HIV Protease: Historical Perspective and Current Research

The retroviral protease of human immunodeficiency virus (HIV) is an excellent target for antiviral inhibitors for treating HIV/AIDS. Despite the efficacy of therapy, current efforts to control the disease are undermined by the growing threat posed by drug resistance. This review covers the historical background of studies on the structure and function of HIV protease, the subsequent development of antiviral inhibitors, and recent studies on drug-resistant protease variants. We highlight the important contributions of Dr. Stephen Oroszlan to fundamental knowledge about the function of the HIV protease and other retroviral proteases. These studies, along with those of his colleagues, laid the foundations for the design of clinical inhibitors of HIV protease. The drug-resistant protease variants also provide an excellent model for investigating the molecular mechanisms and evolution of resistance.     

Long-term deaths from melanoma according to tumor thickness at diagnosis

There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872–879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness <0.80 mm, 10.6% for tumors 0.8 to <1.0 mm and generally more than 30% for melanomas measuring 3 mm and more. For melanomas <1.0 mm, most deaths occurred between 5 and 20 years after diagnosis, whereas for thicker melanomas the reverse was true with most deaths occurring within the first 5 years. Five-year case fatality decreased over successive calendar time periods for melanomas <1.0 mm, but not for melanomas ≥1.0 mm. These findings demonstrate that the time course for fatal melanomas varies markedly according to tumor thickness at diagnosis. Improved understanding of the patient factors and characteristics of melanomas, in addition to tumor thickness, which increase the likelihood of progression, is needed to guide clinical diagnosis, communication with patients and ongoing surveillance pathways of patients with potentially fatal lesions.     

Sensitive skin: correlation with skin surface microrelief appearance

BACKGROUND/PURPOSE: Sensitive skin is a condition associated with reduced tolerance to environmental factors and/or the application of topical products, such as cosmetics. Its pathophysiology has not been fully elucidated and few data are available on its prevalence. The aim of this study was to investigate possible correlation between objective sensitivity and skin surface microrelief. METHODS: During an epidemiological survey conducted for a campaign promoted by International Society of Plastic Dermatology in Italy, 243 adult healthy subjects of both sexes with no evident dermatological disorder but positive to the lactic acid stinging test, were submitted to cyanoacrylate stratum corneum stripping from the volar forearm for the determination of the irregularity of the skin surface microrelief (irregularity skin index (ISI)). RESULTS: A significant correlation was found between intensity of symptoms in stingers and ISI (r(s)=-0.47; P<0.001). CONCLUSION: Sensitive skin is common in the healthy population. ISI can contribute towards the identification of subjects with sensitive skin and the development of more specific skin treatments for this prevalent condition.