Use of antibiotics and risk of type 2 diabetes, overweight and obesity : the Cardiovascular Risk in Young Finns Study and the national FINRISK study

Purpose To investigate whether exposure to systemic antibiotics influences the risk of developing type 2 diabetes and overweight/obesity. Methods The study sample comprised 2209 (110 with incident diabetes) participants from the population-based Cardiovascular Risk in Young Finns Study (YFS) aged 24-39 years in 2001. The exposure was national linked register data on purchased antibiotic courses between 1993 and 2001. Clinical examinations including BMI were conducted in 2001, 2007 and 2011. Participants with prevalent diabetes in 2001 were excluded. Data on type 2 diabetes was also obtained from two national registers until 2017. Data from four population-based National FINRISK studies were used for replication (N = 24,674, 1866 with incident diabetes). Results Prior antibiotic exposure (> 5 versus 0-1 antibiotic courses) was associated with subsequent type 2 diabetes in both YFS (OR 2.29; 95%CI 1.33-3.96) and FINRISK (HR 1.73; 95%CI 1.51-1.99). An increased risk for type 2 diabetes was observed in YFS (OR 1.043; 95%CI 1.013-1.074) and FINRISK (HR 1.022; 95%CI 1.016-1.029) per course. Exposure to antibiotics increased the risk of overweight/obesity (BMI > 25 kg/m(2)) after a 10-year follow-up in YFS (OR 1.043; 95%CI 1.019-1.068) and in FINRISK (OR 1.023; 95%CI 1.018-1.029) at baseline per antibiotic course. Adjustments for confounders from early life in YFS and at baseline in FINRISK, including BMI, socioeconomic status, smoking, insulin, blood pressure, and physical activity, did not appreciably alter the findings. Conclusion Our results show that exposure to antibiotics was associated with increased risk for future type 2 diabetes and overweight/obesity and support judicious antibiotic prescribing.Peer reviewe

Ventilation during continuous compressions or at 30:2 compression-to-ventilation ratio results in similar arterial oxygen and carbon dioxide levels in an experimental model of prolonged cardiac arrest

Background: In refractory out-of-hospital cardiac arrest, transportation to hospital with continuous chest compressions (CCC) from a chest compression device and ventilation with 100% oxygen through an advanced airway is common practice. Despite this, many patients are hypoxic and hypercapnic on arrival, possibly related to suboptimal ventilation due to the counterpressure caused by the CCC. We hypothesized that a compression/ventilation ratio of 30:2 would provide better ventilation and gas exchange compared to asynchronous CCC during prolonged experimental cardiopulmonary resuscitation (CPR).Methods: We randomized 30 anaesthetized domestic swine (weight approximately 50 kg) with electrically induced ventricular fibrillation to the CCC or 30:2 group and bag-valve ventilation with a fraction of inspired oxygen (FiO(2)) of 100%. We started CPR after a 5-min no-flow period and continued until 40 min from the induction of ventricular fibrillation. Chest compressions were performed with a Stryker Medical LUCAS (R) 2 mechanical chest compression device. We collected arterial blood gas samples every 5 min during the CPR, measured ventilation distribution during the CPR using electrical impedance tomography (EIT) and analysed post-mortem computed tomography (CT) scans for differences in lung aeration status.Results: The median (interquartile range [IQR]) partial pressure of oxygen (PaO2) at 30 min was 110 (52-117) mmHg for the 30:2 group and 70 (40-171) mmHg for the CCC group. The median (IQR) partial pressure of carbon dioxide (PaCO2) at 30 min was 70 (45-85) mmHg for the 30:2 group and 68 (42-84) mmHg for the CCC group. No statistically significant differences between the groups in PaO2 (p =0.40), PaCO2 (p = 0.79), lactate (p = 0.37), mean arterial pressure (MAP) (p = 0.47) or EtCO2 (p = 0.19) analysed with a linear mixed model were found. We found a deteriorating trend in PaO2, EtCO2 and MAP and rising PaCO2 and lactate levels through the intervention. There were no differences between the groups in the distribution of ventilation in the EIT data or the post-mortem CT findings.Conclusions: The 30:2 and CCC protocols resulted in similar gas exchange and lung pathology in an experimental prolonged mechanical CPR model.Peer reviewe

Carotid artery longitudinal wall motion alterations associated with metabolic syndrome and insulin resistance

Background and aims: Our objective was to study relationships between the new biomarker of vascular health, carotid artery longitudinal wall motion (CALM) and metabolic syndrome (MetS).Methods: Carotid ultrasound and assessment of MetS and its components were performed with 281 subjects aged 30-45 years. In the longitudinal motion analysis, the amplitude of motion and the antegrade-oriented and retrograde-oriented components of motion between the intima-media complex and adventitial layer of the common carotid artery wall were assessed.Results: Metabolic syndrome, according to the harmonized criteria, was detected in 53 subjects (19%). MetS was significantly associated with increased antegrade and decreased retrograde longitudinal motion in the carotid artery wall. Augmented antegrade amplitude of longitudinal motion was associated with obesity (β = 0.149, p p p p p Conclusion: Metabolic syndrome and insulin resistance were associated with alterations in CALM. In particular, hypertension, obesity and hyperinsulinaemia were associated with reduced total peak-to-peak amplitude as well as increased antegrade and reduced retrograde amplitudes, all of which might be markers of unfavourable vascular health.</div

