35 research outputs found

    Longitudinal association between respiratory muscle strength and cough capacity in persons with spinal cord injury::An explorative analysis of data from a randomized controlled trial

    Get PDF
    Objective: To assess the longitudinal association between respiratory muscle strength and cough capacity in persons with recent spinal cord injury. Design: Longitudinal analyses. Subjects: Forty persons with recent spinal cord injury and impaired pulmonary function. Methods: Measurements were performed 4 weeks after the start of rehabilitation, 9 and 17 weeks after the first measurement, and one year after discharge from inpatient rehabilitation. Peak cough flow was measured with a spirometer. Maximum inspiratory and expiratory pressures (MIP and MEP), expressed in cmH(2)O, were measured at the mouth. Results: Both MIP and MEP were significantly positively associated with peak cough flow. After correction for confounders and time 10 cmH(2)O higher MIP was associated with a 0.32 Us higher peak cough flow, and a 10 cmH(2)O higher MEP was associated with a 0.15 l/s higher peak cough flow. The association between MIP and peak cough flow was mainly based on within-subject variance. The association between MIP and peak cough flow was stronger than between MEP and peak cough flow. Conclusion: Improvement in respiratory muscle strength is associated with improvement in cough capacity in persons with recent spinal cord injury who have impaired pulmonary function

    Comparative genome analysis and genome-guided physiological analysis of Roseobacter litoralis

    Get PDF
    <p>Abstract</p> <p>Background</p> <p><it>Roseobacter litoralis </it>OCh149, the type species of the genus, and <it>Roseobacter denitrificans </it>OCh114 were the first described organisms of the <it>Roseobacter </it>clade, an ecologically important group of marine bacteria. Both species were isolated from seaweed and are able to perform aerobic anoxygenic photosynthesis.</p> <p>Results</p> <p>The genome of <it>R. litoralis </it>OCh149 contains one circular chromosome of 4,505,211 bp and three plasmids of 93,578 bp (pRLO149_94), 83,129 bp (pRLO149_83) and 63,532 bp (pRLO149_63). Of the 4537 genes predicted for <it>R. litoralis</it>, 1122 (24.7%) are not present in the genome of <it>R. denitrificans</it>. Many of the unique genes of <it>R. litoralis </it>are located in genomic islands and on plasmids. On pRLO149_83 several potential heavy metal resistance genes are encoded which are not present in the genome of <it>R. denitrificans</it>. The comparison of the heavy metal tolerance of the two organisms showed an increased zinc tolerance of <it>R. litoralis</it>. In contrast to <it>R. denitrificans</it>, the photosynthesis genes of <it>R. litoralis </it>are plasmid encoded. The activity of the photosynthetic apparatus was confirmed by respiration rate measurements, indicating a growth-phase dependent response to light. Comparative genomics with other members of the <it>Roseobacter </it>clade revealed several genomic regions that were only conserved in the two <it>Roseobacter </it>species. One of those regions encodes a variety of genes that might play a role in host association of the organisms. The catabolism of different carbon and nitrogen sources was predicted from the genome and combined with experimental data. In several cases, e.g. the degradation of some algal osmolytes and sugars, the genome-derived predictions of the metabolic pathways in <it>R. litoralis </it>differed from the phenotype.</p> <p>Conclusions</p> <p>The genomic differences between the two <it>Roseobacter </it>species are mainly due to lateral gene transfer and genomic rearrangements. Plasmid pRLO149_83 contains predominantly recently acquired genetic material whereas pRLO149_94 was probably translocated from the chromosome. Plasmid pRLO149_63 and one plasmid of <it>R. denitrifcans </it>(pTB2) seem to have a common ancestor and are important for cell envelope biosynthesis. Several new mechanisms of substrate degradation were indicated from the combination of experimental and genomic data. The photosynthetic activity of <it>R. litoralis </it>is probably regulated by nutrient availability.</p

    New genetic loci link adipose and insulin biology to body fat distribution.

