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BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.
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BACKGROUND: High rates of physical and mental health comorbidities are associated with functional impairment among persons who are homeless. Cognitive dysfunction is common, but how it contributes to various functional outcomes in this population has not been well investigated. This study examines how cognition covaries with community functioning and subjective quality of life over a 6-year period while accounting for the effects of risk and protective factors. METHODS: Participants were 349 homeless adults (mean age = 39.8) recruited from the Toronto site of the At Home/Chez Soi study, a large Canadian randomized control trial of Housing First. Participants completed up to four clinical evaluations over 6 years. Factor scores were created to index verbal learning and memory (vLM) and processing speed-cognitive flexibility (PSCF). The primary outcomes were community functioning and subjective quality of life. Risk factors included lifetime homelessness, mental health diagnoses, medical comorbidity, and childhood adversity. Linear mixed-effects models were conducted to examine cognition-functional outcome associations over time, with resilience as a moderator. RESULTS: Better vLM (b = 0.787, p = 0.010) and PSCF (b = 1.66, p < 0.001) were associated with better community functioning, but not with quality of life. Resilience conferred a protective effect on subjective quality of life (b = 1.45, p = 0.011) but did not moderate outcomes. CONCLUSIONS: Our findings suggest a need to consider the unique determinants of community functioning and quality of life among homeless adults. Cognition should be prioritized as a key intervention target within existing service delivery models to optimize long-term functional outcomes.
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Personas con Mala Vivienda , Trastornos Mentales , Adulto , Humanos , Calidad de Vida , Estudios de Seguimiento , Canadá/epidemiología , Trastornos Mentales/psicología , CogniciónRESUMEN
PURPOSE: Oral treprostinil and selexipag are drugs targeting the prostacyclin pathway and are approved for treatment of pulmonary arterial hypertension (PAH). In the setting of unsatisfactory clinical response or tolerability issues while on selexipag, there is little data on clinical benefit, safety, or strategies on transitioning to oral treprostinil. Using prospective data from the ADAPT registry, we aimed to evaluate clinical outcomes, safety, and transition strategies in ten patients with PAH transitioning from selexipag to oral treprostinil. METHODS: ADAPT was a prospective, real-world, multicenter, United States-based registry of patients with PAH newly started on oral treprostinil, with a cohort of patients (n = 10) transitioning from selexipag to oral treprostinil. PAH variables of interest were collected from standard-of-care clinic visits. Clinical improvement was defined by modified REPLACE criterion, and risk was assessed by REVEAL Lite 2 from baseline to last follow-up. Real world transition strategies were recorded. Healthcare utilization or worsening PAH was evaluated within 30 days of transitions. RESULTS: Seven patients transitioned due to worsening PAH or lack of efficacy on selexipag, and three patients transitioned due to tolerability issues. Based on the modified REPLACE criterion, five patients demonstrated clinical improvement after transition from selexipag to oral treprostinil. Using REVEAL Lite 2 to assess risk, three patients improved and five patients maintained risk category from baseline to last follow-up. All transitions occurred in an outpatient setting either as abrupt stop/start or cross-titration, without parenteral treprostinil bridging. CONCLUSION: Transition from selexipag to oral treprostinil was safe, performed without parenteral prostacyclin bridging, and resulted in clinical and categorical risk improvements in some patients.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Antihipertensivos , Hipertensión Pulmonar/tratamiento farmacológico , Estudios Prospectivos , Administración Oral , Epoprostenol/efectos adversos , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , Sistema de RegistrosRESUMEN
AIM: To evaluate the reliability of synthetic diffusion-weighted imaging (DWI) using a high b-value in comparison to conventional DWI for paediatric abdominal MRI. MATERIALS AND METHODS: Paediatric patients (<19 years old) who underwent liver or pancreatobiliary MRI with DWI using 10 b-values (b = 0, 25, 50, 75, 100, 200, 400, 600, 800, 1,500 s/mm2) from March to October 2021 were included in this retrospective study. Using the software, synthetic DWI using b = 1,500 s/mm2 was generated automatically by selecting the b-value required as output. Conventional and synthetic DWI values for b = 1,500 s/mm2 were measured at the liver, spleen, paraspinal muscle, and mass lesions, if present, and apparent diffusion coefficient (ADC) values were calculated using the mono-exponential model. Intraclass correlation coefficients (ICCs) were calculated to assess the reliability of conventional and synthetic DWI and ADC values with b = 1,500 s/mm2. RESULTS: Thirty paediatric patients (M:F = 22:8, mean 10.8 ± 3.1 years old) were included and four had tumours on abdominal MRI. ICC values were 0.906-0.995 between conventional and synthetic DWI and ADC with b = 1,500 s/mm2 in the liver, spleen and muscle. For mass lesions, ICC values were 0.997-0.999 for both synthetic DWI and ADC images. CONCLUSIONS: Synthetic DWI and ADC values obtained using a high b-value showed excellent agreement with conventional DWI for the liver, spleen, muscle, and mass in paediatric MRI.
