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We cross-sectionally investigated irregular breakfast consumption and food timing patterns in relation to weight status and inflammation among 644 participants in the Cancer Prevention Study-3 Diet Assessment Sub-study. Breakfast consumption, and the individual means and the intra-individual standard deviation (iSD) of time at first intake of the day, duration of daily intake window, and midpoint of daily intake window were collected via six 24-hour recalls and examined in relation to body mass index (BMI), waist circumference (WC), and inflammation (GlycA). Compared to consuming breakfast on all six recalls, linear regression models showed those who consumed breakfast on 5 or 4 of the days had a 1.29 (95% CI: 0.19, 2.38) and 1.64 kg/m2 (95% CI: 0.12, 3.16) higher BMI; no association for consuming breakfast ≤3 days. 1-hour later in the average time of first intake was associated with a 0.44 kg/m2 higher BMI (95% CI: 0.04, 0.84). A 1-hour increase in the iSD of first intake, was associated with a 1.12 (95% CI: 0.49, 1.75) higher BMI; iSD in duration and midpoint of intake window were significant prior to additional adjustment for iSD in first intake. 1-hour increases in iSD for first intake time (β: 0.15; 95% CI: 0.04, 0.26) and midpoint of intake window (β: 0.16; 95% CI: 0.02, 0.31) were associated with higher GlycA. No associations were observed for WC independent of BMI. The results provide evidence that irregularity in breakfast consumption and daily intake timing patterns, particularly early in the day, may be related to weight status and inflammation.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Oats can be processed in a variety of ways ranging from minimally processed such as steel-cut oats (SCO), to mildly processed such as large-flake oats (old fashioned oats, OFO), moderately processed such as instant oats (IO) or highly processed in ready-to-eat oat cereals such as Honey Nut Cheerios (HNC). Although processing is believed to increase glycaemic and insulinaemic responses, the effect of oat processing in these respects is unclear. Thus, we compared the glycaemic and insulinaemic responses elicited by 628 kJ portions of SCO, OFO, IO and HNC and a portion of Cream of Rice cereal (CR) containing the same amount of available-carbohydrate (23 g) as the oatmeals. Healthy males (n 18) and females (n 12) completed this randomised, cross-over trial. Blood was taken fasting and at intervals for 3 h following test-meal consumption. Glucose and insulin peak-rises and incremental AUC (iAUC) were subjected to repeated-measures ANOVA using Tukey’s test (two-sided P<0·05) to compare individual means. Glucose peak-rise (primary endpoint, mean (sem) mmol/l) after OFO, 2·19 (sem 0·11), was significantly less than after CR, 2·61 (sem 0·13); and glucose peak-rise after SCO, 1·93 (sem 0·13), was significantly less than after CR, HNC, 2·49 (sem 0·13) and IO 2·47 (sem 0·13). Glucose iAUC was significantly lower after SCO than CR and HNC. Insulin peak rise was similar among the test meals, but insulin iAUC was significantly less after SCO than IO. Thus, the results show that oat processing affects glycaemic and insulinaemic responses with lower responses associated with less processing.
Introduction: Pain is a significant driver of demand in emergency care and 65% of adult patients with trauma also report moderate to severe pain. Inhaled low dose methoxyflurane (MEOF) a rapid-acting patient administered inhalational analgesic was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. This study will generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of MEOF in Canadian emergency departments. Methods: This is a phase IV, prospective open label, multi-centre study. Approximately 100 adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10≥4) associated with single system trauma will be enrolled at 5-10 EDs across Canada. Patients will receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication will be permitted at any time, if required. Results: Planned Assessments and Outcome Measures: Pain will be assessed using the NRS0-10 at 4 time points: screening/triage, 5 minutes and 20 minutes post-start of administration (STA) of MEOF, and when ready for discharge. Secondary assessments will include the speed of action of analgesia (from STA of MEOF); patient and physician satisfaction with treatment (as assessed through Global Medical Performance (GMP) at 20 minutes post-STA and when ready for discharge); patient and physician fulfilment of pain relief expectations (assessed when ready for discharge); use of rescue medication and treatment-emergent adverse events. Exploratory outcomes will include the time to disposition, time to readiness for discharge and responder analysis. The primary outcome measure will be the change in pain intensity over 20 minutes from the start of administration of MEOF as measured on the NRS0-10. Conclusion: We report on the methodology of a phase IV, prospective open label, multi-centre study, evaluating the use of MEOF for the management of acute traumatic pain in Canadian Emergency Departments.
