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Background: There are few reports of clinical outcomes or the natural history of definitive diverticular hemorrhage (DDH). Aims: To describe 1-year clinical outcomes of patients with documented DDH treated with colonoscopic hemostasis, angioembolization, surgery, or medical treatment. Methods: DDH was diagnosed when active bleeding or other stigmata of hemorrhage were found in a colonic diverticulum during urgent colonoscopy or extravasation on angiography or red blood cell (RBC) scanning. This was a retrospective analysis of prospectively collected data of DDH patients from two referral centers between 1993 and 2022. Outcomes were compared for the four treatment groups. The Kaplan–Meier analysis was for time-to-first diverticular rebleed. Results: 162 patients with DDH were stratified based on their final treatment before discharge—104 colonoscopic hemostasis, 24 medical treatment alone, 19 colon surgery, and 15 angioembolization. There were no differences in baseline characteristics, except for a higher Glasgow–Blatchford score in the angioembolization group vs. the colonoscopic group. Post-treatment, the colonoscopic hemostasis group had the lowest rate of RBC transfusions and fewer hospital and ICU days compared to surgical and embolization groups. The medical group had significantly higher rates of rebleeding and reintervention. The surgical group had the highest postoperative complications. Conclusions: Medically treated DDH patients had significantly higher 1-year rebleed and reintervention rates than the three other treatments. Those with colonoscopic hemostasis had significantly better clinical outcomes during the index hospitalization. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments. Colonoscopic hemostasis is recommended in patients with definitive diverticular hemorrhage for better clinical outcomes. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments. [ABSTRACT FROM AUTHOR]

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common medical problem worldwide. Independent endoscopic risk factors for rebleeding and mortality of NVUGIB that are treatable are stigmata of recent hemorrhage (SRH) and arterial blood flow underneath SRH. The specific aims of this paper are to describe the importance of arterial blood flow detection for risk stratification and as a guide to definitive hemostasis of severe NVUGIB. Methods: This is a review of randomized controlled trials and prospective cohort study methodologies and results which utilized a Doppler endoscopic probe (DEP) for the detection of arterial blood underneath SRH, for risk stratification, and as a guide to definitive hemostasis. The results are compared to visually guided hemostasis based upon SRH. Results: Although SRH have been utilized to guide endoscopic hemostasis of NVUGIB for 50 years, when most visually guided treatments are applied to lesions with major SRH, arterial blood flow underneath SRH is not obliterated in 25–30% of patients and results in rebleeding. Definitive hemostasis, significantly lower rebleeding rates, and improvements in other clinical outcomes resulted when DEP was used for risk stratification and as a guide to obliteration of arterial blood flow underneath SRH. Conclusions: DEP-guided endoscopic hemostasis is a very effective and safe new method to improve patient outcomes for NVUGIB. [ABSTRACT FROM AUTHOR]

Summary: Background: Acute gastrointestinal bleeding (GIB) remains a common cause of hospitalisation. However, interpretation and comparisons of published studies in GIB have been hampered by disparate study methodology. Aims: To make recommendations about outcome measures to be used in future randomised controlled trials (RCTs) of patients with acute bleeding from any GI source (nonvariceal UGI, variceal, small bowel, or colon) and suggest new RCTs in acute GIB for future peer‐reviewed funding. Methods: As part of a National Institutes of Health conference entitled "Hemostatic Outcomes in Clinical Trials", a group of GIB experts performed targeted critical reviews of available evidence with the goal of proposing a bleeding outcome that could potentially be applied to different disciplines. In addition, the panel sought to develop a clinically meaningful primary endpoint specifically for acute GIB, potentially allowing a more contemporary regrouping of clinically relevant outcomes. Results: The primary endpoint proposed was a composite outcome of further bleeding within 30 days after randomisation leading to red blood cell transfusion, urgent intervention (repeat endoscopy; interventional radiology or surgery), or death. Secondary outcomes may include the individual components of the primary outcome, length of hospitalisation, serious adverse events, and health care resource utilisation. Conclusion: The proposed endpoint may help move the GIB field forward by focusing on the most clinically relevant outcomes for patients with acute GIB of all types and informing study design and importance of sample size determination for future RCTs in GIB. [ABSTRACT FROM AUTHOR]

In our article (Jensen I et al i . 2020), we found spinal motoneurons to be intrinsically more excitable at two different time points in the adult SOD1(G93A) mouse (one pre-symptomatic and one symptomatic time point). Nevertheless, the above observations do not support the hypothesis that the increase in motoneuron responsiveness in this model of ALS is simply due to a loss of large motoneurons. We emphasise this because Manuel and Zytnicki have repeatedly claimed both in the letter and elsewhere that the use of 3 kHz can 'mistakenly transform a non-repetitively-firing motoneuron into a repetitively-firing motoneuron' (Baczyk I et al i . 2021; Manuel, 2021). Incidentally, we also reported that, at 8 kHz, when the cells did not fire repetitively, it was almost always the wild-type (WT) motoneurons, not the SOD1(G93A) motoneurons, that failed (first paragraph p. 4391 of the paper). [Extracted from the article]

Reference equations for fat-free mass (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy X-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45–85 years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted aka index (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1881 healthy participants (57% male) aged 55 [IQR: 50–61] years. Reference equations performed comparably in the validation cohort and discriminated reference values between ostensibly healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45–85 years, although additional validation may be required for those >75 years. [ABSTRACT FROM AUTHOR]

Purpose: This study explored if healthy adults could discriminate between different breathlessness dimensions when rated immediately one after another (successively) during symptom-limited incremental cardiopulmonary cycle exercise testing (CPET) using multiple single-item rating scales.Methods: Fifteen apparently healthy adults (60% male) aged 22 ± 2 years performed six incremental cycle CPETs separated by ≥ 48 h. During each CPET (at rest, every 2-min and at end exercise), participants rated different breathlessness sensations using the 0-10 modified Borg scale using one of six assessment protocols, randomized for order: (1) 'BREATHLESSALL' = breathlessness sensory intensity (SI), breathlessness unpleasantness (UN), work/effort of breathing (SQW/E), and unsatisfied inspiration (SQUI) assessed; (2) SI and UN assessed; and (3-6) SI, UN, SQW/E, and SQUI each assessed alone. Physiological responses to CPET were also evaluated.Results: Physiological and breathlessness responses to CPET were comparable across the six protocols, with the exception of SI rated lower at the highest submaximal power output (220 ± 56 watts) during the BREATHLESSALL protocol (0-10 Borg units 4.2 ± 1.7) compared to SI + UN (5.2 ± 2.1, p = 0.03) and SI alone (5.1 ± 1.9, p = 0.04) protocols. Ratings of SI and SQW/E were not significantly different when assessed in the same protocol, and were significantly higher than UN and SQUI, which were comparable.Conclusion: In healthy younger adults, use of two separate single-item rating scales to assess breathlessness during CPET is feasible and enables the distinct sensory intensity and affective dimensions of exertional breathlessness to be assessed. [ABSTRACT FROM AUTHOR]

