Time With Rapid Change of Glucose.

BACKGROUND: A variety of metrics are used to describe glycemic variation, some of which may be difficult to comprehend or require complex strategies for smoothing of the glucose curve. We aimed to describe a new metric named time with rapid change of glucose (TRC), which is presented as percentage of time, similar to time above range (TAR), time in range (TIR), and time below range (TBR). METHOD: We downloaded glucose data for 90 days from 159 persons with type 1 diabetes using the Abbott Freestyle Libre version 1. We defined TRC as the proportion of time (%) with an absolute rate of change of glucose > 1.5 mmol/L/15 minutes (1.8mg/dL/min) corresponding to a minimum rate of change for glucose in the 3.9-10.0 mmol/L (70-180 mg/dL) range within 1 hour. TRC is related to the other glucose variability metrics: CV within day (CVw) and mean amplitude of glycemic excursion (MAGE). RESULTS: The more than 1.27 million glucose rates were t-location scale distributed with SD 0.91 mmol/L/15 min (1.1 mg/dL/15 min). The median TRC was 6.9% (IQR 4.5%-9.5%). The proportion of TRC with positive slope was 3.9% (2.6%-5.3%) and significantly higher than the proportion with negative slope 2.8% (1.5%-4.4%) P < .001. TRC correlated with CVw and MAGE (Spearman's correlation coefficient .56 and .65, respectively, P < .001). CONCLUSION: TRC is proposed as an easily perceived metric to compare the performance of hybrid or fully automated closed-loop insulin delivery systems to obtain glucose homeostasis.

First-line treatment for femoroacetabular impingement syndrome and hip-related quality of life: study protocol for a multicentre randomised controlled trial comparing a 6-month supervised strength exercise intervention to usual care (the Better Hip Trial).

INTRODUCTION: Femoroacetabular impingement syndrome (FAIS) is a motion-related and position-related clinical condition of the hip associated with pain, reduced physical function and hip-related quality of life (QoL). Interestingly, higher maximal muscle strength is associated with less pain, better physical function and improved QoL in people with FAIS. Furthermore, preliminary evidence suggests that a proportion of patients with FAIS respond positively to strength exercise as first-line treatment. Nonetheless, there is little evidence supporting a specific exercise intervention offered as a first-line treatment. We will conduct a randomised controlled trial investigating the clinical effectiveness and cost-effectiveness of a 6-month strength exercise intervention compared with usual care as first-line treatment in patients with FAIS. METHODS AND ANALYSIS: This is a multicentre randomised controlled trial that will be conducted at hospitals and physiotherapy clinics across Denmark and Australia. A total of 120 patients with FAIS will be randomised (1:1) to 6 months of supervised strength exercise or usual care. The primary outcome is the change in hip-related QoL measured using the International Hip and Outcome Tool 33 (iHOT-33) from baseline to the end of intervention. A health economic evaluation will be conducted from a societal and healthcare perspective based on the data collection over a 12-month period starting at baseline. The analysis will calculate incremental cost-effectiveness ratios using quality-adjusted life-years and iHOT-33 scores while estimating costs using microcosting and cost questionnaires. Secondary outcomes include objectively measured physical function at baseline and after 6 months and patient-reported outcomes measured at baseline, 3-month, 6-month and 12-month follow-up. ETHICS AND DISSEMINATION: The trial has been approved by the Committee on Health Research Ethics in the Central Denmark Region (journal no 1-10-72-45-23) and La Trobe University Human Ethics Committee (HEC24042) and is registered at the Central Denmark Region List of Research Projects (journal no 1-16-02-115-23). Informed consent will be obtained from each participant before randomisation. Results will be published in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05927935.

The online educational tool "Roadmap to EEGs" significantly improved trainee performance in recognizing EEG patterns.

