Synergistic lignin degradation between Phanerochaete chrysosporium and Fenton chemistry is mediated through iron cycling and ligninolytic enzyme induction.

Removal of recalcitrant lignin from wastewater remains a critical bottleneck in multiple aspects relating to microbial carbon cycling ranging from incomplete treatment of biosolids during wastewater treatment to limited conversion of biomass feedstock to biofuels. Based on previous studies showing that the white rot fungus Phanerochaete chrysosporium and Fenton chemistry synergistically degrade lignin, we sought to determine optimum levels of Fenton addition and the mechanisms underlying this synergy. We tested the extent of degradation of lignin under different ratios of Fenton reagents and found that relatively low levels of H2O2 and Fe(II) enhanced fungal lignin degradation, achieving 80.4 ± 1.61 % lignin degradation at 1.5 mM H2O2 and 0.3 mM Fe(II). Using a combination of whole-transcriptome sequencing and iron speciation assays, we determined that at these concentrations, Fenton chemistry induced the upregulation of 80 differentially expressed genes in P. ch including several oxidative enzymes. This study underlines the importance of non-canonical, auxiliary lignin-degrading pathways in the synergy between white rot fungi and Fenton chemistry in lignin degradation. We also found that, relative to the abiotic control, P. ch. increases the availability of Fe(II) for the production of hydroxyl radicals in the Fenton reaction by recycling Fe(III) (p < 0.001), decreasing the Fe(II) inputs necessary for lignin degradation via the Fenton reaction.

Understanding barriers to adherence to home exercise programs in patients with musculoskeletal neck pain.

BACKGROUND: Home exercise program (HEP) prescription is commonplace in physical therapy (PT). Adherence to HEPs is generally poor, with non-adherence as high as 70%. Poor adherence may negatively impact outcomes. OBJECTIVES: To (i) qualitatively assess patients' thoughts and beliefs regarding HEP performance and (ii) quantitatively define the relationship between adherence to HEPs and functional outcomes and identify variables that impact adherence. DESIGN: Mixed-methods. METHOD: Part 1 involved semi-structured interviews with patients attending PT for neck pain. Responses were assessed using thematic analysis. Part 2 involved a retrospective chart review of patients seen in outpatient PT for neck pain. Between-group (adherent and non-adherent) differences in functional scores were analyzed using a linear mixed model. Sex, age, and functional score data was entered into a regression model to explore their ability to predict adherence. RESULTS: 25 participants were interviewed. Qualitative analysis revealed the following themes associated with adherence to a HEP: (i) prior PT, (ii) observability of outcomes, (iii) expectations of PT, and (iv) experience of pain. Retrospective data from 187 patients was analyzed. Functional scores at discharge were significantly higher (p = 0.03, mean difference = 12.4) in the adherent group. Age (OR = 0.98; 95% CI = 0.93-1.02), male sex (OR = 1.23; 95% CI = 0.22-6.91), and functional scores at intake (OR = 0.99; 95% CI = 0.92-1.07) were not significant predictors of non-adherence. CONCLUSIONS: Individual patient experiences such as delayed improvement in symptoms and/or experience of pain associated with HEP performance may contribute to poor adherence to HEPs. Adherence to a HEP was associated with superior functional outcomes compared to non-adherence. Age, sex, and functional scores were not predictors of non-adherence.

Home Exercise Programs Are Infrequently Prescribed in Trials of Supervised Exercise for Individuals With Low Back Pain: A Scoping Review of 292 Randomized Controlled Trials.

