The Future of Municipal Wastewater Reuse Concentrate Management: Drivers, Challenges, and Opportunities.

Water reuse is rapidly becoming an integral feature of resilient water systems, where municipal wastewater undergoes advanced treatment, typically involving a sequence of ultrafiltration (UF), reverse osmosis (RO), and an advanced oxidation process (AOP). When RO is used, a concentrated waste stream is produced that is elevated in not only total dissolved solids but also metals, nutrients, and micropollutants that have passed through conventional wastewater treatment. Management of this RO concentrate─dubbed municipal wastewater reuse concentrate (MWRC)─will be critical to address, especially as water reuse practices become more widespread. Building on existing brine management practices, this review explores MWRC management options by identifying infrastructural needs and opportunities for multi-beneficial disposal. To safeguard environmental systems from the potential hazards of MWRC, disposal, monitoring, and regulatory techniques are discussed to promote the safety and affordability of implementing MWRC management. Furthermore, opportunities for resource recovery and valorization are differentiated, while economic techniques to revamp cost-benefit analysis for MWRC management are examined. The goal of this critical review is to create a common foundation for researchers, practitioners, and regulators by providing an interdisciplinary set of tools and frameworks to address the impending challenges and emerging opportunities of MWRC management.

Ex vivo use of cell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide-poisoned individuals.

The purpose of this study was to evaluate a new pharmacological strategy using a first-generation succinate prodrug, NV118, in peripheral blood mononuclear cells (PBMCs) obtained from subjects with carbon monoxide (CO) poisoning and healthy controls. We obtained human blood cells from subjects with CO poisoning and healthy control subjects. Intact PBMCs from subjects in the CO and Control group were analyzed with high-resolution respirometry measured in pmol O2 per second per 10-6 PBMCs. In addition to obtaining baseline respiration, NV118 (100 µM) was injected, and the same parameters of respiration were obtained for comparison in PBMCs. We measured mitochondrial dynamics with microscopy with the same conditions. We enrolled 37 patients (17 in the CO group and 20 in the Control group for comparison) in the study. PMBCs obtained from subjects in the CO group had overall significantly lower respiration compared with the Control group (P < 0.0001). There was a significant increase in respiration with NV118, specifically with an increase in maximum respiration and respiration from complex II and complex IV (P < 0.0001). The mitochondria in PBMCs demonstrated an overall increase in net movement compared with the Control group. Our results of this study suggest that the therapeutic compound, NV118, increases respiration at complex II and IV as well as restoration of mitochondrial movement in PBMCs obtained from subjects with CO poisoning. Mitochondrial-directed therapy offers a potential future strategy with further exploration in vivo.

Cerebral arterial gas embolism in a patient with hypoplastic left heart syndrome treated with emergent hyperbaric oxygen: case report.

A 30-year-old female with a history of seizure disorder and hypoplastic left heart syndrome treated with a Norwood procedure in 1986 followed by a modified non-fenestrated Fontan (Left SVC to IVC to pulmonary arteries) with a known baffle leak presented to the emergency department. On day of presentation, the patient became unresponsive, with perioral cyanosis, rightward gaze and a left facial droop near the end of a platelet transfusion. An emergent non-contrast head CT revealed intracranial air in the right MCA distribution. She was taken to the hyperbaric chamber and was treated with a U.S. Navy Table 6 in a multiplace chamber with no extensions. Ten minutes into the treatment patient became more alert and spontaneously asked questions. The following day she was treated with a U.S. Navy Table 5. Patient had repeat CT of the head, which showed resolution of intracerebral gas and small areas of ischemia in right frontal lobe and right caudate. On hospital day five neurologic exam was normal, with 5/5 strength and no residual deficits. Treating the patient was a concern because patient has a single ventricle, in which the pulmonary artery is connected directly to the vena cava. There is very little data regarding the effects of hyperbaric oxygen (HBO2)therapy on single-ventricle physiology. Only two case reports of three pediatric patients treated with HBO2 for CAGE in a similar setting are known. In these cases the patients had improvements in their symptoms following HBO2. These cases and ours indicate HBO2 is feasible and indicated for CAGE in patients with cyanotic congenital heart disease.