    Get PDF
    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

    Get PDF
    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency

    No full text
    Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12-65K protein, a component of the minor spliceosome. The minor spliceosome plays a role in the splicing of minor (U12-type) introns, which are present in ~700–800 genes in humans and represent about 0.35% of all introns. Here, we report a second family with biallelic RNPC3 variants in three siblings with a growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. These cases further confirm the association between biallelic RNPC3 variants and severe postnatal growth retardation due to growth hormone deficiency. Furthermore, these cases show that the phenotype of this minor spliceosome-related disease might be broader than previously described

    Prospective analysis of body mass index during and up to 5 years after discharge from inpatient spinal cord injury rehabilitation

    Get PDF
    Objective: To investigate the prevalence of overweight/obesity and the course of the body mass index (BMI) in persons with spinal cord injury during and after inpatient rehabilitation. Design: Multi-centre longitudinal study. Subjects: A total of 184 persons with spinal cord injury. Methods: BMI was determined at the start of active rehabilitation, 3 months later, at discharge, and 1, 2 and 5 years after discharge. Results: The percentage of persons who were overweight/obese (BMI >= 22 kg/m(2)) increased over the years from 56% to 75%. The absolute BMI did not significantly increase during rehabilitation, but showed a significant increase the year after discharge from inpatient rehabilitation (p Conclusion: The BMI of people with spinal cord injuries gradually increases during and after inpatient rehabilitation, with significant increases in the first year after discharge. It is recommended that emphasis is placed on weight-management protocols (diet and exercise) to encourage a healthy lifestyle

    Field triage in the ambulance versus referral via non-percutaneous coronary intervention centre in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: A systematic review

    No full text
    AIMS: The purpose of this study was to determine whether direct ambulance transport of ST-elevation myocardial infarction (STEMI) patients to a percutaneous coronary intervention (PCI) hospital (field triage) leads to a lower 30-day mortality compared to transport via a referral non-PCI hospital (referral via a spoke centre) in STEMI patients. METHODS AND RESULTS: We performed a systematic review of interventions. An experienced librarian searched in PubMed, EMBASE.com and The Cochrane Library (via Wiley) from January 1980-February 2013. Studies that examined field triage and/or referral via a spoke centre in STEMI patients treated with primary or facilitated PCI were included. Two authors independently conducted the study selection and data extraction. Multivariable frequency weighted logistic regression analysis was performed to assess the effect of the type of transfer on the outcome measures. We identified 14 randomised clinical trials (RCTs), including 20 transfer groups and 4474 participants. Thirty-day mortality was lower in patients who underwent field triage (3.0%; 95% confidence interval (CI) 2.2-4.2) compared to patients who were referred via a spoke centre (4.7%; 95% CI 4.0-5.5). In multivariable frequency weighted logistic regression analysis, field triage was independently associated with a lower incidence of 30-day mortality (odds ratio (OR): 0.58; 95% CI 0.37-0.89). CONCLUSION: Field triage compared to referral via a spoke centre leads to a lower 30-day mortality in STEMI patients. Therefore, direct ambulance transport to a PCI hospital should become the transfer type for STEMI patients

    Associations between meeting exercise guidelines, physical fitness, and health in people with spinal cord injury

    Get PDF
    PURPOSE: (1) To estimate the proportion of Dutch wheelchair users with spinal cord injury (SCI) who meet different SCI exercise guidelines; (2) to evaluate which demographic and lesion characteristics are associated with meeting these guidelines; (3) whether meeting these guidelines is associated with physical fitness and health. MATERIALS AND METHODS: Based on the PASIPD questionnaire items, participants were allocated to meeting two SCI aerobic exercise guidelines, which differ in exercise load. Differences in personal, lesion, fitness, and health characteristics between groups were tested with a one-way ANOVA. Multiple regression analyses were performed to evaluate if meeting guidelines was associated with better fitness and health. Statistical significance was accepted at p < 0.05. RESULTS: Of the 358 included participants, 63.1% met at least one aerobic exercise guideline. Being female, older age, having tetraplegia, and lower educational level were associated with a lower likelihood to meet the aerobic exercise guidelines. Meeting aerobic exercise guidelines showed a positive association with all respiratory and exercise capacity parameters. Limited associations were found between meeting exercise guidelines and health. CONCLUSIONS: Meeting exercise guidelines was associated with better respiratory functions and exercise capacity with additional fitness and some body composition benefits in higher exercise activity levels.IMPLICATIONS FOR REHABILITATIONMeeting SCI exercise guidelines are associated with better respiratory functions and exercise capacity with additional fitness and body composition benefits when higher exercising at higher activity levels, emphasizing the value and importance of regular exercise in individuals with SCI
    corecore