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Imagen de Difusión por Resonancia Magnética , Neoplasias , Humanos , Niño , Adulto Joven , Adulto , Adolescente , Estudios Retrospectivos , Reproducibilidad de los Resultados , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodosRESUMEN
Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.
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Neoplasias de la Mama , Niño , Humanos , Femenino , Preescolar , Neoplasias de la Mama/cirugía , Estudios Prospectivos , Estudios de Cohortes , Actividades Cotidianas , Dolor , Factores de Riesgo , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnósticoRESUMEN
OBJECTIVES: SARS-CoV-2 testing has been critical in monitoring and containing the COVID-19 pandemic, but there is a dearth of studies on how individuals' adherence to testing varies according to their working conditions. This study aimed to investigate the association between the type of employment contract and COVID-19 testing among wage workers in South Korea. STUDY DESIGN: We used a nationally representative sample of employees aged 20-65 years collected from March 24 to 31, 2022. To focus on individual responses when the test was recommended, our sample consisted of 1266 participants who had experienced symptoms of COVID-19 or had been exposed to a confirmed case in the household. METHODS: We used multivariate logistic regression to estimate the association between the odds of receiving a PCR test and the type of employment contract while controlling for other potential covariates. RESULTS: The percentage of participants who had a SARS-CoV-2 PCR test was 77.8%. After adjusting for all potential covariates, daily workers (OR = 0.35, 95% CI 0.18 to 0.70, P = 0.003) and part-time workers (OR = 0.58, 95% CI 0.39 to 0.86, P = 0.007) had significantly lower odds of being tested relative to standard workers. Other temporary or atypical workers showed no significant differences from standard workers. CONCLUSION: Our findings suggested that individuals in the most vulnerable job positions, with less job security and working hours, exhibited a decreased inclination to undergo COVID-19 testing. More effective job retention and income support policies are required to improve compliance.
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Prueba de COVID-19 , COVID-19 , Humanos , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiología , SARS-CoV-2 , Empleo , República de Corea/epidemiologíaRESUMEN
BACKGROUND: Currently, there is no consensus on the number of defibrillation attempts that should be made before transfer to a hospital in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the association between the number of defibrillations and a sustained prehospital return of spontaneous circulation (ROSC). METHODS: A retrospective analysis of a multicentre, prospectively collected, registry-based study in Republic of Korea was conducted for OHCA patients with prehospital defibrillation. The primary outcome was sustained prehospital ROSC, and the secondary outcome was a good neurological outcome at hospital discharge, defined as Cerebral Performance Category score 1 or 2. Cumulative incidence of sustained prehospital ROSC and good neurological outcome according to number of defibrillations were examined. Multivariable logistic regression analysis was used to examine whether the number of defibrillations was independently associated with the outcomes. RESULTS: Excluding 172 patients with missing data, a total of 1983 OHCA patients who received prehospital defibrillation were included. The median time from arrest to first defibrillation was 10 (IQR 7-15) min. The numbers of patients with sustained prehospital ROSC and good neurological outcome were 738 (37%) and 549 (28%), respectively. Sustained ROSC rates decreased as the number of defibrillation attempts increased from the first to the sixth (16%, 9%, 5%, 3%, 2% and 1%, respectively). The cumulative sustained ROSC rate, and good neurological outcome rate from initial defibrillation to sixth defibrillation were 16%, 25%, 30%, 34%, 36%, 36% and 11%, 18%, 22%, 25%, 26%, 27%, respectively. With adjustment for clinical characteristics and time to defibrillation, a higher number of defibrillations was independently associated with a lower chance of a sustained ROSC (OR 0.81, 95% CI 0.76 to 0.86) and a lower chance of good neurological outcome (OR 0.86, 95% CI 0.80 to 0.92). CONCLUSIONS: We observed no significant increase in ROSC after five defibrillations, and no absolute increase in ROSC after seven defibrillations. These data provide a starting point for determination of the optimal defibrillation strategy prior to consideration for prehospital extracorporeal cardiopulmonary resuscitation (ECPR) or conveyance to a hospital with an ECPR capability. TRIAL REGISTRATION NUMBER: NCT03222999.
