Hypertension fails to disrupt white matter integrity in young or aged Fisher (F44) Cyp1a1Ren2 transgenic rats

Hypertension is linked with an increased risk of white matter hyperintensities; however, recent findings have questioned this association. We examined whether hypertension and additional cerebrovascular risk factors impacted on white matter integrity in an inducible hypertensive rat. No white matter hyperintensities were observed on magnetic resonance imaging either alone or in conjunction with ageing and high-fat diet. Aged hypertensive rats that were fed a high-fat diet had moderately reduced fractional anisotropy in the corpus callosum with no overt pathological features. Herein we show that moderate hypertension alone or with additional risk factors has minimal impact on white matter integrity in this model.     

Changes in Family-Level Attitudes and Norms and Association with Secondary School Completion and Child Marriage Among Adolescent Girls: Results from an Exploratory Study Nested Within a Cluster-Randomised Controlled Trial in India

Prevention Science - We evaluated the impact of Samata, a 3-year multilayered intervention among scheduled caste/scheduled tribe (SC/ST) adolescent girls in rural northern Karnataka, on...     

The use and impact of quality of life assessment tools in clinical care settings for cancer patients,with a particular emphasis on brain cancer: insights from a systematic review and stakeholder consultations

Purpose

Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice.

Design

We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit.

Results

The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient–physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address.

Conclusion

Our findings suggest that the use of QoL tools in cancer patients may improve patient–physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation.

     

Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma

High-risk neuroblastoma, a predominantly TP53 wild-type (wt) tumour, is incurable in >50% patients supporting the use of MDM2 antagonists as novel therapeutics. Idasanutlin (RG7388) shows in vitro synergy with chemotherapies used to treat neuroblastoma. This is the first study to evaluate the in vivo efficacy of the intravenous idasanutlin prodrug, RO6839921 (RG7775), both alone and in combination with temozolomide in TP53 wt orthotopic neuroblastoma models. Detection of active idasanutlin using liquid chromatography-mass spectrometry and p53 pathway activation by ELISA assays and Western analysis showed peak plasma levels 1 h post-treatment with maximal p53 pathway activation 3–6 h post-treatment. RO6839921 and temozolomide, alone or in combination in mice implanted with TP53 wt SHSY5Y-Luc and NB1691-Luc cells showed that combined RO6839921 and temozolomide led to greater tumour growth inhibition and increase in survival compared to vehicle control. Overall, RO6839921 had a favourable pharmacokinetic profile consistent with intermittent dosing and was well tolerated alone and in combination. These preclinical studies support the further development of idasanutlin in combination with temozolomide in neuroblastoma in early phase clinical trials.     

Effects of incretin-based therapies on neurocognitive function in humans: A systematic review of the literature

We performed a PRISMA systematic review of incretin-based therapies and effects on neurocognitive function in humans. There was observational evidence to support dipeptidyl peptidase-IV inhibitors in improving cognition, whilst glucagon-like peptide-1 had positive effects on cerebral glucose metabolism. Powered clinical trials are now needed in patients with- and without diabetes.