Colwellia marinimaniae sp. nov., a hyperpiezophilic species isolated from an amphipod within the Challenger Deep, Mariana Trench.

An obligately piezophilic strain was isolated from an amphipod crustacean obtained in the Challenger Deep region of the Mariana Trench during the DEEPSEA CHALLENGE expedition. The strain, MTCD1T, grew at extremely high hydrostatic pressures, with a growth range of 80-140 MPa (optimum, 120 MPa) at 6 °C. Phylogenetic analyses based on the 16S rRNA gene sequence indicate that it is closely affiliated with the genus Colwellia. Comparative 16S rRNA gene sequence analyses revealed 95.7, 95.5 and 95.2 % similarity to Colwellia maris ABE-1T, Colwellia piezophila Y233GT and Colwellia psychrerythraea ATCC 27364T, respectively. The major cellular fatty acids were C16 : 1, C16 : 0 and C22 : 6 (docosahexaenoic acid), and the sole isoprenoid quinone produced was ubiqinone-8. DNA G+C content was 48.6 mol%. The strain was positive for oxidase and catalase activities. Based on the results from this study, strain MTCD1T is a novel Gram-negative species of the genus Colwellia, and the name Colwellia marinimaniae sp. nov. (type strain MTCD1T=ATCC TSD-5T=JCM 30270T) is proposed. It is the most piezophilic organism yet described.

Effect of CPAP on arterial stiffness in severely obese patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) may independently increase cardiovascular risk in obesity. Although there is evidence that arterial stiffness is altered in OSA, knowledge of these effects with continuous positive airway pressure (CPAP) in severe obesity (body mass index (BMI) ≥ 35 kg/m(2)) is limited. This study aimed to explore how arterial stiffness, as measured by the augmentation index (Aix), changed in severely obese patients with OSA who were treated with CPAP and in patients without OSA. METHODS: Forty-two patients with severe obesity-22 with OSA, 20 without OSA-were recruited at baseline and followed-up after a median of 13.5 months. Pulse wave analysis (PWA) was performed using applanation tonometry at the radial artery to measure augmentation index (Aix), augmentation pressure (AP) and subendocardial viability ratio (SEVR). Cardiovascular parameters and body composition were also measured. RESULTS: There were significant improvements in Aix, AP (both P < 0.001) and SEVR (P = 0.021) in OSA patients on CPAP compared with subjects without OSA. Epworth scores (P < 0.001), systolic (P < 0.001) and mean arterial pressures (P = 0.002) improved with CPAP. Regression showed that CPAP was significantly associated with change in arterial stiffness from baseline. However, patients with OSA on CPAP continued to have increased arterial stiffness (Aix) (P < 0.001), AP (P = 0.028) and reduced SEVR (P = 0.002) relative to non-OSA patients. CONCLUSION: Although sleepiness and blood pressure improve with CPAP in severe obesity, CPAP alone is not sufficient to modify PWA measures to levels comparable with non-OSA patients. This supports a need for a multifaceted approach when managing cardiovascular risk in patients with severe obesity and obstructive sleep apnoea receiving CPAP therapy.

Serum urate and obstructive sleep apnoea in severe obesity.