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Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , Humanos , Estudios Retrospectivos , Retorno de la Circulación Espontánea , Sistema de RegistrosRESUMEN
BACKGROUND: Identification of perioperative risk factors for recurrent nasal polyps (RNPs) is important for selection of further treatment and determination of appropriate follow-up period. However, the relative prognostic significance of these risk factors has not been investigated. METHODOLOGY: We compared the nasal symptoms, endoscopic polyp and Lund-Mackey computed tomography scores, and the laboratory and pathological findings of RNP and non-RNP patients. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: Patients with poor nasal symptom scores and olfactory dysfunctions and high Lund-Mackey computed tomography scores were at higher risk of postoperative RNPs, as were those with allergic conditions and elevated tissue and serum eosinophil levels. The tissue neutrophil counts/percentages were significantly lower in the RNP than the other group. The tissue eosinophil level was of higher diagnostic utility than the serum eosinophil level. The RNP diagnostic odds ratio afforded by the tissue eosinophil count or percentage was 54.1247. The area under the receiver operating characteristic curve was 0.936. The sensitivity and specificity were 0.8809 and 0.8834, respectively. CONCLUSION: The tissue eosinophil level reliably predicts RNP after endoscopic sinus surgery.
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Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/cirugía , Pólipos Nasales/diagnóstico , Rinitis/complicaciones , Rinitis/cirugía , Rinitis/diagnóstico , Sinusitis/complicaciones , Sinusitis/cirugía , Sinusitis/diagnóstico , Eosinófilos , Olfato , Enfermedad CrónicaRESUMEN
A microporous continuum traversed by a set of mutually perpendicular channels is considered to be a model for a hierarchically porous system of the mesoporous zeolite type. Transient profiles of molecular uptake as determined by kinetic Monte Carlo (kMC) simulation are found to be in excellent agreement with the result attained by the application of the two-region model (the Kärger model) of molecular diffusion. In particular, it is found that, in the two limiting cases referred to as fast exchange and slow exchange, there exist two simple analytical expressions for the rate of molecular uptake and hence for the quantification of transport enhancement in comparison with the purely microporous adsorbent. In the general case, transport enhancement is simply recognized by the reciprocal addition of the expressions in the two limiting cases.
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Zeolitas , Simulación por Computador , Difusión , Cinética , Método de MontecarloRESUMEN
In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}Nâ_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.
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The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of â¼35% ^{24}O_{g.s.}. and â¼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.
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AIM: The main aim of this study was to compare the long-term outcome of a conventional colorectal endoscopic submucosal dissection (ESD) in which submucosal dissection was continued throughout until the completion of resection (ESD-T) to hybrid endoscopic submucosal dissection (ESD-H) in the colorectum. METHOD: Medical records of 836 colorectal neoplasia patients treated by ESD-T or ESD-H were reviewed. ESD-H was defined as colorectal ESD with additional snaring in the final stage of the procedure. Primary outcomes were the overall and metastatic recurrence rates. Secondary outcomes were short-term outcomes such as the en bloc resection rate, procedure time and adverse events. RESULTS: The overall recurrence rate was higher in the ESD-H than in the ESD-T group (5.7% vs 0.7%, P = 0.001). The metastatic recurrence rate showed no significant difference between these groups (1.4% vs 1.4%, P = 1.000). Multivariate analysis revealed that a failed en bloc resection (hazard ratio 24.097; 95% CI 5.446-106.237; P < 0.001) and larger tumour size (hazard ratio 1.042; 95% CI 1.014-1.070; P = 0.003) were independently associated with overall recurrence. The ESD-H group showed a lower en bloc resection rate (56.8% vs 96.5%, P < 0.001), shorter procedure time (45.6 vs 54.3 min, P < 0.001) and higher perforation rate (10.3% vs 6.0%, P = 0.029). CONCLUSION: Although long-term outcomes in terms of overall recurrence are inferior following ESD-H, a failed en bloc resection and large tumour size are the only independent risk factors for recurrence. Further investigations are warranted to improve the long-term outcomes of ESD-H.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Neoplasias Colorrectales/cirugía , Disección , Resección Endoscópica de la Mucosa/efectos adversos , Humanos , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Psoriasis is a chronic inflammatory skin disease characterized by the infiltration of T cell and other immune cells to the skin in response to injury or autoantigens. Conventional, as well as unconventional, γδ T cells are recruited to the dermis and epidermis by CCL20 and other chemokines. Together with its receptor CCR6, CCL20 plays a critical role in the development of psoriasiform dermatitis in mouse models. We screened a panel of CCL20 variants designed to form dimers stabilized by intermolecular disulfide bonds. A single-atom substitution yielded a CCL20 variant (CCL20 S64C) that acted as a partial agonist for the chemokine receptor CCR6. CCL20 S64C bound CCR6 and induced intracellular calcium release, consistent with G-protein activation, but exhibited minimal chemotactic activity. Instead, CCL20 S64C inhibited CCR6-mediated T cell migration with nominal impact on other chemokine receptor signaling. When given in an IL-23-dependent mouse model for psoriasis, CCL20 S64C prevented psoriatic inflammation and the up-regulation of IL-17A and IL-22. Our results validate CCR6 as a tractable therapeutic target for psoriasis and demonstrate the value of CCL20 S64C as a lead compound.
