Pressure-flow characteristics of breathing systems and their components for pediatric and adult patients

Summary

Background

Breathing circuits connect the ventilator to the patients' respiratory system. Breathing tubes, connectors, and sensors contribute to artificial airway resistance to a varying extent. We hypothesized that the flow-dependent resistance is higher in pediatric breathing systems and their components compared to respective types for adults.

Aims

We aimed to characterize the resistance of representative breathing systems and their components used in pediatric patients (including devices for adults) by their nonlinear pressure-flow relationship.

Methods

We used a physical model to measure the flow-dependent pressure gradient (∆P) across breathing tubes, breathing tube extensions, 90°- and Y-connectors, flow- and carbon dioxide sensors, water traps and reusable, disposable and coaxial breathing systems for pediatric and for adult patients. ∆P was analyzed for usual flow ranges and statistically compared at a representative flow rate of 300 mL∙s⁻¹ (∆P₃₀₀).

Results

∆P across pediatric devices always exceeded ∆P across the corresponding devices for adult patients (all P < .001 [no 95% CI includes 0]). ∆P₃₀₀ across breathing system components for adults was always below 0.2 cmH₂O but reached up to 4.6 cmH₂O in a flow sensor for pediatric patients. ∆P₃₀₀ was considerably higher across the reusable compared to the disposable pediatric breathing systems (1.9 vs 0.3 cmH₂O, P < .001, [95% CI −1.59 to −1.56]).

Conclusion

The resistances of pediatric breathing systems and their components result in pressure gradients exceeding those for adults several fold. Considering the resistance of individual components is crucial for composing a breathing system matching the patient's needs. Compensation of the additional resistance should be considered if a large composed resistance is unavoidable.

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New solutions to reduce wrong route medication errors

Summary

Wrong route medication errors due to tubing misconnections are potentially life-threatening complications that have been made possible by the universal use of the Luer connector. The new International Organization of Standardization standards for small bore connectors, ISO 80369 series, have been developed to reduce the risk of these types of erroneous connections. Tubing connectors for different routes of clinical application will contain differently designed connectors that are physically incompatible. However, design and manufacturing standards have progressed slowly, and clinical roll-outs have been delayed, despite the implementation of California laws to promote their use. We are currently in a state of transition where new connectors for enteral and neuraxial use will be entering the clinical market in the next few years, and increasing use will identify additional patient safety concerns.

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Nitroglycerin: An unusual solution to intraoperative hypothermia in a 4-year-old burn patient

Summary

We describe the case of a 4-year-old child undergoing extensive burn surgery with refractory intraoperative hypothermia. A low-dose nitroglycerin infusion was initiated to reverse vasoconstriction and improve heat absorption, after which the child's temperature steadily improved. In hypothermic burn patients, topical vasoconstrictors may hinder surface warming efforts. A vasodilator infusion may aid in warming the pediatric patient undergoing extensive excision and grafting.

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Clinical implications of de Barsy syndrome

Summary

Background

De Barsy syndrome is a rare, autosomal recessive syndrome characterized by cutis laxa, progeroid appearance, ophthalmic opacification, skeletal malformations, growth delays, and intellectual disability.

Aims

The aim of this case series is to identify the anesthetic considerations in the clinical management of patients with de Barsy syndrome.

Methods

A retrospective case review from 1968 to 2016 was performed at a single tertiary medical center to identify patients with de Barsy syndrome who underwent anesthesia for diagnostic and surgical procedures. We collected and analyzed the perioperative records and following data: age, sex, American Society of Anesthesiologists physical status, relevant comorbidities, surgical procedures, anesthesia management, and observed complications.

Results

Three patients underwent 64 unique anesthetics for a diverse collection of diagnostic and surgical procedures. An array of anesthetics and techniques were successfully used. Observations of the perioperative period found 7 episodes of intraoperative hyperthermia (>38.3°), a single difficult airway requiring fiberoptic bronchoscopic-guided intubation, and repeatedly difficult intravenous access.

Conclusion

This expanded case series suggests that providers caring for patients with de Barsy syndrome should be aware of potential challenges with airway management, vascular access, and temperature monitoring.

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The anatomy of the pediatric airway: Has our knowledge changed in 120 years? A review of historic and recent investigations of the anatomy of the pediatric larynx

Summary

Background

There is disagreement regarding the anatomy of the pediatric airway, particularly regarding the shape of the cricoid cartilage and the location of the narrowest portion of the larynx.

