Prediction of pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography.

AIM: To determine whether the pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) can be predicted using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (F-18 FDG-PET). MATERIALS AND METHODS: Twenty-eight patients with PDAC who underwent only neoadjuvant chemotherapy (NAC) before surgery were enrolled in the study. All patients had F-18 FDG-PET examinations before NAC. The resected specimen was pathologically evaluated according to the Classification of Pancreatic Carcinoma (7th edn). Patients were categorised into a non-response group and a response group based on the pathological findings. The non-response group (Grades 1a and 1b) showed ≤50% necrosis in the specimen, while the specimens of the response group (Grades 2-3) showed >50% necrosis. The maximum standardised uptake values (SUVmax) of the tumours on F-18 FDG-PET were measured. The mean values of SUVmax were compared between the two groups. The diagnostic performance of SUVmax in distinguishing the two groups was also evaluated using receiver operating characteristic analysis. RESULTS: The mean SUVmax of the response group was higher than that of the non-response group (9.00 ± 1.78 versus 4.26 ± 2.35; p<0.001). The optimal cut-off value of SUVmax was 9.28 for distinguishing the two groups. The sensitivity, specificity, and accuracy for the prediction in the response group were 80%, 95.7%, and 92.9%, respectively. CONCLUSIONS: SUVmax on F-18 FDG-PET may be useful as a biomarker to predict the pathological response to NAC in patients with PDAC.

Physiological Effects of Pulsed LED Light Added to a Task Lamp to Improve Alertness on Employees of Hospital or Shift Workers / Efectos Fisiológicos de Pulsos de Luz de Diodo Adicionados a una Lámpara de Trabajo para Mejorar el Estado de Alerta en Personal de Hospitales o Trabajadores por Turnos

Abstract The aim of this study is to investigate the effect of a continuous stream of pulses of monochromatic blue pulsed (BP) and a combination of blue and green pulsed (BGP) light-emitting diode (LED) light conditions on physiological responses. This study is an approach to clarify the most suitable LED combination and flickering frequency to evoke alertness when a continuous stream of pulsed LED light is delivered and may suggest applications of continuous pulsed light as support for task illumination for shift workers, hospital nurses, school students or office employees. Combinations were delivered by exposures of BPLED and BGPLED pulses at 100, 200, and 400 Hertz over two background light colors (BLC). Participants were exposed to 12 different light conditions in a counterbalanced procedure. By integrating measures of electroencephalogram (EEG) and pupil constriction; results suggested significant changes in responses during the interaction of BLC, LED, and EEG. Beta waves exhibited a statistically significance (p < 0.05) in arousal levels when exposed to BG light, although no active task was involved during exposure. Furthermore, pupil reacted with larger constriction towards BGPLED exposure than towards monochromatic BPLED exposure, thus demonstrating that a continuous stream of pulses can deliver the same irradiance as if delivered in a continuous flow and without affecting perception as no flickering was perceived in any of the conditions by a qualitative evaluation.

Resumen Este estudio tiene por objetivo determinar cuál es la combinación de luz LED más adecuada y la frecuencia de parpadeo que esta deba tener, para evocar un estado de alerta cuando se emite un flujo continuo de la misma al combinarla con una iluminación de ambiente; y poder sugerir aplicaciones como soporte para la iluminación de tareas para trabajadores por turnos, enfermeras, médicos, estudiantes; o en oficinas y hospitales. Es de original importancia resaltar que en el mercado no existe un producto comercial que se pueda ajustar para apoyar en el trabajo al estado de alerta, se tiene la limitante que estas son pruebas a nivel laboratorio y que posteriores pruebas serán necesarias para validar el producto final. El método usado se basó en las combinaciones que se administraron mediante exposiciones de luz azul pulsada (BPLED) y luz azul y verde combinadas (BGPLED) a frecuencias de 100, 200 y 400 Hz adicionadas a la iluminación ambiental (BLC). Los participantes fueron expuestos a 12 condiciones de luz diferentes en un experimento balanceado y contrapesado. Mediante la integración de medidas electroencefalográficas (EEG) y de constricción pupilar; los resultados sugirieron cambios significativos en las respuestas durante la interacción de BLC, LED y EEG. Las ondas beta mostraron una significancia estadística (p <0.05) en los niveles de activación cuando se expusieron a la luz BGPLED, además, la pupila reaccionó con una mayor constricción hacia la exposición a BGPLED que hacia la exposición BPLED monocromática, adicionalmente se demostró que un flujo continuo de pulsos puede proporcionar una irradiación igual a la que se emite en flujo continuo; se concluyó e identificó además la frecuencia (100 Hz) que mejor evoca estado de alerta encefalográfíca y sin afectar la percepción de los usuarios en cuanto a su percepción del ambiente de acuerdo a la evaluación cualitativa.

