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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Urinary proteomic profiling in severe obesity and obstructive sleep apnoea with CPAP treatment.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in obesity and is associated with cardiovascular and metabolic complications. Continuous positive airway pressure (CPAP) in OSA may lead to physiological changes reflected in the urinary proteome. The aim of this study was to characterise the urinary proteome in severely obese adult subjects with OSA who were receiving CPAP compared with severely obese subjects without OSA. METHODS: Severely obese subjects with and without OSA were recruited. Subjects with OSA were receiving CPAP. Body composition and blood pressure measurements were recorded. Urinary samples were analysed by Capillary Electrophoresis-Mass Spectrometry (CE-MS). RESULTS: Twenty-seven subjects with OSA-on-CPAP (age 49±7years, BMI 43±7 kg/m(2)) and 25 controls without OSA (age 52±9years, BMI 39±4 kg/m(2)) were studied. Age and BMI were not significantly different between groups. Mean CPAP use for OSA patients was 14.5±1.0 months. Metabolic syndrome was present in 14(52%) of those with OSA compared with 6(24%) of controls (p=0.039). A urinary proteome comprising 15 peptides was identified showing differential expression between the groups (p<0.01). Although correction for multiple testing did not reach significance, sequences were determined for 8 peptides demonstrating origins from collagens, fibrinogen beta chain and T-cadherin that may be associated with underlying cardiovascular disease mechanisms in OSA. CONCLUSIONS: The urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA.

Association of microparticles and neutrophil activation with decompression sickness.

Decompression sickness (DCS) is a systemic disorder, assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles (MPs)--vesicular structures with diameters of 0.1-1.0 µm--have been implicated, but data in human divers have been lacking. We hypothesized that the number of blood-borne, Annexin V-positive MPs and neutrophil activation, assessed as surface MPO staining, would differ between self-contained underwater breathing-apparatus divers suffering from DCS vs. asymptomatic divers. Blood was analyzed from 280 divers who had been exposed to maximum depths from 7 to 105 meters; 185 were control/asymptomatic divers, and 90 were diagnosed with DCS. Elevations of MPs and neutrophil activation occurred in all divers but normalized within 24 h in those who were asymptomatic. MPs, bearing the following proteins: CD66b, CD41, CD31, CD142, CD235, and von Willebrand factor, were between 2.4- and 11.7-fold higher in blood from divers with DCS vs. asymptomatic divers, matched for time of sample acquisition, maximum diving depth, and breathing gas. Multiple logistic regression analysis documented significant associations (P < 0.001) between DCS and MPs and for neutrophil MPO staining. Effect estimates were not altered by gender, body mass index, use of nonsteroidal anti-inflammatory agents, or emergency oxygen treatment and were modestly influenced by divers' age, choice of breathing gas during diving, maximum diving depth, and whether repetitive diving had been performed. There were no significant associations between DCS and number of MPs without surface proteins listed above. We conclude that MP production and neutrophil activation exhibit strong associations with DCS.

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.

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.

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.

CD34+/CD45-dim stem cell mobilization by hyperbaric oxygen - changes with oxygen dosage.

Because hyperbaric oxygen treatment mobilizes bone marrow derived-stem/progenitor cells by a free radical mediated mechanism, we hypothesized that there may be differences in mobilization efficiency based on exposure to different oxygen partial pressures. Blood from twenty consecutive patients was obtained before and after the 1st, 10th and 20th treatment at two clinical centers using protocols involving exposures to oxygen at either 2.0 or 2.5 atmospheres absolute (ATA). Post-treatment values of CD34+, CD45-dim leukocytes were always 2-fold greater than the pre-treatment values for both protocols. Values for those treated at 2.5 ATA were significantly greater than those treated at 2.0 ATA by factors of 1.9 to 3-fold after the 10th and before and after the 20th treatments. Intracellular content of hypoxia inducible factors -1, -2, and -3, thioredoxin-1 and poly-ADP-ribose polymerase assessed in permeabilized CD34+ cells with fluorophore-conjugated antibodies were twice as high in all post- versus pre-treatment samples with no significant differences between 2.0 and 2.5 ATA protocols. We conclude that putative progenitor cell mobilization is higher with 2.5 versus 2.0 ATA treatments, and all newly mobilized cells exhibit higher concentrations of an array of regulatory proteins.

Low dietary sodium in diabetes nephropathy.

In a meta-analysis that investigated the effects of dietary sodium restriction in diabetes nephropathy, although blood pressure fell, there were significant increases in plasma renin and aldosterone levels. In this article, we hypothesise that in diabetic nephropathy, ACE-I or ARB treatment attenuates any rise in RAS hormones that might result from dietary salt restriction and that the beneficial effects of the salt restriction such as a lower blood pressure outweigh any potentially negative consequences of RAS activation such as a rise in intraglomerular pressure because of the synergistic effects of sodium restriction and RAS antagonist therapy.

Effect of a cooked meat meal on serum creatinine and estimated glomerular filtration rate in diabetes-related kidney disease.

OBJECTIVE: Fasting is not routinely recommended for renal function tests, despite the known effects of cooked meat on creatinine. We therefore studied variation in creatinine and estimated glomerular filtration rate (eGFR) after a standardized cooked meat meal in 80 subjects: healthy volunteers and diabetic patients with chronic kidney disease (CKD) stages 1 and 2, 3a, 3b, and 4 (n = 16/group). RESEARCH DESIGN AND METHODS: The interventions were a standardized cooked meat and a nonmeat meal, each providing ∼54 g protein, together with 250 mL water, on separate days. Fasting and postprandial blood samples at 1, 2, and 4 h were drawn for creatinine measurement using a kinetic alkaline picrate assay on an Olympus AU640 analyzer. The modified four-variable Modification of Diet in Renal Disease equation traceable to isotope dilution mass spectrometry creatinine was used to calculate eGFR. RESULTS: Consumption of a standardized cooked meat meal significantly increased serum creatinine and resulted in significant fall in eGFR in all stages of CKD studied; 6 of 16 CKD 3a patients were misclassified as CKD 3b. This effect of cooked meat on serum creatinine disappears after 12 h of fasting in all study participants. CONCLUSIONS: Creatine in meat is converted to creatinine on cooking, which is absorbed, causing significant increases in serum creatinine. This could impact management, as threshold for commencing and withdrawing certain medications and expensive investigations is defined by eGFR. eGFR calculated using fasting serum creatinine would be a better reflection of kidney function in these patients.