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Quimiocina CCL20/genética , Dermatitis/terapia , Mutagénesis Sitio-Dirigida/métodos , Psoriasis/terapia , Receptores CCR6/metabolismo , Animales , Terapia Biológica/métodos , Células COS , Quimiocina CCL20/inmunología , Quimiocina CCL20/metabolismo , Chlorocebus aethiops , Cristalografía por Rayos X , Dermatitis/inmunología , Modelos Animales de Enfermedad , Epidermis/inmunología , Epidermis/metabolismo , Humanos , Interleucina-23/inmunología , Ratones , Psoriasis/inmunología , Receptores CCR6/inmunología , Linfocitos T/inmunologíaRESUMEN
The methods for expansion of human cytomegalovirus (HCMV)-specific T lymphocytes are limited due to the complex culture process, long culture duration, and human leukocyte antigen (HLA) restriction. Here, we report that in vitro stimulation with pp65 kDa phosphoprotein (pp65)-derived overlapping synthetic peptides rapidly generates large numbers of HCMV-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) regardless of HLA type. Treatment of PBMCs from healthy volunteers expressing HLA-A*02:01 or HLA-A*24:02 with 138 pp65 overlapping peptides (OLP) resulted in an expansion of HCMV pp65 NLVPMVATV (NLV) pentamer-specific CD8+ T lymphocytes that expressed interferon (IFN)-γ, but the pp65 NLV peptide did not generate HCMV-specific CD8+ T lymphocytes in PBMCs obtained from an HLA-A*24:02 donor due to HLA restriction. The OLP-induced T lymphocytes specific for HCMV derived from PBMCs of HLA-A*02:01- and HLA-A*24:02-expressing donors showed effective cytolytic responses against target cells loaded with OLP or the NLV epitope, but pp65 NLV peptide-induced T lymphocytes did not. Phenotypic analyses demonstrated that OLP increased the frequency of CD3+ CD8+ cells, but not CD3+ CD4+, CD14+, or CD56+ cells, in donor PBMCs. Thus, this study provides evidence that in vitro stimulation with OLP efficiently generates sufficient numbers of HCMV pp65-specific cytotoxic T lymphocytes for adoptive cell therapy. Keywords: human cytomegalovirus; cytotoxic T lymphocyte; overlapping peptides; pp65; cytotoxicity.
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Infecciones por Citomegalovirus/inmunología , Péptidos/inmunología , Linfocitos T Citotóxicos/virología , Proteínas de la Matriz Viral/inmunología , Citomegalovirus , Antígenos HLA-A , Humanos , Leucocitos Mononucleares , Fosfoproteínas/inmunologíaRESUMEN
Clubroot caused by Plasmodiophora brassicae is an important disease of brassica crops. The use of vital stains to determine the viability of P. brassicae resting spores can provide useful information regarding spore longevity, inoculum potential, or the efficacy of antimicrobial treatments. Evans blue is one example of a vital stain that has been reported to differentially stain viable and nonviable resting spores. Some previously published protocols using Evans blue to stain P. brassicae resting spores have not provided accurate or consistent results. In this study, we modified the Evans blue method by increasing the staining time to 8 h or more and evaluated P. brassicae resting spores after heat treatment at various combinations of temperature and time. Extending staining times significantly increased the numbers of stained resting spores up to 7 h, after which the numbers of stained spores did not change significantly (R2 = 96.88; P ≤ 0.001). The accuracy of the modified method to discriminate viable and nonviable spores was evaluated in repeated experiments and by comparing the staining data with those derived from inoculation assays and propidium monoazide quantitative PCR (qPCR). The results demonstrated that the modified Evans blue staining method improved the accuracy and consistency of measurement of P. brassicae resting spore viability. Additionally, it was equivalent to the qPCR method for differentiating viable and nonviable spores (R2 = 99.84; P ≤ 0.001) and confirmed in canola infection bioassays.
