was found between FLG mutations and prescribing of emollients [incidence rate ratio (IRR) 2·19, 95% confidence interval (CI) 1·36-3·52], treatment for severe eczema (IRR 2·18, 95% CI 1·22-3·91) and a combination of a long-acting ß2 -agonist and corticosteroids (IRR 3·29, 95% CI 1·68-6·43). CONCLUSIONS: The presence of FLG mutations in this cohort is associated with increased prescribing for eczema and asthma. Randomized controlled trials are required to determine if these individuals could benefit from management strategies to reduce morbidity and treatment costs.


Assuntos
Asma/terapia , Doença Crônica/terapia , Eczema/terapia , Custos de Cuidados de Saúde/estatística & dados numéricos , Proteínas de Filamentos Intermediários/genética , Proteínas S100/genética , Adolescente , Adulto , Antiasmáticos/economia , Antiasmáticos/uso terapêutico , Asma/economia , Asma/genética , Criança , Pré-Escolar , Doença Crônica/economia , Estudos Transversais , Análise Mutacional de DNA , Prescrições de Medicamentos/estatística & dados numéricos , Eczema/economia , Eczema/genética , Emolientes/economia , Emolientes/uso terapêutico , Feminino , Proteínas Filagrinas , Predisposição Genética para Doença , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Mutação com Perda de Função , Masculino , Medicamentos sob Prescrição/economia , Medicamentos sob Prescrição/uso terapêutico , Escócia , Fatores de Tempo , Adulto Jovem
20.
Eur J Contracept Reprod Health Care ; 23(3): 227-230, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29842838

RESUMO

OBJECTIVES: Tubal sterilisation using Essure is a minimally invasive technique for permanent contraception, with high rates of patient satisfaction. However, some women subsequently choose removal of the inserts, due to side effects such as pelvic pain, abnormal bleeding, dyspareunia or allergic dermatitis. This case series presents the management of eight women who underwent laparoscopic removal of Essure inserts in conjunction with salpingectomy. We describe our surgical technique, its underlying principles and immediate surgical outcomes. METHODS: Eight patients were identified as having undergone removal of Essure inserts, via an electronic search of the surgical procedures database. A retrospective review of case records was undertaken. The primary outcome was safety and feasibility of the laparoscopic salpingectomy approach. Secondary outcome measures included implant fracture rate, operative time, blood loss and length of patient stay. RESULTS: All eight women were able to undergo laparoscopic salpingectomy and removal of the Essure inserts without the need for laparotomy or hysterectomy. There were no incidences of fracture or incomplete removal of the insert. Immediate postoperative recovery was uncomplicated in all eight women; the mean length of stay was 17 h. One patient had a small bowel serosal tear attributed to laparoscopic entry. CONCLUSION: This case series suggests that laparoscopic salpingectomy for removal of Essure inserts is safe and feasible. We acknowledge that the numbers were small. However, consistent use of a laparoscopic approach in these eight patients indicates that this procedure is a feasible and suitable alternative to hysterectomy.


Assuntos
Remoção de Dispositivo/métodos , Histeroscopia/métodos , Salpingectomia/métodos , Esterilização Tubária/métodos , Adulto , Feminino , Humanos , Laparoscopia/métodos , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos
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