Liraglutide enhances insulin secretion and prolongs the remission period in adults with newly diagnosed type 1 diabetes (the NewLira study): A randomized, double-blind, placebo-controlled trial.

AIM: To test the effect of the glucagon-like peptide-1 receptor agonist, liraglutide, on residual beta-cell function in adults with newly diagnosed type 1 diabetes. MATERIALS AND METHODS: In a multicentre, double-blind, parallel-group trial, adults with newly diagnosed type 1 diabetes and stimulated C-peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8-mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow-up with only insulin treatment. The primary endpoint was the between-group difference in C-peptide area under the curve (AUC) following a liquid mixed-meal test after 52 weeks of treatment. RESULTS: Sixty-eight individuals were randomized. After 52 weeks, the 4-hour AUC C-peptide response was maintained with liraglutide, but decreased with placebo (P = .002). Six weeks after end-of-treatment, C-peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 (P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo-treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient. CONCLUSIONS: Treatment with liraglutide improves residual beta-cell function and reduces the dose of insulin during the first year after diagnosis. Beta-cell function was similar at 6 weeks postliraglutide treatment.

Activation of peracetic acid by electrodes using biogenic electrons: A novel energy- and catalyst-free process to eliminate pharmaceuticals.

Peracetic acid (PAA) has received increasing attention as an alternative oxidant for wastewater treatment. However, existing processes for PAA activation to generate reactive species typically require external energy input (e.g., electrically and UV-mediated activation) or catalysts (e.g., Co2+), inevitably increasing treatment costs or introducing potential new contaminants that necessitate additional removal. In this work, we developed a catalyst-free, self-sustaining bioelectrochemical approach within a two-chamber bioelectrochemical system (BES), where a cathode electrode in-situ activates PAA using renewable biogenic electrons generated by anodic exoelectrogens (e.g., Geobacter) degrading biodegradable organic matter (e.g., acetic acid) in wastewater at the anode. This innovative BES-PAA technique achieved 98 % and 81 % removal of 2 µM sulfamethoxazole (SMX) in two hours at pH 2 (cation exchange membrane) and pH 6 (bipolar membrane) using 100 µM PAA without external voltage. Mechanistic studies, including radical quenching, molecular probe validation, electron spin resonance (ESR) experiments, and density functional theory (DFT) calculations, revealed that SMX degradation was driven by reactive species generated via biogenic electron-mediated OO cleavage of PAA, with CH3C(O)OO• contributing 68.1 %, •OH of 18.4 %, and CH3C(O)O• of 9.4 %, where initial formation of •OH and CH3C(O)O• rapidly reacts with PAA to produce CH3C(O)OO•. The presence of common water constituents such as anions (e.g., Cl-, NO3-, and H2PO4-) and humic acid (HA) significantly hinders SMX removal via the BES-PAA technique, whereas CO32- and HCO3- ions have a comparatively minor impact. Additionally, the study investigated the removal of various pharmaceuticals present in secondary treated municipal wastewater, attributing differences in removal efficiency to the selective action of CH3C(O)OO•. This research demonstrates a novel PAA activation method that is ecologically benign, inexpensive, and capable of overcoming catalyst deactivation and secondary pollution issues.

Offshore produced water treatment by a biofilm reactor on the seabed: The effect of temperature and matrix characteristics.

In many industrial processes a large amount of water with high salinity is co-produced whose treatment poses considerable challenges to the available technologies. The produced water (PW) from offshore operations is currently being discharged to sea without treatment for dissolved pollutants due to space limitations. A biofilter on the seabed adjacent to a production platform would negate all size restrictions, thus reducing the environmental impact of oil and gas production offshore. The moving bed biofilm reactor (MBBR) was investigated for PW treatment from different oilfields in the North Sea at 10 °C and 40 °C, corresponding to the sea and PW temperature, respectively. The six PW samples in study were characterized by high salinity and chemical oxygen demand with ecotoxic effects on marine algae S. pseudocostatum (0.4%

Amiloride lowers plasma TNF and interleukin-6 but not interleukin-17A in patients with hypertension and type 2 diabetes.