Aims

The aim of this review is to clarify the origin and the science behind these differing views.

Methods

We undertook a review of published literature, University Libraries, and authoritative textbooks with key search words and phrases.

Results

In vivo observations suggest that the narrowest portion of the airway is more proximal than the cricoid cartilage. However, in vitro studies of autopsy specimens measured with rods or calipers, confirm that the nondistensible and circular or near circular cricoid outlet is the narrowest level. These anatomic studies confirmed the classic "funnel" shape of the pediatric larynx. In vivo studies are potentially misleading as the aryepiglottic, vestibular, and true vocal folds are in constant motion with respiration. These studies also do not consider the effects of normal sleep, inhalation agents, and comorbidities such as adenoid or tonsil hypertrophy that cause some degree of pharyngeal collapse and alter the normal movement of the laryngeal tissues. Thus, the radiologic studies suggesting that the narrowest portion of the airway is not the cricoid cartilage may be the result of an artifact depending upon which phase of respiration was imaged.

Conclusion

In vivo studies do not take into account the motion of the highly pliable laryngeal upper airway structures (aryepiglottic, vestibular, and vocal folds). Maximal abduction of these structures with tracheal tubes or bronchoscopes always demonstrates a larger opening of the glottis compared to the outlet of the cricoid ring. Injury to the larynx depends upon ease of tracheal tube or endoscope passage past the cricoid cartilage and not passage through the readily distensible more proximal structures. The infant larynx is funnel shaped with the narrowest portion the circular or near circular cricoid cartilage confirmed by multiple in vitro autopsy specimens carried out over the past century.

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Donohue syndrome: A review of literature, case series, and anesthetic considerations

Summary

Background

Donohue syndrome is a rare autosomal recessive disorder of insulin resistance, causing a functional defect in insulin receptor function, and affecting the ability of the insulin to bind the receptor. Features include severe hyperinsulinism and fasting hypoglycemia, along with severe failure to thrive despite feeding. An accelerated fasting state results in muscle wasting, decreased subcutaneous fat, and an excess of thick skin. A reduced thoracic diameter is accentuated by increased abdominal distension, which impacts on respiratory reserve.

Cardiac disease develops early in life, with progressive hypertrophic cardiomyopathy as a result of hyperinsulinism. Prognosis is poor with the majority of patients dying in infancy of sepsis. The aim of this review is to report our experience of providing anesthesia for patients with Donohue syndrome, and inform guidance for safe management of these children, based on a comprehensive literature review.

Methods

A literature search was carried out using PubMed, Medline, and the Cochrane Library, and using the MESH search terms detailed below. Patients were identified by formal request to the department of pediatric endocrinology at Great Ormond Street Hospital. Each patient's notes were searched manually and electronically for both clinical presentation and outcome, and anesthesia records.

Discussion

There is currently no published literature relating to anesthetic management of Donohue syndrome. We report a case series of 5 patients with Donohue syndrome who have presented to our institution. This small series of children with this complex disorder demonstrates a clearly increased risk of general anesthesia. Many of the risks relate to restrictive lung disease and abdominal distension which worsens with bag valve mask ventilation and limited respiratory reserve which leads to precipitous desaturation. During induction, a spontaneously breathing technique is recommended. If required, bag valve mask ventilation should be accompanied by constant gastric aspiration. Intubation is challenging, and a difficult airway plan, including a second experienced anesthetist and ENT support, should be in place. These children are predisposed to developing cardiomyopathy and therefore at risk of cardiovascular collapse under anesthesia.

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Fifty Men, 3510 Marathons, Cardiac Risk Factors, and Coronary Artery Calcium Scores

Introduction/Purpose: Many male marathon runners have elevated coronary artery calcium (CAC) scores despite high physical activity. We examined the association between CAC scores, cardiovascular risk factors, and lifestyle habits in long-term marathoners. Methods: We recruited men who had run one or more marathons annually for 25 consecutive years. CAC was assessed using coronary computed tomography angiography. Atherosclerotic cardiovascular disease risk factors were measured with a 12-lead ECG, serum lipid panel, height, weight, resting blood pressure and heart rate, and a risk factor questionnaire. Results: Fifty males, mean age 59 ± 0.9 yr with a combined total of 3510 marathons (median = 58.5, range = 27–171), had a mean BMI of 22.44 ± 0.4 kg·m−2, HDL and LDL cholesterols of 58 ± 1.6 and 112 ± 3.7 mg·dL−1, and CAC scores from 0 to 3153. CAC scores varied from 0 in 16 runners to 1–100 in 12, 101–400 in 12, and >400 in 10. There was no statistical difference in the number of marathons run between the four groups. Compared with marathoners with no CAC, marathoners with moderate and extensive CAC were older (P = 0.002), started running at an older age (P = 0.003), were older when they ran their first marathon (P = 0.006), and had more CAD risk factors (P = 0.005), and marathoners with more CAC had higher rates of previous tobacco use (P = 0.002) and prevalence of hyperlipidemia (P = 0.01). Conclusion: Among experienced males who have run marathons for 26–34 yr and completed between 27 and 171 marathons, CAC score is related to CAD risk factors and not the number of marathons run or years of running. This suggests that among long-term marathoners, more endurance exercise is not associated with an increased risk of CAC.