OBJECTIVES: To (1) determine how often home exercise programs (HEPs) are prescribed in supervised exercise trials for low back pain (LBP) and (2) describe characteristics of the HEP programs (design, purpose, dose, and adherence). DESIGN: Scoping review. LITERATURE SEARCH: PubMed, CINAHL, and Ovid MEDLINE were searched from January 1, 2010, to August 17, 2021. STUDY SELECTION CRITERIA: Randomized controlled trials that included adults with LBP who received exercise interventions. DATA SYNTHESIS: The presence or absence of a prescribed HEP and any details of the HEP including design, dose, and adherence were extracted and summarized. RESULTS: Of 2689 potentially relevant trials, 292 were eligible for inclusion. Ninety-four trials (32%) included a HEP. The most commonly prescribed home exercises were core stability, trunk strengthening, and motor control exercises. There was great variation in the frequency and duration with which HEPs were prescribed. Adherence to HEPs was measured in fewer than half of the trials, and the methods for measuring adherence were inconsistent. Adherence to HEPs ranged from 29% to 82% in the 21 trials that reported adherence. CONCLUSION: Home exercise programs are not regularly prescribed in supervised exercise trials for LBP. There was considerable variation in prescribing HEPs and monitoring exercise adherence in trials of exercise-based treatments for adults with LBP. There is no consistent method used to measure participants' adherence to HEPs, and adherence percentages vary widely. J Orthop Sports Phys Ther 2023;53(3):120-142. Epub: 16 January 2023. doi:10.2519/jospt.2023.11448.

Fundamentals of OA. An initiative of Osteoarthritis and Cartilage. Obesity and metabolic factors in OA.

OBJECTIVE: Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation. DESIGN: This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms. RESULTS: Metabolic syndrome and its components are strongly associated with OA. However, evidence for a causal relationship is context dependent, varying by joint, gender, diagnostic criteria, and demographics, with additional environmental and genetic interactions yet to be fully defined. Importantly, some aspects of the etiology of obesity-induced OA appear to be distinct between men and women, especially regarding the role of adipose tissue. Metabolomic analyses of serum and synovial fluid have identified potential diagnostic biomarkers of knee OA and prognostic biomarkers of disease progression. Connecting these biomarkers to cellular pathophysiology will require future in vivo studies of joint tissue metabolism. Such studies will help reveal when a metabolic process or a metabolite itself is a causal factor in disease progression. Current evidence points towards impaired chondrocyte metabolic homeostasis and metabolic-immune dysregulation as likely factors connecting obesity to the increased risk of OA. CONCLUSIONS: A deeper understanding of how obesity alters metabolic and inflammatory pathways in synovial joint tissues is expected to provide new therapeutic targets and an improved definition of "metabolic" and "obesity" OA phenotypes.

Can a Reduction in Revision Rates Make Robotic Total Knee Arthroplasty Cost Neutral With Manual Total Knee Arthroplasty at Ten-Year Follow-Up? An Episode Cost Analysis.

BACKGROUND: Advocates of robotic total knee arthroplasty (RTKA) suggest that its greater cost may be recaptured through a reduction in revision rates. We sought to determine what reduction in revision TKA would be required for RTKA to become cost neutral with manual TKA (MTKA). METHODS: Episode costs were determined for 2392 RTKAs and 2392 MTKAs. Mean total cost of revision TKA in our health system was identified. Episode cost difference of the RTKA and MTKA cohorts was divided by the mean cost of revision TKA to estimate the reduction in revisions required to make RTKA cost neutral with MTKA. The National Joint Registry was consulted to determine the cumulative revision rate for the implant used in this study. RESULTS: Episode cost for the RTKA cohort was $5.7M greater than MTKA. Mean acute stay cost for revision TKA was $20,972, but post-acute costs were not available. If post-acute costs for revision TKA are conservatively estimated at 50% of episode cost (ie, episode cost = $41,944), 131 revision TKAs would need to be prevented in the RTKA cohort to make it cost neutral with MTKA. The National Joint Registry cumulative revision rate for this implant is 3.37% at 10 years, thus only 81 revisions would be expected per cohort. CONCLUSION: Our data suggest that it is not possible for RTKA to achieve cost parity with MTKA through a reduction in revision rate alone. Future price reductions may make the cost comparison more favorable. In addition, demonstration of improved patient outcomes would undeniably add value to RTKA and change the analysis.

Robotic Versus Manual Total Knee Arthroplasty in High Volume Surgeons: A Comparison of Cost and Quality Metrics.