Interleukin (IL)-17A contributes to hypertension in preclinical models. T helper 17 and dendritic cells are activated by NaCl, which could involve the epithelial Na+ channel (ENaC). We hypothesized that the ENaC blocker amiloride reduces plasma IL-17A and related cytokines in patients with hypertension. Concentrations of IL-17A, IFN-γ, TNF, IL-6, IL-1ß, and IL-10 were determined by immunoassays in plasma from two patient cohorts before and after amiloride treatment: 1) patients with type 2 diabetes mellitus (T2DM) and treatment-resistant hypertension (n = 69, amiloride 5-10 mg/day for 8 wk) and 2) patients with hypertension and type 1 diabetes mellitus (T1DM) (n = 29) on standardized salt intake (amiloride 20-40 mg/day, 2 days). Plasma and tissue from ANG II-hypertensive mice with T1DM treated with amiloride (2 mg/kg/day, 4 days) were analyzed. The effect of amiloride and benzamil on macrophage cytokines was determined in vitro. Plasma cytokines showed higher concentrations (IL-17A ∼40-fold) in patients with T2DM compared with T1DM. In patients with T2DM, amiloride had no effect on IL-17A but lowered TNF and IL-6. In patients with T1DM, amiloride had no effect on IL-17A but increased TNF. In both cohorts, blood pressure decline and plasma K+ increase did not relate to plasma cytokine changes. In mice, amiloride exerted no effect on IL-17A in the plasma, kidney, aorta, or left cardiac ventricle but increased TNF in cardiac and kidney tissues. In lipopolysaccharide-stimulated human THP-1 macrophages, amiloride and benzamil (from 1 nmol/L) decreased TNF, IL-6, IL-10, and IL-1ß. In conclusion, inhibition of ENaC by amiloride reduces proinflammatory cytokines TNF and IL-6 but not IL-17A in patients with T2DM, potentially by a direct action on macrophages.NEW & NOTEWORTHY ENaC activity may contribute to macrophage-derived cytokine release, since amiloride exerts anti-inflammatory effects by suppression of TNF and IL-6 cytokines in patients with resistant hypertension and type 2 diabetes and in THP-1-derived macrophages in vitro.

High-performance hexaferrite magnets tailored through alignment of shape-controlled nanocomposites.

Nanoparticles of strontium hexaferrite, SrFe12O19, were prepared by two different synthesis methods: hydrothermal (autoclave) and sol-gel autocombustion (solid-salt-matrix). The two synthesis pathways yield nanoparticles with different morphologies and correspondingly different magnetic characteristics. The autoclave synthesis results in large plate-like crystallites, which spontaneously align with a preferred crystallographic orientation when applying a uniaxial pressure, but exhibit a relatively poor coercivity. Meanwhile, the solid-salt-matrix synthesis method results in smaller less anisotropic crystallites with enhanced coercivity, but with a relatively limited ability to align under a uniaxial applied pressure. The obtained nanocrystalline powders were dry or wet mixed in different ratios followed by Spark Plasma Sintering (SPS) into dense pellets. A clear correlation between mixing ratio, the level of alignment and resulting coercivity was observed for the dry mixed samples, i.e. as more solid-salt-matrix powder is added, the texture of the pellets decreases and the coercivity increases. The best performing pellet in terms of maximum energy product (BHmax = 32.1(6) kJ m-3) was obtained by dry-mixing of 75 wt% autoclave prepared powder and 25 wt% solid-salt-matrix powder. The results presented here illustrate the potential of mixing magnetic nanoparticle powders with different shape characteristics to gain improved magnetic performance.

Metabolic effect of adrenaline infusion in people with type 1 diabetes and healthy individuals.

AIMS/HYPOTHESIS: As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia. METHODS: Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure. RESULTS: While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant. CONCLUSIONS/INTERPRETATION: In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05095259.

The Chemistry of Spinel Ferrite Nanoparticle Nucleation, Crystallization, and Growth.