This study described the participation in daily and social activities and the perceived barriers and facilitators to participation of individuals with chronic obstructive pulmonary disease (COPD). Individuals, recruited from outpatient clinics, responded to a survey on their participation in, and barriers and facilitators towards, 26 daily and social activities, divided into 3 categories: (1) physical activity and movement (PAM); (2) self-care; and (3) social engagement. For each activity, chi-square analyses were used to examine participation differences by individuals': quartiles of airflow obstruction [percent predicted forced expiratory volume in 1 second (FEV1%predicted)] and breathlessness burden and exacerbation risk. Of the 200 participants (47% women; mean ± standard deviation age = 68 ± 9 years), most wanted to increase their participation in PAM activities (range 21–75%) and significant differences were found in 5/10 PAM activities for individuals' breathlessness burden and exacerbation risk (e.g., more individuals than expected in group A (modified Medical Research Council breathlessness score <2 and 0–1 exacerbations in past 12 months) participated in regular exercise as much as they wanted (χ(9)2=20.43, Cramer's V=.23)). Regardless of the degree of airflow obstruction or breathlessness burden and exacerbation risk, the most common barrier to participation was breathlessness (p<.001, η2p=.86) and the most common facilitator was engaging as part of their routine (p<.001, η2p=.75). Individuals with COPD want to increase their participation in daily and social activities but are limited by breathlessness. Strategies to alleviate breathlessness should be identified/prioritized and incorporated into individuals' daily routines to meet their self-reported participation objectives in daily and social activities. [ABSTRACT FROM AUTHOR]

Key points: Although in vitro recordings using neonatal preparations from mouse models of amyotrophic lateral sclerosis (ALS) suggest increased motoneurone excitability, in vivo recordings in adult ALS mouse models have been conflicting.In adult G93A SOD1 models, spinal motoneurones have previously been shown to have deficits in repetitive firing, in contrast to the G127X SOD1 mouse model.Our in vivo intracellular recordings in barbiturate‐anaesthetized adult male G93A SOD1 mice reveal that the incidence of failure to fire with current injection was equally low in control and ALS mice (∼2%).We show that failure to fire repetitively can be a consequence of experimental protocol and should not be used alone to classify otherwise normal motoneurones as hypo‐excitable.Motoneurones in the G93A SOD1 mice showed an increased response to inputs, with lower rheobase, higher input–output gains and increased activation of persistent inward currents. In vitro studies from transgenic amyotrophic lateral sclerosis models have suggested an increased excitability of spinal motoneurones. However, in vivo intracellular recordings from adult amyotrophic lateral sclerosis mice models have produced conflicting findings. Previous investigations using barbiturate anaesthetized G93A SOD1 mice have suggested that some motoneurones are hypo‐excitable, defined by deficits in repetitive firing. Our own previous recordings in G127X SOD1 mice using different anaesthesia, however, showed no repetitive firing deficits and increased persistent inward currents at symptom onset. These discrepancies may be a result of differences between models, symptomatic stage, anaesthesia or technical differences. To investigate this, we repeated our original experiments, but in adult male G93A SOD1 mice, at both presymptomatic and symptomatic stages, under barbiturate anaesthesia. In vivo intracellular recordings from antidromically identified spinal motoneurones revealed that the incidence of failure to fire with current injection was equally low in control and G93A SOD1 mice (∼2%). Motoneurones in G93A SOD1 mice fired significantly more spontaneous action potentials. Rheobase was significantly lower and the input resistance and input–output gain were significantly higher in both presymptomatic and symptomatic G93A SOD1 mice. This was despite a significant increase in the duration of the post‐spike after‐hyperpolarization in both presymptomatic and symptomatic G93A SOD1 mice. Finally, evidence of increased activation of persistent inward currents was seen in both presymptomatic and symptomatic G93A SOD1 mice. Our results do not confirm previous reports of hypo‐excitability of spinal motoneurones in the G93A SOD1 mouse and demonstrate that the motoneurones show an increased response to inputs. Key points: Although in vitro recordings using neonatal preparations from mouse models of amyotrophic lateral sclerosis (ALS) suggest increased motoneurone excitability, in vivo recordings in adult ALS mouse models have been conflicting.In adult G93A SOD1 models, spinal motoneurones have previously been shown to have deficits in repetitive firing, in contrast to the G127X SOD1 mouse model.Our in vivo intracellular recordings in barbiturate‐anaesthetized adult male G93A SOD1 mice reveal that the incidence of failure to fire with current injection was equally low in control and ALS mice (∼2%).We show that failure to fire repetitively can be a consequence of experimental protocol and should not be used alone to classify otherwise normal motoneurones as hypo‐excitable.Motoneurones in the G93A SOD1 mice showed an increased response to inputs, with lower rheobase, higher input–output gains and increased activation of persistent inward currents. [ABSTRACT FROM AUTHOR]

Background: Impaired gait plays an important role for quality of life in patients with Huntington's disease (HD). Measuring objective gait parameters in HD might provide an unbiased assessment of motor deficits in order to determine potential beneficial effects of future treatments. Objective: To objectively identify characteristic features of gait in HD patients using sensor-based gait analysis. Particularly, gait parameters were correlated to the Unified Huntington's Disease Rating Scale, total motor score (TMS), and total functional capacity (TFC). Methods: Patients with manifest HD at two German sites (n = 43) were included and clinically assessed during their annual ENROLL-HD visit. In addition, patients with HD and a cohort of age- and gender-matched controls performed a defined gait test (4 × 10 m walk). Gait patterns were recorded by inertial sensors attached to both shoes. Machine learning algorithms were applied to calculate spatio-temporal gait parameters and gait variability expressed as coefficient of variance (CV). Results: Stride length (− 15%) and gait velocity (− 19%) were reduced, while stride (+ 7%) and stance time (+ 2%) were increased in patients with HD. However, parameters reflecting gait variability were substantially altered in HD patients (+ 17% stride length CV up to + 41% stride time CV with largest effect size) and showed strong correlations to TMS and TFC (0.416 ≤ rSp ≤ 0.690). Objective gait variability parameters correlated with disease stage based upon TFC. Conclusions: Sensor-based gait variability parameters were identified as clinically most relevant digital biomarker for gait impairment in HD. Altered gait variability represents characteristic irregularity of gait in HD and reflects disease severity. [ABSTRACT FROM AUTHOR]

Background: Screening for colorectal cancer in Denmark has resulted in more patients being diagnosed with benign adenomas and early-stage rectal cancer. In general, TRUS is accepted as a good modality for evaluating the above mentioned before deciding on surgery. Objective: To investigate the accuracy of TRUS in a clinical setting at the Region Hospital in Herning, Denmark. Study design: Retrospective cohort study from January 2016 to June 2018. Methods: Quantitative method. The cohort (117 patients) was recruited by searching for specific procedure codes. Data were collected by going through the electronic patient files. Results: TRUS predicted T0, T1, T2 and T3 with an accuracy of 91%, 35%, 43% and 20% respectively and an overall accuracy of 68%. A weighted Cohens kappa value of 0.30 (p .05). TRUS differentiated between T0/T1 with a sensitivity of 70%, specificity of 85% and an accuracy of 85% and kappa value of 0.44 (p .05). Conclusion: TRUS can with great precision establish whether the tumor is benign so correct local treatment can be instituted. [ABSTRACT FROM AUTHOR]