Continuous mHealth Patch Monitoring for the Algorithm-Based Detection of Atrial Fibrillation: Feasibility and Diagnostic Accuracy Study

Peer reviewe

Continuous 24-h Photoplethysmogram Monitoring Enables Detection of Atrial Fibrillation

Aim: Atrial fibrillation (AF) detection is challenging because it is often asymptomatic and paroxysmal. We evaluated continuous photoplethysmogram (PPG) for signal quality and detection of AF.Methods: PPGs were recorded using a wrist-band device in 173 patients (76 AF, 97 sinus rhythm, SR) for 24 h. Simultaneously recorded 3-lead ambulatory ECG served as control. The recordings were split into 10-, 20-, 30-, and 60-min time-frames. The sensitivity, specificity, and F1-score of AF detection were evaluated for each time-frame. AF alarms were generated to simulate continuous AF monitoring. Sensitivities, specificities, and positive predictive values (PPVs) of the alarms were evaluated. User experiences of PPG and ECG recordings were assessed. The study was registered in the Clinical Trials database (NCT03507335).Results: The quality of PPG signal was better during night-time than in daytime (67.3 +/- 22.4% vs. 30.5 +/- 19.4%, p < 0.001). The 30-min time-frame yielded the highest F1-score (0.9536), identifying AF correctly in 72/76 AF patients (sensitivity 94.7%), only 3/97 SR patients receiving a false AF diagnosis (specificity 96.9%). The sensitivity and PPV of the simulated AF alarms were 78.2 and 97.2% at night, and 49.3 and 97.0% during the daytime. 82% of patients were willing to use the device at home.Conclusion: PPG wrist-band provided reliable AF identification both during daytime and night-time. The PPG data's quality was better at night. The positive user experience suggests that wearable PPG devices could be feasible for continuous rhythm monitoring.Peer reviewe

Determinants of left ventricular diastolic function-The Cardiovascular Risk in Young Finns Study

Decreased left ventricular (LV) diastolic function is associated with increased all-cause mortality and risk for a heart failure. The determinants of LV diastolic function have been mainly studied in elderly populations; however, the origin of LV heart failure may relate to the lifestyle factors acquired during the life course. Therefore, we examined biochemical, physiological, and lifestyle determinants of LV diastolic function in 34-49-year-old participants of the Cardiovascular Risk in Young Finns Study (Young Finns Study). In 2011, clinical examination and echocardiography were performed for 1928 participants (880 men and 1048 women; aged 34-49 years). LV diastolic function was primarily defined using E/e-ratio (population mean 4.8, range 2.1-9.0). In a multivariate model, systolic blood pressure (P <0.005), female sex (P <0.005), age (P <0.005), waist circumference (P = 0.024), smoking (P = 0.028), serum alanine aminotransferase (P = 0.032) were directly associated with E/e-ratio, while an inverse association was found for height (P <0.005). Additionally, a higher E/e-ratio was found in participants with concentric hypertrophy compared to normal cardiac geometry (P <0.005). Other indicators of the LV diastolic function including E/A-ratio and left atrial volume index showed similarly strong associations with systolic blood pressure and age. In conclusion, we identified systolic blood pressure, waist circumference and smoking as modifiable determinants of the LV diastolic function in the 34-49-year-old participants of the Young Finns Study.Peer reviewe

Lower grip strength in youth with obesity identifies those with increased cardiometabolic risk

Background: We examined whether grip strength differentiates youth with obesity with increased cardiometabolic risk.Methods: The sample comprised 43 youth with severe obesity (mean age 14.8, standard deviation 3.0 years) enrolled in the Childhood Overweight BioRepository of Australia. Grip strength was normalized to body mass and categorized as low and moderate/high.Results: Youth with low grip strength had higher systolic blood pressure (mean difference 13 mmHg), lowdensity lipoprotein cholesterol (0.26 mmol/l), continuous metabolic syndrome score (0.36), and carotid intima-media thickness (0.05 mm) compared with those with moderate/high grip strength.Conclusions: Low grip strength may differentiate youth with obesity with increased cardiometabolic risk.</p

Structure and characterization of a novel chicken biotin-binding protein A (BBP-A)

