Will biomarker-based diagnosis of Alzheimer’s disease maximize scientific progress? Evaluating proposed diagnostic criteria

A recently published framework for the diagnosis of Alzheimer’s disease (AD) in research studies would allow diagnosis on the sole basis of two biomarkers (β-amyloid and pathologic tau), even in people with no objective or subjective memory or cognitive changes. This revision will have substantial implications for future Alzheimer’s research, and the changes should be rigorously evaluated before widespread adoption. We propose three principles for evaluating any revision to diagnostic frameworks for AD: (1) does the revision improve the validity of the diagnosis; (2) does the revision improve the reliability or reduce the expense of the diagnosis; and (3) will the revision foster innovative and rigorous research across populations. The new diagnostic framework is unlikely to achieve any of these goals. Instead, it has the potential to handicap future researchers, and slow progress towards identifying effective strategies to prevent or treat AD.     

Vaccination coverage among school children aged 14–15 years in the French department of Sarthe

Objectives

Vaccinations are the main pillar of primary prevention for infectious diseases. To guide and prioritize public health interventions, the Regional Health Agency has asked the Prevention, Vaccination, and Screening Center of the Sarthe department to assess vaccination coverage (VC) at the sub-departmental level. The main objective was to measure the VC among school children aged 14–15 years in Sarthe at the sub-departmental level.

Incidence of pertussis in subjects aged 50 years and older in France in 2013–2014

Objective

To assess the incidence of pertussis (whooping cough) in subjects aged 50 years and older in France.

Notch signaling as a therapeutic target for acute lymphoblastic leukemia

Introduction: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Although the therapy of ALL has significantly improved, the heterogeneous genetic landscape of the disease often causes relapse, which is difficult to treat. Achieving a positive outcome for patients with relapsed or refractory ALL remains a challenging issue. The high prevalence of NOTCH-activating mutations in T-cell acute lymphoblastic leukemia (T-ALL) and the central role of NOTCH signaling in regulating cell survival and growth of ALL provide a rationale for the development of Notch signaling-targeted strategies in this disease. Therapeutic alternatives with effective anti-leukemic potential and low toxicity are needed.

Areas covered: This review provides an overview of the currently available drugs directly or indirectly targeting Notch signaling in ALL. Besides considering the known Notch targeting approaches, such as γ-secretase inhibitors (GSIs) and Notch inhibiting antibodies (mAbs), currently in clinical trials, we focus on the recent insights into the molecular mechanisms underlying the Notch signaling regulation in ALL.

Expert opinion: Novel drugs targeting specific steps of Notch signaling or intersecting pathways could improve the efficiency of the conventional hematological cancers therapies. Further studies are required to translate the new findings into future clinical applications.