Obstructive sleep apnoea (OSA) may increase the risk of hyperuricaemia and predispose to gout. The evidence for the effects of OSA on serum urate in severe obesity is limited. This study investigated whether OSA was associated with serum urate in severe obesity and whether continuous positive airway pressure (CPAP) treatment was associated with a fall in urate. Severely obese subjects without known OSA or gout were recruited. Baseline assessments included urate, metabolic parameters, spirometry and overnight polysomnography. OSA patients were initially naive to treatment and were offered CPAP. At follow-up, change in urate was compared between CPAP-treated and non-CPAP-treated subjects. A high urate was defined as greater than the median. Logistic regression was performed to identify associations between (1) OSA and high urate at baseline and (2) use of CPAP and change in urate at follow-up. In total, 92 subjects were recruited (61 (66%) OSA and 31 (34%) non-OSA). Median urate was 345 µmol/L. OSA was associated with high urate in females at baseline after adjusting for confounders (adjusted odds ratio ORadj = 10.2; 95% CI: 1.1, 93.5). At follow-up (14 months), 58 subjects (28 on CPAP and 30 not on CPAP) were reassessed. CPAP was significantly associated with a fall to a low urate category at follow-up ( = 0.017). Regression revealed a trend for a fall in urate category in the CPAP-treated group (ORadj = 9.3; 95% CI: 0.8, 97). Serum urate is associated with OSA in severely obese females and CPAP may reduce levels in patients with OSA. There may be a need to consider and assess for OSA in obese patients with hyperuricaemia and recurrent attacks of gout.

Urinary proteomics in obstructive sleep apnoea and obesity.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common complication of obesity and can have a substantial negative impact on a patient's quality of life and risk of cardiovascular disease. The aim of this case-control study was to undertake discovery profiling of urinary peptides using capillary electrophoresis-mass spectrometry (CE-MS) in obese subjects with and without OSA, without a history of coronary artery disease. MATERIALS AND METHODS: Urinary samples were analysed by CE-MS. Body composition and blood pressure measurements were recorded. Overnight polysomnography was conducted to confirm or refute OSA. OSA patients were naïve to continuous positive airway pressure treatment. RESULTS: Sixty-one subjects with OSA (age 47 ± 9 years, BMI 43 ± 8 kg/m(2)) and 31 controls (age 49 ± 10 years, BMI 40 ± 5 kg/m(2)) were studied; P = ns for age and BMI. Apnoea-hypopnoea Index was higher in patients with OSA (24 ± 18·6) than controls without OSA (non-OSA) (2·6 ± 1·1; P < 0·0001). Metabolic syndrome was present in 35 (57%) of those with OSA compared with 4 (13%) of controls (P < 0·0001). Twenty-four polypeptides were candidates for differential distribution (P < 0·01), although these differences did not reach significance after multiple testing. Sequences were determined for eight peptides demonstrating origins from collagens and fibrinogen alpha. CONCLUSIONS: In this study, we report for the first time, urinary proteomic profile analyses using CE-MS in OSA and non-OSA obese groups. The differences in urinary proteomic profiles prior to adjustment for multiple testing, with increased metabolic syndrome in obese OSA subjects, suggest that there may be a role for CE-MS in characterising urinary profiles in severely obese populations with OSA.

Obstructive sleep apnea is associated with increased arterial stiffness in severe obesity.

Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non-invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy-two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42 ± 7 kg m(-2) ), without obstructive sleep apnea (non-OSA) 25 (body mass index 40 ± 5 kg m(-2) )] were characterised using anthropometric, respiratory and cardio-metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non-OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P < 0.001), with significantly higher systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P = 0.004) than patients without obstructive sleep apnea (non-OSA). Arterial stiffness correlated with mean arterial blood pressure (P = 0.003) and obstructive sleep apnea severity (apnea-hypopnea index; P < 0.001). apnea-hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.

Psychometric and biomedical outcomes of glycated haemoglobin target-setting in adults with type 1 and type 2 diabetes: Protocol for a mixed-methods parallel-group randomised feasibility study.

