Respiratory response to walking training in overweight men

The aim of the study was to follow up changes in physiological responses to incremental exercise after 4 weeks of moderate-intensity training in overweight men. Prior to the training, all subjects underwent 2 identical control tests (C1 and C2). Each test included three treadmill running exercises, starting at the treadmill speed of 4 km/h, and increased by 1 km/h at the end of each 4 min stage. The same protocol was repeated after 4 weeks of training (T1). The subjects’ body mass index was not changed after the training. Heart rate, oxygen uptake and blood pressure were significantly reduced in C2 as compared with C1 test. After 4 weeks of training the respiratory frequency (Rf), was lower than that in the C2 but a significant difference was noted only at the running speeds of 4 and 6kmhr-1 (P<0.04). Tidal volume (TV) increased after training in comparison with C2. A significant difference was found at the running speeds of 5 and 6 km/h (P<0.03 and P<0.04, respectively). Minute ventilation (VE) was not significantly different between the tests. The present study showed that in obese subjects 4 weeks of moderate uncontrolled walking training is advantageous for changes in the respiratory pattern. However, it is too short for the cardiovascular adaptation and body weight loss. Familiarization of the subjects with the experimental procedure diminished activation of the sympathetic nervous system and has a important role for the results interpretation

Infrared chemical imaging through nondegenerate two-photon absorption in silicon-based cameras

Chemical imaging based on mid-infrared (MIR) spectroscopic contrast is an important technique with a myriad of applications, including biomedical imaging and environmental monitoring. Current MIR cameras, however, lack in performance and are much less affordable compared to mature Si-based devices, which operate in the visible and near-infrared. Here we demonstrate fast MIR chemical imaging through non-degenerate two-photon absorption (NTA) in a standard Si-based charge-coupled device (CCD). We show that wide-field MIR images can be obtained at 100 ms exposure times using picosecond pulse energies of only a few fJ per pixel through NTA directly on the CCD chip. Because this on-chip approach does not rely on phase-matching, it is alignment-free and does not necessitate complex post-processing of the images. We emphasize the utility of this technique through chemically selective MIR imaging of polymers and biological samples, including MIR videos of moving targets, physical processes and live nematodes

Changes in multiple sclerosis epidemiology in Finland over five decades

Finland is a high-risk region for multiple sclerosis (MS) with several epidemiological studies on the subject published since 1964, but these have not been comprehensively scrutinized. The objective of this study was to review previous studies of Finnish MS epidemiology, introduce new data on MS prevalence in western parts of Finland and do further analyses on data from previous studies. We performed a systematic search on articles regarding MS epidemiology in Finland in PubMed database, and all relevant articles were included in this review. MS prevalences in the western hospital districts of Vaasa, South Ostrobothnia and Pirkanmaa were calculated in 1980-2007 by using previously unpublished data obtained from a retrospective search from hospital administrative registries. To enhance comparability of the epidemiological figures, we calculated age-standardized prevalence of MS from the new data from western hospital districts and previous data from North Ostrobothnia, Southwest Finland and North Karelia. Marked regional differences in MS epidemiology were confirmed with concentration of the disease in the western and south-western parts of the country. The highest regional age-standardized MS prevalence of 288/100 000 was reported in South Ostrobothnia in 2007. A clear and stable increase in MS prevalence was observed through the decades, but the only marked increase in incidence happened in 1990s. Methodological differences hampered direct comparisons of different studies, highlighting the importance of common principles of reporting and standardizing the epidemiological figures. More comprehensive studies on MS epidemiology are still warranted to yield important information concerning the aetiology of the disease

Finnish multiple sclerosis patients treated with cladribine tablets : a nationwide registry study