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Respiratory Mechanical and Cardiorespiratory Consequences of Cycling with Aerobars

Purpose: Aerobars place a cyclist in a position where the trunk is flexed forward and the elbows are close to the midline of the body. This position is known to improve cycling aerodynamics and time trial race performance compared with upright cycling positions. However, the aggressive nature of this position may have important cardiorespiratory and metabolic consequences. The purpose of this investigation was to examine the respiratory mechanical, ventilatory, metabolic, and sensory consequences of cycling while using aerobars during laboratory-based cycling. Methods: Eleven endurance-trained male cyclists (age, 26 ± 9 yr; V˙O2peak, 55 ± 5 mL·kg−1·min−1) were recruited. Visit 1 consisted of an incremental cycling test to determine peak power output. Visit 2 consisted of 6-min bouts of constant load cycling at 70% of peak incremental power output in the aerobar position, drop position, and upright position while grasping the brake hoods. Metabolic and ventilatory responses were measured using a commercially available metabolic cart, and respiratory pressures were measured using an esophageal catheter. Results: Cycling in the aerobar position significantly increased the work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure compared with the upright position. Increases in the Wb and Pb in the aerobars relative to the upright position were strongly correlated with the degree of thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r = 0.80, P = 0.01; Pb: r = 0.69, P = 0.04). Conclusions: Aerobars significantly increase the mechanical cost of breathing and leads to greater ventilatory inefficiency compared with upright cycling. Future work is needed to optimize aerobar width to minimize the respiratory mechanical consequences while optimizing aerodynamics.

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Comparison of Lower Limb and Back Exercises for Runners with Chronic Low Back Pain

Introduction: This single-blind randomized trial was conducted to compare the treatment effect of lower limb (LL) exercises versus conventional lumbar extensor (LE) and lumbar stabilization (LS) exercises in recreational runners with chronic low back pain (cLBP), because there is currently no specific protocol for managing runners with cLBP. Methods: Eighty-four recreational runners with cLBP were allocated to three exercise groups (LL, LE, LS) for an 8-wk intervention. Outcome measures included self-rated pain and running capability, LL strength, back muscle function, and running gait. Participants were assessed at preintervention, mid-intervention, and end-intervention; selected outcomes also followed up at 3 and 6 months. Generalized estimating equation was adopted to examine group–time interaction. Results: The LL group improved 0.949 points per time point in Patient-Specific Functional Scale (P

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Effects of Childhood Gymnastics Program on Spatial Working Memory

Purpose: A growing body of evidence has demonstrated the positive effects of physical exercise on cognition in children, and recent studies have specifically investigated the cognitive benefits of exercises involving cognitive–motor interactions, such as gymnastics. This study examined the effect of 8 wk of gymnastics training on behavioral and neurophysiological measures of spatial working memory in children. Methods: Forty-four children age 7 to 10 yr were recruited. The experimental group (n = 24; age, 8.7 ± 1.1 yr) was recruited from Yilan County in Taiwan, while the control group (n = 20; age, 8.6 ± 1.1 yr) resided in Taipei City. The experimental group undertook 8 wk of after-school gymnastics training (2 sessions per week, 90 min per session), whereas the control group received no intervention and were instructed to maintain their routine daily activities. Working memory was assessed by performance on a modified delayed match-to-sample test and by event-related potential including the P3 component. Data were collected before and after treatment for the experimental group and at the same time interval for the control group. Results: Response accuracy improved after the experimental intervention regardless of working memory demands. Likewise, the P3 amplitude was larger at the parietal site after gymnastics training regardless of the task difficulty. Conclusions: Our results suggest that a short period of gymnastics training had a general facilitative effect on spatial working memory at both behavioral and neurophysiological levels in children. These finding highlight the potential importance of exercise programs involving cognitive–motor interactions in stimulating development of spatial cognition during childhood.

