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The epidermal microbiome is a critical element of marine organismal immunity, but the epidermal virome of marine organisms remains largely unexplored. The epidermis of sharks represents a unique viromic ecosystem. Sharks secrete a thin layer of mucus which harbors a diverse microbiome, while their hydrodynamic dermal denticles simultaneously repel environmental microbes. Here, we sampled the virome from the epidermis of three shark species in the family Carcharhinidae : the genetically and morphologically similar Carcharhinus obscurus ( n = 6) and Carcharhinus galapagensis ( n = 10) and the outgroup Galeocerdo cuvier ( n = 15). Virome taxonomy was characterized using shotgun metagenomics and compared with a suite of multivariate analyses. All three sharks retain species-specific but highly similar epidermal viromes dominated by uncharacterized bacteriophages which vary slightly in proportional abundance within and among shark species. Intraspecific variation was lower among C. galapagensis than among C. obscurus and G. cuvier. Using both the annotated and unannotated reads, we were able to determine that the Carcharhinus galapagensis viromes were more similar to that of G. cuvier than they were to that of C. obscurus , suggesting that behavioral niche may be a more prominent driver of virome than host phylogeny.

Objective: To compile and synthesize the available literature describing medical cannabis use across various disease states., Data Sources: PubMed, EBSCO, and Google Scholar searches were conducted using MeSH and/or keywords., Study Selection and Data Extraction: Studies were included if they described the use of cannabis-based products and medications in the treatment of a predefined list of disease states in humans and were published in English. The extraction period had no historical limit and spanned through April 2019., Data Synthesis: Evidence was compiled and summarized for the following medical conditions: Alzheimer disease, amyotrophic lateral sclerosis, autism, cancer and cancer-associated adverse effects, seizure disorders, human immunodeficiency virus, inflammatory bowel disease, multiple sclerosis (MS), nausea, pain, posttraumatic stress disorder, and hospice care., Relevance to Patient Care and Clinical Practice: Based on identified data, the most robust evidence suggests that medical cannabis may be effective in the treatment of chemotherapy-induced nausea and vomiting, seizure disorders, MS-related spasticity, and pain (excluding diabetic neuropathy). Overall, the evidence is inconsistent and generally limited by poor quality. The large variation in cannabis-based products evaluated in studies limits the ability to make direct comparisons. Regardless of the product, a gradual dose titration was utilized in most studies. Cannabis-based therapies were typically well tolerated, with the most common adverse effects being dizziness, somnolence, dry mouth, nausea, and euphoria., Conclusions: As more states authorize medical cannabis use, there is an increasing need for high-quality clinical evidence describing its efficacy and safety. This review is intended to serve as a reference for clinicians, so that the risks and realistic benefits of medical cannabis are better understood.

Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors., (© 2016 by the American Diabetes Association.)

Purpose: A case of eosinophilic pneumonia in a patient receiving ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is reported., Summary: A 65-year-old woman was admitted to a medical intensive care unit after arriving at the emergency room with complaints of progressively worsening shortness of breath. Her medical history included chronic obstructive pulmonary disease, acute respiratory distress syndrome, recent traumatic brain injury, tobacco use, and alcohol abuse. Within the first few days of hospitalization, the patient was diagnosed with MRSA pneumonia based on microbiological data from bronchoscopy bronchial washings. Her renal function liver enzyme levels were within normal limits. Empirical antibiotic therapy included i.v. vancomycin and meropenem and was narrowed to i.v. linezolid monotherapy based on culture and sensitivity results. After 10 days of treatment with linezolid, the patient was persistently febrile, and cultures remained positive. It was decided to switch therapy to a course of i.v. ceftaroline, an anti-MRSA cephalosporin. On the fifth day of treatment with ceftaroline, the patient developed respiratory decompensation and peripheral eosinophilia of 40%. Bronchoalveolar lavage (BAL) results indicated the presence of pulmonary eosinophilia of 13%. Chest radiographs revealed pulmonary infiltrates, and the computed tomography angiography showed no evidence of pulmonary embolism. Ceftaroline was discontinued, and the patient was started on vancomycin and methylprednisolone. The patient responded to methylprednisolone therapy, with repeat BAL and peripheral blood counts showing resolved eosinophilia., Conclusion: A patient with risk factors for respiratory disease developed eosinophilic pneumonia after receiving ceftaroline for the treatment of MRSA pneumonia. Eosinophilia resolved after ceftaroline was discontinued and i.v. methylprednisolone was initiated.