OBJECTIVE: We created a framework to assess the competency-based EEG curriculum, outlined by the International League Against Epilepsy (ILAE) through a video-based online educational resource ("Roadmap to EEGs") and assessed its effectiveness and feasibility in improving trainees' knowledge. METHODS: Ten video-based e-learning modules addressed seven key topics in EEG and epileptology (normal EEG, normal variants, EEG artifacts, interictal epileptiform discharges (IED), focal seizures, idiopathic generalized epilepsy (IGE), and developmental and epileptic encephalopathies (DEE)). We posted the educational videos on YouTube for free access. Pre- and post-tests, each comprising 20 multiple-choice questions, were distributed to institution leadership and advertised on social media platforms to reach a global audience. The tests were administered online to assess the participants' knowledge. Pre- and post-test questions showed different EEG samples to avoid memorization and immediate recall. After completing the post-test, participants were asked to respond to 7 additional questions assessing their confidence levels and recommendations for improvement. RESULTS: A total of 52 complete and matched pre- and post-test responses were collected. The probability of a correct response was 73% before teaching (95% CI: 70%-77%) and 81% after teaching (95% CI: 78%-84%). The odds of a correct response increased significantly by 59% (95% CI: 28%-98%, p < .001). For participants having >4 weeks of EEG training, the probability of a correct response was 76% (95% CI: .72-.79) and 81% after teaching (95% CI: .78-.84). The odds of answering correctly increased by 44% (95% CI: 15%-80%, p = .001). Participants felt completely confident in independently interpreting and identifying EEG findings after completing the teaching modules (17.1% before vs. 37.8% after, p-value < .0001). 86.5% of participants expressed a high likelihood of recommending the module to other trainees. SIGNIFICANCE: The video-based online educational resource allows participants to acquire foundational knowledge in EEG/epilepsy, and participants to review previously learned EEG/epilepsy information.

A prospective evaluation of the diagnostic potential of EBV-DNA in plasma and whole blood.

BACKGROUND: Quantitative polymerase chain reaction (qPCR) for Epstein-Barr virus (EBV)-DNA is an important diagnostic tool for EBV-associated disease, but interpretation of its clinical significance is challenging. OBJECTIVES: We assessed the diagnostic and clinical performance of WHO-standardised qPCR for EBV-DNA (WHO EBV-qPCR) in plasma and whole blood (WB) for proven EBV disease in a prospectively accrued patient cohort. STUDY DESIGN: Central Denmark Region patients, tested with WHO EBV-qPCR from November 2017 to March 2019, were screened for EBV disease. Incidence (IR) was estimated by Poisson regression. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for EBV-qPCR in plasma and WB. Risk of diagnostic latency was compared between patients with EBV-positive and EBV-negative lymphomas. RESULTS: EBV disease was diagnosed in 95 of 1484 participants (IR: 16.3 per 1000 patientyears 95%CI; 13.3-19.9). Sensitivity and specificity of WHO EBV-qPCR in plasma was 82.4% (95% CI; 74.2-90.7%) and 87.8% (95% CI; 85.6-90%), yielding a PPV of 32.2% (95% CI; 24.9-39.5%) and NPV of 98.6% (95% CI; 97.7-99.5%) for proven EBV disease. Sensitivity and NPV were comparable in WB, while specificity and PPV decreased to 66.9% (95% CI; 60.6-73.1%) and 18.1% (95% CI; 7.5-28.7%). Risk of diagnostic latency was 2.3-fold (95% CI 1.4-4.1) higher for patients with EBV-positive compared with EBV-negative lymphomas. CONCLUSIONS: WHO EBV-qPCR in plasma and WB have a low PPV but a high NPV for proven EBV disease. Implementation of WHO EBV-qPCR could improve interpretation and facilitate EBV-positive lymphoma diagnosis.

Muscle Performance during the Menstrual Cycle Correlates with Psychological Well-Being, but Not Fluctuations in Sex Hormones.

