Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target.

The three human SNM1 metallo-β-lactamase fold nucleases (SNM1A-C) play key roles in DNA damage repair and in maintaining telomere integrity. Genetic studies indicate that they are attractive targets for cancer treatment and to potentiate chemo- and radiation-therapy. A high-throughput screen for SNM1A inhibitors identified diverse pharmacophores, some of which were shown by crystallography to coordinate to the di-metal ion centre at the SNM1A active site.

The selective prolyl hydroxylase inhibitor IOX5 stabilizes HIF-1α and compromises development and progression of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a largely incurable disease, for which new treatments are urgently needed. While leukemogenesis occurs in the hypoxic bone marrow, the therapeutic tractability of the hypoxia-inducible factor (HIF) system remains undefined. Given that inactivation of HIF-1α/HIF-2α promotes AML, a possible clinical strategy is to target the HIF-prolyl hydroxylases (PHDs), which promote HIF-1α/HIF-2α degradation.

National recruitment system for pre-registration pharmacist trainees in England and Wales: context, process and outcomes.

In England and Wales, a new National Recruitment Scheme (NRS) for pre-registration pharmacists was introduced in 2017. The NRS replaced the traditional method of employer-led recruitment or the national recruitment system previously limited to some hospital training programmes. NRS uses assessment methodology involving Multiple-Mini Interviews, Situational Judgement Tests and numeracy skills in ranking and appointing candidates to their preferred training providers through a centralised procedure.

Cognitive Function in a Sleep Clinic Cohort of Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with an increased risk of mild cognitive impairment (MCI) within the general population. However, MCI risk in sleep-clinic populations of patients with OSA is poorly characterized. To determine the prevalence of MCI in a sleep-clinic population of patients with OSA and which patients are at the greatest risk for this complication.

Interventions to improve spontaneous adverse drug reaction reporting by healthcare professionals and patients: systematic review and meta-analysis.

Introduction: The aim of this study was to evaluate the effectiveness of interventions used for improving ADR reporting by patients and healthcare professionals.

Areas Covered: A systematic review of literature was conducted by searching Medline, Embase and Cochrane Central Register of Controlled of Trials. Meta-analysis of randomized controlled trials (RCTs; = 5) was conducted to estimate the pooled risk ratio for the effectiveness of interventions on ADR reporting rates.

Multimorbidity and emergency department visits by a homeless population: a database study in specialist general practice.

Background: Estimating healthcare needs of the homeless is associated with challenges in identifying the eligible population.

Aim: To explore the demographic characteristics, disease prevalence, multimorbidity, and emergency department visits of the homeless population.

Design And Setting: EMIS electronic database of patient medical records and Quality and Outcomes Framework (QOF) data of all 928 patients registered with a major specialist homeless primary healthcare centre based in the West Midlands in England, from the period of October 2016 to 11 October 2017.

Metformin inhibits the development, and promotes the resensitization, of treatment-resistant breast cancer.

Multiple drug resistant (MDR) malignancy remains a predictable and often terminal event in cancer therapy, and affects individuals with many cancer types, regardless of the stage at which they were originally diagnosed or the interval from last treatment. Protein biomarkers of MDR are not globally used for clinical decision-making, but include the overexpression of drug-efflux pumps (ABC transporter family) such as MDR-1 and BCRP, as well as HIF1α, a stress responsive transcription factor found elevated within many MDR tumors. Here, we present the important in vitro discovery that the development of MDR (in breast cancer cells) can be prevented, and that established MDR could be resensitized to therapy, by adjunct treatment with metformin.

Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study.

Aim: To determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM).

Methods: We describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase.

Subjective and objective findings in patients with true dehiscence versus thin bone over the superior semicircular canal.

Objective: To compare subjective and objective findings between patients with true dehiscence versus thin bone over the superior semicircular canal (SSC).

Study Design: Retrospective case series.

Setting: Tertiary referral center.

Feedback-mediated dynamics in a model of coupled nephrons with compliant thick ascending limbs.

The tubuloglomerular feedback (TGF) system in the kidney, a key regulator of glomerular filtration rate, has been shown in physiologic experiments in rats to mediate oscillations in thick ascending limb (TAL) tubular fluid pressure, flow, and NaCl concentration. In spontaneously hypertensive rats, TGF-mediated flow oscillations may be highly irregular. We conducted a bifurcation analysis of a mathematical model of nephrons that are coupled through their TGF systems; the TALs of these nephrons are assumed to have compliant tubular walls.

Diagnostic and interventional sialendoscopy: a preliminary experience.

Objectives/hypothesis: To review our preliminary experience with diagnostic and therapeutic sialendoscopy for the management of non-neoplastic disorders of the salivary gland.

Study Design: Retrospective chart review.

Methods: Thirty-three consecutive patients undergoing 36 sialendoscopy procedures performed at a tertiary medical center from July 2008 to July 2010 were included.

Pathological use of electronic media: case studies and commentary.

Since its formal introduction barely a dozen years ago, internet addiction (IA) has been both increasingly researched and much debated. The majority of studies have been conducted on large populations through internet surveys, with the most popular instrument for assessing IA being the Internet Addiction Test (IAT). However, both the large scale anonymous survey approach and the design and application of the IAT yield limited clinical insights.

Percutaneous common iliac artery aneurysm repair - a case report.

Endovascular repair of common iliac artery aneurysms has become the preferred form of treatment, provided the appropriate anatomy for endovascular repair exists. The Zenith abdominal aortic aneurysm graft converter (Cook Medical Inc, USA), by virtue of its design, appears to be the ideal device for such a repair. A case to illustrate the same is presented.

Hepatic resection for recurrent metastatic ovarian cancer.

Background: The role for liver resection in metastatic ovarian cancer has not been defined. The aim of the current study was to investigate the validity of hepatic resection as a treatment option in metastatic ovarian cancer.

Methods: Retrospective review of a single institution's experience of patients undergoing hepatic resection for metastatic ovarian cancer from 1998-2006.