Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis

Recently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the present study was to compare the effects of the flutter and the positive expiratory pressure (PEP) mask on symptoms and lung function in children with CF. In a crossover randomized study 22 patients with CF (mean age 12 yrs, range 7-17 yrs) performed physiotherapy using either the flutter or the PEP mask twice a day during two treatment periods of 2 weeks, separated by a one week wash-out period, in a random sequence. Lung function parameters (peak expiratory flow, forced vital capacity (FVC), forced expiratory volume in one second, maximal midexpiratory flow, maximal expiratory flow at 25% of FVC, thoracic gas volume, total lung capacity, residual volume/total lung capacity, airway resistance and specific airway conductance) and changes in transcutaneous oxygen haemoglobin saturation were assessed before and after the first supervised session and at the end of each treatment period. Throughout the study peak flow was measured and symptoms were scored daily. No significant changes in any lung function parameter occurred after a single session or after 2 weeks of physiotherapy with either method. There was no difference in acceptability and subjective efficacy. In conclusion, any superiority of the flutter over the positive expiratory pressure mask technique for expectoration could not be confirmed during 2 weeks of daily treatment in children with cystic fibrosis. Both methods are well accepted by children and do not change lung function. Long-term comparison of both methods, including expectoration measurements, seems to be required for further evaluation of the potential success of physiotherapy in cystic fibrosis

The low transverse Pfannenstiel incision and the prevalence of incisional hernia and nerve entrapment

Objective: The authors determined the prevalence of incisional hernia and nerve entrapment in patients with a low transverse Pfannenstiel incision. Summary Background Data: The literature on the Pfannenstiel incision suggests an incisional hernia rate of 0.0% to 0.5%. However, in these series, physical examination, which is essential in the authors' view, was not performed. To the authors' knowledge, the prevalence of nerve entrapment after the Pfannenstiel incision is not known or has never been published. Methods: All adult women, operated on between 1986 and 1992 using a Pfannenstiel incision and not having had another lower abdominal incision other than for laparoscopy, were invited for follow-up at the outpatient department. All patients were interviewed and subjected to a physical examination, with special interest to the presence of incisional hernia or nerve entrapment. Results: In patients having had a Pfannenstiel incision, no incisional hernias were found. In patients also having had a laparoscopy, the incisional hernia rate was 3.5%. Nerve entrapment was found in 3.7%. The length of the incision was ide

Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference

BACKGROUND: DNA methylation is a key epigenetic modification in human development and disease, yet there is limited understanding of its highly coordinated regulation. Here, we identify 818 genes that affect DNA methylation patterns in blood using large-scale population genomics data. RESULTS: By employing genetic instruments as causal anchors, we establish directed associations between gene expression and distant DNA methylation levels, while ensuring specificity of the associations by correcting for linkage disequilibrium and pleiotropy among neighboring genes. The identified genes are enriched for transcription factors, of which many consistently increased or decreased DNA methylation levels at multiple CpG sites. In addition, we show that a substantial number of transcription factors affected DNA methylation at their experimentally determined binding sites. We also observe genes encoding proteins with heterogenous functions that have widespread effects on DNA methylation, e.g., NFKBIE, CDCA7(L), and NLRC5, and for several examples, we suggest plausible mechanisms underlying their effect on DNA methylation. CONCLUSION: We report hundreds of genes that affect DNA methylation and provide key insights in the principles underlying epigenetic regulation

Cross-reactive probes on Illumina DNA methylation arrays: a large study on ALS shows that a cautionary approach is warranted in interpreting epigenome-wide association studies