PURPOSE: We aimed to study variations in strength and power performance during the menstrual cycle (MC) in eumenorrheic young women and during the pill cycle in oral contraceptives (OC) users. METHODS: Forty healthy, normal-weight women between 18 and 35 yr (n = 30 eumenorrheic women; n = 10 OC users) completed this prospective cohort study. Seven to nine times during the MC/pill-cycle, the participants completed a physical performance test series, a questionnaire about psychological well-being, blood sampling, and determination of body mass. The physical tests included isometric handgrip strength, elbow flexor strength, countermovement jump (CMJ) height, and a 10-s Wingate bike test. RESULTS: No direct correlation was observed between the variations in sex hormones and physical performance parameters. However, positive correlations were observed between physical performance outcomes and self-reported motivation, perception of own physical performance level, pleasure level, and arousal level. CMJ was 6% lower in the late luteal phase (LL) compared with the midluteal phase (ML) (P = 0.04). Wingate peak power was 3% lower in early follicular (EF) compared with the ML (P = 0.04). Furthermore, Wingate average power was 2%-5% lower in LL compared with all other MC phases. In line with these observations, physical pain was higher in EF and LL, and the pleasure level was lower in EF compared with the other MC phases. In OC users, we observed no variation in performance and self-reported parameters between the placebo-pill phase and the OC-pill phase. CONCLUSIONS: Impairments in CMJ and Wingate performance were observed at the end and start of MC compared with other MC phases, which were associated with lower psychological well-being, but not the sex hormone fluctuations.

Variation of glucose time in range in type 1 diabetes.

INTRODUCTION: The aim of the study was to assess the variation of glucose time in range (TIR) for persons with type 1 diabetes who perform intermittently scanned continuous glucose monitoring (isCGM). METHODS: Glucose data for 8 weeks were analysed for 166 persons. TIR was calculated over four consecutive 2 weeks periods. Sixty-one of the persons had two downloads with an interval of >3 months. RESULTS: A total of 140 individuals (84%) used multiple daily injection, and 26 (16%) used continuous insulin infusion. The within-individual standard deviation (SD) for TIR was 6.3% corresponding to 95% limits of agreement for the difference between two TIR values of ±17.6%. Mean TIR calculated from the first and last 2 weeks was 52.2 ± 17.1% and 53.7 ± 16.4%, respectively (difference 1.5%, SD of the difference 10.4%, p = .07). For persons with two downloads separated by months, the SD of the difference in TIR was 12.6%. CONCLUSIONS: The 95% limit of agreement for TIR is vast for persons using isCGM. It is difficult to draw firm conclusions regarding systematic differences when individual TIR from 2 weeks are compared. This may not be valid for users of insulin pumps with closed-loop insulin delivery.

Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease: A Prospective 2-Center Cohort Study.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P<0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P<0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m2 (95% CI, 4.5-11.1; P<0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

A window of subliminal perception.

Under labels such as unconscious processing and subliminal perception, identification of stimuli falling below the subjective threshold (whether truly unconscious or not) has been found remarkably accurate in some experiments while completely at chance in others. Here, we first identify that an apparent window of subliminal perception arises in humans under specific stimulus conditions using different experimental paradigms and analysis methods. We then show that the standard signal detection theory (SDT) model is unable to account for this window and extend it until it is. We finally compare a range of models on empirical data. The models performing best are notable for their absence of hierarchical levels, indicating that the window could be a base property of any phenomenally conscious system. The models explain previously incompatible findings in the literature, and they allow for estimations of peaks in subthreshold perception across the spectrum of stimulus saliency, which may be used in further studies of subliminal perception.

Glycemic Metrics Derived From Intermittently Scanned Continuous Glucose Monitoring.

BACKGROUND: Glucose data from intermittently scanned continuous glucose monitoring (isCGM) is a combination of scanned and imported glucose values. The present knowledge of glycemic metrics originate mostly from glucose data from real-time CGM sampled every five minutes with a lack of information derived from isCGM. METHODS: Glucose data obtained with isCGM and hemoglobin A1c (HbA1c) were obtained from 169 patients with type 1 diabetes. Sixty-one patients had two observations with an interval of more than three months. RESULTS: The best regression line of HbA1c against mean glucose was observed from 60 days prior to HbA1c measurement as compared to 14, 30, and 90 days. The difference between HbA1c and estimated HbA1c (=glucose management indicator [GMI]) first observed correlated with the second observation (R2 0.61, P < .001). Time in range (TIR, glucose between 3.9 and 10 mmol/L) was significantly related to GMI (R2 0.87, P < .001). A TIR of 70% corresponded to a GMI of 6.8% (95% confidence interval, 6.3-7.4). The fraction of patients with the optimal combination of TIR >70% and time below range (TBR) <4% was 3.6%. The fraction of patients with TBR>4% was four times higher for those with high glycemic variability (coefficient of variation [CV] >36%) than for those with lower CV. CONCLUSION: The individual difference between HbA1c and GMI was reproducible. High glycemic variability was related to increased TBR. A combination of TIR and TBR is suggested as a new composite quality indicator.

Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients.

AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). Here, we investigate associations between plasma ACE2 and outcome of COVID-19. METHODS AND RESULTS: This analysis used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort). Comprehensive clinical data were collected on this cohort, including 28-day outcomes. The samples were run on the Olink® Explore 1536 platform which includes measurement of the ACE2 protein. High admission plasma ACE2 in COVID-19 patients was associated with increased maximal illness severity within 28 days with OR = 1.8, 95%-CI: 1.4-2.3 (P < 0.0001). Plasma ACE2 was significantly higher in COVID-19 patients with hypertension compared with patients without hypertension (P = 0.0045). Circulating ACE2 was also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). CONCLUSION: This study suggests that measuring plasma ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 could be a link between COVID-19 illness severity and its established risk factors hypertension, pre-existing heart disease and pre-existing kidney disease.

Seven Weeks of High-Dose Vitamin D Treatment Reduces the Need for Infliximab Dose-Escalation and Decreases Inflammatory Markers in Crohn's Disease during One-Year Follow-Up.

BACKGROUND: Seven weeks of high-dose vitamin D treatment decreases intestinal IL17A and IFN-γ mRNA expression in active Crohn's disease (CD). In this follow-up study, we investigated whether seven-week vitamin D treatment affected the infliximab response in the following 45 weeks compared to placebo. METHODS: CD patients (n = 40) were initially randomised into four groups: infliximab + vitamin-D; infliximab + placebo-vitamin-D; placebo-infliximab + vitamin-D; and placebo-infliximab + placebo-vitamin-D. Infliximab (5 mg/kg) or placebo-infliximab was administered at weeks 0, 2 and 6. Vitamin D (5 mg bolus followed by 0.5 mg/day for 7 weeks) or placebo-vitamin D was handed out. After the 7-week vitamin D period, all patients received infliximab during follow-up. Results are reported for Group D+ (infliximab + vitamin-D and placebo-infliximab + vitamin-D) and Group D- (infliximab + placebo-vitamin-D and placebo-infliximab + placebo-vitamin-D). RESULTS: Group D- patients had greater needs for infliximab dose escalation during follow-up compared to group D+ (p = 0.05). Group D+ had lower median calprotectin levels week 15 (p = 0.02) and week 23 (p = 0.04) compared to group D-. Throughout follow-up, group D+ had 2.2 times (95% CI: 1.1-4.3) (p = 0.02) lower median CRP levels compared with group D-. CONCLUSIONS: Seven weeks high-dose vitamin D treatment reduces the need for later infliximab dose-escalation and reduces inflammatory markers. EudraCT no. 2013-000971-34.

Organophosphate and carbamate insecticide exposure is related to lung function change among smallholder farmers: a prospective study.

INTRODUCTION AND AIM: Exposure to some insecticides may cause airway obstruction, but existing evidence is limited by cross-sectional designs and inadequate confounder control. We investigated the relation between organophosphate and carbamate insecticides and pulmonary function in a prospective study accounting for important confounders. METHODS: In a cohort of 364 smallholder farmers in Uganda (69% women), participants underwent pre-bronchodilator spirometry at baseline (September/October 2018) and at two follow-up visits (November/December 2018 and January/February 2019). Exposure to carbamate and organophosphate insecticides was assessed using haemoglobin-adjusted erythrocyte acetylcholinesterase (AChE/Hb). Less than 3% of participants were lost to follow-up. We calculated Z-scores for FEV1, FVC and FEV1/FVC using the Global Lung Function Initiative equations. Data were analysed in linear mixed and fixed effect models accounting for family relationships and repeated measures of exposure and outcome. RESULTS: Low AChE/Hb was significantly associated with low FEV1 Z-score in both unadjusted and adjusted analyses. Compared with individuals with AChE/Hb 25.90 U/g (50th percentile, reference), those with lower AChE/Hb 24.50 U/g (35th percentile) had mean FEV1 Z-score 0.045 (0.003 to 0.087) lower, and persons with higher AChE/Hb 27.30 U/g (65th percentile) had a mean FEV1 Z-score 0.043 (-0.002 to 0.087) higher compared with the reference. Similar, but numerically smaller and statistically non-significant effects were seen for Z-scores of FVC and FEV1/FVC. CONCLUSION: Exposure to organophosphate and carbamate insecticides may lead to lung function decline. Our results add to the growing evidence of health effects in relation to exposure to organophosphate and carbamate insecticides, underlining the importance of minimising exposure.