In the motor system, force gradation is achieved by recruitment of motoneurons and rate modulation of their firing frequency. Classical experiments investigating the relationship between injected current to the soma during intracellular recording and the firing frequency (the I-f relation) in cat spinal motoneurons identified two clear ranges: a primary range and a secondary range. Recent work in mice, however, has identified an additional range proposed to be exclusive to rodents, the subprimary range (SPR), due to the presence of mixed mode oscillations of the membrane potential. Surprisingly, fully summated tetanic contractions occurred in mice during SPR frequencies. With the mouse now one of the most popular models to investigate motor control, it is crucial that such discrepancies between observations in mice and basic principles that have been widely accepted in larger animals are resolved. To do this, we have reinvestigated the I-f relation using ramp current injections in spinal motoneurons in both barbiturate-anesthetized and decerebrate (nonanesthetized) cats and mice. We demonstrate the presence of the SPR and mixed mode oscillations in both species and show that the SPR is enhanced by barbiturate anesthetics. Our measurements of the I-f relation in both cats and mice support the classical opinion that firing frequencies in the higher end of the primary range are necessary to obtain a full summation. By systematically varying the leg oil pool temperature (from 37°C to room temperature), we found that only at lower temperatures can maximal summation occur at SPR frequencies due to prolongation of individual muscle twitches. [ABSTRACT FROM AUTHOR]

Objective: Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed. Data Sources: A nonsystematic literature review was conducted using Medline and PubMed for articles related to cannabis/marijuana use and sports/athletic performance; abstracts were reviewed by lead author and key themes identified and explored. Main Results: Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug. Conclusions: Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention. [ABSTRACT FROM AUTHOR]

Purpose: To test the efficacy of an acute intervention derived from acceptance and commitment therapy (ACT) for increasing high-intensity constant work rate (CWR) cycle exercise tolerance in a group of low-active women age 18-45 yr. The secondary goals were to examine whether ACT would reduce perceived effort and improve in-task affect during exercise and increase postexercise enjoyment. Methods: In a randomized controlled trial, 39 women were randomized to either the experimental (using ACT-based cognitive techniques and listening to music during the CWR exercise tests) or a control group (listening to music during the CWR exercise tests). Before (CWR-1) and after the intervention (CWR-2), participants completed a CWR cycle exercise test at 80% of maximal incremental work rate (Wmax) until volitional exhaustion. Results: On average, ACT (n = 18) and control (n = 21) groups were matched for age, body mass index, weekly leisure activity scores, and Wmax (all P > 0.05). Exercise tolerance time (ETT) increased by 15% from CWR-1 to CWR-2 for the ACT group (392.05 ± 146.4 vs 459.39 ± 209.3 s; mean ± SD) and decreased by 8% (384.71 ± 120.1 vs 353.86 ± 127.9 s) for the control group (P = 0.008). RPE were lower (e.g., by 1.5 Borg 6-20 scale units at 55% of ETT, P ≤ 0.01) during CWR-2 in the ACT versus that in the control group. By contrast, ACT had no effect on in-task affect. Exercise enjoyment was higher after CWR-2 in the ACT group versus that in the control group (P < 0.001). Conclusions: An acute ACT intervention increased high-intensity ETT and postexercise enjoyment and reduced perceived effort in low-active women. Further investigations of ACT as an effective intervention for enhancing the established health benefits of high-intensity exercise need to be provided. [ABSTRACT FROM AUTHOR]

Abstract: Context: Activity limitation and dyspnea are the dominant symptoms of chronic obstructive pulmonary disease (COPD). Traditionally, efforts to alleviate these symptoms have focused on improving ventilatory mechanics, reducing ventilatory demand, or both of these in combination. Nevertheless, many patients with COPD remain incapacitated by dyspnea and exercise intolerance despite optimal therapy. Objectives: To determine the effect of single-dose inhalation of nebulized fentanyl citrate (a μ-opioid agonist drug) on exercise tolerance and dyspnea in COPD. Methods: In a randomized, double-blind, placebo-controlled, crossover study, 12 stable patients with COPD (mean±standard error of the mean post-β2-agonist forced expiratory volume in one second [FEV1] and FEV1 to forced vital capacity ratio of 69%±4% predicted and 49%±3%, respectively) received either nebulized fentanyl citrate (50mcg) or placebo on two separate days. After each treatment, patients performed pulmonary function tests and a symptom-limited constant work rate cycle exercise test at 75% of their maximum incremental work rate. Results: There were no significant postdose differences in spirometric parameters or plethysmographic lung volumes. Neither the intensity nor the unpleasantness of perceived dyspnea was, on average, significantly different at isotime (5.0±0.6 minutes) or at peak exercise after treatment with fentanyl citrate vs. placebo. Compared with placebo, fentanyl citrate was associated with 1) increased exercise endurance time by 1.30±0.43 minutes or 25%±8% (P =0.01); 2) small but consistent increases in dynamic inspiratory capacity by ∼0.10L at isotime and at peak exercise (both P ≤0.03); and 3) no concomitant change in ventilatory demand, breathing pattern, pulmonary gas exchange, and/or cardiometabolic function during exercise. The mean rate of increase in dyspnea intensity (1.2±0.3 vs. 2.9±0.8 Borg units/minute, P =0.03) and unpleasantness ratings (0.5±0.2 vs. 2.9±1.3 Borg units/minute, P =0.06) between isotime and peak exercise was less after treatment with fentanyl citrate vs. placebo. Conclusion: Single-dose inhalation of fentanyl citrate was associated with significant and potentially clinically important improvements in exercise tolerance in COPD. These improvements were accompanied by a delay in the onset of intolerable dyspnea during exercise near the limits of tolerance. [Copyright &y& Elsevier]

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy. [ABSTRACT FROM AUTHOR]

Abstract: We examined the effects of dead space loading (DSL) on ventilation , neural respiratory drive (EMGdi%max, diaphragm EMG expressed as a % of maximal EMGdi), contractile respiratory muscle effort (Pes,tidal%PImax, tidal esophageal pressure swing expressed as a % of maximal inspiratory Pes) and exertional dyspnea intensity ratings in 11 healthy adults with normal spirometry. Subjects completed, in random order, symptom-limited incremental cycle exercise tests under control (CTRL) and DSL (500ml) conditions. Compared with CTRL, DSL decreased exercise tolerance by 20–25%; increased exertional dyspnea intensity ratings in direct proportion to concurrent increases in EMGdi%max, Pes,tidal%PImax and ; and had little/no effect on the inter-relationships between EMGdi%max, Pes,tidal%PImax and during exercise. In conclusion, DSL was associated with an earlier onset of intolerable dyspnea; however, neuro-muscular and neuro-ventilatory coupling of the respiratory system remained relatively preserved during exercise in the presence of an increased external dead space. Under these circumstances, DSL-induced increases in exertional dyspnea intensity ratings reflected, at least in part, the awareness of increased neural respiratory drive, contractile respiratory muscle effort and ventilatory output. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to evaluate the physiological basis for sex-differences in exercise-induced dyspnea in patients with mild COPD. We compared operating lung volumes, breathing pattern and dyspnea during incremental cycling in 32 men (FEV1 =86±10% predicted) and women (FEV1 =86±12% predicted) with mild COPD and 32 age-matched controls. There were no sex differences in dyspnea in the control group at any work-rate or ventilation (). Women with COPD had significantly greater dyspnea than men at 60 and 80W. At 80W, dyspnea ratings were 5.7±2.3 and 3.3±2.5Borg units (P <0.05) and the to maximal ventilatory capacity ratio was 72% and 55% in women and men, respectively (P <0.05). Comparable increases in dynamic hyperinflation were seen in both male and female COPD groups at symptom limitation but women reached tidal volume constraints at a lower work rate and than men. Superimposing mild COPD on the normal aging effects had greater sensory consequences in women because of their naturally reduced ventilatory reserve. [Copyright &y& Elsevier]

