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Introduction: Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non‐alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood‐samples. Methods: The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux‐en‐Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal‐samples and intra‐operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra‐operative portal vein blood‐sampling. Fecal‐samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma‐samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq‐analyses. Data will be integrated using state‐of‐the‐art neuronal networks and metabolic modeling. Patient follow‐up will be ten years. Results: Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra‐individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion: The BARIA study can add more understanding in how gut‐microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity‐associated disease epidemic. [ABSTRACT FROM AUTHOR]

Background: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested., Methods: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV 1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes., Results: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV 1 data pairs. The mean (SD) FEV 1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV 1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread., Conclusion: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Objective: We examined relationships between clinical features and pulmonary function before and after inhaled corticosteroid (ICS) treatment in wheezy preschool children, and specifically, whether measuring bronchodilator response (BDR) could predict benefit from ICS., Design: Clinical non-randomised intervention study SETTING: Secondary care., Patients: Preschool children (2 years to <6 years) with recurrent wheeze., Interventions: Inhaled beta-agonist, ICS., Outcome Measures: We measured prebronchodilator and postbronchodilator interrupter resistance (Rint) and symptom scores at 0 (V1), 4 (V2) and 12 (V3) weeks. At V2, those with a predetermined symptom level commenced ICS. Modified Asthma Predictive Index (mAPI) and parental perception of response to bronchodilator were recorded. Response to ICS was defined as a reduction in daily symptom score of >0.26. Positive BDR was defined as fall in Rint of ≥0.26 kPa.s/L, ≥35% predicted or ≥1.25 Z Scores., Results: Out of 138 recruited children, 67 completed the full study. Mean (SD) prebronchodilator Rint at V2 was 1.22 (0.35) kPa.s/L, and fell after starting ICS (V3) to 1.09 (0.33) kPa.s/L (p<0.001), while mean (SD) daily symptom score fell from 0.56 (0.36) to 0.28 (0.36) after ICS (p<0.001). Positive Rint BDR before ICS (at V1 and/or V2), using all three threshold criteria, was significantly associated with response to ICS on symptom scores at V3 (p<0.05). mAPI was not significantly associated with response to ICS, and parents' perception of response to bronchodilator was not related to measured Rint BDR ., Conclusions: Rint BDR may be helpful in selecting which wheezy preschool children are likely to benefit from ICS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is a lack of objective measures to assess children with acute wheezing episodes. Increased respiratory rate (RR) and pulsus paradoxus (PP) are recognised markers, but poorly recorded in practice. We examined whether they can be reliably assessed from a pulse oximeter plethysmogram ('pleth') trace and predict clinical outcome., Patients and Methods: We studied 44 children aged 1-7 years attending hospital with acute wheeze, following initial 'burst' bronchodilator therapy (BT), and used custom software to measure RR and assess PP from oximeter pleth traces. Traces were examined for quality, and the accuracy of the RR measurement was validated against simultaneous respiratory inductive plethysmography (RIP). RR and PP at 1 hour after BT were compared with clinical outcomes., Results: RR from pleth and RIP showed excellent agreement, with a mean difference (RIP minus pleth) of -0.5 breaths per minute (limits of agreement -3.4 to +2.3). 52% of 1 min epochs contained 10 s or more of pleth artefact. At 1 hour after BT, children who subsequently required intravenous bronchodilators had significantly higher RR (median (IQR) 63 (62-66) vs 43 (37-51) breaths per minute) than those who did not, but their heart rate and oxygen saturation were similar. Children with RR ≥55 per minute spent longer in hospital: median (IQR) 30 (22-45) vs 10 (7-21) hours. All children who subsequently required hospital admission had PP-analogous pleth waveforms 1 hour after BT., Conclusion: RR can be reliably measured and PP detected from the pulse oximeter pleth trace in children with acute wheeze and both markers predict clinical outcome., Trial Registration Number: UKCRN15742., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: We aimed to describe differences in the prevalence of intermediate hyperglycaemia (IH) between six ethnic groups. Moreover, to investigate differences in the association of the classifications of IH with the incidence of T2DM between ethnic groups., Methods: We included 3759 Dutch, 2826 African Surinamese, 1646 Ghanaian, 2571 Turkish, 2691 Moroccan and 1970 South Asian Surinamese origin participants of the HELIUS study. IH was measured by fasting plasma glucose (FPG) and HbA1c. We calculated age-, BMI and physical-activity-adjusted prevalence of IH by sex, and calculated age and sex-adjusted hazard ratios (HR)for the association between IH and T2DM in each ethnic group., Results: The prevalence of IH was higher among ethnic minority groups (68.6-41.7%) than the Dutch majority (34.9%). The prevalence of IH categories varied across subgroups. Combined increased FPG and HbA1c was most prevalent in South-Asian Surinamese men (27.6%, 95 %CI: 24.5-30.9%), and in Dutch women (4.2%, 95 %CI: 3.4-5.1%). The HRs for T2DM for each IH-classification did not differ significantly between ethnic groups. HRs were highest for the combined classification, e.g., HR = 8.1, 95 %CI: 2.5-26.6 in the Dutch., Conclusion: We found a higher prevalence of IH in ethnic minority versus majority groups, but did not find evidence for a differential association of IH with incident T2DM., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Asthma is a common problem in children and, if inadequately controlled, may seriously diminish their quality of life. Inhaled short-acting beta2 agonists such as salbutamol are usually prescribed as 'reliever' medication to help control day-to-day symptoms such as wheeze. As with many medications currently prescribed for younger children (defined as those aged 2 years 6 months to 6 years 11 months), there has been no pre-licensing age-specific pharmacological testing; consequently, the doses currently prescribed (200-1000 μg) may be ineffective or likely to induce unnecessary side effects. We plan to use the interrupter technique to measure airway resistance in this age group, allowing us for the first time to correlate inhaled salbutamol dose with changes in clinical response. We will measure urinary salbutamol levels 30 min after dosing as an estimate of salbutamol doses in the lungs, and also look for genetic polymorphisms linked to poor responses to inhaled salbutamol., Methods: This is a phase IV, randomised, controlled, observer-blinded, single-centre trial with four parallel groups (based on a sparse sampling approach) and a primary endpoint of the immediate bronchodilator response to salbutamol so that we can determine the most appropriate dose for an individual younger child. Simple randomisation will be used with a 1:1:1:1 allocation., Discussion: The proposed research will exploit simple, non-invasive and inexpensive tests that can mostly be performed in an outpatient setting in order to help develop the evidence for the correct dose of salbutamol in younger children with recurrent wheeze who have been prescribed salbutamol by their doctor., Trial Registration: EudraCT2014-001978-33, ISRCTN15513131. Registered on 8 April 2015.

