Comments by the Editors

The August 2021 Special Issue of the IEEE Transactions on Nuclear Science (TNS) contains 32 peer-reviewed journal articles that were prepared on the basis of presentations made at the 2020 Conference on Radiation and Its Effects on Components and Systems (RADECS) held online from October 19, 2020, through Friday, November 20, 2020, due to COVID-19 pandemic restrictions. A few more papers may appear in subsequent issues of the Transactions. Additional papers presented at RADECS 2020 are available in the conference proceedings, available through IEEE Xplore.

Safety and efficacy of ALRV5XR in women with androgenetic alopecia or telogen effluvium: A randomised, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Scalp hair loss (alopecia) in women is a common ageing and senescing condition. It usually presents as androgenetic alopecia (AGA) or telogen effluvium (TE) and often has pronounced psychological consequences. ALRV5XR is a novel treatment aiming to regenerate a normal hair phenotype by targeting multiple molecular pathways linked to hair growth promotion and hair follicle stem cell activation. The primary objectives of this 24-week trial were to evaluate the safety and efficacy of ALRV5XR in terminal hair (TH) regrowth in women with AGA or TE. METHODS: This randomised, double-blind, placebo-controlled trial was performed in a USA community clinic. Healthy women 18-65 years of age with AGA or TE of Ludwig classification I-II and Fitzpatrick skin type I-VI were enrolled. They were allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups using a random number table. Masked dermatologist assessments, phototrichograms and blood samples were obtained at baseline, 12 and 24 weeks. Subjects were given a masked treatment regimen of oral capsules, shampoo, conditioner and follicle serum for daily administration. Main outcomes were absolute and per cent changes in TH density and response rates. The trial was registered with clinicaltrials.gov (NCT04450602) and is completed. FINDINGS: 46 subjects (23 ALRV5XR, 23 placebo) were enrolled between April 3 and October 20, 2018. Five subjects dropped out and two were non-compliant. Thirty-nine subjects completed the trial (18 ALRV5XR, 21 placebo). At 24 weeks, the absolute change in TH density improved by 30·1THs/cm2 (95% CI: 15·1-45·1; p=0·0002), and the relative density increased by 19·7% (95% CI: 8·0%-31·4%; p=0·0016). The odds ratio for being a responder (≥0 change) was 2·7. Efficacy increased 133% from week 12 to 24. Efficacy outcomes were similar in AGA and TE subjects. 66·7% of the ALRV5XR group responded by regrowing 40THs/cm2 or more hair. No adverse events were reported. INTERPRETATION: In women with AGA or TE, ALRV5XR treatment significantly increased hair regrowth without adverse events. ALRV5XR displayed a multi-fold improved efficacy and response rate when compared to published trials of standard therapy. Progressive acceleration of TH regrowth suggests regeneration of the structure and function of non-productive telogen follicles and prolonged treatment may restore a normal hair phenotype.

The H+-ATPase (V-ATPase): from proton pump to signaling complex in health and disease.

A primary function of the H+-ATPase (or V-ATPase) is to create an electrochemical proton gradient across eukaryotic cell membranes, which energizes fundamental cellular processes. Its activity allows for the acidification of intracellular vesicles and organelles, which is necessary for many essential cell biological events to occur. In addition, many specialized cell types in various organ systems such as the kidney, bone, male reproductive tract, inner ear, olfactory mucosa, and more, use plasma membrane V-ATPases to perform specific activities that depend on extracellular acidification. It is, however, increasingly apparent that V-ATPases are central players in many normal and pathophysiological processes that directly influence human health in many different and sometimes unexpected ways. These include cancer, neurodegenerative diseases, diabetes, and sensory perception, as well as energy and nutrient-sensing functions within cells. This review first covers the well-established role of the V-ATPase as a transmembrane proton pump in the plasma membrane and intracellular vesicles and outlines factors contributing to its physiological regulation in different cell types. This is followed by a discussion of the more recently emerging unconventional roles for the V-ATPase, such as its role as a protein interaction hub involved in cell signaling, and the (patho)physiological implications of these interactions. Finally, the central importance of endosomal acidification and V-ATPase activity on viral infection will be discussed in the context of the current COVID-19 pandemic.