Background: Cladribine tablets for adult patients with highly active relapsing multiple sclerosis (MS) have been available in Finland since 2018. Real-world data from different genetic and geographical backgrounds are needed to complement data from clinical trials.Methods: We investigated the use of cladribine tablets in Finland in a non-interventional cohort study, based on real-world data from the nationwide Finnish MS registry. All eligible patients who had initiated treatment with cladribine tablets in 2018-2020 were included. Descriptive analyses for outcomes were conducted using summary statistics. Time-dependent endpoints were analyzed using cumulated events analysis based on 1-Kaplan-Meier estimates and curves. Subgroups were analyzed separately according to the number of previous disease-modifying therapies (DMTs) and the most common last preceding therapies.Results: Data of 179 patients were analyzed. Median follow-up time was 19.0 months (interquartile range [IQR] 12.0-26.2). Of the 134 patients who were followed for at least 12 months, 112 patients (83.6%) remained relapse-free during follow-up. Mean annualized relapse rate (ARR) was 1.0 (standard deviation [SD] 0.89) at baseline, and 0.1 (SD 0.30) at follow-up. Patients with two or more previous DMTs had shorter time to first relapse (median 2.5 months, IQR 0.6-9.3) when compared to patients with 0-1 previous DMTs (median 11.4 months, IQR 8.7-13.1) (p=0.013). After excluding patients switching from fingolimod (n=33), a statistically significant difference in time to first relapse was no longer observed between the two groups (p=0.252). Adverse events (AEs) were reported in 30 patients (16.8%). The most frequent AE was headache (n=14, 7.8%). One patient (0.6%) died of cardiac arrest. Discontinuation of cladribine tablets was reported in nine patients (5.0%).Conclusion: The mean ARR observed in this cohort was similar to what has been reported in clinical trials. Approximately half of the patients had used two or more previous DMTs before cladribine tablets. These patients had a shorter time to first relapse when compared to patients with 0-1 previous DMTs, mostly driven by early relapses in patients switching from fingolimod.Peer reviewe

Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition

Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta- coefficient -0.29, p = 0.001) and hippocampal volume (beta- coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p <0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15,95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.Peer reviewe

Epigenome-450K-wide methylation signatures of active cigarette smoking: The Young Finns Study

Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium HumanMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR) <= 0.05, among which is olfactory receptor activity, the flagship novel finding of the present study. Overall, we extended the current knowledge by identifying: (i) three novel smoking related CpG sites, (ii) similar effects as aging on average methylation in shore, and (iii) a novel finding that olfactory receptor activity pathway responds to tobacco smoke and toxin exposure through epigenetic mechanisms

Sport concussion assessment tool-Third edition normative reference values for professional Rugby Union players

Objectives: To establish normative reference data for the SCAT3 in professional Rugby Union players. Design: A cross sectional study in professional Rugby Union players competing in national and international professional competitions between 2015 and 2016. Methods: The SCAT3 was administered pre-season or prior to tournaments. Data was collected electronically using a custom tablet application. SCAT3 subcomponents distributions were described and normative ranges determined using percentile cut-offs for average, unusually low/high, and extremely low/high scores. The association between player characteristics and performance in SCAT3 subcomponents was also investigated in exploratory analyses. Results: A total of 3611 professional Rugby Union players were included. The most common baseline symptom was fatigue (14%). The symptom score median (md) was 0 (interquartile range (IQR) = 0-1). Symptom severity md was 0 (IQR = 0-1). The md of the SAC score was 28 (IQR = 26-29). The md of the MBESS was 2 (IQR = 0-4). The Tandem gait md was 11.1. s (IQR = 10.0-12.7. s). Upper limb coordination was normal in 98.4%. Younger age and lower educational level were associated with worse performance on delayed recall and reverse month sub-components of the SCAT3 (p. < . 0.0001). No statistically significant differences in SCAT3 subcomponents were evident across gender. Conclusions: Representative normative reference values for the SCAT3 among professional Rugby Union players are provided. Baseline performance on concentration and delayed recall tests may be lower in younger athletes or in those with lower educational level

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study

<p>Abstract</p> <p>Background</p> <p>The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM_2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles.</p> <p>Methods</p> <p>Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties.</p> <p>Results</p> <p>The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties.</p> <p>Conclusion</p> <p>When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results.</p

The “Perfect Storm” for Type 1 Diabetes: The Complex Interplay Between Intestinal Microbiota, Gut Permeability, and Mucosal Immunity

It is often stated that type 1 diabetes results from a complex interplay between varying degrees of genetic susceptibility and environmental factors. While agreeing with this principal, our desire is that this Perspectives article will highlight another complex interplay potentially associated with this disease involving facets related to the gut, one where individual factors that, upon their interaction with each another, form a “perfect storm” critical to the development of type 1 diabetes. This trio of factors includes an aberrant intestinal microbiota, a “leaky” intestinal mucosal barrier, and altered intestinal immune responsiveness. Studies examining the microecology of the gastrointestinal tract have identified specific microorganisms whose presence appears related (either quantitatively or qualitatively) to disease; in type 1 diabetes, a role for microflora in the pathogenesis of disease has recently been suggested. Increased intestinal permeability has also been observed in animal models of type 1 diabetes as well as in humans with or at increased-risk for the disease. Finally, an altered mucosal immune system has been associated with the disease and is likely a major contributor to the failure to form tolerance, resulting in the autoimmunity that underlies type 1 diabetes. Herein, we discuss the complex interplay between these factors and raise testable hypotheses that form a fertile area for future investigations as to the role of the gut in the pathogenesis and prevention of type 1 diabetes