Abstract: We examined the impact of human pregnancy on breathlessness intensity at matched levels of ventilation during isoxic hyperoxic CO2 rebreathing and incremental cycle exercise tests in 21 healthy women in the third trimester (TM3) and again ∼5 months post-partum (PP). Pregnancy had no significant (P >0.05) effect on the slope or threshold of the breathlessness relationship during both exercise and rebreathing. By contrast, the slope of the breathlessness relationship was significantly higher, while the threshold of this relationship was consistently lower during rebreathing vs. exercise (both P <0.05), regardless of pregnancy status (P >0.05). As a result, breathlessness intensity was markedly higher at any given (e.g., by ∼4 Borg units at 40L/min) during rebreathing vs. exercise, regardless of pregnancy status. Inter-subject variation in breathlessness slopes during exercise was not associated with inter-subject variation in breathlessness slopes during rebreathing or with increased central chemoreflex responsiveness during pregnancy (both P >0.05). In conclusion, the intensity of perceived breathlessness for a given depends, at least in part, on the nature and source of increased central respiratory motor command output, independent of pregnancy status; and pregnancy-induced increases in activity-related breathlessness cannot be easily explained by increased central chemoreflex responsiveness. [Copyright &y& Elsevier]

Abstract: We tested the hypothesis that the magnitude of the pregnancy-induced increase in exercise hyperpnea is predictable based on the level at which is regulated at rest. We performed a detailed retrospective analysis of previous data from 25 healthy young women who performed exercise and rebreathing tests in the third trimester (TM3; 36.5±0.2 weeks gestation; mean±SEM) and again 20.4±1.7 weeks post-partum (PP). At rest, arterialized venous blood was obtained for the estimation of , [H+] and [HCO3 −]; and serum progesterone ([P4]) and 17β-estradiol ([E2]) concentrations. Duffin''s modified hyperoxic rebreathing procedure was used to evaluate changes in central ventilatory chemoreflex control characteristics at rest. Breath-by-breath ventilatory and gas exchange variables were measured at rest and during symptom-limited incremental cycle exercise tests. At rest in TM3 compared with PP: , [H+], [HCO3 −] and the central chemoreflex ventilatory recruitment threshold for () decreased, while ventilation (), [P4], [E2] and central chemoreflex sensitivity () increased (all p ≤0.001). The slope of the linear relation between and during exercise was significantly higher in TM3 vs. PP (31.2±0.6 vs. 27.5±0.5, p <0.001). The magnitude of this change in the slope correlated significantly with concurrent reductions in each of the (R 2 =0.619, p <0.001), (R 2 =0.203, p =0.024) and [HCO3 −] (R 2 =0.189, p =0.030); and was independent (p >0.05) of changes in [P4], [E2] and . In conclusion, the increased ventilatory response to exercise in pregnancy can be explained, in large part, by reductions in the respiratory control system''s resting equilibrium point as manifest primarily by reductions in the . [Copyright &y& Elsevier]

Abstract: We quantified the magnitude of within- and between-day, within-subject variability of the ventilatory response to Duffin''s modified rebreathing procedure in 20 healthy humans. The at which ventilation increased with progressive increases in during rebreathing was identified as the ventilatory recruitment threshold (); the ventilatory response below and above the was taken as an estimate of non-chemoreflex drives to breathe () and chemoreflex sensitivity (), respectively. Within- and between-day intraclass correlation coefficients for each of these parameters were >0.60 (range: 0.62–0.93), indicating good-to-excellent test–retest reliability. Within- and between-day, within-subject coefficients of variation for hyperoxic and hypoxic (range: 24.6–30.7%) and (range: 18.5–32.7%) were relatively high but acceptable, while those for the were very small (range: 3.0–3.8%). In conclusion, Duffin''s modified rebreathing procedure, in both its hyperoxic and hypoxic form, is a highly reliable tool for measurement of chemoreflex and non-chemoreflex ventilatory control characteristics over short and long periods of time in healthy humans. [Copyright &y& Elsevier]

OBJECTIVES:Our purpose was to compare the efficacy, complications, success rate, recurrence rate at 1 year, and crossovers of rubber band ligation (RBL) with those of bipolar electrocoagulation (BPEC) treatment for chronically bleeding internal hemorrhoids.METHODS:A total of 45 patients of mean age 51.5 years, who had rectal bleeding from grade II or III hemorrhoids and in whom intensive medical therapy failed, were randomized in a prospective study comparing RBL with BPEC. Treatment failure was predefined as continued bleeding, occurrence of a major complication, or failure to reduce the size of all internal hemorrhoidal segments to grade I in 3 treatments. Patients were followed up for 1 year.RESULTS:With similar patients, rectal bleeding and other symptoms were controlled with significantly fewer treatments of RBL than of BPEC (2.3±0.2 vs. 3.8±0.4, P<0.05), and RBL had a significantly higher success rate (92% vs. 62%, P<0.05). RBL had more cases of severe pain during treatment (8% vs. 0%, P<0.05), but significantly fewer failures and crossovers (8% vs. 38%). Symptomatic recurrence at 1 year was 10% RBL and 15% BPEC.CONCLUSIONS:For patients with chronically bleeding grade II or III internal hemorrhoids that are unresponsive to medical therapy, safety and complication rates of banding and BPEC were similar. The success rate was significantly higher with RBL than with BPEC. Symptom recurrence rates at 1 year were similar.Am J Gastroenterol 2009; 104:2057–2064; doi:10.1038/ajg.2009.292; published online 9 June 2009 [ABSTRACT FROM AUTHOR]

