The construction of canine distal limb models used in teaching sonography identification of vegetal foreign bodies.

Musculoskeletal ultrasonography is a useful tool to identify radiolucent vegetal foreign bodies (VFBs). However, limited ultrasound experience and unfamiliarity with the normal sonographic appearance of anatomical structures can decrease clinician confidence. This study aimed to design a reusable silicone model that can teach VFB identification within the canine distal limb. Four canine hindlimbs were used to design the silicone models, and 12 canine distal forelimbs were constructed. The model was constructed using cadaver bones, barley grass (Avena fatua) seeds, and silicone to mimic the anatomy of the canine distal limb with a grass seed VFB. Limbs were randomly grouped based on grass seed locations: (1) the interdigital webbing, (2) the palmar surface of the canine forelimb immediately proximal to the metacarpal pad, (3) the dorsal surface of the distal limb immediately proximal to the proximal phalange, or (4) no grass seed (control) placed. Each limb was systematically ultrasounded and compared with cadaver limbs and clinical VFB cases. A comparison of ultrasonographic images validated the construction, revealing that the simulation model replicates the anatomical and echotexture characteristics of the normal canine distal limb. Furthermore, these models also have a likeness to clinical canine distal limb VFB cases and can be utilized as a training tool.

Changes in the number and outcome of takeaway food outlet planning applications in response to adoption of management zones around schools in England: A time series analysis.

Physical exposure to takeaway food outlets ("takeaways") is associated with poor diet and excess weight, which are leading causes of excess morbidity and mortality. At the end of 2017, 35 local authorities (LAs) in England had adopted takeaway management zones (or "exclusion zones"), which is an urban planning intervention designed to reduce physical exposure to takeaways around schools. In this nationwide, natural experimental study, we used interrupted time series analyses to estimate the impact of this intervention on changes in the total number of takeaway planning applications received by LAs and the percentage rejected, at both first decision and after any appeal, within management zones, per quarter of calendar year. Changes in these proximal process measures would precede downstream retail and health impacts. We observed an overall decrease in the number of applications received by intervention LAs at 12 months post-intervention (6.3 fewer, 95% CI -0.1, -12.5), and an increase in the percentage of applications that were rejected at first (additional 18.8%, 95% CI 3.7, 33.9) and final (additional 19.6%, 95% CI 4.7, 34.6) decision, the latter taking into account any appeal outcomes. This effect size for the number of planning applications was maintained at 24 months, although it was not statistically significant. We also identified three distinct sub-types of management zone regulations (full, town centre exempt, and time management zones). The changes observed in rejections were most prominent for full management zones (where the regulations are applied irrespective of overlap with town centres), where the percentage of applications rejected was increased by an additional 46.1% at 24 months. Our findings suggest that takeaway management zone policies may have the potential to curb the proliferation of new takeaways near schools and subsequently impact on population health.

Hemorheological, cardiorespiratory, and cerebrovascular effects of pentoxifylline following acclimatization to 3,800 m.

Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, ∼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg; P = 0.021) and isocapnic hypoxia (placebo, 22 ± 5; pentoxifylline, 20 ± 4 mmHg; P = 0.029), but not in males. Acute pentoxifylline administration in lowlanders at 3,800 m had no impact on arterial blood gases, hemorheology, inflammation, gCBF, or ventilation. Unexpectedly, however, pentoxifylline reduced PASP in female participants, indicating a potential effect of sex on the pulmonary vascular responses to pentoxifylline.NEW & NOTEWORTHY We conducted a double-blind, placebo-controlled study on the rheological, cardiorespiratory and cerebrovascular effects of acute pentoxifylline in healthy lowlanders after 11-14 days at 3,800 m. Although red blood cell deformability was reduced and blood viscosity increased compared with low altitude, acute pentoxifylline administration had no impact on arterial blood gases, hemorheology, inflammation, cerebral blood flow, or ventilation. Pentoxifylline decreased pulmonary artery systolic pressure in female, but not male, participants.

Attenuating intrathoracic pressure swings decreases cardiac output at different intensities of exercise.

