Natural History of Conduction Abnormalities in a Patient with Kearns-Sayre Syndrome

Kearns-Sayre syndrome is a rare mitochondrial disorder characterized by large-scale deletion or rearrangement of mitochondrial DNA, which is usually not inherited but occur spontaneously probably at the germ cell level or very early in embryonic development by Mehndiratta et al. (Neurol India 50:162–167, 2002). Neuromuscular and cardiac conduction abnormalities are most commonly involved in these patients, which may have subtle presenting signs.     

Right atrial function early after tetralogy of Fallot repair

The International Journal of Cardiovascular Imaging - Diastolic dysfunction after repair for Tetralogy of Fallot (TOF) is associated with adverse long-term outcomes. Right atrial (RA) mechanics as...     

Novel insights linking BRCA1-IRIS role in mammary gland development to formation of aggressive PABCs: the case for longer breastfeeding

Pregnancy-associated breast cancer (PABC) is diagnosed during or shortly after pregnancy. Although rare, PABC is a serious occurrence often of the triple negative (TNBC) subtype. Here we show progesterone, prolactin, and RANKL upregulate BRCA1-IRIS (IRIS) in separate and overlapping subpopulations of human mammary epithelial cell lines, which exacerbates the proliferation, survival, and the TNBC-like phenotype in them. Conversely, vitamin D₃ reduces IRIS expression in TNBC cell lines, which attenuates growth, survival, and the TNBC-like phenotype in them. In the mouse, Brca1-Iris (Iris, mouse IRIS homolog) is expressed at low-level in nulliparous mice, increases ~10-fold in pregnant/lactating mice, to completely disappear in involuting mice, and reappears at low-level in regressed glands. Mice underwent 3 constitutive pregnancies followed by a forced involution (after 5 days of lactation) contained ~10-fold higher Iris in their mammary glands compared to those underwent physiological involution (after 21 days of lactation). While protein extracts from lactating glands promote proliferation in IRIS^low and IRIS overexpressing (IRISOE) cells, extracts from involuting glands promote apoptosis in IRIS^low, and aneuploidy in IRISOE cells. In a cohort of breast cancer patients, lack of breastfeeding was associated with formation of chemotherapy resistant, metastatic IRISOE breast cancers. We propose that terminal differentiation triggered by long-term breastfeeding reduces IRIS expression in mammary cells allowing their elimination by the inflammatory microenvironment during physiological involution. No/short-term breastfeeding retains in the mammary gland IRISOE cells that thrive in the inflammatory microenvironment during forced involution to become precursors for aggressive breast cancers shortly after pregnancy.     

Survival predictors of Burkitt's lymphoma in children,adults and elderly in the United States during 2000–2013

Burkitt's Lymphoma (BL) has three peaks of occurrence, in children, adults and elderly, at 10, 40 and 70 years respectively. To the best of our knowledge, no study has been conducted to assess predictors of survival in the three age groups. We hypothesized that survival predictors may differ by age group. We, therefore, sought to determine survival predictors for BL in these three groups: children (<15 years of age), adults (40–70 years of age) and elderly (>70 years of age). Using the Surveillance, Epidemiology, and End Results (SEER) database covering the years 2000‐2013, we identified 797 children, 1,994 adults and 757 elderly patients newly diagnosed with BL. We used adjusted Cox proportional hazards regression models to determine prognostic factors for survival for each age group. Five‐year relative survival in BL for children, adults and elderly were 90.4, 47.8 and 28.9%, respectively. Having at least Stage II disease and multiple primaries were associated with higher mortality in the elderly group. In adults, multiple primaries, Stage III or IV disease, African American race and bone marrow primary were associated with increased mortality whereas Stage IV disease and multiple primaries were associated with worse outcome in children. These findings demonstrate commonalities and differences in predictors of survival that may have implications for management of BL patients.