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Self-reported Concussion History and Sensorimotor Tests Predict Head/Neck Injuries

Purpose: Sport-related concussion (SRC) is a risk for players involved in high-impact, collision sports. A history of SRC is a risk factor for future concussions, but the mechanisms underlying this are unknown. Despite evidence that most visible signs and symptoms associated with sports concussion resolve within 7–10 d, it has been proposed that subclinical loss of neuromuscular control and impaired motor functioning may persist and be associated with further injury. Alternatively, indicators of poor sensorimotor performance could be independent risk factors. This study investigated if a history of SRC and/or preseason sensorimotor performance predicted season head/neck injuries. Methods: A total of 190 male rugby league, rugby union, and Australian Football League players participated. Preseason assessments included self-report of SRC within the previous 12 months and a suite of measures of sensorimotor function (balance, vestibular function, cervical proprioception, and trunk muscle function). Head/neck injury data were collected in the playing season. Results: Forty-seven players (25%) reported a history of SRC. A history of concussion was related to changes in size and contraction of trunk muscles. Twenty-two (11.6%) players sustained a head/neck injury during the playing season, of which, 14 (63.6%) players had a history of SRC. Predictors of in-season head/neck injuries included history of SRC, trunk muscle function, and cervical proprioceptive errors. Five risk factors were identified, and players with three or more of these had 14 times greater risk of sustaining a season neck/head injury (sensitivity of 75% and specificity of 82.5%) than did players with two or fewer risk factors. Conclusions: The modifiable risk factors identified could be used to screen football players in the preseason and guide the development of exercise programs aimed at injury reduction.

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Are RCP and Critical Power Equivalent? The Issue of Mean Response Time

No abstract available

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Exercise Protects Skeletal Muscle during Chronic Doxorubicin Administration

Purpose: This study aimed to assess the ability for exercise training performed before and during biweekly doxorubicin (DOX) administration to attenuate adverse effects of DOX on skeletal muscle. We hypothesized that DOX treatment would increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce muscle fiber size, and that exercise training would attenuate these responses. Methods: Eight-week-old ovariectomized female Sprague–Dawley rats were randomized to one of four treatments: exercise + DOX (Ex-Dox), Ex + vehicle (Ex-Veh), sedentary + DOX (Sed-Dox), and Sed + Veh (Sed-Veh). DOX (4 mg·kg−1) or vehicle (saline) intraperitoneal injections were performed biweekly for a total of three injections (cumulative dose, 12 mg·kg−1). Ex animals performed interval exercise (4 × 4 min, 85%–90% V˙O2peak) 5 d·wk−1 starting 1 wk before the first injection and continued throughout study duration. Animals were euthanized ~5 d after the last injection, during which the soleus muscle was dissected and prepared for immunoblot and immunohistochemical analyses. Results: REDD1 mRNA and protein were increased only in Sed-Dox (P 0.05). LC3BI was higher, and the LC3BII/I ratio was lower in Sed-Dox versus Sed-Veh (P 0.05). Conclusion: These data suggest that DOX may inhibit mTORC1 activity and reduce MHCI and MHCIIa fiber size, potentially through elevated REDD1, and that exercise may provide a therapeutic strategy to preserve skeletal muscle size during chronic DOX treatment.

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Effects of Altering Trunk Position during Landings on Patellar Tendon Force and Pain

Purpose: This study aimed to verify the immediate effects of altering sagittal plane trunk position during jump landings on lower limb biomechanics, patellar tendon force, and pain of athletes with and without patellar tendinopathy. Methods: Twenty-one elite male athletes were categorized into three groups: athletes with patellar tendinopathy (TG; n = 7), asymptomatic athletes with patellar tendon abnormalities (n = 7), and asymptomatic athletes without tendon abnormalities (CG; n = 7). A biomechanical evaluation was conducted while the athletes performed drop landings from a bench in a self-selected trunk position (SS). Afterward, the athletes were randomly assigned to land with either a flexed trunk position (FLX) or an extended trunk position (EXT). Variables of interest for this study included sagittal plane peak kinematics, kinetics, patellar tendon force, and pain during the landing tasks. Results: Peak patellar tendon force, knee extensor moment, and knee pain decreased in the FLX landing compared with the SS landing, regardless of group. In addition, peak patellar tendon force, knee extensor moment, and vertical ground reaction force were smaller in the FLX landing compared with the EXT landing. The TG had smaller peak ankle dorsiflexion compared with the CG during jump landings, regardless of trunk position. Conclusions: Landing with greater trunk flexion decreased patellar tendon force in elite jumping athletes. An immediate decrease in knee pain was also observed in symptomatic athletes with a more flexed trunk position during landing. Increasing trunk flexion during landing might be an important strategy to reduce tendon overload in jumping athletes.