Illumina DNA methylation arrays are a widely used tool for performing genome-wide DNA methylation analyses. However, measurements obtained from these arrays may be affected by technical artefacts that result in spurious associations if left unchecked. Cross-reactivity represents one of the major challenges, meaning that probes may map to multiple regions in the genome. Although several studies have reported on this issue, few studies have empirically examined the impact of cross-reactivity in an epigenome-wide association study (EWAS). In this paper, we report on cross-reactivity issues that we discovered in a large EWAS on the presence of the C9orf72 repeat expansion in ALS patients. Specifically, we found that that the majority of the significant probes inadvertently cross-hybridized to the C9orf72 locus. Importantly, these probes were not flagged as cross-reactive in previous studies, leading to novel insights into the extent to which cross-reactivity can impact EWAS. Our findings are particularly relevant for epigenetic studies into diseases associated with repeat expansions and other types of structural variation. More generally however, considering that most spurious associations were not excluded based on pre-defined sets of cross-reactive probes, we believe that the presented data-driven flag and consider approach is relevant for any type of EWAS

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor

Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference

Background DNA methylation is a key epigenetic modification in human development and disease, yet there is limited understanding of its highly coordinated regulation. Here, we identify 818 genes that affect DNA methylation patterns in blood using large-scale population genomics data. Results By employing genetic instruments as causal anchors, we establish directed associations between gene expression and distant DNA methylation levels, while ensuring specificity of the associations by correcting for linkage disequilibrium and pleiotropy among neighboring genes. The identified genes are enriched for transcription factors, of which many consistently increased or decreased DNA methylation levels at multiple CpG sites. In addition, we show that a substantial number of transcription factors affected DNA methylation at their experimentally determined binding sites. We also observe genes encoding proteins with heterogenous functions that have widespread effects on DNA methylation, e.g.,NFKBIE,CDCA7(L), andNLRC5, and for several examples, we suggest plausible mechanisms underlying their effect on DNA methylation. Conclusion We report hundreds of genes that affect DNA methylation and provide key insights in the principles underlying epigenetic regulation.Development and application of statistical models for medical scientific researc

Dry-off and dairy cow udder health and welfare : Effects of different milk cessation methods

The cessation of milking at the end of lactation is a routine management practice in dairy herds, and the importance of the dry period for milk production and udder health, has long been recognized. Among countries and herds, drying-off practices differ and include various milk cessation methods, such as changes in milking frequency and in feeding, the use of antibiotic dry cow therapy and teat sealants, and changes in housing. Published studies reporting methods of stopping milk production are scarce, and there are no uniform recommendations on optimal procedures to dry cows off for good udder health, cow welfare, and milk production. This review describes methods to stop mik production to prepare cows for the dry period and their effects on mammary involution, udder health, and dairy cow welfare. Milk yield at dry-off (the final milking at the end of lactation) is important for rapid involution, which stimulates the immune system and promotes good udder health and cow welfare. Based on the findings of this review, gradual cessation of milking over several days before the final milking can effectively reduce milk yield at dry-off and accelerate mammary gland involution while maximizing cow comfort and welfare. Data from this review indicate a target production level of 15 kg/day of milk or less at dry-off. (c) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Innovative virtual reality measurements for embryonic growth and development

Background Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. Methods In a longitudinal study, three-dimensional (3D) measurements were performed from 6 to 14 weeks gestational age in 32 pregnancies (n = 16 spontaneous conception, n = 16 IVF/ICSI). A total of 125 3D volumes were analysed in the I-Space VR system, which allows binocular depth perception, providing a realistic 3D illusion. Crown-rump length (CRL), biparietal diameter (BPD), occipito-frontal diameter (OFD), head circumference (HC) and abdominal circumference (AC) were measured as well as arm length, shoulder width, elbow width, hip width and knee width. Result SCRL, BPD, OFD and HC could be measured in more than 96 of patients, and AC in 78. Shoulder width, elbow width, hip width and knee width could be measured in more than 95 of cases, and arm length in 82 of cases. Growth curves were constructed for all variables. Ear and foot measurements were only possible beyond 9 weeks gestation. Conclusions This study provides a detailed, longitudinal description of normal human embryonic growth, facilitated by a VR system. Growth curves were created for embryonic biometry of the CRL, BPD, HC and AC early in pregnancy and also of several 'new' biometric measurements. Applying virtual embryoscopy will enable us to diagnose growth and/or developmental delay earlier and more accurately. This is especially important for pregnancies at risk of severe complications, such as recurrent late miscarriage and early growth restriction