BACKGROUND: Robotic-assisted total knee arthroplasty (RTKA) was introduced to improve surgical accuracy and patient outcomes. However, RTKA may also increase operating time and add cost to TKA. This study sought to compare the differences in cost and quality measures between manual TKA (MTKA) and RTKA METHODS: All MTKAs and RTKAs performed between January 1, 2017 and December 31, 2019, by 6 high volume surgeons in each cohort, were retrospectively reviewed. Cohorts were propensity score matched. Operative time, length of stay (LOS), total direct cost, 90-day complications, utilization of postacute services, and 30-day readmissions were studied. RESULTS: After one-to-one matching, 2392 MTKAs and 2392 RTKAs were studied. In-room/out-of-room operating time was longer for RTKA (139 minutes) than for MTKA (107 minutes) P < .0001, as was procedure time (RTKA 78 minutes; MTKA 70 minutes), P < .0001. Median LOS was equal for MTKA and RTKA (33 hours). Total cost per case was greater for RTKA ($11,615) than MTKA ($8674), P < .0001. Home health care was utilized more frequently after RTKA (38%) than MTKA (29%), P < .0001. There was no significant difference in 90-day complication rates. Thirty-day readmissions occurred more often after MTKA (4.9%) than RTKA (1.2%), P < .0001. CONCLUSION: RTKA was a longer and costlier procedure than MTKA for experienced surgeons, without clinically significant differences in LOS or complications. Home health care was utilized more often after RTKA, but fewer readmissions occurred after RTKA. Longer term follow-up and functional outcome studies are required to determine if the greater cost of RTKA is offset by lower revision rates and/or improved functional results.

Effects of long-term exercise and a high-fat diet on synovial fluid metabolomics and joint structural phenotypes in mice: an integrated network analysis.

OBJECTIVE: To explore how systemic factors that modify knee osteoarthritis risk are connected to 'whole-joint' structural changes by evaluating the effects of high-fat diet and wheel running exercise on synovial fluid (SF) metabolomics. METHODS: Male mice were fed a defined control or high-fat (60% kcal fat) diet from 6 to 52 weeks of age, and half the animals were housed with running wheels from 26 to 52 weeks of age (n = 9-13 per group). Joint tissue structure and osteoarthritis pathology were evaluated by histology and micro-computed tomography. Systemic metabolic and inflammatory changes were evaluated by body composition, glucose tolerance testing, and serum biomarkers. SF metabolites were analyzed by high performance-liquid chromatography mass spectrometry. We built correlation-based network models to evaluate the connectivity between systemic and local metabolic biomarkers and osteoarthritis structural pathology within each experimental group. RESULTS: High-fat diet caused moderate osteoarthritis, including cartilage pathology, synovitis and increased subchondral bone density. In contrast, voluntary exercise had a negligible effect on these joint structure components. 1,412 SF metabolite features were detected, with high-fat sedentary mice being the most distinct. Diet and activity uniquely altered SF metabolites attributed to amino acids, lipids, and steroids. Notably, high-fat diet increased network connections to systemic biomarkers such as interleukin-1ß and glucose intolerance. In contrast, exercise increased local joint-level network connections, especially among subchondral bone features and SF metabolites. CONCLUSION: Network mapping showed that obesity strengthened SF metabolite links to blood glucose and inflammation, whereas exercise strengthened SF metabolite links to subchondral bone structure.

A comparison of artificial urinary sphincter outcomes after primary implantation and first revision surgery.

OBJECTIVE: The artificial urinary sphincter (AUS) is the gold standard for severe male stress urinary incontinence, though evaluations of specific predictors for device outcomes are sparse. We sought to compare outcomes between primary and revision AUS surgery for non-infectious failures. METHODS: We identified 2045 consecutive AUS surgeries at Mayo Clinic (Rochester, MN, USA) from 1983 to 2013. Of these, 1079 were primary AUS implantations and 281 were initial revision surgeries, which comprised our study group. Device survival rates, including overall and specific rates for device infection/erosion, urethral atrophy and mechanical failure, were compared between primary AUS placements versus revision surgeries. Patient follow-up was obtained through office examination, written correspondence, or telephone correspondence. RESULTS: During the study period, 1079 (79.3%) patients had a primary AUS placement and 281 (20.7%) patients underwent a first revision surgery for mechanical failure or urethral atrophy. Patients undergoing revision surgery were found to have adverse 1- and 5-year AUS device survival on Kaplan-Meier analysis, 90% vs. 85% and 74% vs. 61%, respectively (p<0.001). Specifically, revision surgery was associated with a significantly increased cumulative incidence of explantation for device infection/urethral erosion (4.2% vs. 7.5% at 1 year; p=0.02), with similar rates of repeat surgery for mechanical failure (p=0.43) and urethral atrophy (p=0.77). CONCLUSIONS: Our findings suggest a significantly higher rate of overall device failure following revision AUS surgery, which is likely secondary to an increased rate of infection/urethral erosion events.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Novel protein pathways in development and progression of pulmonary sarcoidosis.

