Modes of ever marijuana use among adult tobacco users and non-tobacco users—Styles 2014

Background: Tobacco and marijuana use are related behaviors; therefore, it is important to identify how users consume marijuana, and how it varies with tobacco use status. We estimated the modes of ever marijuana use among current, former, and never adult tobacco users.

Methods: Weighted data were analyzed for 4181 adults from 2014 Styles, an online consumer panel survey of US adults, to estimate proportions for modes of ever marijuana use. Differences in modes of ever marijuana use between categories of tobacco use status were assessed (p-value <0.05).

Results: More than half of current (56.6%) and former tobacco users (50.9%) had ever used marijuana, whereas only 13.0% of never tobacco users had ever used marijuana. Among ever marijuana users, joint use was the most common mode of use among current (86.4%), former (92.5%), and never (79.8%) tobacco users. Similarly, other modes of marijuana use were significantly higher in current and former tobacco users compared to never tobacco users.

Conclusions: Prevalence of all modes of ever marijuana use was higher in current and former tobacco users. These findings underscore the importance of considering the relationship between marijuana and tobacco use when developing programs and policies aimed at preventing and reducing marijuana use.     

Long-term clinical outcomes of submacular blood removal with isolated autologous retinal pigment epithelium-choroid patch graft transplantation in long-standing large-sized submacular hematomas: An Indian experience

Purpose:To study the outcomes of submacular blood removal with isolated autologous full-thickness retinal pigment epithelial (RPE)-choroid patch graft transplantation in long-standing large-sized submacular hematomas in Indian population.Methods:A retrospective study was done on eight consecutive patients of long-standing large-sized submacular hematoma from east India. In all cases, 23G vitrectomy was performed with the induction of retinal detachment (performed with or without 38G or 41G subretinal cannula) and a temporal 180° retinectomy was done. Submacular blood along with choroidal neovascular tissue was removed. A full-thickness RPE-choroid autologous patch graft was taken from a relatively healthy quadrant at the mid periphery and then the graft transferred under perfluorocarbon liquid (PFCL) to place it in the subfoveal area. Then, retina was re-attached using PFCL and laser completed. Silicone oil (5000 cst) was used as a tamponade. Post-operatively, wide-field fundus photographs (Optos), serial optical coherence tomography (OCT), indocyanine green angiography (ICGA), and multifocal electroretinography (ERG) were done.Results:The mean age of the patients at presentation was 67.88 ± 10.03 years. Mean pre-operative best corrected visual acquity (BCVA) was 2.64 ± 0.3 log MAR and mean postoperative BCVA was 1.095 ± 0.27 log MAR (P < 0.05). The mean follow-up was 20 ± 16.57 months. ICG showed re-vascularization of translocated graft in all at 2 months. Multifocal ERG (after 6 months) showed some waveform in all. None of the cases developed re-bleed.Conclusion:Removal of submacular blood and neovascular membrane with autologous RPE-choroid graft is a viable option in cases with long-standing large submacular hematomas.     

A Review of Daclatasvir Drug–Drug Interactions

The treatment of hepatitis C virus (HCV) infection has been revolutionized in recent years by the development of direct-acting antiviral regimens that do not contain peginterferon (pegIFN) and/or ribavirin (RBV). While direct-acting antiviral-based regimens have been shown to be greatly superior to pegIFN/RBV-based regimens in terms of efficacy and safety, they have a greater susceptibility to drug–drug interactions (DDIs). Daclatasvir (DCV)—the benchmark pangenotypic nonstructural protein 5A inhibitor—has been shown to be efficacious and generally well tolerated in partnership with other HCV direct-acting antivirals, including sofosbuvir, asunaprevir (ASV), and ASV plus beclabuvir. DCV may be the object of a DDI via the induction or inhibition of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) by the concomitant medication, or the precipitant of a DDI via DCV-based induction/inhibition of CYP 3A4 or inhibition of P-gp, organic anion transporting polypeptide 1B1/B3, and/or breast cancer resistance protein. This article presents an overview of the drug interaction studies conducted during the clinical development of DCV, the findings of these studies that led to the guidance on concomitant medication use and dosage along with any required DCV dose modifications, and the use of the known metabolic pathway of DCV to guide concomitant dosing where direct drug–drug studies have not been conducted. The robust characterization of the DCV clinical pharmacology program has demonstrated that DCV has few or no clinically relevant DDIs with medications with which it is likely to be co-administered, and the majority of DDIs that do occur can be predicted and easily managed. Funding: Bristol-Myers Squibb.     