Intrathoracic pressure (ITP) swings that permit spontaneous ventilation have physiological implications for the heart. We sought to determine the effect of respiration on cardiac output ( Q ̇ $\dot Q$ ) during semi-supine cycle exercise using a proportional assist ventilator to minimize ITP changes and lower the work of breathing (Wb ). Twenty-four participants (12 females) completed three exercise trials at 30%, 60% and 80% peak power (Wmax ) with unloaded (using a proportional assist ventilator, PAV) and spontaneous breathing. Intrathoracic and intraabdominal pressures were measured with balloon catheters placed in the oesophagus and stomach. Left ventricular (LV) volumes and Q ̇ $\dot Q$ were determined via echocardiography. Heart rate (HR) was measured with electrocardiogram and a customized metabolic cart measured oxygen uptake ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}}}$ ). Oesophageal pressure swings decreased from spontaneous to PAV breathing by -2.8 ± 3.1, -4.9 ± 5.7 and -8.1 ± 7.7 cmH2 O at 30%, 60% and 80% Wmax , respectively (P = 0.01). However, the decreases in Wb were similar across exercise intensities (27 ± 42 vs. 35 ± 24 vs. 41 ± 22%, respectively, P = 0.156). During PAV breathing compared to spontaneous breathing, Q ̇ $\dot Q$ decreased by -1.0 ± 1.3 vs. -1.4 ± 1.4 vs. -1.5 ± 1.9 l min-1 (all P < 0.05) and stroke volume decreased during PAV breathing by -11 ± 12 vs. -9 ± 10 vs. -7 ± 11 ml from spontaneous breathing at 30%, 60% and 80% Wmax , respectively (all P < 0.05). HR was lower during PAV breathing by -5 ± 4 beats min-1 at 80% Wmax (P < 0.0001). Oxygen uptake decreased by 100 ml min-1 during PAV breathing compared to spontaneous breathing at 80% Wmax (P < 0.0001). Overall, attenuating ITPs mitigated LV preload and ejection, thereby suggesting that the ITPs associated with spontaneous respiration impact cardiac function during exercise. KEY POINTS: Pulmonary ventilation is accomplished by alterations in intrathoracic pressure (ITP), which have physiological implications on the heart and dynamically influence the loading parameters of the heart. Proportional assist ventilation was used to attenuate ITP changes and decrease the work of breathing during exercise to examine its effects on left ventricular (LV) function. Proportional assist ventilation with progressive exercise intensities (30%, 60% and 80% Wmax ) led to reductions in cardiac output at all intensities, primarily through reductions in stroke volume. Decreases in LV end-diastolic volume (30% and 60% Wmax ) and increases in LV end-systolic volume (80% Wmax ) were responsible for the reduction in stroke volume. The relationship between cardiac output and oxygen uptake is disrupted during respiratory muscle unloading.

Methods for analyzing infant heart rate variability: A preliminary study.

Heart rate (HR) and heart rate variability (HRV) reflect autonomic development in infants. To better understand the autonomic response in infants, reliable HRV recordings are vital, yet no protocol exists. The purpose of this paper is to present reliability of a common procedure for analysis from two different file types. In the procedure, continuous electrocardiograph recordings of 5-10 min are obtained at rest in infants at 1 month of age by using a Hexoskin Shirt-Junior's (Carre Technologies Inc., Montreal, QC, Canada). Electrocardiograph (ECG; .wav) and R-R interval (RRi; .csv) files are extracted. The RRi of the ECG signal is generated by VivoSense (Great Lakes NeuroTechnologies, Independence, OH). Two MATLAB (The MathWorks, Inc., Natick, MA) scripts converted files for analysis with Kubios HRV Premium (Kubios Oy, Kuopio, Finland). A comparison was made between RRi and ECG files for HR and HRV parameters, and then tested with t tests and correlations via SPSS. There are significant differences in root mean squared successive differences between recording types, with only HR and low-frequency measures significantly correlated together. Recording with Hexoskin and analysis with MATLAB and Kubios enable infant HRV analysis. Differences in outcomes exist between procedures, and standard methodology for infant HR analysis is needed.

Sex differences in heart disease prevalence among individuals with spinal cord injury: A population-based study.

