Ventilatory and upper-airway resistance responses to upper-airway cooling and CO2 in anaesthetised rats

The effects of upper airway (UA) cool air and CO₂ on breathing and on laryngeal and supraglottic resistances were studied in anaesthetised rats breathing spontaneously through a tracheostomy. Warm, humidified air containing 0, 5 and 9–10% CO₂ and cool, room-humidity air were delivered at constant flow to either the isolated larynx to exit through a pharyngotomy or to the supraglottic UA to exit through the mouth and/or nose (nose open or sealed). Spontaneous tracheal airflow and UA airflows, temperatures and pressures were recorded. CO₂ had no effect on breathing but caused a slight increase in laryngeal resistance which was abolished by cutting the superior laryngeal nerves (SLN). Cool air caused a decrease in respiratory frequency and/or peak inspiratory flow when applied to the isolated larynx or to the supraglottic airway with the nose closed. These effects were abolished by SLN section. With the nose open, the ventilatory inhibition was not abolished by SLN section. Cool air also caused substantial decreases in laryngeal and supraglottic resistances which were attenuated by SLN section and which persisted following recurrent laryngeal nerve section. In conclusion, whilst UA cooling inhibits breathing and decreases UA resistances, UA CO₂ has minimal effects.     

How Many Swallows Are Required to Establish Reliable Esophageal Peristaltic Parameters in Normal Subjects? An On-Line Computer Analysis

Esophageal manometric parameters are often examined using from four to 10 or more swallows to obtain a manometric profile without addressing the question of the reproducibility of these data. We asked the question of "how much is enough?" by statistically comparing five sets of 10 wet swallows (5 ml) each separated by 20 min in eight volunteers using constant infusion manometry. Peristaltic waves were evaluated for amplitude, duration, and velocity using an on-line computer program. Statistical analyses included analysis of variance and the Newman-Keuls test for uniformity among sets of swallows. The sets of 10 swallows showed no evidence of a training effect over time. Less than 5% of all comparisons (Newman-Keuls) showed significant differences. Using 5% variability outside of 1 SD as a cutoff (95% confidence interval) amplitude of normal wet swallows could be adequately defined by more than or equal to five swallows and velocity by more than or equal to seven swallows. Duration shows the greatest overall variability and required more than or equal to eight swallows for accurate assessment. These data suggest that at least five to eight wet swallows should be performed to describe "typical" manometry parameters for normal subjects.     

Assessing the Impact of Salt Reduction Initiatives on the Chronic Disease Burden of Singapore

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.     

The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study

Probiotics have been suggested to be effective for functional dyspepsia, but their effect on gastric motility is not clear. We evaluated the effect of Lactobacillus gasseri OLL2716 (LG21 strain) on mild to moderate delayed gastric emptying by a double-blind, parallel-group, placebo-controlled, randomized trial. Participants (n = 28) were randomly assigned to ingest LG21 strain-containing yogurt (LG21 strain group) or LG21 strain-free yogurt (placebo group) for 12 weeks. The ¹³C gastric emptying breath test was performed to measure the gastric emptying rate over time following ingestion of a liquid meal, and the time to reach the peak (Tmax) was used as an indicator of gastric emptying. We also measured the salivary amylase concentration, an indicator of autonomic dysfunction under stress. The per-protocol population (n = 27, male n = 4, female n = 23) was evaluated for efficacy. When a ≥30% reduction in the difference between participant’s Tmax and the Japanese mean Tmax was defined as an improvement, the odds ratio of improvement in delayed gastric emptying compared to placebo after 12 weeks was 4.1 (95% confidence interval, 0.8 to 20.2). Moreover, salivary amylase concentrations were significantly lower than in the placebo group, indicating an improvement in autonomic function. The present data were not enough to support the beneficial effects of the LG21 strain on delayed gastric emptying. However, if we define the odds ratio in further study investigated with a larger number of participants, LG21 strain might be expected to have some impact on delayed gastric emptying.     

Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.     

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II,randomized, double-blind,placebo-controlled clinical study

Clinical and Experimental Nephrology - The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be...     