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Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents

Purpose: The purpose of this study was to investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation. Methods: Eight healthy men performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4−), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (31P-MRS). Results: The magnitude of metabolic perturbation was significantly greater in FENT compared with CTRL for [Pi] (37.8 ± 16.8 vs 28.6 ± 8.6 mM), [H2PO4−] (24.3 ± 12.2 vs 17.9 ± 7.1 mM), and [ATP] (75.8% ± 17.5% vs 81.9% ± 15.8% of baseline), whereas there was no significant difference in [PCr] (4.5 ± 2.4 vs 4.4 ± 2.3 mM) or pH (6.51 ± 0.10 vs 6.54 ± 0.14). The rate of perturbation in [PCr], [Pi], [H2PO4−], and pH was significantly faster in FENT compared with CTRL. Oxidative ATP synthesis was not significantly different between conditions. However, anaerobic ATP synthesis, through augmented creatine kinase and glycolysis reactions, was significantly greater in FENT than in CTRL, resulting in a significantly greater ATP cost of contraction (0.049 ± 0.016 vs 0.038 ± 0.010 mM·min−1·N−1). Conclusion: Group III/IV muscle afferents not only constrain the magnitude of perturbation in intramuscular Pi, H2PO4−, and ATP during small muscle mass exercise but also seem to play a role in maintaining efficient skeletal muscle contractile function in men.

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The Effect of Sex on Heart Rate Variability at High Altitude

There is evidence suggesting that high altitude (HA) exposure leads to a fall in heart rate variability (HRV) that is linked to the development of acute mountain sickness (AMS). The effects of sex on changes in HRV at HA and its relationship to AMS are unknown. Methods: HRV (5-min single-lead ECG) was measured in 63 healthy adults (41 men and 22 women) 18–56 yr of age at sea level (SL) and during a HA trek at 3619, 4600, and 5140 m, respectively. The main effects of altitude (SL, 3619 m, 4600 m, and 5140 m) and sex (men vs women) and their potential interaction were assessed using a factorial repeated-measures ANOVA. Logistic regression analyses were performed to assess the ability of HRV to predict AMS. Results: Men and women were of similar age (31.2 ± 9.3 vs 31.7 ± 7.5 yr), ethnicity, and body and mass index. There was main effect for altitude on heart rate, SD of normal-to-normal (NN) intervals (SDNN), root mean square of successive differences (RMSSD), number of pairs of successive NN differing by >50 ms (NN50), NN50/total number of NN, very low-frequency power, low-frequency (LF) power, high-frequency (HF) power, and total power (TP). The most consistent effect on post hoc analysis was reduction in these HRV measures between 3619 and 5140 m at HA. Heart rate was significantly lower and SDNN, RMSSD, LF power, HF power, and TP were higher in men compared with women at HA. There was no interaction between sex and altitude for any of the HRV indices measured. HRV was not predictive of AMS development. Conclusions: Increasing HA leads to a reduction in HRV. Significant differences between men and women emerge at HA. HRV was not predictive of AMS.

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Potential Causes of Elevated REE after High-Intensity Exercise