CONTEXT/OBJECTIVE: The risk for cardiovascular disease is amplified following spinal cord injury, but whether risk differs between the sexes remains unknown. Here, we evaluated sex differences in the prevalence of heart disease among individuals with spinal cord injury, and compared sex differences with able-bodied individuals. DESIGN: The design was a cross-sectional study. Multivariable logistic regression analysis was conducted, using inverse probability weighting to account for the sampling method and to adjust for confounders. SETTING: Canada. PARTICIPANTS: Individuals who participated in the national Canadian Community Health Survey. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Self-reported heart disease. RESULTS: Among 354 individuals with spinal cord injury, the weighted prevalence of self-reported heart disease was 22.9% in males and 8.7% in females, with an inverse-probability weighted odds ratio of 3.44 (95% CI 1.70-6.95) for males versus females. Among 60,605 able-bodied individuals, the prevalence of self-reported heart disease was 5.8% in males and 4.0% in females, with an inverse probability weighted odds ratio of 1.62 (95% CI 1.50-1.75) for males versus females. The effect of male sex on increasing heart disease prevalence was about two times higher among individuals with spinal cord injury than able-bodied individuals (relative difference in inverse probability weighted odds ratios = 2.12, 95% CI 1.08-4.51). CONCLUSION: Males with spinal cord injury exhibit a significantly higher prevalence of heart disease, compared with females with spinal cord injury. Moreover, relative to able-bodied individuals, spinal cord injury amplifies sex-related differences in heart disease. Overall, this work will inform targeted cardiovascular prevention strategies, and may also inform a better understanding of cardiovascular disease progression in both able-bodied and individuals with spinal cord injury.

Pulmonary vascular reactivity to supplemental oxygen in Sherpa and lowlanders during gradual ascent to high altitude.

NEW FINDINGS: What is the central question of this study? How does hypoxic pulmonary vasoconstriction and the response to supplemental oxygen change over time at high altitude? What is the main finding and its importance? Lowlanders and partially de-acclimatized Sherpa both demonstrated pulmonary vascular responsiveness to supplemental oxygen that was maintained for 12 days' exposure to progressively increasing altitude. An additional 2 weeks' acclimatization at 5050 m altitude rendered the pulmonary vasculature minimally responsive to oxygen similar to the fully acclimatized non-ascent Sherpa. Additional hypoxic exposure at that time point did not augment hypoxic pulmonary vasoconstriction. ABSTRACT: Prolonged alveolar hypoxia leads to pulmonary vascular remodelling. We examined the time course at altitude, over which hypoxic pulmonary vasoconstriction goes from being acutely reversible to potentially irreversible. Study subjects were lowlanders (n = 20) and two Sherpa groups. All Sherpa were born and raised at altitude. One group (ascent Sherpa, n = 11) left altitude and after de-acclimatization in Kathmandu for ∼7 days re-ascended with the lowlanders over 8-10 days to 5050 m. The second Sherpa group (non-ascent Sherpa, n = 12) remained continuously at altitude. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured while breathing ambient air and following supplemental oxygen. During ascent PASP and PVR increased in lowlanders and ascent Sherpa; however, with supplemental oxygen, lowlanders had significantly greater decrease in PASP (P = 0.02) and PVR (P = 0.02). After ∼14 days at 5050 m, PASP decreased with supplemental oxygen (mean decrease: 3.9 mmHg, 95% CI 2.1-5.7 mmHg, P < 0.001); however, PVR was unchanged (P = 0.49). In conclusion, PASP and PVR increased with gradual ascent to altitude and decreased via oxygen supplementation in both lowlanders and ascent Sherpa. Following ∼14 days at 5050 m altitude, there was no change in PVR to hypoxia or O2  supplementation in lowlanders or either Sherpa group. These data show that both duration of exposure and residential altitude influence the pulmonary vascular responses to hypoxia.

Exploring the perceptions of former ICU patients and clinical staff on barriers and facilitators to the implementation of virtual reality exposure therapy: A qualitative study.