BACKGROUND: The disease burden of diabetes can have wide-ranging implications on patients' psychological well-being and health-related quality of life. Glycated haemoglobin targets are commonly used to guide patient management in diabetes to reduce the future risk of developing diabetes complications, but little is known of the psychological impact of glycated haemoglobin target-setting. This protocol describes a study to determine the feasibility of evaluating psychological outcomes when setting explicit glycated haemoglobin targets in people with diabetes. METHODS: This single-centre randomised feasibility study will follow a mixed-methods approach across four sub-studies. In sub-study A, eligible adults (aged 18 and over) with type 1 or type 2 diabetes will complete baseline validated psychometric questionnaires evaluating health-related quality of life (EuroQoL-5D-5L), diabetes-related distress (Problem Areas In Diabetes), self-care (Summary of Diabetes Self-Care Activities), well-being (Well-Being Quetionnaire-12) and diabetes-related psychosocial self-efficacy (Diabetes Empowerment Scale-Long Form). Participants will be randomised to receive explicit glycated haemoglobin intervention targets 5mmol/mol above or below current glycated haemoglobin readings. Rates of eligibility, recruitment, retention and questionnaire response rate will be measured. Psychometric outcomes will be re-evaluated 3-months post-intervention. Sub-studies B and C will use qualitative semi-structured interviews to evaluate experiences, views and opinions of diabetes patients and healthcare professionals in relation to the acceptability of study processes, the use of glycated haemoglobin targets, the impact of diabetes on psychological well-being and, in sub-study D, barriers to participation in diabetes research. DISCUSSION: This mixed-methods study aims to provide a novel insight into the psychological implications of glycated haemoglobin target-setting for people with diabetes in secondary care, alongside testing the feasibility of undertaking a larger project of this nature. TRIAL REGISTRATION: The study is registered with the ISRCTN (registration number: 12461724; date registered: 11th June 2021). Protocol version: 2.0.5, 26th February 2021.

The individualisation of glycaemic targets in response to patient characteristics in type 2 diabetes: a scoping review.

BACKGROUND: Evidence and guidelines increasingly support an individualised approach to care for people with type 2 diabetes and individualisation of glycaemic targets in response to patient factors. METHODS: We undertook a scoping review of the literature for evidence of factors impacting upon glycated haemoglobin target individualisation in adults with type 2 diabetes. Data were analysed thematically with the themes inductively derived from article review. FINDINGS: Evidence suggests that presence of cardiovascular disease, hypoglycaemia unawareness, severe hypoglycaemia, limited life expectancy, advanced age, long diabetes duration, frailty, cognitive impairment, disability, extensive comorbidity, diabetes distress and patient preference should inform the setting of glycaemic targets. CONCLUSION: The management of people with diabetes is complex. In clinical practice, many patients will have a variety of factors that should be considered when personalising their care. Approaches to personalised care and glycaemic treatment targets should be undertaken as part of a shared decision-making process between physician and patient. Use of electronic records might enable greater efficiency and more widespread use of personalised care plans for people with diabetes.

Isolation and characterization of a psychropiezophilic alphaproteobacterium.

Cultivated psychropiezophilic (low-temperature- and high-pressure-adapted) bacteria are currently restricted to phylogenetically narrow groupings capable of growth under nutrient-replete conditions, limiting current knowledge of the extant functional attributes and evolutionary constraints of diverse microorganisms inhabiting the cold, deep ocean. This study documents the isolation of a deep-sea bacterium following dilution-to-extinction cultivation using a natural seawater medium at high hydrostatic pressure and low temperature. To our knowledge, this isolate, designated PRT1, is the slowest-growing (minimal doubling time, 36 h) and lowest cell density-producing (maximal densities of 5.0 × 106 cells ml⁻¹) piezophile yet obtained. Optimal growth was at 80 MPa, correlating with the depth of capture (8,350 m), and 10°C, with average cell sizes of 1.46 µm in length and 0.59 µm in width. Through detailed growth studies, we provide further evidence for the temperature-pressure dependence of the growth rate for deep-ocean bacteria. PRT1 was phylogenetically placed within the Roseobacter clade, a bacterial lineage known for widespread geographic distribution and assorted lifestyle strategies in the marine environment. Additionally, the gene transfer agent (GTA) g5 capsid protein gene was amplified from PRT1, indicating a potential mechanism for increased genetic diversification through horizontal gene transfer within the hadopelagic environment. This study provides a phylogenetically novel isolate for future investigations of high-pressure adaptation, expands the known physiological traits of cultivated members of the Roseobacter lineage, and demonstrates the feasibility of cultivating novel microbial members from the deep ocean using natural seawater.

Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy.

Diabetic patients undergoing hyperbaric oxygen therapies (HBO(2)T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post-HBO(2)T CD34(+) cell population contains two- to threefold higher levels of hypoxia inducible factors-1, -2, and -3, as well as thioredoxin-1 (p<0.003), than cells present in blood before HBO(2)T. Skin margins obtained from 2-day-old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor-1, and Trx-1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO(2)T (p<0.003). HBO(2)T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO(2)T and remains elevated for at least 20 hours. We conclude that HBO(2) T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.

Operative Nd:YAG laser plus postoperative hyperbaric oxygen reduces surgical morbidity after radical head and neck cancer surgery and complex reconstruction.

UNLABELLED: Complications after radical head and neck cancer surgery in irradiated patients are frequent and life-threatening. Hemorrhage, salivary fistulas, wound infections that expose the carotid sheath, among others, make these patients difficult management challenges in the ICU. We studied the effects of Nd:YAG laser surgery plus hyperbaric oxygen (HBO2) therapy on radical head and neck resections and complex reconstruction as a means of reducing postoperative morbidity and mortality. METHODS: 43 head and neck cancer patients were reviewed. Eight (STD) had standard surgery; 35 (YAG:HBO2) had Nd:YAG laser and postoperative HBO2. RESULTS: Age, staging, primary tumor site, sex, reconstruction procedure and transfusion did not differ between STD and YAG/HBO2. All STD and Nd:YAG/HBO2 patients were irradiated, median dosages 5,000 centi-Gray (cGy) and 7,000 cGy, respectively (p = 0.073). Median blood loss was 1,000 ml STD and 700 ml YAG/HBO2 (p = 0.046). There were no postoperative deaths. Major surgical site complications developed in 63% of the STD and 17% of the YAG/HBO2 patients (p = 0.017). All STD and 62% of YAG/HBO2 cancers recurred within 28 months of surgery (p = 0.152). Within the STD and YAG/HBO2 groups, 100% and 77% of deaths, respectively, were due to cancer. CONCLUSIONS: Combined Nd:YAG laser surgery and HBO2 reduces morbidity in radical head and neck cancer surgery. Recurrent disease and poor cancer survival remain common in this high-risk population.

Perspectives From a Regional Plastic Surgery Centre on Evidence for the Purported Link Between SGLT2 Inhibitors and Fournier's Gangrene.

Introduction: The recent report issued by the MHRA indicating an association of Sodium glucose linked transporter type 2 (SGLT2) Inhibitors with the contraction of Fournier's Gangrene (FG), has been drawn with insufficient supporting evidence and without an adequately powered study to make any meaningful assertions or recommendations. We aimed to look specifically at the currently available dataset used to link SGLT2 Inhibitors to FG and highlight what conclusions or inferences can meaningfully be made, in particular the power of any study that would be required to make sensible conclusions. Methods: World literature review of SGLT2 Inhibitors and FG was performed. With a subsequent 10-year review of cases of FG seen in a regional burns and plastics centre. Data was collected retrospectively from the coding department at Whiston Hospital for all patients with necrotising fasciitis. An electronic document management system was used to identify patients with FG specifically as well as their diabetes state and medication history. Results: Seventy-eight patients were admitted with FG, of whom 32 had diabetes mellitus (DM). Of those with DM none was taking an SGLT2 Inhibitor, 17 patients were taking metformin, a further nine patients were taking a second line medication and 14 required insulin injections. Discussions: DM is a known major risk factor for FG, which is clearly observed in our patient cohort. The risk of patients with DM developing FG is irrespective of the medication patients are taking. The current articles and reports published have little ground to claim an association between SGLT2 Inhibitors and FG and are missing the crucial message that needs to be conveyed to the public: that DM is a major risk factor for FG and patients suffering with diabetes need to be extra vigilant.