The nucleation, crystallization, and growth mechanisms of MnFe2O4, CoFe2O4, NiFe2O4, and ZnFe2O4 nanocrystallites prepared from coprecipitated transition metal (TM) hydroxide precursors treated at sub-, near-, and supercritical hydrothermal conditions have been studied by in situ X-ray total scattering (TS) with pair distribution function (PDF) analysis, and in situ synchrotron powder X-ray diffraction (PXRD) with Rietveld analysis. The in situ TS experiments were carried out on 0.6 M TM hydroxide precursors prepared from aqueous metal chloride solutions using 24.5% NH4OH as the precipitating base. The PDF analysis reveals equivalent nucleation processes for the four spinel ferrite compounds under the studied hydrothermal conditions, where the TMs form edge-sharing octahedrally coordinated hydroxide units (monomers/dimers and in some cases trimers) in the aqueous precursor, which upon hydrothermal treatment nucleate through linking by tetrahedrally coordinated TMs. The in situ PXRD experiments were carried out on 1.2 M TM hydroxide precursors prepared from aqueous metal nitrate solutions using 16 M NaOH as the precipitating base. The crystallization and growth of the nanocrystallites were found to progress via different processes depending on the specific TMs and synthesis temperatures. The PXRD data show that MnFe2O4 and CoFe2O4 nanocrystallites rapidly grow (typically <1 min) to equilibrium sizes of 20-25 nm and 10-12 nm, respectively, regardless of applied temperature in the 170-420 °C range, indicating limited possibility of targeted size control. However, varying the reaction time (0-30 min) and temperature (150-400 °C) allows different sizes to be obtained for NiFe2O4 (3-30 nm) and ZnFe2O4 (3-12 nm) nanocrystallites. The mechanisms controlling the crystallization and growth (nucleation, growth by diffusion, Ostwald ripening, etc.) were examined by qualitative analysis of the evolution in refined scale factor (proportional to extent of crystallization) and mean crystallite volume (proportional to extent of growth). Interestingly, lower kinetic barriers are observed for the formation of the mixed spinels (MnFe2O4 and CoFe2O4) compared to the inverse (NiFe2O4) and normal (ZnFe2O4) spinel structured compounds, suggesting that the energy barrier for formation may be lowered when the TMs have no site preference.

Sustainable bioelectric activation of periodate for highly efficient micropollutant abatement.

The periodate (PI)-based advanced oxidation process is valued for environmental remediation, but current activation methods involve high costs, secondary contamination risks, and limited applicability due to external energy inputs (e.g., UV), catalyst incorporation (e.g., Fe2+), or environmental modifications (e.g., freezing). In this work, novel bioelectric activation of PI using the electrons generated by electroactive bacteria was developed and investigated for rapid removal of carbamazepine (CBZ), achieving 100 %, 100 %, and 76 % removal efficiency for 4.22 µM of CBZ in 20 min at pH 2, 120 min at pH 6.4, and HRT of 30 min at pH 8.5, respectively, with a 1 mM PI dose and without an input voltage. It was deduced that electrons derived from bacteria could directly activate PI using Ti mesh electrodes and generate •IO3 via single electron transfer under strongly acidic conditions (e.g., pH 2). Nevertheless, under weak alkaline conditions (e.g., pH 8.5), biogenic electrons indirectly activated PI by generating OH-via 4e-reduction at the Ti mesh cathode, resulting in the formation of •O2- and 1O2. In addition to the metal cathode, a carbon-based cathode finely modulates the 2e-reduction, yielding H2O2 and activating PI to mainly form •OH. Moreover, primarily non-toxic IO3- was produced during treatment, while no detectable reactive iodine species (HOI, I2, and I3-) were observed. Furthermore, the bioelectric activation of PI demonstrated its capability to remove various micropollutants present in secondary-treated municipal wastewater, showcasing its broad-spectrum degradation ability. This study introduces a novel, cost-effective, and environmentally friendly PI activation technique with promising applicability for micropollutant elimination in water treatment.

Computed tomographic-based three-dimensional printing of giant coronary artery fistulas to guide surgical strategy: a case series.