BACKGROUND: Virtual reality (VR) as a digital technology has developed rapidly, becoming more realistic, portable, sensory and easier to navigate. Although studies have found VR to be effective for many clinical applications, patients and clinicians have described several barriers to the successful implementation of this technology. To remove barriers for implementation of VR in health care, a greater understanding is needed of how VR can integrate into clinical environments, particularly complex settings such as an intensive care unit. AIM: This study aimed to explore the perceived barriers and facilitators for the implementation of VR exposure therapy for intensive care patients and clinical staff. STUDY DESIGN: A qualitative study using an Interpretative Description approach was undertaken. Semi-structured focus groups were conducted with 13 participants: nine patients and four health care professionals. Focus groups explored barriers and facilitators of using virtual reality (VR) exposure therapy in intensive care. Thematic analysis was employed to produce codes and themes. RESULTS: In total, eight themes describing the perceived barriers and facilitators to implementing VR exposure therapy were identified. Four themes related to the perceived barriers of implementing VR exposure therapy in intensive care were identified: psychological, sensory, environmental and staff competency and confidence. There were a further four themes related to the perceived facilitators to the implementation of VR exposure therapy: staff training, patient capacity, orientation to technology and support during the intervention. CONCLUSIONS: This study identified novel barriers and facilitators that could be expected when implementing VR exposure therapy for patients' post-intensive care unit stay. The findings suggest that psychological barriers of fear and apprehension were expected to provoke patient avoidance of exposure therapy. Perceived barriers for staff focused on preparedness to deliver the VR exposure therapy and a lack of technological competence. Both patients and staff stated that a comprehensive induction, orientation and training could facilitate VR exposure therapy, improving engagement. RELEVANCE TO CLINICAL PRACTICE: This study has identified that with appropriate staff training, resources, and integration into current patient care pathways, VR exposure therapy may be a valuable intervention to support patient recovery following critical illness. Prior to undertaking VR exposure therapy, patients often need reassurance that side-effects can be managed, and that they can easily control their virtual exposure experience.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular (LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

A change of heart: Mechanisms of cardiac adaptation to acute and chronic hypoxia.

Over the last 100 years, high-altitude researchers have amassed a comprehensive understanding of the global cardiac responses to acute, prolonged and lifelong hypoxia. When lowlanders are exposed to hypoxia, the drop in arterial oxygen content demands an increase in cardiac output, which is facilitated by an elevated heart rate at the same time as ventricular volumes are maintained. As exposure is prolonged, haemoconcentration restores arterial oxygen content, whereas left ventricular filling and stroke volume are lowered as a result of a combination of reduced blood volume and hypoxic pulmonary vasoconstriction. Populations native to high-altitude, such as the Sherpa in Asia, exhibit unique lifelong or generational adaptations to hypoxia. For example, they have smaller left ventricular volumes compared to lowlanders despite having larger total blood volume. More recent investigations have begun to explore the mechanisms underlying such adaptive responses by combining novel imaging techniques with interventions that manipulate cardiac preload, afterload, and/or contractility. This work has revealed the contributions and interactions of (i) plasma volume constriction; (ii) sympathoexcitation; and (iii) hypoxic pulmonary vasoconstriction with respect to altering cardiac loading, or otherwise preserving or enhancing biventricular systolic and diastolic function even amongst high altitude natives with excessive erythrocytosis. Despite these advances, various areas of investigation remain understudied, including potential sex-related differences in response to high altitude. Collectively, the available evidence supports the conclusion that the human heart successfully adapts to hypoxia over the short- and long-term, without signs of myocardial dysfunction in healthy humans, except in very rare cases of maladaptation.

Interventions for the treatment and prevention of pressure ulcers.

Pressure ulcers can affect multiple aspects of an individual's life. Though preventable, pressure ulcers place a substantial economic burden on healthcare services. Countries around the world have set pressure ulcer prevention and treatment as a high priority. National Clinical Guidelines recommend a wide range of preventative and curative treatments. However, there is still much uncertainty regarding the effectiveness of preventative and curative treatments. This overview of systematic reviews aims to describe the findings of 15 Cochrane reviews on the treatment and prevention of pressure ulcers included in a previous umbrella review and to expand upon their findings in the context of clinical practice.

Influence of respiratory loading on left-ventricular function in cervical spinal cord injury.