Alterations in mitochondrial respiration and reactive oxygen species in patients poisoned with carbon monoxide treated with hyperbaric oxygen.

BACKGROUND: Carbon monoxide (CO) poisoning is the leading cause of poisoning mortality and morbidity in the USA. Carboxyhemoglobin (COHb) levels are not predictive of severity or prognosis. At this time, the measurement of mitochondrial respiration may serve as a biomarker in CO poisoning. The primary objective of this study was to assess changes in mitochondrial function consisting of respiration and generation of reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) obtained from patients with CO poisoning. METHODS: PBMCs from patients having confirmed CO exposure treated with hyperbaric oxygen or HBO (CO group) and healthy controls (control group) were analyzed with high-resolution respirometry. PBMCs were placed in a 2-ml chamber at a final concentration of 3-4 × 106 cells/ml to simultaneously obtain both respiration and hydrogen peroxide (H2O2) production. In the CO group, we performed measurements before and after patients underwent their first HBO treatment. RESULTS: We enrolled a total of 17 subjects, including 7 subjects with confirmed CO poisoning and 10 subjects in the control group. The CO group included five (71.4%) men and two (28.6%) women having a median COHb of 28%. There was a significant decrease in respiration as measured in pmol O2 × s- 1 × 10- 6 PBMCs in the CO group (pre-HBO) when compared to the control group: maximal respiration (18.4 ± 2.4 versus 35.4 ± 2.8, P < 0.001); uncoupled Complex I respiration (19.8 ± 1.8 versus 41.1 ± 3.8, P < 0.001); uncoupled Complex I + II respiration (32.3 ± 3.2 versus 58.3 ± 3.1, P < 0.001); Complex IV respiration (43.5 ± 2.9 versus 63.6 ± 6.31, P < 0.05). There were also similar differences measured in the CO group before and after HBO treatment with an overall increase in respiration present after treatment. We also determined the rate of H2O2 production simultaneously with the measurement of respiration. There was an overall significant increase in the H2O2 production in the CO group after HBO treatment when compared to prior HBO treatment and the control group. CONCLUSIONS: In this study, PBMCs obtained from subjects with CO poisoning have an overall decrease in respiration (similar H2O2 production) when compared to controls. The inhibition of Complex IV respiration is from CO binding leading to a downstream decrease in respiration at other complexes. PBMCs obtained from CO-poisoned individuals immediately following initial HBO therapy displayed an overall increase in both respiration and H2O2 production. The study findings demonstrate that treatment with HBO resulted in improved cellular respiration but a higher H2O2 production. It is unclear if the increased production of H2O2 in HBO treatment is detrimental.

A preliminary study in the alterations of mitochondrial respiration in patients with carbon monoxide poisoning measured in blood cells.

OBJECTIVES: Carbon monoxide (CO) is a colorless and odorless gas responsible for poisoning mortality and morbidity in the United States. At this time, there is no reliable method to predict the severity of poisoning or clinical prognosis following CO exposure. Whole blood cells, such as peripheral blood mononuclear cells (PBMCs) and platelets, have been explored for their potential use to act as sensitive biomarkers for mitochondrial dysfunction which may have a role in CO poisoning. DESIGN: The objective of this study was to measure mitochondrial respiration using intact cells obtained from patients exposed to CO as a potential biomarker for mitochondrial inhibition with results that can be obtained in a time frame useful for guiding clinical care. This was a prospective, observational pilot study performed from July 2015 to July 2016 at a single academic tertiary care center that is the location of the region's only multi chamber hyperbaric. MEASUREMENTS: Clinical characteristics, patient demographics, mitochondrial respiration and outcomes were recorded. MAIN RESULTS: There were 7 patients enrolled with a mean COHb level 26.8 ± 10 and with a mean lactate of 1.1 ± 0.4 mmol/L. All 7 CO exposures were related to heat generators used during winter months with two deaths. There was a positive correlation between maximal respiration and COHb levels with both high maximal respiration and high spare respiratory capacity correlating with a high COHb level. There was a subset of PBMCs (n = 4) that were analyzed for Complex IV (cytochrome c oxidase) activity. CONCLUSIONS: In this pilot study, measurements can be performed in an appropriate timeline for clinical care with potential to serve as a prognostic marker. Further work is necessary to develop high-resolution respirometry as a clinical tool for assessing the severity of illness and guiding therapy.

