Is a sense of community belonging associated with problem gambling in Canada?

Purpose

Despite the increasing demand for public health measures to prevent problem gambling, few studies have examined the association between community characteristics and problem gambling. The aim of this nationally representative cross-sectional study was to investigate the relationship between a sense of community belonging and problem gambling in Canada. We also examined whether this relationship was modified by sex and marital status.

Methods

Canadian Community Health Survey (2013–2014) data from 38,968 residents of Quebec, Saskatchewan, Manitoba, and British Columbia were analyzed. Problem gambling was assessed using the Canadian Problem Gambling Index. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for problem gambling.

Results

The prevalence of problem gambling was 1.4% (1.9% among males; 0.9% among females). We observed an inverse dose–response relationship between a sense of community belonging and problem gambling. Compared with those with a very strong sense of community belonging, the adjusted ORs for problem gambling were 1.07 (95% CI 0.65–1.76) for a somewhat strong sense, 1.27 (95% CI 0.77–2.11) for a somewhat weak sense, and 2.32 (95% CI 1.34–4.02) for a very weak sense of community belonging. The association was more prominent among females (except for those widowed/divorced/separated), whereas no clear association was found among males, irrespective of marital status.

Conclusion

When implementing public health measures to reduce problem gambling, it would be useful to account for possible differential impacts of a sense of community belonging by sex and marital status, which may reflect significant social contexts among residents.

     

Mutational analyses of the AML1 gene in patients with myelodysplastic syndrome

The AML1 gene is the most frequent target of translocations associated with human leukemias. We recently found somatic point mutations of the AML1 gene, V105ter and R139G, in two cases of myelodysplastic syndrome (MDS). Both mutations are present in the region encoding the Runt domain of AML1, and cause loss of the DNA-binding ability of the resultant products. Of these mutants, V105ter has also lost the ability to heterodimerize with PEBP2beta/CBFbeta. On the other hand, the R139G mutant acts as a dominant negative inhibitor through competing with wild-type AML1 for interaction with PEBP2beta/CBFbeta. In this review, we summarize mutational changes of the AML1 gene in hematological malignancies, especially in MDS and discuss the mechanism whereby the mutant acts as a dominant negative inhibitor of wild-type AML1.     

Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies

Identification of genetic alterations through next‐generation sequencing (NGS) can guide treatment decision‐making by providing information on diagnosis, therapy selection, and prognostic stratification in patients with hematological malignancies. Although the utility of NGS‐based genomic profiling assays was investigated in hematological malignancies, no assays sufficiently cover driver mutations, including recently discovered ones, as well as fusions and/or pathogenic germline variants. To address these issues, here we have devised an integrated DNA/RNA profiling assay to detect various types of somatic alterations and germline variants at once. Particularly, our assay can successfully identify copy number alterations and structural variations, including immunoglobulin heavy chain translocations, IKZF1 intragenic deletions, and rare fusions. Using this assay, we conducted a prospective study to investigate the feasibility and clinical usefulness of comprehensive genomic profiling for 452 recurrently altered genes in hematological malignancies. In total, 176 patients (with 188 specimens) were analyzed, in which at least one alteration was detected in 171 (97%) patients, with a median number of total alterations of 7 (0–55). Among them, 145 (82%), 86 (49%), and 102 (58%) patients harbored at least one clinically relevant alteration for diagnosis, treatment, and prognosis, respectively. The proportion of patients with clinically relevant alterations was the highest in acute myeloid leukemia, whereas this assay was less informative in T/natural killer‐cell lymphoma. These results suggest the clinical utility of NGS‐based genomic profiling, particularly for their diagnosis and prognostic prediction, thereby highlighting the promise of precision medicine in hematological malignancies.     