Cervical spinal cord injury (C-SCI) negatively impacts cardiac and respiratory function. As the heart and lungs are linked via the pulmonary circuit these systems are interdependent. Here, we utilized inspiratory and expiratory loading to assess whether augmenting the respiratory pump improves left-ventricular (LV) filling and output in individuals with motor-complete C-SCI. We hypothesized LV end-diastolic volume (LVEDV) would increase and decrease with inspiratory and expiratory loading, respectively. Participants (C-SCI: 7M/1F, 35 ± 7 years; able-bodied: 7M/1F, 32 ± 6 years) were assessed under five conditions during 45° head-up tilt; unloaded, inspiratory loading with -10 and -20 cmH2 O oesophageal pressure (Poes ) on inspiration, and expiratory loading with +10 and +20 cmH2 O Poes on expiration. An oesophageal balloon catheter monitored Poes , and LV structure and function were assessed by echocardiography. In C-SCI only, (1) +20 cmH2 O reduced LVEDV vs. unloaded (81 ± 15 vs. 88 ± 11 ml, P = 0.006); (2) heart rate was higher during +20 cmH2 O compared to unloaded (P = 0.001) and +10 cmH2 O (P = 0.002); (3) cardiac output was higher during +20 cmH2 O than unloaded (P = 0.002); and (4) end-expiratory lung volume was higher during +20 cmH2 O vs. unloaded (63 ± 10 vs. 55 ± 13% total lung capacity, P = 0.003) but was unaffected by inspiratory loading. In both groups, -10 and -20 cmH2 O had no significant effect on LVEDV. These findings suggest greater expiratory positive pressure acutely impairs LV filling in C-SCI, potentially via impaired venous return, mediastinal constraint and/or direct ventricular interaction subsequent to dynamic hyperinflation. Inspiratory loading did not significantly improve LV function in C-SCI and neither inspiratory nor expiratory loading affected cardiac function or lung volumes in able-bodied participants. KEY POINTS: Cervical spinal cord injury (C-SCI) alters both the cardiac and the respiratory system, but little is known about how these systems interact following injury. Here, we manipulated inspiratory or expiratory intrathoracic pressure (ITP) to mechanistically test the role of the respiratory pump in circulatory function in highly trained individuals with C-SCI and an able-bodied reference group. In individuals with C-SCI, greater ITP during expiratory loading caused dynamic hyperinflation that was associated with impaired left-ventricular filling. More negative ITP during inspiratory loading did not significantly alter left-ventricular volumes in either group. Interventions that prevent dynamic hyperinflation and/or enhance the ability to generate expiratory pressures may help preserve left-ventricular filling in individuals with C-SCI.

Spinal cord injury impairs cardiac function due to impaired bulbospinal sympathetic control.

Spinal cord injury chronically alters cardiac structure and function and is associated with increased odds for cardiovascular disease. Here, we investigate the cardiac consequences of spinal cord injury on the acute-to-chronic continuum, and the contribution of altered bulbospinal sympathetic control to the decline in cardiac function following spinal cord injury. By combining experimental rat models of spinal cord injury with prospective clinical studies, we demonstrate that spinal cord injury causes a rapid and sustained reduction in left ventricular contractile function that precedes structural changes. In rodents, we experimentally demonstrate that this decline in left ventricular contractile function following spinal cord injury is underpinned by interrupted bulbospinal sympathetic control. In humans, we find that activation of the sympathetic circuitry below the level of spinal cord injury causes an immediate increase in systolic function. Our findings highlight the importance for early interventions to mitigate the cardiac functional decline following spinal cord injury.

Developmental changes in cardiac expression of KCNQ1 and SCN5A spliceoforms: Implications for sudden unexpected infant death.

