RESUMEN
Higher cognitive functions such as linguistic comprehension must ultimately relate to perceptual systems in the brain, though how and why this forms remains unclear. Different brain networks that mediate perception when hearing real-world natural sounds has recently been proposed to respect a taxonomic model of acoustic-semantic categories. Using functional magnetic resonance imaging (fMRI) with Chinese/English bilingual listeners, the present study explored whether reception of short spoken phrases, in both Chinese (Mandarin) and English, describing corresponding sound-producing events would engage overlapping brain regions at a semantic category level. The results revealed a double-dissociation of cortical regions that were preferential for representing knowledge of human versus environmental action events, whether conveyed through natural sounds or the corresponding spoken phrases depicted by either language. These findings of cortical hubs exhibiting linguistic-perceptual knowledge links at a semantic category level should help to advance neurocomputational models of the neurodevelopment of language systems.
RESUMEN
The use of algorithms such as HLAMatchmaker to redefine donor-recipient HLA matching is gaining increasing attention. Our research has previously demonstrated that higher HLA class II eplet mismatches correlated with the development of chronic lung allograft dysfunction (CLAD). In this study of lung transplant recipients we prospectively examined the association between donor-recipient HLA eplet mismatches as defined by HLAMatchmaker (version 2.1) and de-novo anti-HLA donor-specific antibody (DSA) formation, as assessed by single antigen-bead solid phase assay. HLA class II eplet mismatch, when split at the median for the cohort, predicted the development of de-novo HLA class II DSA at 3â¯months but not at 12â¯months. Having previously shown that high HLA class II eplet mismatches was associated with CLAD, we now show that the same factors are associated with de-novo HLA class II DSA post-transplant.
Asunto(s)
Rechazo de Injerto/diagnóstico , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Prueba de Histocompatibilidad/métodos , Trasplante de Pulmón , Estudios de Cohortes , Citometría de Flujo , Supervivencia de Injerto , Antígenos HLA-DQ/sangre , Antígenos HLA-DR/sangre , Histocompatibilidad , Humanos , Separación Inmunomagnética , Isoanticuerpos/metabolismo , Pronóstico , Programas Informáticos , Receptores de TrasplantesRESUMEN
Thrombotic microangiopathy (TMA) is a well-recognised complication following transplantation, often due to an underlying genetic predisposition, medications or rejection. The use of eculizumab in these settings has been previously described, but its role still remains to be clarified. A 45-year-old man, with a history of type 1 diabetes mellitus and subsequent end-stage kidney failure, presented for a simultaneous pancreas-kidney transplant. Immunologically, he was well matched with the donor, and he received standard induction immunosuppression including tacrolimus. His early transplant course was complicated by Haemophilus parainfluenzae paronychia and a Pseudomonas aeruginosa catheter-associated urinary tract infection. Within 1 week, he developed thrombotic microangiopathy with significant renal dysfunction and eventual dialysis dependence, without evidence of transplant rejection on biopsy. He was also noted to have antiphospholipid antibodies in moderate titres. The TMA did not resolve despite cessation of tacrolimus, and he was subsequently commenced on eculizumab. The patient achieved a partial remission from TMA, with ongoing biochemical evidence of haemolysis, although now with stable graft function, despite significant damage. His transplanted pancreas remained seemingly unaffected by TMA, and continues to function well. This case describes an unusual presentation of TMA post-transplantation and is the only described case of eculizumab use following pancreas-kidney transplant. It remains unclear in this case what the likely precipitant for TMA was, although it seems to be, at least in part, controlled by ongoing use of eculizumab, presumably by terminal complement inhibition.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Trasplante de Riñón/efectos adversos , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias/tratamiento farmacológico , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/etiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/cirugía , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Microangiopatías Trombóticas/diagnósticoRESUMEN
BACKGROUND: Participation of compatible pairs (CP) in kidney paired donation (KPD) could be attractive to CPs who have a high degree of HLA mismatch, if the CP recipient will gain a better HLA match. Because KPD programs were not designed to help CP, it is important to define allocation metrics that enable CP to receive a better-matched kidney, without disadvantage to incompatible pairs (ICP). METHODS: Simulations using 46 ICPs and 11 fully HLA-mismatched CPs were undertaken using the Australian KPD matching algorithm. Allocations were preformed adding 1 CP at a time or all 11 CPs at once, and with and without exclusion of unacceptable antigens selected to give a virtual calculated panel-reactive antibody ranging 70% to 80% to improve HLA matching in CP recipients. RESULTS: On average, most CP recipients could be matched and had a lower eplet mismatch (EpMM) with the matched donor (57 ± 15) than with their own donor (78 ± 19, P < 0.02). However, only recipients who had an EpMM to own donor greater than 65 achieved a significant reduction in the EpMM with the matched donor. The gain in EpMM was larger when CPs were listed with unacceptable antigens. Furthermore, inclusion of 1 CP at a time increased matching in ICP by up to 33%, and inclusion of all 11 CPs at once increased ICP matching by 50%. CONCLUSIONS: Compatible pair participation in KPD can increase match rates in ICP and can provide a better immunological profile in CP recipients who have a high EpMM to their own donor when using allocation based on virtual crossmatch.
Asunto(s)
Selección de Donante , Rechazo de Injerto/prevención & control , Antígenos HLA-A/inmunología , Prueba de Histocompatibilidad/métodos , Histocompatibilidad , Trasplante de Riñón/métodos , Donantes de Tejidos , Sistema del Grupo Sanguíneo ABO/inmunología , Algoritmos , Australia , Biomarcadores/sangre , Simulación por Computador , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Humanos , Isoanticuerpos/sangre , Trasplante de Riñón/efectos adversos , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Malignancies metastatic to the larynx are rare, accounting for fewer than 1% of all laryngeal cancers with metastatic sources; the most common of these metastases are cutaneous melanomas and renal cell carcinomas. Only 13 cases of colon cancer and 2 cases of rectal adenocarcinoma metastatic to the larynx have been previously reported in the literature. We report a new case of rectal adenocarcinoma metastatic to the larynx that resulted in subglottic stenosis in a 60-year-old man. We also review the literature, and we discuss the presentations of and treatments for this rare entity.
Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/secundario , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/secundario , Neoplasias del Recto/patología , Broncoscopía , Humanos , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana EdadRESUMEN
The potential role of cancer stem-like cells (CSCs) in chemoresistance of human oral squamous cell carcinoma (OSCC) was examined. A small subpopulation (1-2%) of CD133(+) CSCs was identified in OSCC cell lines and tissues. These CD133(+) CSCs possess higher clonogenicity, invasiveness, and increased in vivo tumorigenicity as compared to CD133(-) counterparts. Meanwhile, CD133(+) CSCs were substantially resistant to standard chemotherapy, wherein both in vitro and in vivo treatment with paclitaxel resulted in a marked enrichment for CD133(+) CSCs. Our data suggest that CD133(+) cells represent a small subpopulation of CSCs that may contribute to chemoresistance in human OSCC.