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21.
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. 相似文献
22.
David M. Presby Michael C. Rudolph Vanessa D. Sherk Matthew R. Jackman Rebecca M. Foright Kenneth L. Jones Julie A. Houck Ginger C. Johnson Janine A. Higgins P. Darrell Neufer Robert H. Eckel Paul S. MacLean 《Diabetes》2021,70(4):867
Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain. 相似文献
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Yasmine Yousef Etienne St-Louis Robert Baird Emily R. Smith Elena Guadagno Dickens St-Vil Dan Poenaru 《Journal of pediatric surgery》2019,54(4):831-837
Background
The Lancet Commission on Global Surgery highlighted global surgical need but offered little insight into the specific surgical challenges of children in low-resource settings. Efforts to strengthen the quality of global pediatric surgical care have resulted in a proliferation of partnerships between low-and middle-income countries (LMICs) and high-income countries (HICs). Standardized tools able to reliably measure gaps in delivery and quality of care are important aids for these partnerships. We undertook a systematic review (SR) of capacity assessment tools (CATs) focused on needs assessment in pediatric surgery.Methods
A comprehensive search strategy of multiple electronic databases was conducted per PRISMA guidelines without linguistic or temporal restrictions. CATs were selected according to pre-defined inclusion criteria. Articles were assessed by two independent reviewers. Methodological quality of studies was appraised using the COSMIN checklist with 4-point scale.Results
The search strategy generated 16,641 original publications, of which three CATs were deemed eligible. Eligible tools were either excessively detailed or oversimplified. None used weighted scores to identify finer granularity between institutions. No CATs comprehensively included measures of resources, outcomes, accessibility/impact and training.Discussion
The results of this study identify the need for a CAT capable of objectively measuring key aspects of surgical capacity and performance in a weighted tool designed for pediatric surgical centers in LMICs.Type of Study
Systematic Review.Level of Evidence
II. 相似文献25.
26.
Chronic pain in the UK affects up to 43% of the population. The consequences include physical and psychological distress, loss of function, employment, family and social strain and increased utilization of healthcare services. Modern pain management services operate across primary, secondary and tertiary care and incorporate general practitioners, psychologists, physiotherapists, pharmacists, specialist nurses, pain physicians and surgeons. This allows for a coordinated approach to chronic pain, engaging the patient in a structured pathway from conservative measures, through to surgery if necessary. Surgical interventions have been utilized effectively throughout the 20th century for the treatment of a variety of conditions, some of which are now effectively managed with improved pharmacological approaches or novel neuromodulation techniques. Ablative procedures that aim to permanently interrupt the pain pathway still represent the final solution for some conditions, particularly those with cancer associated pain; however, the search for less invasive, less risky measures continues. This is stimulated by an increased understanding of the neurobiology of pain transmission and the physiological changes which occur in persistent pain. 相似文献
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Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma
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Julia H. Vermylen Gordon J. Wood Elaine R. Cohen Jeffrey H. Barsuk William C. McGaghie Diane B. Wayne 《Journal of pain and symptom management》2019,57(3):682-687