BACKGROUND: Sudden unexpected infant death (SUID) occurs unpredictably and remains unexplained after scene investigation and autopsy. Approximately 1 in 7 cases of SUID can be related to a cardiac cause, and developmental regulation of cardiac ion channel genes may contribute to SUID. OBJECTIVE: The goal of this study was to investigate the developmental changes in the spliceoforms of SCN5A and KCNQ1, 2 genes implicated in SUID. METHODS: Using reverse transcription quantitative real-time polymerase chain reaction, we quantified expression of SCN5A (adult and fetal) and KCNQ1 (KCNQ1a and b) spliceoforms in 153 human cardiac tissue samples from decedents that succumbed to SUID ("unexplained") and other known causes of death ("explained noncardiac"). RESULTS: There is a stepwise increase in the adult/fetal SCN5A spliceoform ratio from <2 months (4.55 ± 0.36; n = 51) through infancy and into adulthood (17.41 ± 3.33; n = 5). For KCNQ1, there is a decrease in the ratio of KCNQ1b to KCNQ1a between the <2-month (0.37 ± 0.02; n = 46) and the 2- to 4-month (0.28 ± 0.02; n = 52) age groups. When broken down by sex, race, or cause of death, there were no differences in SCN5A or KCNQ1 spliceoform expression, except for a higher ratio of KCNQ1b to KCNQ1a at 5-12 months of age for SUID females (0.40 ± 0.04; n = 9) than for males (0.25 ± 0.03; n = 6) and at <2 months of age for SUID white (0.42 ± 0.03; n = 19) than for black (0.33 ± 0.05; n = 9) infants. CONCLUSION: This study documents the developmental changes in SCN5A and KCNQ1 spliceoforms in humans. Our data suggest that spliceoform expression ratios change significantly throughout the first year of life.

Fibre-optic, electronic pH test device compared with current NHS guidance to confirm nasogastric tube placement.

The clinical objectives of this prospective, random, convenience series were: 1. Compare a novel fibre-optic pH test device (NGPOD) to gastric aspirate and pH testing for nasogastric tube (NGT) confirmation. 2. Determine if the new device reduces the need for chest radiography (chest X-ray, CXR). Methods: Recruitment of patients over the age of 18, requiring NGT feeding.Exclusion criteria: oesophageal gastrointestinal surgery within 3 months; all those with partial or total gastrectomy; bleeding gastric and duodenal ulcers; gastric cancer; those with oesophageal varices; those considered to be inappropriate.The index test, NGPOD, comprises a fine, flexible fibre-optic sensor passed down the NGT, then connected to an electronic device. A green light indicates pH ≤5.5, and a red light if pH is >5.5.The reference test is withdrawal of gastric aspirate and testing with universal pH indicator strips then comparison to a colour chart. Second-line testing is establishing NGT position by CXR or subjective clinical assessment (SCA) in intensive care unit (ICU). Results: The analysed data set contained 174 subjects who had undergone 496 tests, 96 initial and 400 repeat NGT checks.For all patients, NGPOD can reduce the need for CXR or SCA by 21.2%.In ICU, NGPOD can reduce the need for CXR or SCA by 24.5%.When performing initial tests, immediately after tube placement, NGPOD can reduce the need for CXR or SCA in 61% of patients.With repeat testing, NGPOD can reduce the need to progress to CXR or SCA in 16% of tests. Conclusions: The objective, yes-no result delivered by NGPOD, eliminates the subjective reading of a pH strip colour change, reducing the subjective element. The index test has the opportunity to reduce risk, improve safety and decrease the numbers of patients requiring X-ray. It, therefore, has the potential to reduce never events associated with NGT misplacement.

Global REACH 2018: volume regulation in high-altitude Andeans with and without chronic mountain sickness.