Abstract: The healthy human respiratory system has impressive ventilatory reserve and can easily meet the demands placed upon it by strenuous exercise. Several acute physiological adaptations during exercise ensure harmonious neuromechanical coupling of the respiratory system, which allow healthy humans to reach high levels of ventilation without perceiving undue respiratory discomfort (breathlessness). However, in certain circumstances, such as pregnancy, obesity and natural aging, ventilatory reserve becomes diminished and exertional breathlessness is present. In this review, we focus on what is known about the mechanisms of increased activity-related breathlessness in these populations. Notwithstanding the obvious physiological differences between the three conditions, they share some common perceptual and ventilatory responses to exercise. Breathlessness intensity ratings (described as an increased “sense of effort”) are consistently higher than normal at any given submaximal power output; and central motor drive to the respiratory muscles is consistently increased, reflecting increased ventilatory stimulation. The increased contractile respiratory muscle effort required to support the increased ventilatory requirements of exercise remains the most plausible source of increased activity-related breathlessness in pregnant, obese and elderly humans. In all three conditions, static and dynamic respiratory mechanical/muscular function is, to some extent, altered or impaired. Nevertheless, breathlessness intensity ratings are not significantly increased (compared to normal) at any given exercise ventilation in any of these three conditions. This strongly suggests that respiratory mechanical/muscular factors, per se, may be less important in the genesis of breathlessness. Moreover, in pregnancy and obesity, we present evidence that effective physiological adjustments exist to counterbalance the potentially negative sensory consequences of the altered respiratory mechanical/muscular function peculiar to these conditions. [Copyright &y& Elsevier]

We examined the contribution of alterations in central ventilatory control, static and dynamic respiratory mechanics and their interaction to exertional breathlessness in healthy human pregnancy. Detailed ventilatory, respiratory mechanical/muscular and perceptual responses to incremental cycle exercise were compared in the third trimester (TM(3)) and again approximately 5 months post-partum (PP) in women with (B, n = 12) and without (NB, n = 15) clinically significant activity-related breathlessness (measured by the baseline dyspnea index). In contrast to NB, breathlessness intensity ratings were significantly higher at any given work rate during exercise in TM(3) versus PP within B. This difference could not be explained by differences in central ventilatory control or respiratory mechanical/muscular factors. When compared with NB, the B group had an exaggerated ventilatory response to exercise in PP and TM(3), and appeared to lack central desensitization to the perceptual effects of maternal hyperventilation that was manifest within the NB group. In conclusion, gestational breathlessness could not be explained by alterations in central ventilatory control or respiratory mechanical/muscular factors, but reflected the normal awareness of increased ventilation. [ABSTRACT FROM AUTHOR]

This study examined the role of alterations in the chemoreflex control of breathing, acid-base balance, and their interaction in postmeno- pausal ventilatory adaptations. A modified iso-oxic hyperoxic and hypoxic CO2-rebreathing procedure was employed to evaluate central and peripheral chemoreflex drives to breathe, respectively, in 15 healthy postmenopausal and 20 premenopausal women of similar age. Arterialized venous blood samples were collected at rest for the estimation of arterial PCO2 (PaCO2) and H+ concentration ([H+]), plasma strong ion difference ([SID]) and total weak acid ([A]tot) concentrations, and serum progesterone ([P4]) and 17β`-estradiol ([E2]) concentrations. In post- compared with premenopausal women, PaCO2, [SID], and the central chemoreflex ventilatory recruitment threshold for PCO2 (VRTCO2) were higher, whereas [P4] and [B2] were lower (all P < 0.05), with no significant change in central or peripheral chemoreflex sensitivity, peripheral chemorefiex VRTCO2, and [A]~0~. The acidifying effect of an increased PaCO2 was offset by the alkalizing effect of an increased [SID], such that [H+] was preserved in post- compared with premenopausal women. PaCO2 correlated positively with the central chemoreflex VRTCO2 (r = 0.67, P < 0.01), which in turn correlated positively with [SID] (r = 0.53, P < 0.01) within the pooled data. In conclusion, the relative alveolar hypoventilation and attendant arterial hypercapnia in healthy post- compared with premenopausal women could be explained, in part, by the interaction of 1) reduced central, but not peripheral, chemoreflex VRTCO2, 2) increased [SID], and 3) reduced circulating female sex steroid hormone concentrations. [ABSTRACT FROM AUTHOR]

• Ingestion of sodium bicarbonate (0.3 g/kg) induced a metabolic alkalosis. • Acute induced metabolic alkalosis decreased the V̇ E /V̇CO 2 response to exercise. We tested the hypothesis that increasing the respiratory control systems' arterial PCO 2 equilibrium point via induced acute metabolic alkalosis by ingestion of sodium bicarbonate (NaHCO 3 , 0.3 g/kg) would decrease the ventilatory equivalent for CO 2 (V̇ E /V̇CO 2) at its lowest point ("nadir") during constant-load cycle exercise testing performed at 80 % of peak power output in 18 healthy young adults. Compared to the sodium chloride (4 g) control condition, ingestion of NaHCO 3 : increased arterialized venous pH, HCO 3 - and PCO 2 at rest by 0.05 ± 0.01 units (mean ± SE), 6.4 ± 0.4 mEq/L and 4.3 ± 0.7 mmHg, respectively (all p < 0.0001); and decreased the V̇ E /V̇CO 2 nadir during exercise by 9.4 % (p < 0.0001) secondary to a 4.7 ± 1.8 L/min decrease in V̇ E (p = 0.019). In conclusion, induced acute metabolic alkalosis by ingestion of NaHCO 3 decreased the V̇ E /V̇CO 2 response to strenuous exercise in healthy adults. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the physiological mechanisms of exertional respiratory discomfort (breathlessness) in pregnancy by comparing ventilatory (breathing pattern, airway function, operating lung volumes, oesophageal pressure ( Poes)-derived indices of respiratory mechanics) and perceptual (breathlessness intensity) responses to incremental cycle exercise in 15 young, healthy women in the third trimester (TM3; between 34 and 38 weeks gestation) and again 4–5 months postpartum (PP). During pregnancy, resting inspiratory capacity (IC) increased ( P < 0.01) and end-expiratory lung volume decreased ( P < 0.001), with no associated change in total lung capacity (TLC) or static respiratory muscle strength. This permitted greater tidal volume ( VT) expansion throughout exercise in TM3, while preserving the relationship between contractile respiratory muscle effort (tidal Poes swing expressed as a percentage of maximum inspiratory pressure ( PImax)) and thoracic volume displacement ( VT expressed as a percentage of vital capacity) and between breathlessness and ventilation . At the highest equivalent work rate (HEWR = 128 ± 5 W) in TM3 compared with PP: , tidal Poes/ PImax and breathlessness intensity ratings increased by 10.2 l min−1 ( P < 0.001), 8.8% PImax ( P < 0.05) and 0.9 Borg units ( P < 0.05), respectively. Pulmonary resistance was not increased at rest or during exercise at the HEWR in TM3, despite marked increases in mean tidal inspiratory and expiratory flow rates, suggesting increased bronchodilatation. Dynamic mechanical constraints on VT expansion ( P < 0.05) with associated increased breathlessness intensity ratings ( P < 0.05) were observed near peak exercise in TM3 compared with PP. In conclusion: (1) pregnancy-induced increases in exertional breathlessness reflected the normal awareness of increased and contractile respiratory muscle effort; (2) mechanical adaptations of the respiratory system, including recruitment of resting IC and increased bronchodilatation, accommodated the increased VT while preserving effort–displacement and breathlessness– relationships; and (3) dynamic mechanical ventilatory constraints contributed to respiratory discomfort near the limits of tolerance in late gestation. [ABSTRACT FROM AUTHOR]

