Post-transcriptional regulation of redox homeostasis by the small RNA SHOxi in haloarchaea.

While haloarchaea are highly resistant to oxidative stress, a comprehensive understanding of the processes regulating this remarkable response is lacking. Oxidative stress-responsive small non-coding RNAs (sRNAs) have been reported in the model archaeon, Haloferax volc anii, but targets and mechanisms have not been elucidated. Using a combination of high throughput and reverse molecular genetic approaches, we elucidated the functional role of the most up-regulated intergenic sRNA during oxidative stress in H. volcanii, named Small RNA in Haloferax Oxidative Stress (SHOxi). SHOxi was predicted to form a stable secondary structure with a conserved stem-loop region as the potential binding site for trans-targets. NAD-dependent malic enzyme mRNA, identified as a putative target of SHOxi, interacted directly with a putative 'seed' region within the predicted stem loop of SHOxi. Malic enzyme catalyzes the oxidative decarboxylation of malate into pyruvate using NAD+ as a cofactor. The destabilization of malic enzyme mRNA, and the decrease in the NAD+/NADH ratio, resulting from the direct RNA-RNA interaction between SHOxi and its trans-target was essential for the survival of H. volcanii to oxidative stress. These findings indicate that SHOxi likely regulates redox homoeostasis during oxidative stress by the post-transcriptional destabilization of malic enzyme mRNA. SHOxi-mediated regulation provides evidence that the fine-tuning of metabolic cofactors could be a core strategy to mitigate damage from oxidative stress and confer resistance. This study is the first to establish the regulatory effects of sRNAs on mRNAs during the oxidative stress response in Archaea.

Identification and treatment of obstructive sleep apnea by a primary care team with a subset focus on chronic pain management.

BACKGROUND: Patients diagnosed with obstructive sleep apnea (OSA), who also consume prescription opioids, have a greater likelihood of morbidity and mortality. This study evaluated whether a primary care team, focused on chronic pain care management, could use a validated questionnaire (STOP-Bang) and motivational follow-up, to increase identification and treatment of OSA. METHODS: This study was a retrospective, dual arm, pre/post controlled study. Participants of this study included the complete chronic pain management sub group treated by this primary care team. Participants were ≥ 18 years old and prescribed daily opioids for treatment of chronic pain. All participants had a multifaceted, individualized, educational meeting that included completing a STOP-Bang questionnaire. Participants who received a score ≥ three were advised to follow up with their primary care physician. Participants were seen quarterly throughout the study. RESULTS: The primary outcome of this study was that 65% of participants with likely OSA were using CPAP for a minimum of 12 months (range of 12-25 months, 18-month average) post-intervention vs. 37% CPAP-use in the control group (12 months of observation), both groups were chronic opioid users with OSA. This was a 28% relative improvement (p = 0.0034). A secondary outcome was that 8.9% of non-prior CPAP users obtained CPAP post- intervention; a 56.7% pre-post improvement (p = 0.0064, x2 = 10.08 with 1 degree of freedom). Also, participants who were likely to have OSA (STOP-Bang score ≥ 3 or had a positive polysomnography (AHI >5 with comorbidities)) compared to those unlikely to have OSA (STOP-Bang score <3 or had a negative polysomnography (AHI <5)) in this study were more likely to be male, have a higher BMI, have hypertension, have cardiovascular disease and/or have diabetes (all types). CONCLUSION: Team based care management for participants taking prescription opioids, where STOP-Bang questionnaires were completed, were associated with an increase in the identification and treatment of OSA.

One-on-one care management and procurement of Naloxone for ambulatory use.

Background: Morbidity and mortality from prescription opioids has reached unprecedented levels. Opioids remain part of chronic pain treatment in primary care. This study was designed to determine whether one-on-one care management increases procurement of Naloxone, an opioid antagonist shown to reduce morbidity and mortality in opioid overdoses. Methods: Participants included all patients ≥18 years enrolled in a primary care-based chronic pain management program and who were prescribed a daily dose of opioids for treatment of chronic pain. In total, 153 patients chose to participate. Each had a 1 h one-on-one education meeting with a registered nurse. Results: Among the enrolled, eight patients (5.2%) had procured Naloxone prior to intervention. Overall, 31 additional patients (20.2%) procured Naloxone after intervention, a 288% relative improvement in the attainment of Naloxone (P < 0.0001) (χ2 = 29.032 with 1 degree freedom). Of the 114 participants who never procured Naloxone, 69.3% believed it was unnecessary, 20% forgot about Naloxone, 8% said it was cost prohibitive, 3.5% had access concerns and 0.9% had concerns about side effects. Conclusion: Direct one-on-one nurse care management sessions were associated with an increased procurement of Naloxone in a primary care-based pain management program. A significant number of patients believed Naloxone was unnecessary after the intervention.