Contribution to oral and maxillary surgery and surgical technique of osteo-odontokeratoprosthesis in Japan.

Osteo-odontokeratoprosthesis (OOKP) is a technique invented by Strampelli in 1963, in which the patient's own tooth root is used to support an optical cylinder. It uses an autologous tooth-bone-periodontal complex to mount an optical cylinder, which is stabilised by overlying autologous buccal mucosa. OOKP involves two, staged procedures done by ophthalmologists and oral surgeons, and the main contribution from the oral surgeon is during the first stage. To date we have done nine first-stage, and completed eight second-stage, OOKP operations in Japan with a mean follow-up of eight years and 11 months by modifying the original method of the oral surgery. All OOKP procedures were unilateral, and canines were selected as the donor teeth. Patients developed ocular blindness as a result of Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and chemical and thermal burns to the cornea and ocular surface. All eight patients who completed the second stage have been stable, and there have been no major perioperative or postoperative oral complications. The patients' visual acuities were stable with no serious complications. Here we report the technical details of the oral contribution to OOKP.

Physiological Effects of Blue Pulsed LED in an Indoor Lighting Environment / Efectos Fisiológicos de Luz LED Azul Intermitente en un Ambiente de Iluminación en Interiores

Abstract Purpose: An experiment was conducted to investigate the physiological effects of a continuous blue pulsed light emitting diode (BP-LED) added to a task lamp in an actual indoor lighting environment and its influence in alertness having as a final purpose to develop a commercial product that could be applied in situations similar to those depicted in the present work. Design methodology: Previous research studies have stated that the addition of pulsed light evokes physiological changes that may induce alertness. The participants were exposed to four different lighting conditions. Electroencephalograms (EEG), pupil sizes, heart rates (HR), performance tests, and subjective reactions were measured. Findings: Low colour temperature light and the BP-LED revealed an improved alertness according to the data from the EEG recordings. The intervention of the BP-LED in a high colour temperature ambiance was beneficial in maintaining high levels of alertness compared to the conditions where the BP-LED was not used. It was tested that the use of a BP-LED in a task lamp may be beneficial in improving or maintaining alertness levels in an indoor workplace ambiance. Originality and Value: Designing of an adequate workplace task lamp light that improves alertness for in-house, office, or classroom situations in which it is essential.

Resumen Propósito: Un experimento fue llevado a cabo para investigar los efectos fisiológicos que una luz azul LED pulsada de manera intermitente (BP-LED), adicionada a una lámpara de escritorio, y en un ambiente interior; pueda influir en el estado de alerta de una persona con la finalidad de desarrollar un producto comercial que pueda ser aplicado para los casos desarrollados y otros posibles escenarios. Metodología de Diseño: En estudios anteriores se establece que la adición de luz en pulsaciones evoca cambios fisiológicos que pueden inducir al estado de alerta. Los participantes experimentaron cuatro escenarios de iluminación. Se registraron mediciones con respecto a encefalografía (EEG), tamaño pupilar, ritmo cardiaco, prueba de performance, así como evaluación subjetiva. Hallazgos: Los datos de EEG revelaron un mayor estado de alerta durante la exposición a iluminación cálida aunado a luz BP-LED. La intervención de luz fría y BP-LED denotó ser benéfica en el nivel de estado de alerta en comparación con las condiciones donde el BP-LED no intervino. Se logró evaluar que el uso de BP-LED en una lámpara de escritorio puede ser benéfico para mejorar o mantener el estado de alerta cuando sea usado en un espacio interior. Originalidad y Valor: Propuesta para diseñar una luminaria de escritorio; para uso casero, laboral o de estudio; que mejore el estado de alerta de las personas.