Purpose: The contribution of intestinal bacterial strains (gut microbiota) in human metabolism and obesity is being increasingly recognized. The goal of this article was to provide a commentary on the clinical usefulness of these data., Methods: We performed a review of the currently available articles on PubMed., Findings: Because most of the data are based on germ-free animal research, translation to human disease may be difficult. However, changes in the intestinal bacterial composition and subsequent altered diversity have been associated with the presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus., Implications: It is still not proven whether intestinal bacteria play a causal role in glucose and lipid metabolism. Intervention studies including fecal transplantation and supplementation of single bacterial strains in humans might provide more insight. Moreover, prospective cohorts of healthy subjects using fecal samples collected at baseline can help to identify causally involved specific intestinal bacterial strains that drive aberrant human metabolism. Ultimately, it would be a great asset if potential diagnostic and therapeutic targets could be derived from this novel player in human cardiometabolism., (Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.)

The term 'therapeutic angiogenesis' originated almost two decades ago, following evidence that factors that promote blood vessel formation could be delivered to ischaemic tissues and restore blood flow. Following this proof-of-principle, safety and efficacy of the best-studied angiogenic factors (eg, vascular endothelial growth factor) were demonstrated in early clinical studies. Promising results led to the development of larger controlled trials that, unfortunately, have failed to satisfy the initial expectations of therapeutic angiogenesis for ischaemic heart disease. As the quest to delay the progression to heart failure secondary to ischaemic heart disease continues, alternative therapies have emerged as potential novel treatments to improve myocardial reperfusion and long-term heart function. The disappointing results of the clinical studies using angiogenic factors were followed by mixed results from the cell therapy trials. This review reflects the current angiogenic strategies for the ischaemic heart, their limitations and discusses future perspectives in the light of recent scientific and clinical evidence. It is proposed that combination therapies may be a new direction to advance therapeutic repair and regeneration of blood vessels in the ischaemic heart.