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 × 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (Met-HeFT).

OBJECTIVES: The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 × 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT). METHODS: Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4 years. RESULTS: As of May 2020, 296 patients have been randomized at 20 centers in Denmark. CONCLUSION: The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of 2 commonly prescribed drugs with limited randomized data in patients with HFrEF.

Decrease in Mucosal IL17A, IFNγ and IL10 Expressions in Active Crohn's Disease Patients Treated with High-Dose Vitamin Alone or Combined with Infliximab.

BACKGROUND: Vitamin D treatment may reduce Crohn's disease (CD) activity by modulating the mucosal immune function. We investigated if high-dose vitamin D +/- infliximab modulated the mucosal cytokine expression in active CD. METHODS: Forty CD patients were randomized into: infliximab + vitamin D; infliximab + placebo-vitamin D; placebo-infliximab + vitamin D or placebo-infliximab + placebo-vitamin D. Infliximab (5 mg/kg) and placebo-infliximab were administered at weeks 0, 2 and 6. Oral vitamin D was administered as bolus 200,000 international units (IU) per week 0 followed by 20,000 IU/day for 7 weeks or placebo. Endoscopy with biopsies was performed at weeks 0 and 7 where endoscopic activity was measured and mucosal mRNA cytokine expression was examined. C-reactive protein (CRP), fecal calprotectin and Harvey-Bradshaw Index (HBI) were measured at weeks 0, 2 and 6. RESULTS: High-dose vitamin D treatment alone and combined with infliximab decreased the IL17A, IFNγ and IL10 expression. High-dose vitamin D alone did not significantly decrease the disease activity, CRP or calprotectin. Combined infliximab and vitamin D treatment was not clinically significantly superior to monotherapy with infliximab. CONCLUSIONS: High-dose vitamin D as monotherapy and combined with infliximab decreases IL17A, IFNγ and IL-10 expression in mucosa within treatment groups. This did not induce a statistically significant decreased disease activity. EudraCT no.2013-000971-34.

A bivariate logistic regression model based on latent variables.

Bivariate observations of binary and ordinal data arise frequently and require a bivariate modeling approach in cases where one is interested in aspects of the marginal distributions as separate outcomes along with the association between the two. We consider methods for constructing such bivariate models based on latent variables with logistic marginals and propose a model based on the Ali-Mikhail-Haq bivariate logistic distribution. We motivate the model as an extension of that based on the Gumbel type 2 distribution as considered by other authors and as a bivariate extension of the logistic distribution, which preserves certain natural characteristics. Basic properties of the obtained model are studied and the proposed methods are illustrated through analysis of two data sets: a basic science cognitive experiment of visual recognition and awareness and a clinical data set describing assessments of walking disability among multiple sclerosis patients.

Exposure to cholinesterase inhibiting insecticides and blood glucose level in a population of Ugandan smallholder farmers.