Substance P induces interleukin-8 secretion from human dental pulp cells

OBJECTIVE: The role of neuropeptides in recruiting leukocytes in dental pulps is not known; therefore, we investigated whether interleukin-8 (IL-8) secretion from human pulp cells is increased after stimulation with substance P (SP) or calcitonin gene-related peptide (CGRP). METHODS: Primary pulp cells exhibiting a fibroblast-like phenotype and an endothelial cell line were stimulated with various doses of SP or CGRP, and IL-8 secretion was measured by enzyme-linked immunosorbent assays. RESULTS: IL-8 secretion from pulp cells increased significantly at 10(-8) to 10(-4) mol/L of SP stimulation (5- to 13.8-fold; P <.05); however, no significant IL-8 increase with CGRP (up to 10(-4) mol/L) stimulation was observed, nor was there synergistic induction of IL-8 with SP plus CGRP. The IL-8 increase reached its maximum at 8 hours after SP stimulation of the pulp cells. SP at a concentration of 10(-4) mol/L created minimal IL-8 induction in the endothelial cells and no synergistic induction by SP and CGRP. CONCLUSIONS: Pulp cells may up-regulate IL-8 secretion by SP stimulation, which suggests that SP released in dental pulp may play a role in the influx of leukocytes, attracted by IL-8, into the pulp tissue.     

Targeted cell-ablation in Xenopus embryos using the conditional, toxic viral protein M2(H37A).

Harnessing toxic proteins to destroy selective cells in an embryo is an attractive method for exploring details of cell fate and cell-cell interdependency. However, no existing "suicide gene" system has proved suitable for aquatic vertebrates. We use the M2(H37A) toxic ion channel of the influenza-A virus to induce cell-ablations in Xenopus laevis. M2(H37A) RNA injected into blastomeres of early stage embryos causes death of their progeny by late-blastula stages. Moreover, M2(H37A) toxicity can be controlled using the M2 inhibitor rimantadine. We have tested the ablation system using transgenesis to target M2(H37A) expression to selected cells in the embryo. Using the myocardial MLC2 promoter, M2(H37A)-mediated cell death causes dramatic loss of cardiac structure and function by stage 39. With the LURP1 promoter, we induce cell-ablations of macrophages. These experiments demonstrate the effectiveness of M2(H37A)-ablation in Xenopus and its utility in monitoring the progression of developmental abnormalities during targeted cell death experiments.     

microRNAs in liver disease: From diagnostics to therapeutics

There is a need to identify effective biomarkers for diagnosis, prognosis and prediction of treatment efficacy for many liver diseases such as hepatocellular cancer, and chronic viral hepatitis. The identification of disease-specific alterations in microRNA expression and the ability to detect microRNAs in the circulation provide the basis for identifying novel clinically effective treatments and biomarkers. Knowledge regarding miRNA in human liver disease may eventually lead to serum or tissue biomarkers with clinical utility. A selection of relevant studies is reviewed. There are major challenges that need to be addressed prior to clinical application such as the need for careful validation of diagnostic miRNA candidates in well described clinical cohorts, and technical issues such as quantitation and standardization of assays. The rapid progress in therapeutic interventions using miRNA based strategies for chronic hepatitis C and hepatocellular cancer provides optimism for novel approaches that will build on the existing and emerging knowledge regarding miRNA in liver diseases.     

Physiologic Benefits of Pulsatile Perfusion During Mechanical Circulatory Support for the Treatment of Acute and Chronic Heart Failure in Adults

A growing population experiencing heart failure (100 000 patients/year), combined with a shortage of donor organs (less than 2200 hearts/year), has led to increased and expanded use of mechanical circulatory support (MCS) devices. MCS devices have successfully improved clinical outcomes, which are comparable with heart transplantation and result in better 1‐year survival than optimal medical management therapies. The quality of perfusion provided during MCS therapy may play an important role in patient outcomes. Despite demonstrated physiologic benefits of pulsatile perfusion, continued use or development of pulsatile MCS devices has been widely abandoned in favor of continuous flow pumps owing to the large size and adverse risks events in the former class, which pose issues of thrombogenic surfaces, percutaneous lead infection, and durability. Next‐generation MCS device development should ideally implement designs that offer the benefits of rotary pump technology while providing the physiologic benefits of pulsatile end‐organ perfusion.