Background: Coronary artery fistulas (CAFs) are abnormal communications between the coronary arteries and the heart chambers, arteries, or veins, potentially leading to significant shunting, myocardial ischaemia and heart failure. Computed tomographic (CT) angiography or conventional invasive angiography is the reference standard for the diagnosis of coronary fistulas. The fistula anatomy can become very complex, which makes surgical or interventional planning challenging. Case summary: We report two cases of hugely dilated and tortuous coronary circumflex artery fistulas draining into the coronary sinus. Both patients were followed up for more than 10 years because of very complex coronary fistula anatomy and mild symptoms. From two-dimensional (2D) sliced CT images alone it, was uncertain whether surgery was feasible. However, since both patients had symptom progression (Patient 1 developed heart failure, and Patient 2 had recurrent pericardial effusions), three-dimensional (3D) heart models were printed for better understanding of the complex fistula anatomy and improved surgical planning. Both patients had successful surgery and symptomatic relief at follow-up. Discussion: The delay in surgery, until clinical deterioration, may partly be a consequence of a general reluctance in performing complex surgery in patients with CAFs. As of now, CT-based 3D printing has primarily been used in isolated cases. However, 3D printing is evolving rapidly and supplementing 2D sliced CT images with a physical 3D heart model may improve the anatomical understanding and pre-surgical planning that could lead to better surgical outcome.

The use of artificial intelligence to assess diabetic eye disease among the Greenlandic population.

Background: Retina fundus images conducted in Greenland are telemedically assessed for diabetic retinopathy by ophthalmological nurses in Denmark. Applying an AI grading solution, in a Greenlandic setting, could potentially improve the efficiency and cost-effectiveness of DR screening.Method: We developed an AI model using retina fundus photos, performed on persons registered with diabetes in Greenland and Denmark, using Optos® ultra wide-field scanning laser ophthalmoscope, graded according to ICDR.Using the ResNet50 network we compared the model's ability to distinguish between different images of ICDR severity levels in a confusion matrix.Results: Comparing images with ICDR level 0 to images of ICDR level 4 resulted in an accuracy of 0.9655, AUC of 0.9905, sensitivity and specificity of 96.6%.Comparing ICDR levels 0,1,2 with ICDR levels 3,4, we achieved a performance with an accuracy of 0.8077, an AUC of 0.8728, a sensitivity of 84.6% and a specificity of 78.8%. For the other comparisons, we achieved a modest performance.Conclusion: We developed an AI model using Greenlandic data, to automatically detect DR on Optos retina fundus images. The sensitivity and specificity were too low for our model to be applied directly in a clinical setting, thus optimising the model should be prioritised.

Enhanced permanganate oxidation of phenolic pollutants by alumina and potential industrial application.

In this study, we found that alumina (Al2O3) may improve the degradation of phenolic pollutants by KMnO4 oxidation. In KMnO4/Al2O3 system, the removal efficiency of 2,4-Dibromophenol (2,4-DBP) was increased by 26.5%, and the apparent activation energy was decreased from 44.5 kJ/mol to 30.9 kJ/mol. The mechanism of Al2O3-catalytic was elucidated by electrochemical processes, X-ray photoelectron spectroscopy (XPS) characterization and theoretical analysis that the oxidation potential of MnO4- was improved from 0.46 V to 0.49 V. The improvement was attributed to the formation of coordination bonds between the O atoms in MnO4- and the empty P orbitals of the Al atoms in Al2O3 crystal leading to the even-more electron deficient state of MnO4-. The excellent reusability of Al2O3, the good performance on degradation of 2,4-DBP in real water, the satisfactory degradation of fixed-bed reactor, and the enhanced removal of 6 other phenolic pollutants demonstrated that the KMnO4/Al2O3 system has satisfactory potential industrial application value. This study offers evidence for the improvement of highly-efficient MnO4- oxidation systems.

Amiloride Reduces Urokinase/Plasminogen-Driven Intratubular Complement Activation in Glomerular Proteinuria.