Upper gastrointestinal (UGI) bleeding occurs frequently and results in substantial patient morbidity, mortality and medical expense. After initial resuscitation to stabilize the patient, carefully performed endoscopy provides an accurate diagnosis and can identify high-risk subgroups in ulcer patients who are likely to rebleed with medical therapy alone and would benefit most from endoscopic haemostasis. Several different pharmacological therapies have been used for patients with bleeding ulcers, including intravenous histamine H2-receptor antagonists, proton pump inhibitors, somatostatin and octreotide, and tranexamic acid. The results of several studies and meta-analyses favour high-dose, intravenous proton pump inhibitors, such as omeprazole or pantoprazole, after successful endoscopic haemostasis. For patients with ulcer bleeding and low-risk endoscopic stigmata, high-dose oral proton pump inhibitor therapy is suggested. Medical management with proton pump inhibitors is not a substitute for appropriate endoscopic therapy for patients with UGI bleeding and high-risk ulcer stigmata. [ABSTRACT FROM AUTHOR]

The article highlights the research on the existence of gender differences for ventilatory threshold (VT), lactate threshold (LT) and Vo2max during on-ice skating in college hockey players. The study shows that ventilatory threshold in women occurred at a higher percentage of maximal heart rate (HRmx) than in men. In addition, competitive female hockey players have a lower Vo2max and higher VT compared to their male counterparts.

Abstract: This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid–base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM3; 36.3±1.0 weeks gestation; mean±S.D.) and again 20.2±7.8 weeks post-partum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO2 (PaCO2) and [H+]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P4]) and 17β-estradiol ([E2]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P4] and [E2], ventilation and increased, whereas PaCO2 and the central chemoreflex ventilatory recruitment threshold for PCO2 (VRTCO2) decreased from PP to TM3 (all p <0.01). The reductions in PaCO2 were not related to the increases in [P4] and [E2]. The alkalinizing effects of reductions in PaCO2 and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H+] was still reduced in TM3 vs. PP (all p <0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid–base balance, and cerebral blood flow account for the reductions in PaCO2, [H+] and VRTCO2. This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid–base balance, metabolic rate and cerebral blood flow. [Copyright &y& Elsevier]

Human pregnancy is characterized by significant increases in ventilatory drive both at rest and during exercise. The increased ventilation and attendant hypocapnia of pregnancy has been attributed primarily to the stimulatory effects of female sex hormones (progesterone and estrogen) on central and peripheral chemoreflex drives to breathe. However, recent research from our laboratory suggests that hormone-mediated increases in neural (or non-chemoreflex) drives to breathe may contribute importantly to the hyperventilation of pregnancy. This review challenges traditional views of ventilatory control, and outlines an alternative hypothesis of the control of breathing during human pregnancy that is currently being tested in our laboratory. Conventional wisdom suggests that pregnancy-induced increases in central respiratory motor output command in combination with progressive thoraco–abdominal distortion may compromise the normal mechanical response of the respiratory system to exercise, increase the perception of exertional breathlessness, and curtail aerobic exercise performance in otherwise healthy pregnant women. The majority of available evidence suggests, however, that neither pregnancy nor advancing gestation are associated with reduced aerobic working capacity or increased breathlessness at any given work rate or ventilation during exhaustive weight-supported exercise. [ABSTRACT FROM AUTHOR]

Abstract: We examined the effect of menstrual cycle (MC) phase on acid–base regulation and ventilatory control at rest in monophasic oral contraceptive (OC) users. Twelve healthy women (25±1 years; mean±S.E.) were tested during the inactive (IP; 5.1±0.2 days) and active (AP; 21.1±0.7 days) pill phase of the MC. Central and peripheral chemoreflex responsiveness was examined using a modified CO2 rebreathing procedure. Minute ventilation (), breathing pattern and metabolic rate were measured during 10min of quiet, resting breathing. Blood for the determination of arterial () and hydrogen ion concentration ([H+]); plasma concentrations of the strong ion difference ([SID]) and total weak acid ([A tot]); serum concentrations of progesterone ([P4]) and 17β-estradiol ([E2]) were also obtained. Although [E2] (p <0.05) and [A tot] (p =0.05) were increased in the IP versus AP, MC phase had no significant effect on resting , breathing pattern, metabolic rate, [H+], , [SID], [P4] and central or peripheral chemoreflex characteristics. Overall, OC had no significant physiological effect on acid–base regulation or ventilatory control at rest in healthy women. This may reflect suppression of endogenous fluctuations in circulating [P4] typically observed across the MC in healthy, eumenorrheic non-OC users. [Copyright &y& Elsevier]

Abstract: This study examined the effects of human pregnancy and advancing gestation on the intensity of respiratory discomfort (dyspnea) during cycle exercise. Fourteen pregnant women (PG) performed a progressive cycle ergometer exercise test involving 20W/min increases in work rate to symptom limitation and/or a heart rate of 170–175beats/min at 19.7±1.2 weeks (ENTRY), 28.2±0.3 weeks (TM2) and 36.3±0.3 weeks (TM3) gestation. Eight, age-matched, sedentary non-pregnant women (CG) were also studied for comparison purposes. Measurements included dyspnea intensity (Borg scale), minute ventilation , breathing pattern and other cardiorespiratory parameters. At peak exercise, neither pregnancy nor advancing gestation had an effect on dyspnea, , breathing pattern, oxygen uptake or work rate (p >0.05). was significantly greater (by 11L/min at 100W) in the PG at TM3 versus CG (p <0.05) at all submaximal work rates. also increased progressively from ENTRY to TM2 and TM3 during submaximal exercise. Dyspnea was not significantly different at any submaximal work rate in the PG at TM3 versus CG or with advancing gestation in the PG. In addition, dyspnea at a standardized exercise of 40L/min was not different at TM3 versus ENTRY or in the PG at TM3 versus CG. Neither pregnancy nor advancing gestation were associated with increased respiratory discomfort during strenuous non-weight bearing cycle ergometer exercise, despite substantial increases in and progressive mechanical adaptations of the respiratory system to accommodate the increasing size of the gravid uterus. [Copyright &y& Elsevier]

Abstract: This study examined the effects of menstrual cycle phase on ventilatory control. Fourteen eumenorrheic women were studied in the early follicular (FP; 1–6 days) and mid-luteal (LP; 20–24 days) phase of the menstrual cycle. Blood for the determination of arterial , plasma strong ion difference ([SID]), progesterone ([P4]), and 17β-estradiol ([E2]) concentrations were obtained at rest. Subjects performed a CO2 rebreathing procedure that included prior hyperventilation and maintenance of iso-oxia to evaluate central and peripheral chemoreflex, and nonchemoreflex drives to breathe. Resting and [SID] were lower; minute ventilation , [P4] and [E2] were higher in the LP versus FP. Within the LP, significant correlations were observed for with [P4], [E2] and [SID]. Menstrual cycle phase had no effect on the threshold or sensitivity of the central and/or peripheral ventilatory chemoreflex response to CO2. Both and the ventilatory response to hypocapnia (representing nonchemoreflex drives to breathe) were ∼1L/min greater in the LP versus FP accounting for the reduction in . These data support the hypothesis that phasic menstrual cycle changes in may be due, at least in part, to the stimulatory effects of [P4], [E2] and [SID] on ventilatory drive. [Copyright &y& Elsevier]