Introduction: Acute migraine headaches are common causes of presentation to the emergency department (ED). There is great variability in the efficacy of the available parenteral agents to manage pain, though triptans are among the recommended treatments. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review examined pain management in emergency settings and assessed the effectiveness of triptan agents. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Pain scale scores were analyzed using standardized mean difference (SMD) with 95% confidence intervals (CIs) calculated using a random effects model; heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Pain was measured within the ED or equivalent acute care setting using a variety of pain scales, most commonly the 0-10 cm or 100 mm visual analog scale. Four studies compared pain scores between patients receiving sumatriptan vs. other agents, of which, patients receiving sumatriptan reported higher pain scale scores (SMD = 0.53; 95% CI: 0.04, 1.02; I2 = 80%). In particular, patients receiving sumatriptan reported higher pain scale scores than patients receiving metoclopramide (SMD = 0.68; 95% CI: 0.31, 1.04; n = 1) or ketorolac (SMD = 1.39; 95% CI: 0.56, 2.21; n = 1). Overall, studies comparing anti-inflammatory agents (i.e., ketorolac or dexketoprofen) to other agents reported improved pain scale scores among patients receiving anti-inflammatory agents (SMD = -0.38; 95% CI: -0.73, -0.03; I2 = 66%; n = 5). Conclusion: Limited evidence suggests that patients treated with metoclopramide or anti-inflammatory agents experience greater pain reduction compared to patients treated with sumatriptan. This review will conduct a network analysis of parenteral agents to examine the comparative effectiveness of parenteral agents to manage pain among patients with acute migraine. Further analysis will also consider the balance between efficacy and adverse events.
Introduction: Although a variety of parenteral agents exist for the treatment of acute migraine, relapse after an emergency department (ED) visit is still a common occurrence. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review focused on those studies aiming a reduction in relapse after an ED visit. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to identify comparative studies to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Relapse was reported in 44 (38%) included studies and occurred commonly in patients receiving placebo or no interventions (median = 39%; IQR: 14%, 47%). Overall, no differences in headache relapse were found between patients receiving sumatriptan or placebo (RR = 1.09; 95% CI: 0.55, 2.17; I2 = 93%; n = 8). Conversely, patients receiving neuroleptic agents experienced fewer relapses compared to placebo (RR = 0.27; 95% CI: 0.12, 0.58; I2 = 0%; n = 3); however, patients receiving neuroleptics reported an increase in adverse events (RR = 1.87; 95% CI: 1.17, 3.00; I2 = 0%; n = 3). Compared to placebo, patients receiving dexamethasone were less likely to experience a headache recurrence (RR = 0.71; 95% CI: 0.53, 0.95; I2 = 60%, n = 9); however, no differences were found in reported adverse events (RR = 1.09; 95% CI: 0.81, 1.47; I2 = 0%; n = 3). Conclusion: Relapse is a common occurrence for patients with migraine headaches. This review found patients receiving neuroleptics or dexamethasone experienced fewer headache recurrences. Conversely, triptan agents appear to have minimal effect on reducing the risk for headache recurrence following discharge from an acute care setting. Limited available data on adverse events is an important limitation to inform decision-making. Guidelines should be revised to reflect these results.
To describe the use of balloon dilation with non-invasive ventilation in the treatment of pregnant patients with idiopathic subglottic stenosis.
The medical charts of four consecutive patients who underwent jet ventilation or high-flow nasal cannula oxygenation with balloon dilation for the treatment of idiopathic subglottic stenosis during pregnancy were reviewed.
Objective improvement of subglottic stenosis was seen in all four cases, with end-result Myer–Cotton grade 1 lesions down from pre-procedure grade 3 lesions. Patients also reported subjective improvements in symptomatology, with no further airway issues. All patients delivered normally, at term.
Laryngeal dilation with continuous radial expansion pulmonary balloons using non-invasive ventilation for the treatment of idiopathic subglottic stenosis in pregnant patients is safe and efficacious, and should be the first line treatment option for this patient population. The improvement in symptoms, and lack of labour and pregnancy complications, distinguish this method of treatment from others reported in the literature.
