Translational research : the journal of laboratory and clinical medicine
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Frailty and cognitive impairment are among the 2 most common geriatric syndromes. Their presence poses major risks to the elderly including greater disability, reduced quality of life, and higher morbi-mortality. Recent evidence suggest that frailty can be a risk factor for incident dementia. ⋯ Here, we will review the current evidence of the association between frailty and cognitive impairment. We will also review the possible biological mechanistic links between the 2 conditions. Finally, we will address potential therapeutic targets and interventions that can mitigate both conditions.
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Genital herpes increases the risk of acquiring and transmitting Human Immunodeficiency Virus (HIV), is a source of anxiety for many about transmitting infection to intimate partners, and is life-threatening to newborns. A vaccine that prevents genital herpes infection is a high public health priority. An ideal vaccine will prevent both genital lesions and asymptomatic subclinical infection to reduce the risk of inadvertent transmission to partners, will be effective against genital herpes caused by herpes simplex virus types 1 and 2 (HSV-1, HSV-2), and will protect against neonatal herpes. ⋯ Many vaccine candidates are under development, including DNA, modified mRNA, protein subunit, killed virus, and attenuated live virus vaccines. Lessons learned from prior vaccine studies and select candidate vaccines are discussed, including a trivalent nucleoside-modified mRNA vaccine that our laboratory is pursuing. We are optimistic that an effective vaccine for prevention of genital herpes will emerge in this decade.
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This perspective provides an overview of the evolution of antibiotic discovery from a largely phenotypic-based effort, through an intensive structure-based design focus, to a more holistic approach today. The current focus on antibiotic development incorporates assay and discovery conditions that replicate the host environment as much as feasible. They also incorporate several strategies, including target identification and validation within the whole cell environment, a variety of target deconvolution methods, and continued refinement of structure-based design approaches.
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The global burden of bacterial infections is rising due to increasing resistance to the majority of first-line antibiotics, rendering these drugs ineffective against several clinically important pathogens. Limited transport of antibiotics into cells compounds this problem for gram-negative bacteria that exhibit prominent intracellular lifecycles. Furthermore, poor bioavailability of antibiotics in infected tissues necessitates higher doses and longer treatment regimens to treat resistant infections. ⋯ However, in vivo therapeutic efficacy of HDTs is reliant on adequate bioavailability. Particle-based formulations demonstrate the potential to enable targeted drug delivery, enhance cellular uptake, and increase drug concentration in the host cell of HDTs. This review selected HDTs for clinically important pathogens, identifies formulation strategies that can improve their therapeutic efficacy and offers insights toward further development of HDTs for bacterial infections.