Life Cycle Inventory and Assessment Datasets on the Operational Sustainability of the Ammonia Process.

This article presents data affiliated with life cycle inventories, environmental impact and operational sustainability used in, the influence of raw material availability and utility power consumption on the sustainability of the ammonia process [1]. Scenario specific operating conditions were used to simulate the ammonia process based on unique constraints occurring within the Trinidad and Tobago energy sector. The data was collected using AspenⓇ Plus simulations and validated against plant operating data. The data consists of an economic cost evaluation as well as environmental impact using the CML-IA Baseline midpoint approach. The data was derived from life cycle inventories aligned to input/output material and energy flows within the ammonia process as well as life cycle assessment databases utilizing Ecoinvent v3.4. The data can be applied to the wider ammonia supply chain, aiding in achieving greater sustainable development within ammonia-based process industries.

Protein Kinase R Restricts the Intracellular Survival of Mycobacterium tuberculosis by Promoting Selective Autophagy.

Tuberculosis (TB) is a deadly infectious lung disease caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb). The identification of macrophage signaling proteins exploited by Mtb during infection will enable the development of alternative host-directed therapies (HDT) for TB. HDT strategies will boost host immunity to restrict the intracellular replication of Mtb and therefore hold promise to overcome antimicrobial resistance, a growing crisis in TB therapy. Protein Kinase R (PKR) is a key host sensor that functions in the cellular antiviral response. However, its role in defense against intracellular bacterial pathogens is not clearly defined. Herein, we demonstrate that expression and activation of PKR is upregulated in macrophages infected with Mtb. Immunological profiling of human THP-1 macrophages that overexpress PKR (THP-PKR) showed increased production of IP-10 and reduced production of IL-6, two cytokines that are reported to activate and inhibit IFNγ-dependent autophagy, respectively. Indeed, sustained expression and activation of PKR reduced the intracellular survival of Mtb, an effect that could be enhanced by IFNγ treatment. We further demonstrate that the enhanced anti-mycobacterial activity of THP-PKR macrophages is mediated by a mechanism dependent on selective autophagy, as indicated by increased levels of LC3B-II that colocalize with intracellular Mtb. Consistent with this mechanism, inhibition of autophagolysosome maturation with bafilomycin A1 abrogated the ability of THP-PKR macrophages to limit replication of Mtb, whereas pharmacological activation of autophagy enhanced the anti-mycobacterial effect of PKR overexpression. As such, PKR represents a novel and attractive host target for development of HDT for TB, and our data suggest value in the design of more specific and potent activators of PKR.

Nabiximols for the Treatment of Cannabis Dependence: A Randomized Clinical Trial.

IMPORTANCE: There are no effective medications for treating dependence on cannabis. OBJECTIVE: To examine the safety and efficacy of nabiximols in the treatment of patients with cannabis dependence. DESIGN, SETTING, AND PARTICIPANTS: This parallel double-blind randomized clinical trial comparing nabiximols with placebo in a 12-week, multisite outpatient study recruited participants from February 3, 2016, to June 14, 2017, at 4 outpatient specialist alcohol and drug treatment services in New South Wales, Australia. Participants had cannabis dependence (as defined by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and were seeking treatment, were nonresponsive to prior treatment attempts, were 18 to 64 years of age, had no other substance use disorder, had no severe medical or psychiatric conditions, were not pregnant, were not mandated by a court to undergo treatment, and provided informed consent. Results for primary efficacy measures and all secondary outcomes were obtained using a modified intention-to-treat data set. INTERVENTIONS: Participants received 12-week treatment involving weekly clinical reviews, structured counseling, and flexible medication doses-up to 32 sprays daily (tetrahydrocannabinol, 86.4 mg, and cannabidiol, 80 mg), dispensed weekly. MAIN OUTCOMES AND MEASURES: Primary outcome was self-reported number of days using illicit cannabis during the 12-week period. Other outcomes included alternate cannabis use parameters (periods of abstinence, withdrawal, cravings, and problems), safety parameters (adverse events and aberrant medication use), health status, other substance use, and treatment retention. RESULTS: A total of 128 participants (30 women and 98 men; mean [SD] age, 35.0 [10.9] years) were randomized and received at least 1 dose of study medication. Participants had used a mean (SD) of 2.3 (2.1) g of cannabis on a mean (SD) of 25.7 (4.5) days in the past 28 days. Treatment retention was comparable for the 2 groups (placebo, 30 of 67 participants [44.8%]; nabiximols, 30 of 61 participants [49.2%]), and both groups used similar mean (SD) doses (placebo, 18.5 [9.5] sprays daily; nabiximols, 17.6 [9.5] sprays daily, equivalent to a mean [SD] of 47.5 [25.7] mg of tetrahydrocannabinol and 44.0 [23.8] mg of cannabidiol). For the primary end point, the placebo group reported significantly more days using cannabis during the 12 weeks (mean [SD], 53.1 [33.0] days) than the nabiximols group (mean [SD], 35.0 [32.4] days; estimated difference, 18.6 days; 95% CI, 3.5-33.7 days; P = .02). Both groups showed comparable improvements in health status, with no substantial changes in other substance use. Medication was well tolerated with few adverse events. CONCLUSIONS AND RELEVANCE: This study demonstrates that cannabinoid agonist treatment, in this case using nabiximols, in combination with psychosocial interventions is a safe approach for reducing cannabis use among individuals with cannabis dependence who are seeking treatment. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12616000103460.

Infections and severe sepsis in solid-organ transplant patients admitted from a university-based ED.

The objective was to provide a descriptive analysis of infectious processes in transplant patients admitted from the emergency department (ED). A database of all adult transplant patients at a university medical center was cross-referenced with a computerized record of all ED visits over an 18-month period. ED charts, inpatient records, and microbiology data were retrospectively reviewed. Final diagnoses and outcomes were analyzed. There were 352 ED visits by transplant patients (kidney 66%, kidney/pancreas 15%, liver 13%, lung 3%, heart 3%). Infections were the most common indications for admission (77/217, 35%). Urinary tract infection and pneumonia were the most common infections. Nine of 77 patients (11.7%) with documented infections developed severe sepsis, which was the most common reason for ICU utilization. Thirty-five percent of transplant patients admitted from the ED had acute infections, and 11.7% of these patients had severe sepsis. The emergency physician must have a high index of suspicion for infections when evaluating organ transplant recipients.