We estimate the values of bull phenotypic traits, performance measurements, and expected progeny differences (EPDs) over time using bull sale data from an auction in Tennessee from 2006 to 2016. Moreover, we determine how a state partial-cost reimbursement program for bulls with certain EPDs affects bull sale price. Purebred seed stock producers in this region should focus on selling large, fast-growing, mature bulls that produce lighter calves for reduced calving stress. The state cost-share payment did not significantly increase bull prices in most years, meaning this payment was retained by cow-calf producers in most years.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
A number of procedures for fluorescent X-ray analysis have been introduced to accommodate the samples that are produced from research on the recovery of values from secondary metal sources. For some applications, standards are conveniently available such as those that can be purchased from the National Bureau of Standards. For other applications, secondary standards must be prepared and analyzed by independent methods. The sample preparation procedures vary considerably. For monitoring process efficiency, sample preparation is often kept at a minimum such as simply pouring loose powders into disposable cups. For the most accurate analyses, sample preparatton requires casting the alloys and finishing the surfaces. Matrix correction procedures are employed where concentrations of major constituents vary over wide ranges.
Resin-loaded papers composed of approximately 50% cellulose and 50% ion-exchange or chelating resin provide an ideal matrix for many X-ray spectrographic analyses. Standards are prepared by multiple filtration of solutions of known composition through the paper to achieve quantitative collection or by the use of a radiotracer as a monitor for nonquantitative collection. Solutions prepared fram unknown samples are processed in the same manner as the standards.
Advantages of the resin-loaded papers are: reduction of interelement effects because standards and unknowns are present in a similar low X-ray absorbing matrix; physical parameters such as metallurgical history, grain size, and surface preparation are eliminated; and sampling errors are significantly reduced and sensitivity greatly increased by concentrating trace elements separated from large samples.
Application of these papers to a variety of metallurgical, geological, and water samples will be summarized. The possible use of resin-loaded papers as standards for air pollution monitoring will be examined.
X-ray fluorescence induced by charged particles has been employed in trace element analysis of both animal and human blood, tissue and bone samples. Preparation techniques included microtome slicing and wet digestion in nitric acid, internal chemical standards being used in the latter case.
Most of the specimens arose from a study of interactions between the toxic elements lead and zinc in growing foals; this was motivated by reports of sickness and death in foals raised near lead-zinc smelters. The cause of toxicity in animals from environmental pollution is often attributed to Single factors, whereas in reality interactions among many factors, including a variety of toxic and nutrient trace elements, should be considered.
A variety of spectra are presented and elemental concentrations derived. Agreement between the X-ray data and atomic absorption spectrophotometry is encouraging. The results demonstrate the potential of particle-excited X-ray fluorescenee as a broad-range analytical technique for the study of trace element interactions.
Getting a better understanding of the evolution and nucleosynthetic yields of the most metal-poor stars (Z ≲ 10−5) is critical because they are part of the big picture of the history of the primitive universe. Yet many of the remaining unknowns of stellar evolution lie in the birth, life, and death of these objects. We review stellar evolution of intermediate-mass Z ≤ 10−5 models existing in the literature, with a particular focus on the problem of their final fates. We emphasise the importance of the mixing episodes between the stellar envelope and the nuclearly processed core, which occur after stars exhaust their central He (second dredge-up and dredge-out episodes). The depth and efficiency of these episodes are critical to determine the mass limits for the formation of electron-capture SNe. Our knowledge of these phenomena is not complete because they are strongly affected by the choice of input physics. These uncertainties affect stars in all mass and metallicity ranges. However, difficulties in calibration pose additional challenges in the case of the most metal-poor stars. We also consider the alternative SN I1/2 channel to form SNe out of the most metal-poor intermediate-mass objects. In this case, it is critical to understand the thermally pulsing Asymptotic Giant Branch evolution until the late stages. Efficient second dredge-up and, later, third dredge-up episodes could be able to pollute stellar envelopes enough for the stars to undergo thermal pulses in a way very similar to that of higher initial Z objects. Inefficient second and/or third dredge-up may leave an almost pristine envelope, unable to sustain strong stellar winds. This may allow the H-exhausted core to grow to the Chandrasekhar mass before the envelope is completely lost, and thus let the star explode as an SN I1/2. After reviewing the information available on these two possible channels for the formation of SNe, we discuss existing nucleosynthetic yields of stars of metallicity Z ≤ 10−5 and present an example of nucleosynthetic calculations for a thermally pulsing Super-Asymptotic Giant Branch star of Z = 10−5. We compare theoretical predictions with observations of the lowest [Fe/H] objects detected. The review closes by discussing current open questions as well as possible fruitful avenues for future research.