Pulmonary involvement occurs in up to 95% of sarcoidosis cases. In this pilot study, we examine lung compartment-specific protein expression to identify pathways linked to development and progression of pulmonary sarcoidosis. We characterized bronchoalveolar lavage (BAL) cells and fluid (BALF) proteins in recently diagnosed sarcoidosis cases. We identified 4,306 proteins in BAL cells, of which 272 proteins were differentially expressed in sarcoidosis compared to controls. These proteins map to novel pathways such as integrin-linked kinase and IL-8 signaling and previously implicated pathways in sarcoidosis, including phagosome maturation, clathrin-mediated endocytic signaling and redox balance. In the BALF, the differentially expressed proteins map to several pathways identified in the BAL cells. The differentially expressed BALF proteins also map to aryl hydrocarbon signaling, communication between innate and adaptive immune response, integrin, PTEN and phospholipase C signaling, serotonin and tryptophan metabolism, autophagy, and B cell receptor signaling. Additional pathways that were different between progressive and non-progressive sarcoidosis in the BALF included CD28 signaling and PFKFB4 signaling. Our studies demonstrate the power of contemporary proteomics to reveal novel mechanisms operational in sarcoidosis. Application of our workflows in well-phenotyped large cohorts maybe beneficial to identify biomarkers for diagnosis and prognosis and therapeutically tenable molecular mechanisms.

Use of aspirin to intentionally induce gastrointestinal tract barrier dysfunction in feedlot cattle.

Stress negatively affects the gastrointestinal tract (GIT) barrier function, resulting in compromised animal health. A deeper understanding of how diet and stress impacts the GIT barrier function in feedlot cattle is needed. Aspirin decreases mucus production and mucosal repair in the GIT and could be used as a model for GIT barrier dysfunction research. The objective of this study was to evaluate the effectiveness of aspirin to induce GIT barrier dysfunction in beef cattle. In experiment 1, sixteen crossbred heifers (425.0 ± 8.6 kg) were allotted to 0, 50, 100, or 200 mg/kg body weight (BW) aspirin doses based on BW. Experiment 1 consisted of two periods separated by 4 wk where four heifers per treatment received the same aspirin dose during each period. Heifers were fed a 49.4% corn silage and 50.6% concentrate diet. The 200 mg/kg BW aspirin treatment was dosed as a 100 mg/kg BW aspirin oral bolus 36 and 24 h prior to Cr-ethylenediaminetetraacetic acid (EDTA) dosing (1 liter; 180 mM). The 50 and 100 mg/kg BW aspirin treatments were dosed as an oral bolus 24 h prior to Cr-EDTA dosing. Urine was collected every 3 h for 48 h and analyzed for Cr. Serum was collected at 0 and 48 h and analyzed for lipopolysaccharide-binding protein (LBP), interleukin-6, serum amyloid A (SAA), haptoglobin, and aspartate aminotransferase. In experiment 2, sixteen crossbred steers (576.0 ± 14.2 kg) fed a similar diet were allotted by BW to the 0 and 200 mg/kg BW aspirin treatments (eight steers/treatment) and were slaughtered 24 h after the last dose. Jejunal tissues were collected, and claudin (CLDN) 1, 2, and 3, occludin, and zonula occludens tight junction messenger ribonucleic acid (mRNA) expression was determined. Data were analyzed using the MIXED procedure of SAS. Urinary Cr excretion increased linearly at hours 3, 6, 9, and 12 (P ≤ 0.04) as aspirin dose increased from 0 to 200 mg/kg. Aspirin linearly increased Cr absorption (P = 0.02) and elimination (P = 0.04) rates and linearly decreased mean retention time of Cr (P = 0.02). Aspirin increased SAA (P = 0.04) and tended to increase LBP (P = 0.09) in serum but did not affect any other serum inflammatory marker (P ≥ 0.19). Aspirin tended to increase jejunal CLDN-1 mRNA expression (P = 0.10) but did not affect the mRNA expression of other genes regulating tight junction function (P ≥ 0.20). Results from this study indicate that aspirin disrupts the GIT barrier function in beef cattle and has a potential as a model in GIT permeability research.

