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It would be apt to say that one of the greatest accomplishments in modern medicine has been the development of vaccines against COVID-19, which had paralyzed the entire world for more than a year. Pfizer and BioNTech codeveloped the first COVID-19 vaccine that was granted emergency-use authorization or conditional approval in several regions globally. This article is an attempt to go 'behind-the-scenes' of this development process and highlight key factors that allowed us to move with this unprecedented speed, while adhering to normal vaccine-development requirements to generate the information the regulatory authorities needed to assess the safety and effectiveness of a vaccine to prevent an infectious disease, including quality and manufacturing standards. This is also a story of how Pfizer and BioNTech leveraged our combined skill sets and experience to respond to the global health crisis to progress this program swiftly while ensuring the compliance with our high-quality standards and keeping patient safety at the forefront. We will also highlight multiple other factors that were instrumental in our success., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A decrease in neurogenesis in the aged brain has been correlated with cognitive decline. The molecular signaling that regulates age-related decline in neurogenesis is still not fully understood. We found that different subtypes of neural stem cells (NSCs) in the hippocampus were differentially impaired by aging. The quiescent NSCs decreased slowly, although the active NSCs exhibited a sharp and dramatic decline from the ages of 6-9 months and became more quiescent at an early stage during the aging process. The activity of the mammalian target of rapamycin (mTOR) signal pathway is compromised in the NSCs of the aged brain. Activating the mTOR signaling pathway increased NSC proliferation and promoted neurogenesis in aged mice. In contrast, inhibiting the mTOR signaling pathway decreased NSCs proliferation. These results indicate that an age-associated decline in neurogenesis is mainly because of the reduction in proliferation of active NSCs, at least partially because of the compromise in the mTOR signaling activity. Stimulating the mTOR signaling revitalizes the NSCs, restores their proliferation, and enhances neurogenesis in the hippocampus of the aged brain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Chronic progressive multiple sclerosis (MS) is a severely disabling demyelinating disease in which autoimmune processes seem to have a major role. The nucleoside drug cladribine is a potent lympholytic agent with few side-effects. We have studied its efficacy and safety in a randomised double-blind trial. 51 patients (48 entered as matched pairs) received four monthly courses of 0.7 mg/kg cladribine or placebo (saline) given through a surgically implanted central line. Neurologists with no knowledge of which medication the patient was receiving examined the patients monthly and noted two rating scale scores (Kurtzke and Scripps). Cerebrospinal fluid and brain magnetic resonance imaging (MRI) examinations were done at 6 and 12 months. Average neurological scores, demyelinated volumes on MRI, and concentrations of oligoclonal bands in cerebrospinal fluid were stable or improved in the patients receiving cladrabine but continued to deteriorate in patients on placebo. Mean paired (placebo minus matched cladribine) differences at 12 months relative to baseline were 1.0 (SE 0.4) for the Kurtzke scores, -13.9 (2.3) for the Scripps scores, 4.57 (1.17) mL for demyelinated volumes, and 7.3 (3.3) arbitrary units for concentrations of oligoclonal bands. Cladribine was generally well tolerated and clinically significant toxicity occurred in only 1 patient, in whom severe marrow suppression developed with complete recovery after several months. 1 patient died of newly acquired hepatitis B, an event unlikely to be related to cladribine. We conclude that the immunosuppressive drug cladribine influences favourably the course of chronic progressive MS.

The P300 component of the event-related brain potential (ERP) elicited with auditory stimuli and pattern-shift visual evoked potentials (VEPs) was obtained from 16 patients with multiple sclerosis (MS) and 16 matched control subjects. P300 latency was significantly longer and component amplitude relatively depressed in the MS patients compared to control subjects. The P100 potential of the VEP also was delayed for both full-field and half-field stimulus conditions in the patients compared to control subjects. The findings suggest that the P300 ERP may reflect the cognitive decline associated with MS.