OBJECTIVES: No North American randomized study has compared ulcer rebleeding rates after endoscopic hemostasis in high-risk patients treated with high-dose intravenous (IV) proton pump inhibitors (PPIs) or IV histamine-2 receptor antagonists. Our hypothesis was that ulcer rebleeding with IV pantoprazole (PAN) would be lower than with IV ranitidine (RAN). METHODS: This was a multicenter, randomized, double-blind, U.S. study. Patients with bleeding peptic ulcers and major stigmata of hemorrhage had endoscopic hemostasis with thermal probes with or without epinephrine injection, then were randomly assigned to IV PAN 80 mg plus 8 mg/h or IV RAN 50 mg plus 6.25 mg/h for 72 h, and subsequently had an oral PPI (1/day). Patients with signs of rebleeding had repeat endoscopy. Rebleeding rates up to 30 days were compared in an intention-to-treat analysis. RESULTS: The study was stopped early because of slow enrollment (total N = 149, PAN 72, RAN 77). Demographics, APACHE II scores, ulcer type/location, stigmata, and hemostasis used were similar. The 7- and 30-day rebleeding rate was 6.9% (5 of 72 patients) with PAN and 14.3% (11 of 77) for RAN ( p= 0.19). Rebleeds occurred within 72 h in 56% and between 4 and 7 days in 44% of patients. The 30-day mortality rate was 4%. Nonbleeding severe adverse events were more common in the RAN than in the PAN group (14 [18.1%] vs 7 [9.7%], p= 0.16). CONCLUSIONS: Because of the small sample size of this study, there was an arithmetic but not significant difference in ulcer rebleeding rates. [ABSTRACT FROM AUTHOR]

A randomized controlled trial (RCT) of routine urgent colonoscopy in severe lower gastrointestinal tract bleeding is reported in this journal from Duke. The only significant differences in results between the standard management (emergency red blood cell (RBC) scanning and angiography with elective colonoscopy) and urgent colonoscopy were in rates of finding a definitive bleeding site—one with a major stigmata of hemorrhage—and in not making a diagnosis. The trial was stopped early for logistics reasons a decade ago. The strengths and limitations of the study are discussed and contrasted with recent reports of other investigators. Similar to management of patients with non-variceal upper gastrointestinal tract (UGI) hemorrhage, triaging patients to level of care by comorbidity scores and stigmata of hemorrhage, successful colonoscopic hemostasis of focal lesions, and individualization of long-term medical, endoscopic, and surgical care are recommended based on promising reports by other investigators. Meanwhile, further RCTs for patients with severe hematochezia are warranted. [ABSTRACT FROM AUTHOR]

This study examined the effects of aerobic conditioning during the second and third trimesters of human pregnancy on ventilatory responses to graded cycling. Previously sedentary pregnant women were assigned randomly to an exercise group (n = 14) or a nonexercising control group (n = 14). Data were collected at 15–17 weeks, 25–27 weeks and 34–36 weeks of pregnancy. Testing involved 20 W·min–1 increases in work rate to a heart rate of 170 beats·min–1 and (or) volitional fatigue. Breath-by-breath ventilatory and alveolar gas exchange measurements were compared at rest, a standard submaximal O2 and peak exercise. Within both groups, resting E, A, and VT/TI increased significantly with advancing gestation. Peak work rate, O2 pulse (O2/HR), E, A respiratory rate, VT/TI, O2, CO2, and the ventilatory threshold (Tvent) were increased after physical conditioning. Chronic maternal exercise has no significant effect on pregnancy-induced changes in ventilation and (or) alveolar gas exchange at rest or during standard submaximal exercise. Training-induced increases in Tvent and peak oxygen pulse support the efficacy of prenatal fitness programs to improve maternal work capacity. [ABSTRACT FROM AUTHOR]

This study examined the effects of human pregnancy on the central chemoreflex control of breathing. Subjects were two groups (n = 11) of pregnant subjects (PG, gestational age, 36.5 ± 0.4 wk) and nonpregnant control subjects (CG), equated for mean age, body height, prepregnant body mass, parity, and aerobic fitness. All subjects performed a hyperoxic CO2 rebreathing procedure, which includes prior hyperventilation and maintenance of iso-oxia. Resting blood gases and plasma progesterone and estradiol concentrations were measured. During rebreathing trials, end-tidal Pco2 increased, whereas end-tidal Po2 was maintained at a constant hyperoxic level. The point at which ventilation (VE) began to rise as end-tidal Pco2 increased was identified as the central chemoreflex ventilatory recruitment threshold for CO2 (VRTco2). VE levels below (basal VE) and above (central chemoreflex sensitivity) the VRTco2 were determined. The VRTco2 was significantly lower in the PG vs. CG (40.5 ± 0.8 vs. 45.8 ± 1.6 Torr), and both basal VE (14.8 ± 1.1 vs. 9.3 ± 1.6 1/min) and central chemoreflex sensitivity (5.07 ± 0.74 vs. 3.16 ± 0.29 l·min-1 Torr-1) were significantly higher in the PG vs. CG. Pooled data from the two groups showed significant correlations for resting arterial Pco2 with basal VE, central chemoreflex sensitivity, and the VRTco2. The VRTco2 was also correlated with progesterone and estradiol concentrations. These data support the hypothesis that pregnancy decreases the threshold and increases the sensitivity of the central chemoreflex response to CO2. These changes may be due to the effects of gestational hormones on chemoreflex and/or nonchemoreflex drives to breathe. [ABSTRACT FROM AUTHOR]

Investigates the mineralization of [sup 14]C-labeled nolyphenol (NP) in homogenized and nonhomogenized sludge-soil mixtures. Correlation between the aerobic volume of the spherical sludge aggregate and NP mineralization; Factors that affect the assimilation of litho-autotrophic growth of carbon dioxide and ammonia-oxidizing bacteria in the soil.