Exploring the impact of feedback on prescribing error rates: a pilot study.

Background Prescribing errors are prevalent in hospital settings with feedback identified as one potential error reduction strategy. Hospital pharmacists work alongside prescribers at ward level and are credible facilitators of prescribing error feedback. A formalised programme of pharmacist-led prescribing error feedback was designed and implemented Objective To determine the impact of the feedback intervention on prescribing error rates. Method Prospective prescribing audits were undertaken at baseline for control (n = 11) and intervention group (n = 10) prescribers. The intervention group received pharmacist-led, individualised constructive feedback on their prescribing, whilst the control group continued with existing practice. Prescribing was re-audited following 3-months of the intervention. Data were analysed using chi-squared and independent t-tests. Results Error frequency (123/641 intervention and 121/649 control) was comparable between groups at baseline (p = 0.819) with significant differences (90/1677 intervention and 236/984 control) post intervention (p = <0.005). Prescribing error rates were lower in the intervention group (mean change of -11.5%) and higher in the control group (mean change of +5.9%) following the intervention, with a mean significant difference of 17.4% (SD 4.7, 95% CI, -27.3 to -7.6), t = -3.694, p < 0.05, between groups. Conclusion Pharmacist-led prescribing error feedback positively influences prescribing. This intervention shows promise for wider application in hospital settings to optimise patient safety.

Identification of Free-Living and Particle-Associated Microbial Communities Present in Hadal Regions of the Mariana Trench.

Relatively few studies have described the microbial populations present in ultra-deep hadal environments, largely as a result of difficulties associated with sampling. Here we report Illumina-tag V6 16S rRNA sequence-based analyses of the free-living and particle-associated microbial communities recovered from locations within two of the deepest hadal sites on Earth, the Challenger Deep (10,918 meters below surface-mbs) and the Sirena Deep (10,667 mbs) within the Mariana Trench, as well as one control site (Ulithi Atoll, 761 mbs). Seawater samples were collected using an autonomous lander positioned ~1 m above the seafloor. The bacterial populations within the Mariana Trench bottom water samples were dissimilar to other deep-sea microbial communities, though with overlap with those of diffuse flow hydrothermal vents and deep-subsurface locations. Distinct particle-associated and free-living bacterial communities were found to exist. The hadal bacterial populations were also markedly different from one another, indicating the likelihood of different chemical conditions at the two sites. In contrast to the bacteria, the hadal archaeal communities were more similar to other less deep datasets and to each other due to an abundance of cosmopolitan deep-sea taxa. The hadal communities were enriched in 34 bacterial and 4 archaeal operational taxonomic units (OTUs) including members of the Gammaproteobacteria, Epsilonproteobacteria, Marinimicrobia, Cyanobacteria, Deltaproteobacteria, Gemmatimonadetes, Atribacteria, Spirochaetes, and Euryarchaeota. Sequences matching cultivated piezophiles were notably enriched in the Challenger Deep, especially within the particle-associated fraction, and were found in higher abundances than in other hadal studies, where they were either far less prevalent or missing. Our results indicate the importance of heterotrophy, sulfur-cycling, and methane and hydrogen utilization within the bottom waters of the deeper regions of the Mariana Trench, and highlight novel community features of these extreme habitats.