BACKGROUND: The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin. RESULTS: Here, we expand the repertoire of known macromolecular biotin binders by reporting a novel biotin-binding protein A (BBP-A) from chicken. The BBP-A recombinant protein was expressed using two different expression systems and purified with affinity chromatography, biochemically characterized and two X-ray structures were solved – in complex with D-biotin (BTN) and in complex with D-biotin D-sulfoxide (BSO). The BBP-A protein binds free biotin with high, "streptavidin-like" affinity (K(d )~ 10(-13 )M), which is about 50 times lower than that of chicken avidin. Surprisingly, the affinity of BBP-A for BSO is even higher than the affinity for BTN. Furthermore, the solved structures of the BBP-A – BTN and BBP-A – BSO complexes, which share the fold with the members of the avidin and lipocalin protein families, are extremely similar to each other. CONCLUSION: BBP-A is an avidin-like protein having a β-barrel fold and high affinity towards BTN. However, BBP-A differs from the other known members of the avidin protein family in thermal stability and immunological properties. BBP-A also has a unique ligand-binding property, the ability to bind BTN and BSO at comparable affinities. BBP-A may have use as a novel material in, e.g. modern bio(nano)technological applications

Structure and characterization of a novel chicken biotin-binding protein A (BBP-A)

Background. The chicken genome contains a BBP-A gene showing similar characteristics to avidin family genes. In a previous study we reported that the BBP-A gene may encode a biotin-binding protein due to the high sequence similarity with chicken avidin, especially at regions encoding residues known to be located at the ligand-binding site of avidin. Results. Here, we expand the repertoire of known macromolecular biotin binders by reporting a novel biotin-binding protein A (BBP-A) from chicken. The BBP-A recombinant protein was expressed using two different expression systems and purified with affinity chromatography, biochemically characterized and two X-ray structures were solved – in complex with D-biotin (BTN) and in complex with D-biotin D-sulfoxide (BSO). The BBP-A protein binds free biotin with high, "streptavidin-like" affinity (Kd ~ 10-¹³ M), which is about 50 times lower than that of chicken avidin. Surprisingly, the affinity of BBP-A for BSO is even higher than the affinity for BTN. Furthermore, the solved structures of the BBP-A – BTN and BBP-A – BSO complexes, which share the fold with the members of the avidin and lipocalin protein families, are extremely similar to each other. Conclusion. BBP-A is an avidin-like protein having a β-barrel fold and high affinity towards BTN. However, BBP-A differs from the other known members of the avidin protein family in thermal stability and immunological properties. BBP-A also has a unique ligand-binding property, the ability to bind BTN and BSO at comparable affinities. BBP-A may have use as a novel material in, e.g. modern bio(nano)technological applications.peerReviewe

Association of Childhood Oral Infections With Cardiovascular Risk Factors and Subclinical Atherosclerosis in Adulthood

Importance:  Severe forms of common chronic oral infections or inflammations are associated with increased cardiovascular risk in adults. To date, the role of childhood oral infections in cardiovascular risk is not known because no long-term studies have been conducted.Objective:  To investigate whether signs of oral infections in childhood are associated with cardiovascular risk factors and subclinical atherosclerosis in adulthood.Design, Setting, and Participants:  The cohort study (n = 755) was derived from the Cardiovascular Risk in Young Finns Study, an ongoing prospective cohort study in Finland initiated in 1980. Participants underwent clinical oral examinations during childhood, when they were aged 6, 9, or 12 years and a clinical cardiovascular follow-up in adulthood in 2001 at age 27, 30, or 33 years and/or in 2007 at age 33, 36, or 39 years. Cardiovascular risk factors were measured at baseline and during the follow-up until the end of 2007. Final statistical analyses were completed on February 19, 2019.Main Outcomes and Measures:  Four signs of oral infections (bleeding on probing, periodontal probing pocket depth, caries, and dental fillings) were documented. Cumulative lifetime exposure to 6 cardiovascular risk factors was calculated from dichotomized variables obtained by using the area-under-the-curve method. Subclinical atherosclerosis (ie, carotid artery intima-media thickness [IMT]) was quantified in 2001 (n = 468) and 2007 (n = 489).Results:  This study included 755 participants, of whom 371 (49.1%) were male; the mean (SD) age at baseline examination was 8.07 (2.00) years. In this cohort, 33 children (4.5%) had no sign of oral infections, whereas 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, and 248 (34.1%) had 4 signs. The cumulative exposure to risk factors increased with the increasing number of oral infections both in childhood and adulthood. In multiple linear regression models, childhood oral infections, including signs of either periodontal disease (R2 = 0.018; P = .01), caries (R2 = 0.022; P = .008), or both (R2 = 0.024; P = .004), were associated with adulthood IMT. The presence of any sign of oral infection in childhood was associated with increased IMT (third tertile vs tertiles 1 and 2) with a relative risk of 1.87 (95% CI, 1.25-2.79), whereas the presence of all 4 signs produced a relative risk of 1.95 (95% CI, 1.28-3.00). The associations were more obvious in boys: if periodontal disease were present, the corresponding estimate was 1.69 (95% CI, 1.21-2.36); if caries, 1.46 (95% CI, 1.04-2.05); and if all 4 signs of oral infections, 2.25 (95% CI, 1.30-3.89). The associations were independent of cardiovascular risk factors.Conclusions and Relevance:  Oral infections in childhood appear to be associated with the subclinical carotid atherosclerosis seen in adulthood.</p