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis

ObjectivesTo investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis.MethodsIn this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n = 50) or patients previously treated with bisphosphonates (BP; n = 37) or denosumab (DMAb; n = 45) or teriparatide (TPTD; n = 16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] ?3.2 and total hip [TH] ?2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months.ResultsAt 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P < 0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P < 0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r = ?2.8, P < 0.001) and value of PINP at 1 month (r = 0.04, P < 0.01) for LS, and difference of prior treatment (r = ?1.3, P < 0.05) and percentage change of TRACP-5b at 1 month (r = ?0.06, P < 0.05) for TH.ConclusionsThe early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.     

Lumbar degenerative spondylolisthesis: factors associated with the decision to fuse

BACKGROUND CONTEXTThe indication to perform a fusion and decompression surgery as opposed to decompression alone for lumbar degenerative spondylolisthesis (LDS) remains controversial. A variety of factors are considered when deciding on whether to fuse, including patient demographics, radiographic parameters, and symptom presentation. Likely surgeon preference has an important influence as well.PURPOSEThe aim of this study was to assess factors associated with the decision of a Canadian academic spine surgeon to perform a fusion for LDS.STUDY DESIGN/SETTINGThis study is a retrospective analysis of patients prospectively enrolled in a multicenter Canadian study that was designed to evaluate the assessment and surgical management of LDS.PATIENT SAMPLEInclusion criteria were patients with: radiographic evidence of LDS and neurogenic claudication or radicular pain, undergoing posterior decompression alone or posterior decompression and fusion, performed in one of seven, participating academic centers from 2015 to 2019.OUTCOME MEASURESPatient demographics, patient-rated outcome measures (Oswestry Disability Index [ODI], numberical rating scale back pain and leg pain, SF-12), and imaging parameters were recorded in the Canadian Spine Outcomes Research Network (CSORN) database. Surgeon factors were retrieved by survey of each participating surgeon and then linked to their specific patients within the database.METHODSUnivariate analysis was used to compare patient characteristics, imaging measures, and surgeon variables between those that had a fusion and those that had decompression alone. Multivariate backward logistic regression was used to identify the best combination of factors associated with the decision to perform a fusion.RESULTSThis study includes 241 consecutively enrolled patients receiving surgery from 11 surgeons at 7 sites. Patients that had a fusion were younger (65.3±8.3 vs. 68.6±9.7 years, p=.012), had worse ODI scores (45.9±14.7 vs. 40.2±13.5, p=.007), a smaller average disc height (6.1±2.7 vs. 8.0±7.3 mm, p=.005), were more likely to have grade II spondylolisthesis (31% vs. 14%, p=.008), facet distraction (34% vs. 60%, p=.034), and a nonlordotic disc angle (26% vs. 17%, p=.038). The rate of fusion varied by individual surgeon and practice location (p<.001, respectively). Surgeons that were fellowship trained in Canada more frequently fused than those who fellowship trained outside of Canada (76% vs. 57%, p=.027). Surgeons on salary fused more frequently than surgeons remunerated by fee-for-service (80% vs. 64%, p=.004). In the multivariate analysis the clinical factors associated with an increased odds of fusion were decreasing age, decreasing disc height, and increasing ODI score; the radiographic factors were grade II spondylolisthesis and neutral or kyphotic standing disc type; and the surgeon factors were fellowship location, renumeration type and practice region. The odds of having a fusion surgery was more than two times greater for patients with a grade II spondylolisthesis or neutral and/or kyphotic standing disc type (opposed to lordotic standing disc type). Patients whose surgeon completed their fellowship in Canada, or whose surgeon was salaried (opposed to fee-for-service), or whose surgeon practiced in western Canada had twice the odds of having fusion surgery.CONCLUSIONSThe decision to perform a fusion in addition to decompression for LDS is multifactorial. Although patient and radiographic parameters are important in the decision-making process, multiple surgeon factors are associated with the preference of a Canadian spine surgeon to perform a fusion for LDS. Future work is necessary to decrease treatment variability between surgeons and help facilitate the implementation of evidence-based decision making.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.