Huntington disease (HD) model mice with heterozygous knock-in (KI) of an expanded CAG tract in exon 1 of the mouse huntingtin (Htt) gene homolog genetically recapitulate the mutation that causes HD, and might be favoured for preclinical studies. However, historically these mice have failed to phenotypically recapitulate the human disease. Thus, homozygous KI mice, which lack wildtype Htt, and are much less relevant to human HD, have been used. The zQ175 model was the first KI mouse to exhibit significant HD-like phenotypes when heterozygous. In an effort to exacerbate HD-like phenotypes and enhance preclinical utility, we have backcrossed zQ175 mice to FVB/N, a strain highly susceptible to neurodegeneration. These Q175F mice display significant HD-like phenotypes along with sudden early death from fatal seizures. The zQ175 KI allele retains a floxed neomycin resistance cassette upstream of the Htt gene locus and produces dramatically reduced mutant Htt as compared to the endogenous wildtype Htt allele. By intercrossing with mice expressing cre in germ line cells, we have excised the neo cassette from Q175F mice generating a new line, Q175FΔneo (Q175FDN). Removal of the neo cassette resulted in a ∼2 fold increase in mutant Htt and rescue of fatal seizures, indicating that the early death phenotype of Q175F mice is caused by Htt deficiency rather than by mutant Htt. Additionally, Q175FDN mice exhibit earlier onset and a greater variety and severity of HD-like phenotypes than Q175F mice or any previously reported KI HD mouse model, making them valuable for preclinical studies.

Introduction: The objectives of this review paper were to synthesize the data from randomized controlled trials in the literature to come to a conclusion on the effects of e-health interventions on promoting physical activity in older people. Methods: The Medline, CINAHL, Embase, PsycINFO, and SportDiscus databases were searched for articles about studies that 1) recruited subjects with a mean age of > 50 years, 2) tested e-health interventions, 3) employed control groups with no or less advanced e-health strategies, 4) measured physical activity as an outcome, 5) were published between 1st January 2008 and 31st May 2019, and 6) employed randomized controlled trials. The risk of bias in individual studies was assessed using the Physiotherapy Evidence Database scale. To examine the effects of the interventions, variables quantifying the amount of physical activity were extracted. The within-group effects of individual studies were summarized using Hedges g and 95% confidence intervals. Between-group effects were summarized by meta-analyses using RevMan 5.0 with a random effect model. Results: Of the 2810 identified studies, 38 were eligible, 25 were included in the meta-analyses. The within-group effect sizes (Hedges g) of physical activity in the intervention group at T1 ranged from small to large: physical activity time (0.12 to 0.84), step counts (− 0.01 to 11.19), energy expenditure (− 0.05 to 0.86), walking time (0.13 to 3.33), and sedentary time (− 0.12 to − 0.28). The delayed effects as observed in T2 and T3 also ranged from small to large: physical activity time (0.24 to 1.24) and energy expenditure (0.15 to 1.32). In the meta-analysis, the betweengroup effect of the e-health intervention on physical activity time measured by questionnaires, physical activity time measured by objective wearable devices, energy expenditure, and step counts were all significant with minimal heterogeneity. Conclusion: E-health interventions are effective at increasing the time spent on physical activity, energy expenditure in physical activity, and the number of walking steps. It is recommended that e-health interventions be included in guidelines to enhance physical activity in older people. Further studies should be conducted to determine the most effective e-health strategies.

Epithelial ovarian cancer consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC) and low-grade serous (LGSC). Each can have a broad spectrum of morphological appearances, and one histotype can closely mimic histopathological features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present based on routine histopathological assessment, histotype carcinoma diagnoses (3–11%), however recent immunohistochemical studies identifying histotype specific markers and allowing more refined histotype diagnoses suggests a much lower incidence. We reviewed hematoxylin and eosin stained slides from 871 cases of epithelial ovarian cancer and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed epithelial ovarian cancers, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC and 4 other combinations. We interrogated the molecular differences between the different components of each case using immunohistochemistry, gene expression and hotspot sequencing analyses. Immunohistochemical data alone suggested 9 of the 22 cases were not mixed tumors as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphological mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. Based on these results, true mixed carcinomas with both morphological and molecular support for the presence of more than one histotype within a given tumor represent less than 1% of epithelial ovarian cancers.

and Loqus23. All honoraria for these engagements were paid through the offices of UCL Consultants Ltd., a wholly owned subsidiary of University College, London. MRH currently serves on the public boards of Ionis Pharmaceuticals, Xenon Pharmaceuticals, Aurinia Pharmaceuticals and 89bio.