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Azul de Evans , Plasmodiophorida , Esporas Protozoarias , Coloración y Etiquetado , Azul de Evans/metabolismo , Enfermedades de las Plantas , Plasmodiophorida/fisiología , Esporas Protozoarias/fisiología , Coloración y Etiquetado/métodos , Coloración y Etiquetado/normasRESUMEN
ABO-incompatible (ABOi) dual-graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short- and long-term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end-stage liver disease score was 12.2 ± 4.6. The 1-, 3-, and 5-year patient survival rate was 96.4% during the mean follow-up period of 57.0 ± 22.4 months. The 1-, 3-, and 5-year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO-compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.
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Sistema del Grupo Sanguíneo ABO/efectos adversos , Enfermedades de las Vías Biliares/mortalidad , Incompatibilidad de Grupos Sanguíneos/complicaciones , Rechazo de Injerto/mortalidad , Trasplante de Hígado/efectos adversos , Donadores Vivos , Adulto , Anciano , Enfermedades de las Vías Biliares/etiología , Enfermedades de las Vías Biliares/patología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: P2Y10, along with GPR34 and GPR174, is a G protein-coupled receptor that is activated by an endogenous lipid mediator lysophosphatidylserine (LysoPS). Its expression pattern and its function are completely unknown. We have previously shown that P2Y10 is one of the highly up-regulated genes at the late differentiation stage during in vitro eosinophilopoiesis. OBJECTIVE: We explored the expression and functions of P2Y10 in human cord blood (CB)-derived and peripheral blood (PB) eosinophils. METHODS: Real-time PCR, FACS, Western blot, ELISA, and chemotaxis assays were performed to determine the expression and function of P2Y10. RESULTS: As CB cells differentiated towards eosinophils, P2Y10 mRNA and protein were abundantly expressed. P2Y10 was the most highly expressed in the granulocytes from PB, to a lesser extent in monocytes, and least in lymphocytes. Further fractionation of granulocytes revealed that eosinophils express P2Y10 much more strongly than do neutrophils. PB eosinophils solely expressed P2Y10 among the three LysoPS receptors, while PB neutrophils expressed the three at comparable levels. LysoPS activated both CB and PB eosinophils to induce a robust ERK phosphorylation. Importantly, LysoPS was capable of triggering degranulation of ECP in PB eosinophils. This response was significantly reduced by pharmacological inhibitors of TNF-alpha-converting enzyme (TACE), epidermal growth factor receptor (EGFR), and ERK1/2, which were known to be required in P2Y10-mediated signalling pathways. However, LysoPS had no effect on chemotaxis, differentiation, or eosinophil survival. CONCLUSIONS AND CLINICAL RELEVANCE: LysoPS provokes eosinophil degranulation through P2Y10. Therefore, P2Y10 is a potential therapeutic target to control eosinophil-associated diseases.
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Degranulación de la Célula/inmunología , Eosinófilos/inmunología , Eosinófilos/metabolismo , Receptores Purinérgicos P2/metabolismo , Biomarcadores , Degranulación de la Célula/genética , Diferenciación Celular/inmunología , Quimiotaxis/inmunología , Susceptibilidad a Enfermedades , Humanos , Lisofosfolípidos/metabolismo , Sistema de Señalización de MAP Quinasas , Receptores Acoplados a Proteínas G/metabolismo , Receptores Purinérgicos P2/genética , Transducción de SeñalRESUMEN
Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.
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Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Neoplasias Hepáticas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hepatitis C Crónica/epidemiología , Humanos , Incidencia , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}â1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}â1/2^{+}), E1(1/2^{-}â1/2^{+}), and E1(1/2^{-}â3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.
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Differential cross sections and photon-beam asymmetries for the γ[over â]pâπ^{-}Δ^{++}(1232) reaction have been measured for 0.7