A Rare Case of Infertility: SRY Positive 46, XX Testicular Disorder of Sexual Differentiation.

Aim To highlight the complexity of infertility causes by describing the rare case of a man with a testicular disorder of sexual differentiation. Diagnosis A 33 years old Caucasian male presented with a 3-year-old history of primary infertility. His investigations revealed a low testosterone and a raised LH and FSH levels. A sample sent for sperm analysis revealed azoospermia. Chromosomal analysis and karyotyping revealed a 46 XX SRY positive karyotype. Treatment The patient was initiated on testosterone replacement and on calcium/vitamin D supplements. Conclusion Fertility evaluation requires complex assessments and a broad knowledge of possible causes.

Insertional characteristics of three types of transfixation pin taps in third metacarpal bones from equine cadavers.

OBJECTIVE: To compare heat generation and mechanical bone damage achieved with 2 tapered and 1 cylindrical transfixation pin taps in third metacarpal bones from equine cadavers. SAMPLE: 18 pairs (36 specimens) of third metacarpal bones from euthanized horses with no known metacarpal disease. PROCEDURES: In each bone, an investigator drilled 3 holes for placement of a 6.3-mm cylindrical transfixation pin, a 6.3-mm tapered pin using a prototype tapered tap, and a 6.3-mm tapered pin using a revised tapered tap. One bone of each pair was tapped by hand and the other with an electric drill. Temperatures of the drill bits, reamers, and taps were measured and used to compare heat generation among tap groups and tapping methods (hand vs power tapping). Macrodamage (all bone pairs) and microdamage (6 bone pairs) were assessed. RESULTS: The revised tapered tap resulted in less heat generation and less total thread microdamage, compared with the prototype tapered and cylindrical taps. Power tapping created less bone damage but higher temperatures than did hand tapping for all bone groups. CONCLUSIONS AND CLINICAL RELEVANCE: The revised tap design for tapered pin insertion was superior to the prototype tap design and yielded similar or less bone damage than achieved with cylindrical pin insertion in equine third metacarpal bone specimens. We recommend careful hand tapping for tapered pin insertion rather than power tapping, which generated greater heat. The revised tapered tap could be expected to perform better than a cylindrical pin tap in terms of thermal and mechanical microdamage and should be used for insertion of tapered transfixation pins.

GC-MS method for metabolic profiling of mouse femoral head articular cartilage reveals distinct effects of tissue culture and development.

OBJECTIVE: The metabolic profile of cartilage is important to define as it relates to both normal and pathophysiological conditions. Our aim was to develop a precise, high-throughput method for gas/chromatography-mass/spectrometry (GC-MS) semi-targeted metabolic profiling of mouse cartilage. METHOD: Femoral head (hip) cartilage was isolated from 5- and 15-week-old male C57BL/6J mice immediately after death for in vivo analyses. In vitro conditions were evaluated in 5-week-old samples cultured ±10% fetal bovine serum (FBS). We optimized cartilage processing for GC-MS analysis and evaluated group-specific differences by multivariate and parametric statistical analyses. RESULTS: 55 metabolites were identified in pooled cartilage (4 animals per sample), with 29 metabolites shared between in vivo and in vitro conditions. Multivariate analysis of these common metabolites demonstrated that culturing explants was the strongest factor altering cartilage metabolism, followed by age and serum starvation. In vitro culture altered the relative abundance of specific metabolites; whereas, cartilage development between five and 15-weeks of age reduced the levels of 36 out of 43 metabolites >2-fold, especially in TCA cycle and alanine, aspartate, and glutamate pathways. In vitro serum starvation depleted six out of 41 metabolites. CONCLUSION: This study describes the first GC-MS method for mouse cartilage metabolite identification and quantification. We observed fundamental differences in femoral head cartilage metabolic profiles between in vivo and in vitro conditions, suggesting opportunities to optimize in vitro conditions for studying cartilage metabolism. In addition, the reductions in TCA cycle and amino acid metabolites during cartilage maturation illustrate the plasticity of chondrocyte metabolism during development.