SIGNIFICANCE STATEMENT: Proteinuria predicts accelerated decline in kidney function in CKD. The pathologic mechanisms are not well known, but aberrantly filtered proteins with enzymatic activity might be involved. The urokinase-type plasminogen activator (uPA)-plasminogen cascade activates complement and generates C3a and C5a in vitro / ex vivo in urine from healthy persons when exogenous, inactive, plasminogen, and complement factors are added. Amiloride inhibits uPA and attenuates complement activation in vitro and in vivo . In conditional podocin knockout (KO) mice with severe proteinuria, blocking of uPA with monoclonal antibodies significantly reduces the urine excretion of C3a and C5a and lowers tissue NLRP3-inflammasome protein without major changes in early fibrosis markers. This mechanism provides a link to proinflammatory signaling in proteinuria with possible long-term consequences for kidney function. BACKGROUND: Persistent proteinuria is associated with tubular interstitial inflammation and predicts progressive kidney injury. In proteinuria, plasminogen is aberrantly filtered and activated by urokinase-type plasminogen activator (uPA), which promotes kidney fibrosis. We hypothesized that plasmin activates filtered complement factors C3 and C5 directly in tubular fluid, generating anaphylatoxins, and that this is attenuated by amiloride, an off-target uPA inhibitor. METHODS: Purified C3, C5, plasminogen, urokinase, and urine from healthy humans were used for in vitro / ex vivo studies. Complement activation was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and ELISA. Urine and plasma from patients with diabetic nephropathy treated with high-dose amiloride and from mice with proteinuria (podocin knockout [KO]) treated with amiloride or inhibitory anti-uPA antibodies were analyzed. RESULTS: The combination of uPA and plasminogen generated anaphylatoxins C3a and C5a from intact C3 and C5 and was inhibited by amiloride. Addition of exogenous plasminogen was sufficient for urine from healthy humans to activate complement. Conditional podocin KO in mice led to severe proteinuria and C3a and C5a urine excretion, which was attenuated reversibly by amiloride treatment for 4 days and reduced by >50% by inhibitory anti-uPA antibodies without altering proteinuria. NOD-, LRR- and pyrin domain-containing protein 3-inflammasome protein was reduced with no concomitant effect on fibrosis. In patients with diabetic nephropathy, amiloride reduced urinary excretion of C3dg and sC5b-9 significantly. CONCLUSIONS: In conditions with proteinuria, uPA-plasmin generates anaphylatoxins in tubular fluid and promotes downstream complement activation sensitive to amiloride. This mechanism links proteinuria to intratubular proinflammatory signaling. In perspective, amiloride could exert reno-protective effects beyond natriuresis and BP reduction. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Increased Activity of a Renal Salt Transporter (ENaC) in Diabetic Kidney Disease, NCT01918488 and Increased Activity of ENaC in Proteinuric Kidney Transplant Recipients, NCT03036748 .

Ratio of transmitral early filling velocity to diastolic strain rate and prognosis in type-1 diabetes.

BACKGROUND: Impaired diastolic function is a hallmark of diabetic cardiomyopathy and a common feature in type 1 diabetes mellitus (T1DM). The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to have strong prognostic value. This study aimed to investigate the prognostic value of E/e'sr compared to E/e' in T1DM without known heart disease. METHODS: In this prospective cohort of T1DM patients, echocardiography was performed including two-dimensional speckle tracking. Follow-up was performed using nationwide registries. Outcomes were all-cause mortality and major cardiovascular events (MACE). RESULTS: In total 1079 patients (age: 49.6 ± 14.5 years, 52.5% male, duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, IQR:5.7-6.9) 13.2% experienced MACE and 5.8% died. Following multivariable adjustment, both E/e'sr and E/e' was significantly associated with both MACE (E/e'sr: HR 1.16 CI95%:[1.05-1.29], p = 0.005, per 10 cm increase) vs. (E/e': HR 1.09 CI95%:[1.03-1.15], p = 0.001, per 1 unit increase) and all-cause mortality (E/e'sr: HR 1.20 [1.03-1.40], p = 0.016) vs. (E/e': HR: 1.11 [1.02-1.20], p = 0.016). Sex modified the association between E/e'sr and MACE (p for interaction = 0.008) such that E/e'sr after multivariable adjustment only remained significantly associated with MACE in females (HR: 1.41 [1.19-1.67], p < 0.001) but not in males (HR: 1.06 [0.93-1.20], p = 0.42). In females, E/e'sr provided incremental information beyond the Steno T1 Risk Engine (Harrell's C-statistic: 0.78 (0.72-0.83) vs. 0.81 (0.75-0.86), p = 0.007). CONCLUSION: In patients with T1DM, both E/e'sr and E/e' provides independent prognostic information regarding prognosis. E/e'sr seems to have stronger prognostic value in females with T1DM.

Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

The impact of upper extremity impairments on work and everyday life of people with type 1 diabetes-A nationwide controlled study.

AIMS: The study objective was to explore how upper extremity impairments (UEIs) affect the everyday life and work-life of people with type 1 diabetes (T1D) and to compare them to a control group without T1D to determine if there are diabetes-specific consequences of UEIs. METHODS: In a controlled cross-sectional study, a survey was distributed across all regions of Denmark. A total of 2174 people with T1D and 827 controls were included in the study population. The survey addressed UEI symptoms, employment status, functional disability, mental well-being and diabetes distress. Data were analysed using multivariable logistic and linear regression. RESULTS: Upper extremity impairments were associated with a higher rate of work absence and modification, but no more so for people with T1D than for the control group. Among people with T1D, UEIs were significantly associated with worse mental well-being and diabetes distress, and across all outcomes including functional disability, additive effects were found with an increasing number of coexisting impairments. The impact of UEIs on functional disability was more severe for the T1D group than the control group, but this was primarily due to differences in the number of coexisting impairments. CONCLUSIONS: Upper extremity impairments have significant negative implications for the work-life and everyday life of people with T1D, and interventions to reduce UEIs and their impact among this group are highly relevant.

The Role of Obstructive Sleep Apnea in Vision-Threatening Diabetic Retinopathy-A National Register-Based Study.

INTRODUCTION: we investigated the association between OSA and vision-threatening diabetic retinopathy (VTDR). METHODS: we used three nationwide registers to identify subjects with and without OSA and patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). The Danish Civil Registration System was used to link OSA with diabetes diagnosis. The primary outcome was the occurrence of VTDR in diabetic patients with and without OSA. The secondary outcome was the prevalence of diabetes mellitus in patients with and without OSA. RESULTS: we included 532,828 diabetic subjects comprising 13,279 patients with OSA (2.5%) and 519,549 without OSA (97.5%). Diabetic patients with OSA had a 57% lower risk of VTDR compared to diabetic patients without OSA (OR 0.43, 95% CI 0.38-0.50, p < 0.0001). CONCLUSIONS: our findings indicate that OSA is associated with a lower risk of VTDR. Since we did not adjust our outcomes for diabetes duration, hypertension control and hemoglobin A1c, future studies are needed to confirm our findings.

The Effect of Insulin Degludec Versus Insulin Glargine U100 on Glucose Metrics Recorded During Continuous Glucose Monitoring in People With Type 1 Diabetes and Recurrent Nocturnal Severe Hypoglycemia.

AIM: Comparing continuous glucose monitoring (CGM)-recorded metrics during treatment with insulin degludec (IDeg) versus insulin glargine U100 (IGlar-100) in people with type 1 diabetes (T1D) and recurrent nocturnal severe hypoglycemia. MATERIALS AND METHODS: This is a multicenter, two-year, randomized, crossover trial, including 149 adults with T1D and minimum one episode of nocturnal severe hypoglycemia within the last two years. Participants were randomized 1:1 to treatment with IDeg or IGlar-100 and given the option of six days of blinded CGM twice during each treatment. CGM traces were reviewed for the percentage of time-within-target glucose range (TIR), time-below-range (TBR), time-above-range (TAR), and coefficient of variation (CV). RESULTS: Seventy-four participants were included in the analysis. Differences between treatments were greatest during the night (23:00-06:59). Treatment with IGlar-100 resulted in 54.0% vs 49.0% with IDeg TIR (70-180 mg/dL) (estimated treatment difference [ETD]: -4.6%, 95% confidence interval [CI]: -9.1, -0.0, P = .049). TBR was lower with IDeg at level 1 (54-69 mg/dL) (ETD: -1.7% [95% CI: -2.9, -0.5], P < .05) and level 2 (<54 mg/dL) (ETD: -1.3% [95% CI: -2.1, -0.5], P = .001). TAR was higher with IDeg compared with IGlar-100 at level 1 (181-250 mg/dL) (ETD: 4.0% [95% CI: 0.8, 7.3], P < .05) and level 2 (> 250 mg/dL) (ETD: 4.0% [95% CI: 0.8, 7.2], P < .05). The mean CV was lower with IDeg than that with IGlar-100 (ETD: -3.4% [95% CI: -5.6, -1.2], P < .05). CONCLUSION: For people with T1D suffering from recurrent nocturnal severe hypoglycemia, treatment with IDeg, compared with IGlar-100, results in a lower TBR and CV during the night at the expense of more TAR.

