Sir2, a member of the sirtuin family of protein acylases, deacetylates lysine residues within many proteins and is associated with lifespan extension in a variety of model organisms. Recent studies have questioned the positive effects of Sir2 on lifespan in Drosophila. Several studies have shown that increased expression of the Drosophila Sir2 homolog (dSir2) extends life span while other studies have reported no effect on life span or suggested that increased dSir2 expression was cytotoxic. To attempt to reconcile the differences in these observed effects of dSir2 on Drosophila life span, we hypothesized that a critical level of dSir2 may be necessary to mediate life span extension. Using approaches that allow us to titrate dSir2 expression, we describe here a strong dose-dependent effect of dSir2 on life span. Using the two transgenic dSir2 lines that were reported not to extend life span, we are able to show significant life span extension when dSir2 expression is induced between 2 and 5-fold. However, higher levels decrease life span and can induce cellular toxicity, manifested by increased expression of the JNK-signaling molecule Puc phosphatase and induction of dnaJ-H. Our results help to resolve the apparently conflicting reports by demonstrating that the effects of increased dSir2 expression on life span in Drosophila are dependent upon dSir2 dosage.
A previously healthy 37-year-old man presented with fever, nonproductive cough, and 2 days of diffuse rash that started on his chest. He denied dyspnea. He had never received the chickenpox vaccine. Physical examination revealed vesicular lesions of various stages on the trunk, neck (Image 1), head, and extremities. Chest radiograph revealed bilateral patchy opacities, and a CT scan of the chest (Image 2) showed diffuse ground-glass opacities. The patient was treated with intravenous acyclovir for severe chickenpox (varicellazoster virus), which was subsequently confirmed on vesicular fluid PCR. Human immunodeficiency virus testing was negative. On hospital day two, he developed respiratory failure requiring mechanical ventilation for 5 days. He had a full recovery and was discharged with a 10-day course of oral acyclovir.Varicella pneumonia is the most common complication of adult chickenpox, with an incidence of one-in-400 cases. 1 Risk factors include immunosuppression, smoking, and underlying lung disease. Mortality ranges from 10 to 30% overall and up to 50% in those on mechanical ventilation. 1 Common imaging findings include ill-defined confluent nodules and ground-glass opacities that may surround the nodules (halo sign) or be diffuse. 2 Treatment consists of early intravenous acyclovir, and steroid use remains controversial. 3 This case highlights the importance of early diagnosis of varicellazoster infections to minimize complication-related mortality.
The increasing use of advanced biologic therapies for patients with severe asthma is transforming the standard of care, clinic workflow, and the clinic business model. Expanded patient access to at-home injection treatment possibilities with some biologics has the potential to improve patient adherence and outcomes. Simultaneously, transition to the home setting can address the escalating costs that limit access for certain patients and healthcare facilities. Such moves come with recognized risks. Garnering input from physicians and other healthcare specialists as well as scrutinizing best practice position statements are vital to implementing truly patient-safe and cost-effective strategies in medicine. Mepolizumab is the first anti-IL-5 inhibitor to receive FDA approval in late 2015. We focus on this injectable medication and discuss the specific indications and contraindications for transitioning patients to at-home injection with mepolizumab. In doing so, we review our recent real-world experiences in the University of California, Davis and Loma Linda University severe asthma clinics, which can provide the foundation for building a comprehensive clinic and home-based biologics asthma program. In addition, we offer insight into the barriers to implementing a successful program and strategies for overcoming them.
Multiple myeloma (MM) is estimated to be diagnosed in over 20,000 people in the United States in 2014, representing only 1% of all malignancies and 10% of all blood cancers. 1 The estimated death rate, however, is 45%; in comparison, breast cancer is expected to be diagnosed in 235,000 and the death rate is 17%. 2 MM is characterized by a clonal proliferation of plasma cells that in most cases produces a monoclonal immunoglobulin. One difficulty in diagnosing patients with MM is that the clinical presentation can be highly variable depending on the involved organ leading to broad differential diagnoses and potential diagnostic delays. The diagnosis of MM may be suspected because of one or more of the following clinical findings that is not explained by another unrelated disease or disorder: hypercalcemia, renal failure, anemia, and bone lesions (commonly referred to by the acronym "CRAB"). 3 The most common symptoms reported are those related to lytic bone lesions such as unexplained backache. Renal disease associated with MM most often results from the deposition of monoclonal light
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