The aim of this study was to investigate whether respiratory information can be derived from pulse oximetry plethysmogram (pleth) recordings in acutely wheezy preschool children. A digital pulse oximeter was connected via 'Bluetooth' to a notebook computer in order to acquire pleth data. Low pass filtering and frequency analysis were used to derive respiratory rate from the pleth trace; the ratio of heart rate to respiratory rate (HR/RR) was also calculated. Recordings were obtained during acute wheezy episodes in 18 children of median age 31 months and follow-up recordings from 16 of the children were obtained when they were wheeze-free. For the acutely wheezy children, frequency analysis of the pleth waveform was within 10 breaths/min of clinical assessment in 25 of 29 recordings in 15 children. For the follow-up measurements, frequency analysis of the pleth waveform showed similarly good agreement in recordings on 15 of the 16 children. Respiratory rate was higher (p < 0.001), and HR/RR ratio was lower (p = 0.03) during acute wheeze than at follow-up. This study suggests that respiratory rate can be derived from pleth traces in wheezy preschool children.

Introduction: Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare recessive disorder of cholesterol metabolism characterized by the absence of high density lipoprotein (HDL) and the triad of corneal opacification, hemolytic anemia and glomerulopathy., Patients: We here report on FLD in three siblings of a kindred of Moroccan descent with HDL deficiency. In all cases (17, 12 and 3 years of age) corneal opacification and proteinuria were observed. In the 17-year-old female proband, anemia with target cells was observed., Results: Homozygosity for a mutation in LCAT resulted in the exchange of cysteine to tyrosine at position 337, disrupting the second disulfide bond in LCAT. LCAT protein and activity were undetectable in the patients' plasma and in media of COS7 cells transfected with an expression vector with mutant LCAT cDNA. Upon treatment with an ACE inhibitor and a thiazide diuretic, proteinuria in the proband decreased from 6g to 2g/24h., Conclusion: This is the first report that FLD can cause nephropathy at a very early age., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine and compare select temporal-distance measures of stepping-in-place with gait ability in 2 age-matched groups., Design: Repeated measures, matched research design., Setting: Gait laboratory and hospital outpatient unit., Participants: Convenience sample recruited from within the community and the outpatient unit of a local rehabilitation hospital included 30 healthy adults (age range, 58.1 +/- 10.8yr) and 30 age-matched adults with hemiplegia (age range, 58.6 +/- 10.3yr), secondary to a cerebrovascular accident., Interventions: Subjects were videotaped in the sagittal plane performing stepping-in-place and while walking. Select temporal-distance measures obtained by manual calculations from the video recordings were determined for 3 20-second trials of each activity., Main Outcome Measures: Single limb support duration (SLSD) of the lower extremities (LEs) and step frequency during stepping-in-place and during gait., Results: A significant difference was found between the step frequency of each activity for the adults with hemiplegia (p <.05), but not for the healthy adults. A significant difference was also found between SLSD of the same LE across activities for each group (p <.05). SLSD of each LE during each individual activity, stepping-in-place, or gait, was not significantly different for the healthy adults, indicating LE symmetry; but it was significantly different for the adults with hemiplegia (p <.05), indicating LE asymmetry., Conclusions: Stepping-in-place incorporates reciprocal, rhythmic LE movement patterns similar to gait. And, although SLSD of the LEs was different between the activities in both groups, each group showed similar LE movement patterns during each individual activity. In addition, step frequency was consistent between the activities for the healthy adults. These results seem to indicate that the reciprocal, rhythmic LE movement patterns, which are invoked during gait, may also be invoked during stepping-in-place. However, further research is needed to enhance the data related to stepping-in-place and gait ability in clinical populations.

Background: Type II diabetes mellitus is a major health problem among Native Americans, and diabetic retinopathy is a frequent complication of this disease. Screening for retinopathy can identify early disease and prevent major vision loss, but the most cost-effective screening method has not yet been determined., Methods: In a rural clinic that served more than 400 Native Americans with diabetes, we compared the accuracy of referrals made based on two screening methods: ophthalmoscopy by trained primary care physicians and seven-view nonstereoscopic, mydriatic fundal photography read by two general ophthalmologists and a retinal specialist. Patients in whom abnormal findings were detected by either screening method were then referred to a general ophthalmologist for further evaluation., Results: Two hundred forty-three examinations were performed and 83 referrals made. Both screening methods had high sensitivity for referring patients with retinopathy that required treatment or follow-up sooner than 1 year (100% for direct ophthalmoscopy by primary care physicians, 94% for the general ophthalmologist photography readers, and 100% for the retinal specialist reader). The calculated costs of screening by direct ophthalmoscopy and by retinal photography were 64% less and 44% to 35% less, respectively, than the cost of yearly ophthalmological examinations by ophthalmologists., Conclusions: Careful screening for treatable diabetic eye disease by trained primary care physicians proved to be a clinically acceptable, cost-effective strategy. Screening methods for diabetic retinopathy should be evaluated based on the absolute sensitivity, specificity, and predictive values of their ability to correctly refer patients rather than their diagnostic accuracy.