Glucose Monitoring Metrics in Individuals With Type 1 Diabetes Using Different Treatment Modalities: A Real-World Observational Study.

OBJECTIVE: This study aimed to investigate the association between continuous glucose monitoring (CGM)-derived glycemic metrics and different insulin treatment modalities using real-world data. RESEARCH DESIGN AND METHODS: A cross-sectional study at Steno Diabetes Center Copenhagen, Denmark, included individuals with type 1 diabetes using CGM. Data from September 2021 to August 2022 were analyzed if CGM was used for at least 20% of a 4-week period. Individuals were divided into four groups: multiple daily injection (MDI) therapy, insulin pumps with unintegrated CGM (SUP), sensor-augmented pumps with low glucose management (SAP), and automated insulin delivery (AID). The MDI and SUP groups were further subdivided based on CGM alarm features. The primary outcome was percentage of time in range (TIR: 3.9-10.0 mmol/L) for each treatment group. Secondary outcomes included other glucose metrics and HbA1c. RESULTS: Out of 6,314 attendees, 3,184 CGM users were included in the analysis. Among them, 1,622 used MDI, 504 used SUP, 354 used SAP, and 561 used AID. Median TIR was 54.0% for MDI, 54.9% for SUP, 62,9% for SAP, and 72,1% for AID users. The proportion of individuals achieving all recommended glycemic targets (TIR >70%, time above range <25%, and time below range <4%) was significantly higher in SAP (odds ratio [OR] 2.4 [95% CI 1.6-3.5]) and AID (OR 9.4 [95% CI 6.7-13.0]) compared with MDI without alarm features. CONCLUSIONS: AID appears superior to other insulin treatment modalities with CGM. Although bias may be present because of indications, AID should be considered the preferred choice for insulin pump therapy.

Corrigendum: Effect of oxic and anoxic conditions on intracellular storage of polyhydroxyalkanoate and polyphosphate in Magnetospirillum magneticum strain AMB-1.

[This corrects the article DOI: 10.3389/fmicb.2023.1203805.].

Methanotrophic oxidation of organic micropollutants and nitrogen upcycling in a hybrid membrane biofilm reactor (hMBfR) for simultaneous O2 and CH4 supply.

Pharmaceuticals and other organic micropollutants (OMPs) present in wastewater effluents are of growing concern, as they threaten environmental and human health. Conventional biological treatments lead to limited removal of OMPs. Methanotrophic bacteria can degrade a variety of OMPs. By employing a novel bubble-free hybrid membrane biofilm bioreactor (hMBfR), we grew methanotrophic bacteria at three CH4 loading rates. Biomass productivity and CH4 loading showed a linear correlation, with a maximum productivity of 372 mg-VSS·L-1·d-1, with corresponding biomass concentration of 1117.6 ± 56.4 mg-VSS·L-1. Furthermore, the biodegradation of sulfamethoxazole and 1H-benzotriazole positively correlated with CH4 oxidation rates, with highest biodegradation kinetic constants of 3.58 L·g-1·d-1 and 5.42 L·g-1·d-1, respectively. Additionally, the hMBfR recovered nutrients as microbial proteins, with an average content 39% DW. The biofilm community was dominated by Methylomonas, while the bulk was dominated by aerobic heterotrophic bacteria. The hMBfR removed OMPs, allowing for safer water reuse while valorising CH4 and nutrients.