Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.

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Introduction Digital health – the convergence of digital technologies within health and health care to enhance the efficiency of health-care delivery – is fast becoming an integral part of routine medical practice. The integration of digital health into traditional practice brings significant changes. Logic dictates that for medical practitioners to operate in this new digitally enabled environment, they require specific knowledge, skills and competencies relating to digital health. However, very few medical programmes in Australia and globally include digital health within their regular curriculum. This pilot study aimed to explore medical students’ perceptions and expectations of digital health education and training (ET). Methods An online survey and focus groups were used to collect information about medical students’ perceptions and expectations relating to digital health and ET relating to this field within the medical programme at the University of Queensland. Sixty-three students took part in the survey, and 17 students were involved in four focus groups. Results Most participants had no formal ET in digital health. Most participants ( n = 43; 68%) expressed a willingness to learn about digital health as part of their medical programme. Discussion Primarily, knowledge- and practice-related factors have motivated students to learn about digital health. The analysis of focus group data identified two superordinate themes: (a) drivers of digital health ET and (b) expectations relating to digital health ET. Students agreed that digital health is a relevant field for their future practice that should be taught as part of their regular curriculum.

CXCR2 has emerged as a therapeutic target for not only peripheral inflammatory diseases but also neurological abnormalities in the central nervous system (CNS). Herein, we describe the discovery of a novel 1-cyclopentenyl-3-phenylurea series as potent and CNS penetrant CXCR2 antagonists. Extensive SAR studies, wherein molecules' property forecast index (PFI) was carefully optimized for overall balanced developability profiles, led to the discovery of the advanced lead compound 68 with a desirable PFI. Compound 68 demonstrated good in vitro pharmacology with excellent selectivity over CXCR1 and other chemokine receptors. Rat and dog pharmacokinetics (PK) revealed good oral bioavailability, high oral exposure, and desirable elimination half-life of the compound in both species. In addition, the compound demonstrated dose-dependent efficacy in the in vivo pharmacology neutrophil infiltration "air pouch" model in rodents after oral administration. Further, compound 68 is a CNS penetrant molecule with high unbound fraction in brain tissue.

Hearing loss is an unusual presenting feature of Cryptococcus gattii meningoencephalitis. Two cases of HIV-negative patients who presented with hearing loss are discussed and a literature review of published cases was conducted. Possible mechanisms for hearing loss with C. gattii infection are explored. This case series aims to raise awareness among clinicians that hearing loss can be a concerning feature in patients with persistent headache necessitating further investigation.