The high-altitude maladaptation syndrome known as chronic mountain sickness (CMS) is characterized by polycythemia and is associated with proteinuria despite unaltered glomerular filtration rate. However, it remains unclear if indigenous highlanders with CMS have altered volume regulatory hormones. We assessed NH2-terminal pro-B-type natriuretic peptide (NT pro-BNP), plasma aldosterone concentration, plasma renin activity, kidney function (urinary microalbumin, glomerular filtration rate), blood volume, and estimated pulmonary artery systolic pressure (ePASP) in Andean males without (n = 14; age = 39 ± 11 yr) and with (n = 10; age = 40 ± 12 yr) CMS at 4,330 m (Cerro de Pasco, Peru). Plasma renin activity (non-CMS: 15.8 ± 7.9 ng/mL vs. CMS: 8.7 ± 5.4 ng/mL; P = 0.025) and plasma aldosterone concentration (non-CMS: 77.5 ± 35.5 pg/mL vs. CMS: 54.2 ± 28.9 pg/mL; P = 0.018) were lower in highlanders with CMS compared with non-CMS, whereas NT pro-BNP was not different between groups (non-CMS: 1394.9 ± 214.3 pg/mL vs. CMS: 1451.1 ± 327.8 pg/mL; P = 0.15). Highlanders had similar total blood volume (non-CMS: 90 ± 15 mL·kg-1 vs. CMS: 103 ± 18 mL·kg-1; P = 0.071), but Andeans with CMS had greater total red blood cell volume (non-CMS: 46 ± 10 mL·kg-1 vs. CMS: 66 ± 14 mL·kg-1; P < 0.01) and smaller plasma volume (non-CMS: 43 ± 7 mL·kg-1 vs. CMS: 35 ± 5 mL·kg-1; P = 0.03) compared with non-CMS. There were no differences in ePASP between groups (non-CMS: 32 ± 9 mmHg vs. CMS: 31 ± 8 mmHg; P = 0.6). A negative correlation was found between plasma renin activity and glomerular filtration rate in both groups (group: r = -0.66; P < 0.01; non-CMS: r = -0.60; P = 0.022; CMS: r = -0.63; P = 0.049). A smaller plasma volume in Andeans with CMS may indicate an additional CMS maladaptation to high altitude, causing potentially greater polycythemia and clinical symptoms.

The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia.

Hemoconcentration can influence hypoxic pulmonary vasoconstriction (HPV) via increased frictional force and vasoactive signaling from erythrocytes, but whether the balance of these mechanism is modified by the duration of hypoxia remains to be determined. We performed three sequential studies: 1) at sea level, in normoxia and isocapnic hypoxia with and without isovolumic hemodilution (n = 10, aged 29 ± 7 yr); 2) at altitude (6 ± 2 days acclimatization at 5,050 m), before and during hypervolumic hemodilution (n = 11, aged 27 ± 5 yr) with room air and additional hypoxia [fraction of inspired oxygen ([Formula: see text])= 0.15]; and 3) at altitude (4,340 m) in Andean high-altitude natives with excessive erythrocytosis (EE; n = 6, aged 39 ± 17 yr), before and during isovolumic hemodilution with room air and hyperoxia (end-tidal Po2 = 100 mmHg). At sea level, hemodilution mildly increased pulmonary artery systolic pressure (PASP; +1.6 ± 1.5 mmHg, P = 0.01) and pulmonary vascular resistance (PVR; +0.7 ± 0.8 wu, P = 0.04). In contrast, after acclimation to 5,050 m, hemodilution did not significantly alter PASP (22.7 ± 5.2 vs. 24.5 ± 5.2 mmHg, P = 0.14) or PVR (2.2 ± 0.9 vs. 2.3 ± 1.2 wu, P = 0.77), although both remained sensitive to additional acute hypoxia. In Andeans with EE at 4,340 m, hemodilution lowered PVR in room air (2.9 ± 0.9 vs. 2.3 ± 0.8 wu, P = 0.03), but PASP remained unchanged (31.3 ± 6.7 vs. 30.9 ± 6.9 mmHg, P = 0.80) due to an increase in cardiac output. Collectively, our series of studies reveal that HPV is modified by the duration of exposure and the prevailing hematocrit level. In application, these findings emphasize the importance of accounting for hematocrit and duration of exposure when interpreting the pulmonary vascular responses to hypoxemia.NEW & NOTEWORTHY Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.

Effects of a Tailored Physical Activity Intervention on Cardiovascular Structure and Function in Individuals With Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) leads to a loss of descending motor and sympathetic control below the level of injury (LOI), which ultimately results in chronically altered cardiovascular function and remodeling. While supervised, laboratory-based exercise training can generate cardiovascular adaptations in people with SCI, it is unknown whether behavioral community-based interventions effectively generate such adaptations for individuals with SCI. OBJECTIVE: Examine the effects of a tailored behavioral physical activity (PA) intervention on cardiac and vascular structure and function in individuals with SCI. METHODS: In this randomized controlled trial, 32 participants with SCI (18-65 years, SCI >1 year) were assigned to PA (8-week behavioral intervention) or control (CON) groups. At baseline and postintervention, measures of resting left ventricular (LV) structure and function, carotid intima-media thickness and pulse-wave velocity were assessed with ultrasound and tonometry. RESULTS: Twenty-eight participants completed the study (n = 14/group). Across the full study cohort there were no significant changes in indices of LV or vascular structure and function, despite notable improvements in peak power and oxygen uptake in the PA group. However, in a subanalysis for LOI, individuals in the PA group with LOIs below T6 had evidence of altered LV geometry (ie, increased LV internal diameter, reduced sphericity index and relative wall thickness; group × time P < 0.05 for all), which was not seen in individuals with higher LOIs at or above T6. CONCLUSION: An 8-week behavioral PA intervention appears to promote adaptations in cardiac geometry more readily in individuals with lower level SCI than those with higher-level SCI.