Elevated bone marrow eosinophil count is associated with high incidence of severe acute GvHD after allogeneic hematopoietic stem cell transplantation.

Predicting severe acute GvHD (aGvHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging but critical. Mild aGvHD may have a favorable impact on relapse, whereas severe aGvHD is associated with poor outcomes. The aim of this study was to evaluate whether elevated eosinophil count in the bone marrow (BM) at 1 month after HSCT is associated with a high incidence of new and severe aGvHD. We enrolled 101 consecutive patients; median age was 50 years, and 50.5% patients were male. The median eosinophil concentration in BM at 1 month after HSCT was 1.1% (quartile 0.4-2.2%). The adjusted hazards ratio at 95% confidence interval for severe aGvHD was 1.26 (1.12-1.42, P<0.001), per 1% increase in eosinophil concentration, and 3.76 (1.41-10.05, P=0.008) for the high-risk group at a cutoff value of 4.0%. In addition, the predictive accuracy described by area under the curve of receiver operating characteristics, increased from 0.784 to 0.866 (P=0.033) with the increasing concentration of eosinophils. In conclusion, elevated concentration of eosinophils in BM was associated with high incidence and predictive accuracy of severe aGvHD. BM eosinophil concentration can be one of the key markers to predict aGvHD.

A novel mutation in the RSPO4 gene in a patient with autosomal recessive anonychia.

The Wnt signalling pathway is a major pathway involved in the embryogenic development of the various organs of the body. Appropriate signalling in this pathway relies on the proper functioning of several proteins including the R-spondin family of proteins. Deactivating mutations in R-spondin 4 are associated with anonychia. We present the case of a 26-year-old man presenting with anonychia of the 20 nails, which had been present since birth. Using genetic studies, we identified a novel nonsense mutation, c.164-165TC>AA, characterized by two consecutive mismatch bases. To our knowledge, this mutation is the first to be reported in R-spondin 4 in a Lebanese population. Evaluating new patients with anonychia provides fruitful clinical and molecular findings.

Erythropoietic protoporphyria a clinical and molecular study from Lebanon: Ferrochelatase a potential tumor suppressor gene in colon cancer.

Erythropoietic protoporphyria (EPP) is a rare cutaneous and systemic disease caused by mutations in the ferrochelatase gene (FECH). The molecular underpinnings of EPP in Middle Eastern populations and relative to other ethnic groups secondary to increased consanguinity are unknown. To understand the molecular pathogenesis of Middle Eastern EPP, we surveyed clinicopathological and molecular features in 6 large consanguineous families from Lebanon and Syria presenting with cutaneous and systemic features consistent with EPP. We observed 30% increased liver disease and 20% elevated end-stage liver complications in our EPP cohort compared to EPP patients previously reported elsewhere. In addition, Middle Eastern EPP patients in our cohort exhibited uniquely an increased incidence of colon cancer. Sequence analysis revealed 2 novel non-synonymous FECH mutations in the studied families designated p.M294T and p.I230M. In addition, FECH activity was significantly decreased (6%) in fibroblasts obtained from sun-exposed sites in a patient with p.M294T mutation, whereas in sharp contrast, protected sites from the same patient exhibited 54% activity for the gene. We also found that sun-exposed fibroblasts, relative to sun-protected and control fibroblasts, exhibited suppressed growth and atypical morphology in vitro, and that these effects were alleviated when the cells were co-cultured with sun-protected fibroblasts. Our findings on the increased incidence of colon cancer in EPP patients prompted us to survey FECH expression patterns in cancer. Using publicly available microarray datasets we found that FECH mRNA was largely significantly decreased in colon adenocarcinomas relative to normal colon tissues. Our findings suggest that families with autosomal recessive EPP should be screened more extensively for systemic involvement including liver diseases and colon cancer, and point to a previously unknown yet plausible tumor suppressor role for FECH in colon malignancy.

Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan.

Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/µl) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6±9.7% and 73.5±8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.