A cross-sectional study of associations between the 13C-sucrose breath test, the lactulose rhamnose assay, and growth in children at high risk of environmental enteropathy

Background: Environmental enteropathy’ (EE) is common among children who are highly exposed to enteric pathogens in low-resource settings. We optimised and validated a stable isotope-based breath test of intestinal sucrase activity (13C-SBT) as a non-invasive test of carbohydrate digestion and metabolism. Objectives: The primary objective of this study was to assess the relationship between the 13C-SBT and the lactulose/rhamnose ratio (LR) and growth in children. Secondary objectives were to assess the relationship between the 13C-SBT and additional biomarkers of EE. We also characterised the relationship between the 13C-SBT and child sex anddietary diversity, and household socioeconomic status and food security. Methods: In this cross-sectional study, 12-to-15-month-old children were recruited in Bangladesh, India, Kenya, and Peru. Children were assessed with a 4-hour 13C-SBT and a 90-minute LR test. Plasma was collected for the determination of citrulline and the kynurenine/tryptophan ratio. Length and weight were measured, and other variables were assessed through questionnaires. For a subset of children, anthropometry was re-measured after three months. inear regression was used to examine associations corresponding to each objective. Results: Three sites generated 13C-SBT breath curves that enabled pooled analysis. Differences in 13C-SBT breath curves, LR ratios, and other EE biomarkers were observed between sites. No associations were observed for 13C-SBT summary measures and LR, or child growth (e.g., association between LR and cumulative percent dose recovered at 90 minutes (cPDR90): -0.39, 95%CI: -1.79, 0.70). Length-for-age and weight-for-age were positively associated with the time to 50% of dose recovered (T50) (0.05, 95%CI: 0.01, 0.09, and 0.05, 95%CI: 0.02, 0.07, respectively), and dietary diversity was associated with T50 and cPDR90(-0.10, 95%CI: -0.18, -0.02 and 2.67, 95%CI: 0.47, 4.88, respectively). Conclusions: In children at risk of EE there were no associations between the 13C-SBT, LR or other EE biomarkers encompassing different pathophysiological domains of EE

Case of a CD3 Negative Hepatosplenic T-Cell Lymphoma: Diagnostic and Therapeutic Challenges

Hepatosplenic T-cell lymphomas (TCLs) are a rare, aggressive subset of TCLs, accounting for less than 5% of all peripheral T-cell and natural killer (NK) cell lymphomas. We report the case of a CD3 negative hepatosplenic T-cell lymphoma in a 42-year-old female, who presented with left-sided abdominal pain. She underwent a liver biopsy that showed marked abnormal sinusoidal lymphoid infiltration. PET scan revealed increased splenic and pharyngeal lymph node uptake. Immunophenotype was remarkable for negative CD3, gamma delta T-cell receptor, and alpha beta-T-cell receptor expression. She received 6 cycles of DA-EPOCH, had primary refractory disease and then underwent palliative splenectomy secondary to painful necrosis. Then, she was started on pralatrexate as a single agent and then in combination with romidepsin as a potential bridge to an allogeneic stem cell transplantation from her sibling

Single-agent obatoclax (GX15-070) potently induces apoptosis and pro-survival autophagy in head and neck squamous cell carcinoma cells.

ObjectivesMore than half of head and neck squamous cell carcinoma (HNSCC) patients are initially treated with curative intent, but will relapse over the course of their disease and have poor prognosis with a median survival of approximately 6months. Novel therapeutic approaches are in desperate need for this patient population. The anti-apoptotic BCL-2 family proteins such as BCL-2, BCL-XL, and MCL-1 are involved in oncogenesis and chemoresistance and are overexpressed in HNSCC. Obatoclax is a small-molecule antagonist of the BH3-binding groove of anti-apoptotic BCL-2 family. We evaluated the activity of obatoclax against 4 HNSCC cell lines (UMSCC-1, Cal33, 1483, UMSCC-22A).MethodsCell viability was determined by MTT assay, cell cycle status by propidium iodide staining, and apoptosis by Annexin-V staining and immunoblotting. Autophagy was assessed by immunofluorescence and immunoblotting.ResultsAll four HNSCC cell lines were highly sensitive to single-agent obatoclax with IC50's ranging from 46 to 177nM. Obatoclax induced apoptosis in all four HNSCC cell lines as evidenced by increases in sub-G1 DNA content, Annexin-V staining, and PARP cleavage. In addition, obatoclax induced autophagy in all 4 cell lines, and the addition of the autophagy inhibitor chloroquine enhanced obatoclax cytotoxicity.ConclusionOur findings demonstrate potent monotherapeutic activity of obatoclax against HNSCC cells, and enhancement of this activity in the presence of chloroquine. This preclinical study suggests that obatoclax might have therapeutic value in the treatment of HNSCC, either alone or in combination with inhibitors of autophagy

Single-agent obatoclax (GX15-070) potently induces apoptosis and pro-survival autophagy in head and neck squamous cell carcinoma cells.