LINKED CONTENT: This article is linked to Jensen et al and Lamb & Stanley papers. To view these articles, https://doi.org/10.1111/apt.16483 and https://doi.org/10.1111/apt.16517 [ABSTRACT FROM AUTHOR]

Context: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxic effects, such as upper GI tract perforations, symptomatic gastroduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be attributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically inhibits COX-2 and has demonstrated a low potential for causing upper GI injury.Objective: To compare the incidence of PUBs in patients with osteoarthritis treated with rofecoxib vs NSAIDs.Design: Prespecified analysis of all 8 double-blind, randomized phase 2b/3 rofecoxib osteoarthritis trials conducted from December 1996 through March 1998, including one 6-week dose-ranging study, two 6-week efficacy studies vs ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-month endoscopy studies vs ibuprofen and placebo, and one 6-week efficacy study vs nabumetone and placebo.Setting: Multinational sites. Participants Osteoarthritis patients (N = 5435; mean age, 63 years [range, 38-94 years]; 72.9% women).Interventions: Rofecoxib, 12.5, 25, or 50 mg/d (n = 1209, 1603, and 545, respectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclofenac, 50 mg 3 times per day (n = 590); or nabumetone, 1500 mg/d (n = 127) (combined).Main Outcome Measure: Cumulative incidence of PUBs for rofecoxib vs NSAIDs, based on survival analysis of time to first PUB diagnosis, using PUBs that met pre-specified criteria judged by a blinded, external adjudication committee.Results: The incidence of PUBs over 12 months was significantly lower with rofecoxib vs NSAIDs (12-month cumulative incidence, 1.3% vs 1.8%; P = .046; rate per 100 patient-years, 1.33 vs 2.60; relative risk, 0.51; 95% confidence interval, 0.26-1.00). The cumulative incidence of dyspeptic GI adverse experiences was also lower with rofecoxib vs NSAIDS over 6 months (23.5% vs 25.5%; P = .02), after which the incidence rates converged.Conclusion: In a combined analysis of 8 trials of patients with osteoarthritis, treatment with rofecoxib was associated with a significantly lower incidence of PUBs than treatment with NSAIDs. [ABSTRACT FROM AUTHOR]

B PURPOSE: b Exertional dyspnea is a cardinal feature of chronic obstructive pulmonary disease (COPD) and a major cause of activity limitation. B CONCLUSIONS: b Although the reduction in exertional dyspnea was similar between the two bronchodilator therapies at week 3, G/I provided greater immediate exertional dyspnea relief than TIO alone. B CLINICAL IMPLICATIONS: b Dual bronchodilation provides acute exertional dyspnea relief compared to bronchodilator monotherapy but this effect was not sustained at week 3. [Extracted from the article]

Purpose: To compare short- and long-term outcomes of hospitalized patients with ischemic colitis (IC) presenting with severe hematochezia and treated medically or colectomy and also those with inpatient vs. outpatient start of hematochezia. Methods: A retrospective analysis of prospectively collected data for IC patients hospitalized for severe hematochezia from two teaching hospitals was done from 1994 to 2020, with the diagnosis of IC made colonoscopically and confirmed histologically. Results: Ninety-seven patients initially all had medical management for IC. Seventy-two (74.2%) were stable and had no further bleeding; 17 (17.5%) had colon resection; and 8 were critically ill and not surgical candidates. Surgical patients and non-surgical candidate had higher comorbidity scores; received more red blood cell (RBC) transfusion (median (IQR) 5 (3–10) vs. 4.5 (3–6.5) vs. 1 (0–4) units, p < 0.001); had significantly longer hospital and ICU days; had higher severe complication rates (35.3% vs. 100%. vs. 5.6%, p < 0.001); and had higher 30-day all-cause mortality rates (23.5% vs. 87.5% vs. 0, p < 0.001). Inpatients developing IC hemorrhage had more RBC transfusions, more complications, longer hospital stays, and higher mortality than patients whose IC bleeding started as outpatients. Conclusions: The majority of IC patients hospitalized for severe hematochezia were successfully treated medically. Patients who were not surgical candidate had the highest rates of severe complications and mortality. Surgical patients and those who were not surgical candidate had worse outcomes than the medical group. Patients with inpatient start of bleeding from IC had significantly worse outcomes than those with outpatient start of bleeding. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. The name of one author is not presented correctly in the author group. [ABSTRACT FROM AUTHOR]

Introduction: Contrary to common belief, a growing body of evidence suggests that unsatisfied inspiration (UI), an inherently uncomfortable quality of dyspnea, is experienced by ostensibly healthy adults during highintensity exercise. Based on our understanding of the mechanisms of UI among people with chronic respiratory conditions, this analysis tested the hypothesis that the experience of UI at peak exercise in young, healthy adults reflects the combination of high ventilatory demand and critical inspiratory constraints. Methods: In a retrospective analysis design, data included 321 healthy individuals (129 females) aged 25 ± 5 yr. Data were collected during one visit to the laboratory, which included anthropometrics, spirometry, and an incremental cardiopulmonary cycling test to exhaustion. Metabolic and cardiorespiratory variables were measured at peak exercise, and qualitative descriptors of dyspnea at peak exercise were assessed using a list of 15 descriptor phrases. Results: Thirty-four percent of participants (n = 109) reported sensations of UI at peak exercise. Compared with the non-UI group, the UI group achieved a significantly higher peak work rate (243 ± 77 vs 235 ± 69 W, P = 0.016, d = 0.10), rate of O2 consumption (3.32 ± 1.02 vs 3.27 ± 0.96 L·min-1, P = 0.018, d = 0.05), minute ventilation (120 ± 38 vs 116 ± 35L·min-1, P = 0.047, d = 0.11), and breathing frequency (50 ± 9 vs 47 ± 9 breaths per minute, P = 0.014, d = 0.33), while having a lower exercise-induced change (peak-baseline) in inspiratory capacity (0.07 ± 0.41 vs 0.20 ± 0.49 L, P = 0.023, d = 0.29). The inspiratory reserve volume to minute ventilation ratio at peak exercise was also lower in the UI versus non-UI group. Dyspnea intensity and unpleasantness ratings were significantly higher in the UI versus non-UI group at peak exercise (both P < 0.001). Conclusions: Healthy individuals reporting UI at peak exercise have relatively greater inspiratory constraints compared with those who do not select UI. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension affects females more frequently than males, and there are known sex‐related differences in the lungs. However, normal sex‐related differences in pulmonary vascular structure remain incompletely described. We aimed to contrast computed tomography‐derived pulmonary vascular volume and its distribution within the lungs of healthy adult females and males. From the CanCOLD Study, we retrospectively identified healthy never‐smokers. We analyzed full‐inspiration computed tomography images, using vessel and airway segmentation to generate pulmonary vessel volume, vessel counts, and airway counts. Vessels were classified by cross‐sectional area >10, 5–10, and <5 mm2 into bins, with volume summed within each area bin and in total. We included 46 females and 36 males (62 ± 9 years old). Females had lower total lung volume, total airway counts, total vessel counts, and total vessel volume (117 ± 31 vs. 164 ± 28 mL) versus males (all p < 0.001). Females also had lower vessel volume >10 mm2 (14 ± 8 vs. 27 ± 9 mL), vessel volume 5–10 mm2 (35 ± 11 vs. 55 ± 10 mL), and vessel volume <5 mm2 (68 ± 18 vs. 82 ± 19 mL) (all p < 0.001). Normalized to total vessel volume, vessel volume >10 mm2 (11 ± 4 vs. 16 ± 4%, p < 0.001) and 5–10 mm2 (30 ± 6 vs. 34 ± 5%, p = 0.001) remained lower in females but vessel volume <5 mm2 relative to total volume was 18% higher (59 ± 8 vs. 50 ± 7%, p < 0.001). Among healthy older adults, pulmonary vessel volume is distributed into smaller vessels in females versus males. [ABSTRACT FROM AUTHOR]