Scanning electron microscopic studies on the cell surface and cell synchronized culture of human endometrial adenocarcinoma (HEC-1) cells

The cell cycle of cultured human endometrial adenocarcinoma cells were observed with a SEM using the synchronous culture method and the following results were obtained. In the M phase, the cells changed morphologically to become a minimum size and rounded in shape. Filopodia became thin and straight and reached their maximum length. Moreover, blebs reaches their greatest number. In the G0+1 phase, the cells developed from a round shape to an oval shape, and finally became polymorphic. The ends of the filopodia degenerated and became shortened. The number of blebs was decreased only in this stage. During the S phase, the cells became slender and reached maximum size. Short filopodia reappeared. No blebs but the largest microvilli were found. When we compared the late G1 with the early G2 phase, we found polymorphism of the cells and coexistence of microvilli and blebs common to both phases. However, ruffles were observed only in the former phase, while in the latter phase renewal of short filopodia together with thick and bent filopodia was evident. When we compared the late G2 with the early G1 phase, we found that the cells were small in size and round shape, and that the existence of blebs was common to both phases. However, the tips of the filopodia were destroyed in the latter phase, while in the former phase thick and bent filopodia were observed.     

Phase II study of tazemetostat for relapsed or refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan

Tazemetostat is a selective, reversible, small-molecule inhibitor of the histone methyltransferase enzyme, enhancer of zest homolog 2 (EZH2). In this multicenter, open-label, phase II study, we assessed the efficacy and safety of tazemetostat in Japanese patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma harboring the EZH2 mutation. Tazemetostat (800 mg twice daily) was given orally (28-day cycle) until disease progression or unacceptable toxicity. Among the 20 eligible patients, 17 were enrolled in cohort 1 (follicular lymphoma [FL]), and three were enrolled in cohort 2 (diffuse large B-cell lymphoma). At data cut-off, the objective response rate in cohort 1 was 76.5%, including six patients (35.3%) with complete response and seven patients (41.2%) with partial response (PR). All three patients in cohort 2 achieved PR. In cohort 1, median progression-free survival (PFS) was not reached at the median follow-up of 12.9 months. The estimated PFS rate at 12 and 15 months was 94.1% and 73.2%, respectively. The most common grade 3 treatment-emergent adverse event (TEAE) was lymphopenia (n = 2). Grade 4 TEAEs included hypertriglyceridemia and pneumonia aspiration (n = 1 each), which were not related to tazemetostat. Treatment-emergent adverse events leading to study drug discontinuation were reported in four of the 20 patients, indicating that the safety profile of tazemetostat was acceptable and manageable. Tazemetostat 800 mg twice daily showed encouraging efficacy in patients with R/R EZH2 mutation-positive FL with a manageable safety profile in the overall population. Thus, tazemetostat could be a potential treatment for R/R EZH2 mutation-positive FL.     

Metagenomic profile of gut microbiota in children during cholera and recovery

Background

The diverse bacterial communities colonizing the gut (gastrointestinal tract) of infants as commensal flora, which play an important role in nutrient absorption and determining the state of health, are known to alter due to diarrhea.

Method

Bacterial community dynamics in children suffering from cholera and during recovery period were examined in the present study by employing metagenomic tool, followed by DNA sequencing and analysis. For this, bacterial community DNA was extracted from fecal samples of nine clinically confirmed cholera children (age 2–3 years) at day 0 (acute cholera), day 2 (antibiotic therapy), day 7 and, and day 28, and the variable region of 16S rRNA genes were amplified by universal primer PCR.

Results

454 parallel sequencing of the amplified DNA followed by similarity search of the sequenced data against an rRNA database allowed us to identify V. cholerae, the cause of cholera, in all nine children at day 0, and as predominant species in six children, accounting for 35% of the total gut microbiota on an average in all the nine children. The relative abundance (mean ± sem %) of bacteria belonging to phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, was 55 ± 7, 18 ± 4, 13 ± 4, and 8 ± 4, respectively, at day 0, while these values were 12 ± 4, 43 ± 4, 33 ± 3, and 12 ± 2, respectively, at day 28. As antibiotic therapy began, V. cholerae count declined significantly (p< 0.001) and was found only in four children at day 2 and two children at day 7 with the relative abundance of 3.7% and 0.01%, respectively, which continued up to day 28 in the two children. Compared to acute cholera condition (day 0), the relative abundance of Escherichia coli, Enterococcus, and Veillonella increased at day 2 (antibiotic therapy) while Bifidobacterium, Bacteroides, and Ruminococcus decreased.

Conclusion

Cholera results expulsion of major commensal bacteria of phyla Bacteroidetes, Firmicutes, and Actinobacteria, and increase of harmful Proteobacteria to colonize the gut during acute and convalescence states. The observed microbiota disruption might explain the prevalent malnutrition in children of Bangladesh where diarrheal diseases are endemic.