Study to evaluate the optimal dose of remifentanil required to ensure apnea during magnetic resonance imaging of the heart under general anesthesia.

BACKGROUND: Magnetic resonance (MRI) scanning of the heart is an established part of the investigation of cardiovascular conditions in children. In young children, sedation is likely to be needed, and multiple controlled periods of apnea are often required to allow image acquisition. Suppression of spontaneous ventilation is possible with remifentanil; however, the dose required is uncertain. AIMS: To establish the dose of remifentanil, by infusion, required to suppress ventilation sufficiently to allow a 30-s apnea during MRI imaging of the heart. METHOD: Patients aged 1-6 years were exposed to different doses of remifentanil, and the success in achieving a 30-s apnea was recorded. A dose recommendation was made for each patient, informed by responses of previous patients using an adaptive Bayesian dose-escalation design. Other aspects of anesthesia were standardized. A final estimate of the dose needed to achieve a successful outcome in 80% of patients (ED80) was made using logistic regression. RESULTS: 38 patients were recruited, and apnea achieved in 31 patients. The estimate of the ED80 was 0.184 µg/kg/min (95% CI 0.178-0.190). Post hoc analysis revealed that higher doses were required in younger patients. CONCLUSION: The ED80 for this indication was 0.184 µg/kg/min (95% CI 0.178-0.190). This is different from optimal dosing identified for other indications and dosing of remifentanil should be specific to the clinical context in which it is used.

Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m.

KEY POINTS: Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders during either (1) ascent to high altitude, or (2) following partial acclimatization, when compared to high-altitude adapted Sherpa. During ascent to 5050 m, the rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders; however, upon arrival to 5050 m, PASP levels were comparable in both groups, but the reduction in iron bioavailability was more prevalent in lowlanders compared to Sherpa. Following partial acclimatization to 5050 m, there were differential influences of iron status manipulation (via iron infusion or chelation) at rest and during exercise between lowlanders and Sherpa on the pulmonary vasculature. ABSTRACT: To examine the adaptational role of iron bioavailability on the pulmonary vascular responses to acute and chronic hypobaric hypoxia, the haematological and cardiopulmonary profile of lowlanders and Sherpa were determined during: (1) a 9-day ascent to 5050 m (20 lowlanders; 12 Sherpa), and (2) following partial acclimatization (11 ± 4 days) to 5050 m (18 lowlanders; 20 Sherpa), where both groups received an i.v. infusion of either iron (iron (iii)-hydroxide sucrose) or an iron chelator (desferrioxamine). During ascent, there were reductions in iron status in both lowlanders and Sherpa; however, Sherpa appeared to demonstrate a more efficient capacity to mobilize stored iron, compared to lowlanders, when expressed as a Δhepcidin per unit change in either body iron or the soluble transferrin receptor index, between 3400-5050 m (P = 0.016 and P = 0.029, respectively). The rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders during ascent; however, PASP was comparable in both groups upon arrival to 5050 m. Following partial acclimatization, despite Sherpa demonstrating a blunted hypoxic ventilatory response and greater resting hypoxaemia, they had similar hypoxic pulmonary vasoconstriction when compared to lowlanders at rest. Iron-infusion attenuated PASP in both groups at rest (P = 0.005), while chelation did not exaggerate PASP in either group at rest or during exaggerated hypoxaemia ( PIO2  = 67 mmHg). During exercise at 25% peak wattage, PASP was only consistently elevated in Sherpa, which persisted following both iron infusion or chelation. These findings provide new evidence on the complex interplay of iron regulation on pulmonary vascular regulation during acclimatization and adaptation to high altitude.