Characterization of Methyl-Functionalized Silica Nanosprings for Superhydrophobic and Defrosting Coatings.

Thin non-perfluoroalkoxy superhydrophobic coatings are desirable for heat exchangers because of their lower thermal resistance and reduced environmental concerns. Coatings requirements must also include robustness and longevity and facilitate high defrosting rates in refrigeration applications to warrant their adoption and use. Methyl-functionalized silica nanosprings (SN) possess water droplet static contact angles above 160° with contact angle hysteresis values as low as 6.9° for a sub-micrometer-thick coating. The methyl functional groups render the silica surface hydrophobic, whereas the geometrical and topographical characteristics of the nanosprings make it super-hydrophobic. Results show that SN are capable of removing 95% of the frost from the surface at a lower temperature than the base aluminum substrate. The sub-micrometer SN coating also decreases the time to defrost by ≈1.5 times and can withstand more than 20 frosting-defrosting cycles in a high humidity environment akin to real working conditions for heat exchangers.

Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension.

Introduction Hyperglycaemia increases succinate concentrations and succinate receptor activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin values and activation of the renin-angiotensin-aldosterone system in patients with type 2 diabetes mellitus and hypertension. Methods A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015. Participants ( n = 66) were identified following interrogation of the electronic database for patients with type 2 diabetes mellitus. Baseline clinical demographics, aldosterone, plasma renin activity, direct renin concentration, urea and electrolytes, glycated haemoglobin, cholesterol, urine sodium and albumin creatinine ratio were recorded. Results There was a significant positive linear correlation between glycated haemoglobin and renin (both plasma renin activity [ P = 0.002] and direct renin concentration [ P = 0.008]) and between serum creatinine and aldosterone measured using both radioimmunoassay ( P = 0.008) and immunochemiluminometric assay ( P = 0.008). A significant negative linear correlation was demonstrated between serum sodium and plasma renin activity ( P = 0.005) and direct renin concentration ( P = 0.015) and between estimated glomerular filtration rate and aldosterone measured using radioimmunoassay ( P = 0.02) and immunochemiluminometric assay ( P = 0.016). A significant negative linear correlation existed between urine sodium and plasma renin activity ( P = 0.04) and aldosterone measured using radioimmunoassay ( P = 0.045). Conclusions There is a direct positive association between glycaemic control and renin. We advocate for renin measurement to be part of the diabetologist's armamentarium to assess, guide and optimize therapeutic strategies in patients with diabetes.

Screening for primary aldosteronism using the newly developed IDS-iSYS® automated assay system.

BACKGROUND: The recommended approach to screening for primary aldosteronism (PA) in at-risk populations is to determine the ratio of aldosterone concentration (serum (SAC)/plasma (PAC)) to renin measured in plasma as activity (PRA) or concentration (DRC). However, lack of assay standardisation mandates the need for method-specific decision thresholds and clinical validation in the local population. AIM: The study objective was to establish method-specific aldosterone: renin ratio (ARR) cut-offs for PA in men and women using the IDS-iSYS® assay system (IDS plc). METHODS: A prospective cohort study design was used. PAC and DRC were measured immunochemically in ethylenediamine-tetraacetic acid (EDTA) plasma on the IDS-iSYS® instrument. RESULTS: A total of 437 subjects (218 men, 219 women) were recruited including: healthy normotensive volunteers (n=266) and women taking the oral contraceptive pill (OCP; n=15); patients with essential hypertension (EH; n=128); confirmed PA (n=16); adrenal cortical carcinoma (ACC; n=3); Addison's disease (AD; n=4) and phaeochromocytoma/paraganglioma (PPGL; n=5). In this population, an ARR cut-off at >37.4 pmol/mIU provided 100% diagnostic sensitivity, 96% specificity and positive likelihood ratio for PA of 23:1. When the ARR decision threshold was stratified according to gender, a cut-off of >26.1 pmol/mIU in men and >113.6 pmol/mIU in women resulted in diagnostic sensitivity and specificity of 100%. CONCLUSION: This study demonstrates that decision thresholds for PA should not only be method-specific but also gender-specific. However, given the small number of PA patients (n=16), particularly women (n=4), further validation through a prospective study with a larger PA cohort is required before the thresholds presented here could be recommended for routine clinical use.