Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

BACKGROUND: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). METHODS: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. RESULTS: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). CONCLUSION: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.     

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed.     

Cannabis and symptoms of PMS and PMDD

Cannabis has been found to alleviate a wide array of medical symptoms, including those that overlap with physical and emotional symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), including insomnia, irritability, depression, and joint pain. Little work has addressed the use of cannabis as a treatment for PMS or PMDD or the role of women’s cannabis treatment expectancies as a predictor of consumption. Women who reported having experienced PMS and PMDD and endorsed lifetime cannabis use (N?=?145), completed an online survey assessing their frequency of cannabis use, PMS/PMDD symptoms, expectancies of cannabis-induced relief from symptoms, as well as cannabis-related problems. Women were found to hold meaningful expectancies that cannabis would treat all PMS/PMDD symptoms, except for overeating/food cravings. Cannabis treatment expectancies were positively associated with PMS/PMDD symptoms and with monthly cannabis use, and were negatively associated with cannabis-related problems. Research should further examine the relationship of cannabis treatment expectancies with individuals’ cannabis use, as findings indicate the potential for these expectancies to serve a punitive or protective role in the development of cannabis-related problems. Increased research on how cannabis might ameliorate symptoms of PMS and PMDD could help establish an alternative treatment plan that offers relief with fewer negative side effects.     

Expression of common housekeeping genes is affected by disease in human hepatitis C virus‐infected liver

Background: Comparative gene expression is commonly determined with reference to the expression of a housekeeping gene (HKG), the level of which is assumed to be unregulated. There are little data to date on the effect of disease on the expression of classic HKGs in hepatitis C virus (HCV)‐infected human liver. Aims: To identity HKGs stable across a wide spectrum of disease in human HCV‐infected liver. Methods: β‐Actin, hypoxanthine phosphoribosyltransferase 1 (HPRT1), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), splicing factor arginine/serine‐rich 4, β‐glucuronidase and 18S ribosomal RNA (18S rRNA) were measured by real‐time polymerase chain reaction in liver biopsy tissue. Samples were categorised for inflammation, fibrosis and steatosis, and allocated into groups with mild or severe liver disease. Values were analysed using Spearman's rank correlation, NormFinder, BestKeeper and geNorm programs. Results: All genes performed well in the samples of patients with low disease activity, but HPRT1, β‐actin, GAPDH and 18S rRNA ranked poorly in samples with severe fibrosis or inflammation. Conclusions: Our results indicate that liver disease affects the expression of common HKGs and that β‐glucuronidase and splicing factor arginine/serine‐rich 4 are the most stable HKGs from this group for studies of gene expression in HCV‐infected human liver.     

Correlates of psychological distress in study partners of older people with and without mild cognitive impairment (MCI) – the Sydney Memory and Ageing Study

Objectives: Psychological effects of supporting someone with mild cognitive impairment (MCI) are often overlooked. We aimed to establish correlates of psychological distress in study partners of individuals with and without nonclinical MCI.Methods: Demographic, psychosocial and health measures were obtained cross-sectionally from 714 participants (39% MCI) and study partners of a longitudinal community-based study on cognitive aging. Study partners (i.e. family members/friends) were categorized as providing support with instrumental everyday activities or not. Psychological distress was measured by the Kessler psychological distress scale. Multiple hierarchical regressions examined determinants of psychological distress within Pearlin's stress process model.Results: Psychological distress was generally low and not associated with MCI or whether study partners provided support or not. Instead, distress was greater if participants were male irrespective of study partners’ sex and if study partners reported negative reactions to participants’ behavioral symptoms, felt burdened by providing support and showed worse coping abilities; overall explaining 37% variance. Self-rated disability and aspects of health-related quality of life explained additional 7%.Conclusion: Objective impairment measures were not associated with distress in partners or supporters. However, study partners’ appraisals of functional and behavioral symptoms were linked to increased distress even in this very mildly affected community cohort.