91 research outputs found

    Standards for Specialized Nutrition Support: Home Care Patients

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141435/1/ncp0579.pd

    Sex-differences in the oxygenation levels of intercostales and vastus lateralis muscles during incremental exercise

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    This study aimed to examine sex differences in oxygen saturation in respiratory (SmO2-m.intercostales) and locomotor muscles (SmO2-m.vastus lateralis) while performing physical exercise. Twenty-five (12 women) healthy and physically active participants were evaluated during an incremental test with a cycle ergometer, while ventilatory variables (lung ventilation [V ̇E], tidal volume [Vt], and respiratory rate [RR]) were acquired through the breath-by-breath method. SmO2 was acquired using the MOXY devices on the m.intercostales and m.vastus lateralis. A two-way ANOVA (sex × time) indicated that women showed a greater significant decrease of SmO2-m.intercostales, and men showed a greater significant decrease of SmO2-m.vastus lateralis. Additionally, women reached a higher level of ΔSmO2-m.intercostales normalized to V ̇E (L·min-1) (p<0.001), whereas men had a higher level of ΔSmO2-m.vastus lateralis normalized to peak workload-to-weight (watts·kg-1, PtW) (p=0.049), as confirmed by Student's t-test. During an incremental physical exercise, women experienced a greater cost of breathing, reflected by greater deoxygenation of the respiratory muscles, whereas men had a higher peripheral load, indicated by greater deoxygenation of the locomotor muscles

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

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    BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

    The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

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    We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations

    Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

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    Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

    Fatigue and rest of the hamster diaphragm

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    Decreased respiratory muscle strength and/or excessive loads imposed on the respiratory muscles by disease may result in respiratory muscle fatigue and ventilatory failure. Once the respiratory muscles fatigue, the only treatment is rest by mechanical ventilation. However, no one has yet determined the best protocol of rest. The purpose of these studies was to develop an animal model in the hamster in order to examine the time course of recovery following fatigue of the diaphragm and specifically, to test whether mechanical ventilation or spontaneous unloaded breathing was a better mode for functional recovery. The studies required the initial development of an anesthetic regimen which produced minimal respiratory depression in the hamster. A new method of stimulating the diaphragm in small animals was developed by apposing plate electrodes directly against the diaphragm. The validity of this technique was examined and comparison of the mechanical and electrophysiological response to that of phrenic nerve stimulation were similar at maximal stimulation. The histological characteristics of the normal hamster diaphragm were determined for fibre type proportions and sizes, oxidative capacity and glycogen levels in the costal and crural regions of this muscle. The examination revealed three distinct areas of the diaphragm with different histological features: the abdominal surface of the crural region, the thoracic surface of the crural region and the sternal and costal region. Diaphragmatic fatigue was induced in vivo by repetitive electrical stimulation which resulted in both high and low frequency fatigue. The fatigue stimulus also produced muscle fibre damage, primarily along the abdominal surface of the diaphragm over the electrodes, and glycogen depletion in the type lib fibres. Rest by continuous mechanical ventilation resulted in recovery of high frequency fatigue in the hamster diaphragm whereas rest by spontaneous unloaded breathing resulted in no recovery. Sham fatigue groups rested by either mechanical ventilation or spontaneous breathing demonstrated progressive deterioration in transdiaphragmatic pressure throughout the rest period. Decreased muscle fibre damage but increased inflammation and glycogen depletion was demonstrated in all four fatigue/sham fatigue and rest groups compared to that demonstrated by the fatigue/sham fatigue only groups. The results suggest that passive rest by continuous mechanical ventilation promotes recovery following fatigue induced by electrical stimulation. Additional factors such as prolonged fasting, loads imposed on the diaphragm by the plate electrode apparatus, positive pressure ventilation, and cumulative effects of intraperitoneal urethane likely contributed to the progressive deterioration of diaphragmatic function demonstrated in the animals of the two sham groups rested by either spontaneous breathing or mechanical ventilation, and confounded the results shown by the two fatigue groups rested by either spontaneous breathing or mechanical ventilation.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat
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