OBJECTIVES: The risk of diabetes mellitus may be elevated among persons exposed to some pesticides, including cholinesterase-inhibiting insecticides (organophosphates and carbamates). The objective of this study was to investigate how acetylcholinesterase activity was associated with mean blood glucose levels among smallholder farmers in Uganda. METHODS: We conducted a short-term follow-up study among 364 smallholder farmers in Uganda. Participants were examined three times from September 2018 to February 2019. At each visit, we measured glycosylated haemoglobin A (HbA1c) as a measure of long-term average blood glucose levels. Exposure to organophosphate and carbamate insecticides was quantified using erythrocyte acetylcholinesterase normalised by haemoglobin (AChE/Hb). For a subgroup of participants, fasting plasma glucose (FPG) was also available. We analysed HbA1c and FPG versus AChE/Hb in linear mixed and fixed effect models adjusting for age, sex, physical activity level, and consumption of fruits and vegetables, alcohol and tobacco. RESULTS: Contrary to our hypothesis, our mixed effect models showed significant correlation between low AChE/Hb and low HbA1c. Adjusted mean HbA1c was 0.74 (95% CI 0.17 to 1.31) mmol/mol lower for subjects with AChE/Hb=24.3 U/g (35th percentile) compared with subjects with AChE/Hb=25.8 U/g (50th percentile). Similar results were demonstrated for FPG. Fixed effect models showed less clear correlations for between-phase changes in AChE/Hb and HbA1c. CONCLUSIONS: Our results do not clearly support a causal link between exposure to cholinesterase-inhibiting insecticides and elevated blood glucose levels (expressed as HbA1c and FPG), but results should be interpreted with caution due to the risk of reverse causality.

Early Immunological Effects of Ischemia-Reperfusion Injury: No Modulation by Ischemic Preconditioning in a Randomised Crossover Trial in Healthy Humans.

Ischemic preconditioning (IPC) has been protective against ischemia-reperfusion injury (IRI), but the underlying mechanism is poorly understood. We examined whether IPC modulates the early inflammatory response after IRI. Nineteen healthy males participated in a randomised crossover trial with and without IPC before IRI. IPC and IRI were performed by cuff inflation on the forearm. IPC consisted of four cycles of five minutes followed by five minutes of reperfusion. IRI consisted of twenty minutes followed by 15 min of reperfusion. Blood was collected at baseline, 0 min, 85 min and 24 h after IRI. Circulating monocytes, T-cells subsets and dendritic cells together with intracellular activation markers were quantified by flow cytometry. Luminex measured a panel of inflammation-related cytokines in plasma. IRI resulted in dynamic regulations of the measured immune cells and their intracellular activation markers, however IPC did not significantly alter these patterns. Neither IRI nor the IPC protocol significantly affected the levels of inflammatory-related cytokines. In healthy volunteers, it was not possible to detect an effect of the investigated IPC-protocol on early IRI-induced inflammatory responses. This study indicates that protective effects of IPC on IRI is not explained by direct modulation of early inflammatory events.

Effect of a Whey Protein Supplement on Preservation of Fat Free Mass in Overweight and Obese Individuals on an Energy Restricted Very Low Caloric Diet.

The obesity epidemic has caused a widespread interest in strategies to achieve a healthy "high quality" weight loss, where excess fat is lost, while fat free mass (FFM) is preserved. In this study, we aimed to examine the effect of whey protein supplementation given before night sleep on FFM preservation during a 4-week (wk) period on a very low caloric diet (VLCD). Twenty-nine obese subjects (body mass index (BMI) > 28 kg/m²) completed a 4-week intervention including a VLCD and a walking program (30 min walking × 5 times per week). Subjects were randomly assigned to either control (CON, n = 15) or a whey protein supplement (PRO, 0.4 g protein/kg/day, n = 14), ingested before bedtime. Body composition (dual-energy X-ray absorptiometry, DXA), blood analysis and physical test were performed pre and post intervention. We measured nitrogen excretion in three 24 h urine collections (Day 0, 7 and 28) to assess nitrogen balance. Changes in nitrogen balance (NB) after 7 and 28 days was different between treatment groups (interaction p < 0.05). PRO was in NB after 7 days and in positive NB at day 28. In contrast, CON was in negative NB at day 7, but in NB at day 28. Nevertheless, no significant group differences were observed in the change in pre- and post-FFM measurements (-2.5 kg, [95% CI: 1.9; 3.1], p = 0.65). In conclusion, ingestion of a whey protein supplement before bedtime during a 4-week period on a VLCD improved nitrogen balance, but did not lead to any significant improvement in the quality of the weight loss in regard to observed changes in body composition and health parameters compared with controls.