ObjectivesMore than half of head and neck squamous cell carcinoma (HNSCC) patients are initially treated with curative intent, but will relapse over the course of their disease and have poor prognosis with a median survival of approximately 6months. Novel therapeutic approaches are in desperate need for this patient population. The anti-apoptotic BCL-2 family proteins such as BCL-2, BCL-XL, and MCL-1 are involved in oncogenesis and chemoresistance and are overexpressed in HNSCC. Obatoclax is a small-molecule antagonist of the BH3-binding groove of anti-apoptotic BCL-2 family. We evaluated the activity of obatoclax against 4 HNSCC cell lines (UMSCC-1, Cal33, 1483, UMSCC-22A).MethodsCell viability was determined by MTT assay, cell cycle status by propidium iodide staining, and apoptosis by Annexin-V staining and immunoblotting. Autophagy was assessed by immunofluorescence and immunoblotting.ResultsAll four HNSCC cell lines were highly sensitive to single-agent obatoclax with IC50's ranging from 46 to 177nM. Obatoclax induced apoptosis in all four HNSCC cell lines as evidenced by increases in sub-G1 DNA content, Annexin-V staining, and PARP cleavage. In addition, obatoclax induced autophagy in all 4 cell lines, and the addition of the autophagy inhibitor chloroquine enhanced obatoclax cytotoxicity.ConclusionOur findings demonstrate potent monotherapeutic activity of obatoclax against HNSCC cells, and enhancement of this activity in the presence of chloroquine. This preclinical study suggests that obatoclax might have therapeutic value in the treatment of HNSCC, either alone or in combination with inhibitors of autophagy

Ellis-van Creveld Syndrome: Mutations Uncovered in Lebanese Families

Background. Ellis-van Creveld (EvC) syndrome is a rare, autosomal recessive disorder characterized by short stature, short limbs, growth retardation, polydactyly, and ectodermal defects with cardiac anomalies occurring in around 60% of cases. EVC syndrome has been linked to mutations in EVC and EVC2 genes. Case Presentation. We report EvC syndrome in two unrelated Lebanese families both having homozygous mutations in the EVC2 gene, c.2653C>T (p.(Arg885*)) and c.2012_2015del (p.(Leu671*)) in exons 15 and 13, respectively, with the latter being reported for the first time. Conclusion. Although EvC has been largely described in the medical literature, clinical features of this syndrome vary. While more research is required to explore other genes involved in EvC, early diagnosis and therapeutic care are important to achieve a better quality of life

Propiedades Psicométricas del Inventario de Personalidad (PAI) en México

No obstante que el Inventario de Evaluación de la Personalidad (PAI) se ha convertido en una opción importante alrededor del mundo, se necesita una versión adaptada y válida de este instrumento psicológico para México. Este estudio presenta las propiedades psicométricas preliminares del PAI en México. Un total de 961 personas, de cuatro Ciudades Mexicanas (Aguascalientes, Distrito Federal, Mazatlán y Pachuca Hidalgo), contestaron la versión en “Español para México” del PAI, adaptado y reproducido mediante un permiso especial otorgado por la Editorial PAR. La media de edad fue 23,5 años con una D. E. de 9,63 años. Los procedimientos psicométricos estandarizados que se siguieron fueron: capacidad discriminativa de reactivos; confiabilidad por Alfa de Cronbach; Análisis Factorial exploratorio y finalmente Análisis Factorial Confirmatorio con AMOS. Basados en los resultados de AMOS de la muestra mexicana, se eliminaron 123 reactivos porque no tuvieron valores estadísticos que les permitiera ser incluidos en el modelo. Como resultado se obtuvo una versión recortada (adaptada y valida) del PAI con 221 reactivos. Concluimos que las traducciones transculturales del PAI deben ser revisadas cuidadosamente a la luz del Análisis Factorial Confirmatorio