2,325 research outputs found
Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing ÎČ-Cell Function and Reducing Insulin Clearance in T2D
CONTEXT: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on ÎČ-cell function and insulin kinetics remains unclear. OBJECTIVE: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and ÎČ-cell function. METHODS: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and ÎČ-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. RESULTS: ÎČ-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). CONCLUSION: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in ÎČ-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further ÎČ-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146
Risk of bone fracture is not increased in women with TS compared to women with ovarian failure
An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5âŻyears (KLIMB).
BACKGROUND: KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5âŻyears with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI. METHODS: Children received age- and weight-based ivacaftor dosages for 84âŻweeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function. RESULTS: All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84âŻweeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3âŻĂâŻupper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8âŻĂâŻULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters. CONCLUSIONS: Ivacaftor was generally well tolerated for up to 108âŻweeks in children aged 2 to 5âŻyears with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24âŻweeks of treatment were maintained for up to an additional 84âŻweeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension
Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.
Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (pâ=â0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US 11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings
Identification of Ventricular Tachycardia Using Intracavitary Ventricular Electrograms: Analysis of Time and Frequency Domain Patterns
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74961/1/j.1540-8159.1988.tb06279.x.pd
Chronic digital infection presenting with gross enlargement of the toes: two case reports and review of the literature
There are many conditions ranging from the benign to the malignant, which can present with enlargement of one or more digits. An understanding of the differential diagnosis is important such that the potentially serious aetiologies are not missed and patients can therefore be treated appropriately
Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods
<p>Abstract</p> <p>Background</p> <p>The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model.</p> <p>Methods</p> <p>Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model.</p> <p>Results</p> <p>The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range.</p> <p>Conclusion</p> <p>Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10 mSv are obtained from the 0 - 20 mSv and 5 - 500 mSv subcohorts. Large and significant cancer risks for Japanese survivors exposed to less than 20 mSv external radiation from the atomic bombs in 1945 cast doubt on the ICRP recommended annual occupational dose limit.</p
Towards the glueball spectrum from unquenched lattice QCD
We use a variational technique to study heavy glueballs on gauge
configurations generated with 2+1 flavours of ASQTAD improved staggered
fermions. The variational technique includes glueball scattering states. The
measurements were made using 2150 configurations at 0.092 fm with a pion mass
of 360 MeV. We report masses for 10 glueball states. We discuss the prospects
for unquenched lattice QCD calculations of the oddballs.Comment: 19 pages, 4 tables and 8 figures. One figure added. Now matches the
published versio
A randomised, open label, active comparator trial assessing the effects of 26âweeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes
Aim
To compare the effects of a glucagonâlike peptideâ1 receptor agonist and a dipeptidyl peptidaseâ4 inhibitor on magnetic resonance imagingâderived measures of cardiovascular function.
Materials and methods
In a prospective, randomized, openâlabel, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100âmg) were compared in asymptomatic, nonâinsulin treated young (aged 18â50âyears) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26âweeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight.
Results
Seventyâsix participants were randomized (54% female, meanâ±âSD age 44â± 6âyears, diabetes duration 4.4âyears, body mass index 35.3â±â6.1 kgâmâ2), of whom 65% had â„1 cardiovascular risk factor. Sixtyâone participants had primary outcome data available. There were no statistically significant betweenâgroup differences (intentionâtoâtreat; mean [95% confidence interval]) in PEDSR change (â0.01 [â0.07, +0.06] sâ1), left ventricular ejection fraction (â1.98 [â4.90, +0.94]%), left ventricular mass (+1.14 [â5.23, +7.50] g) or aortic distensibility (â0.35 [â0.98, +0.28] mmHgâ1âĂâ10â3) after 26âweeks. Reductions in HbA1c (â4.57 [â9.10, â0.37] mmolâmolâ1) and body weight (â3.88 [â5.74, â2.01] kg) were greater with liraglutide.
Conclusion
There were no differences in cardiovascular structure or function after shortâterm use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretinâbased therapies
On the stability of high-speed milling with spindle speed variation
Spindle speed variation is a well-known technique to suppress regenerative machine tool vibrations, but it is usually considered to be effective only for low spindle speeds. In this paper, the effect of spindle speed variation is analyzed in the high-speed domain for spindle speeds corresponding to the first flip (period doubling) and to the first Hopf lobes. The optimal amplitudes and frequencies of the speed modulations are computed using the semidiscre- tization method. It is shown that period doubling chatter can effectively be suppressed by spindle speed variation, although, the technique is not effective for the quasiperiodic chatter above the Hopf lobe. The results are verified by cutting tests. Some special cases are also discussed where the practical behavior of the system differs from the predicted one in some ways. For these cases, it is pointed out that the concept of stability is understood on the scale of the principal period of the systemâthat is, the speed modulation period for variable spindle speed machining and the tooth passing period for constant spindle speed machining
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