Introduction: Resting energy expenditure (REE) increases after an intense exercise; however, little is known concerning mechanisms. Purpose: The purpose of this study was to determine effects of a single bout of moderate-intensity continuous (MIC) aerobic exercise, or high-intensity interval (HII) exercise on REE under energy balance conditions. Methods: Thirty-three untrained premenopausal women were evaluated at baseline, after 8–16 wk of training, 22 h after either MIC (50% peak V˙O2) or HII (84% peak V˙O2). Participants were in a room calorimeter during and after the exercise challenge. Food intake was adjusted to obtain energy balance across 23 h. REE was measured after 22 h after all conditions. Twenty-three-hour urine norepinephrine concentration and serum creatine kinase activity (CrKact) were obtained. Muscle biopsies were obtained in a subset of 15 participants to examine muscle mitochondrial state 2, 3, and 4 fat oxidation. Results: REE was increased 22 h after MIC (64 ± 119 kcal) and HII (103 ± 137 kcal). Markers of muscle damage (CrKact) increased after HII (9.6 ± 25.5 U·L−1) and MIC (22.2 ± 22.8 U·L−1), whereas sympathetic tone (urine norepinephrine) increased after HII (1.1 ± 10.6 ng·mg−1). Uncoupled phosphorylation (states 2 and 4) fat oxidation were related to REE (r = 0.65 and r = 0.55, respectively); however, neither state 2 nor state 4 fat oxidation increased after MIC or HII. REE was not increased after 8 wk of aerobic training when exercise was restrained for 60 h. Conclusions: Under energy balance conditions, REE increased 22 h after both moderate-intensity and high-intensity exercise. Exercise-induced muscle damage/repair and increased sympathetic tone may contribute to increased REE, whereas uncoupled phosphorylation does not. These results suggest that moderate- to high-intensity exercise may be valuable for increasing energy expenditure for at least 22 h after the exercise.

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Validity and Reliability of Assessing Body Composition Using a Mobile Application

Purpose: The purpose of this study was to determine the validity and reliability of the LeanScreenTM (LS) mobile application that estimates percent body fat (%BF) using estimates of circumferences from photographs. Methods: The %BF of 148 weight-stable adults was estimated once using dual-energy x-ray absorptiometry (DXA). Each of two administrators assessed the %BF of each subject twice using the LS app and manually measured circumferences. A mixed-model ANOVA and Bland–Altman analyses were used to compare the estimates of %BF obtained from each method. Interrater and intrarater reliabilities values were determined using multiple measurements taken by each of the two administrators. Results: The LS app and manually measured circumferences significantly underestimated (P

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Exercise-induced Fatigue in Severe Hypoxia after an Intermittent Hypoxic Protocol

Purpose: Exercise-induced central fatigue is alleviated after acclimatization to high altitude. The adaptations underpinning this effect may also be induced with brief, repeated exposures to severe hypoxia. The purpose of this study was to determine whether (i) exercise tolerance in severe hypoxia would be improved after an intermittent hypoxic (IH) protocol and (ii) exercise-induced central fatigue would be alleviated after an IH protocol. Methods: Nineteen recreationally active men were randomized into two groups who completed ten 2-h exposures in severe hypoxia (IH: partial pressure of inspired O2 82 mm Hg; n = 11) or normoxia (control; n = 8). Seven sessions involved cycling for 30 min at 25% peak power (W˙peak) in IH and at a matched heart rate in normoxia. Participants performed baseline constant-power cycling to task failure in severe hypoxia (TTF-Pre). After the intervention, the cycling trial was repeated (TTF-Post). Before and after exercise, responses to transcranial magnetic stimulation and supramaximal femoral nerve stimulation were obtained to assess central and peripheral contributions to neuromuscular fatigue. Results: From pre- to postexercise in TTF-Pre, maximal voluntary contraction (MVC), cortical voluntary activation (VATMS), and potentiated twitch force (Qtw,pot) decreased in both groups (all P

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Umbrella Reviews: Evidence Synthesis with Overviews of Reviews and Meta-Epidemiologic Studies

No abstract available

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Evidence of Heritable Determinants of Decompression Sickness in Rats

Introduction: Decompression sickness (DCS) is a complex and poorly understood systemic disease caused by inadequate desaturation after a decrease of ambient pressure. Strong variability between individuals is observed for DCS occurrence. This raises questions concerning factors that may be involved in the interindividual variability of DCS occurrence. This study aimed to experimentally assess the existence of heritable factors involved in DCS occurrence by selectively breeding individuals resistant to DCS from a population stock of Wistar rats. Methods: Fifty-two male and 52 female Wistar rats were submitted to a simulated air dive known to reliably induce about 63% DCS: compression was performed at 100 kPa·min−1 up to 1000 kPa absolute pressure before a 45-min long stay. Decompression was performed at 100 kPa·min−1 with three decompression stops: 5 min at 200 kPa, 5 min at 160 kPa, and 10 min at 130 kPa. Animals were observed for 1 h to detect DCS symptoms. Individuals without DCS were selected and bred to create a new generation, subsequently subjected to the same hyperbaric protocol. This procedure was repeated up to the third generation of rats. Results: As reported previously, this diving profile induced 67% of DCS, and 33% asymptomatic animals in the founding population. DCS/asymptomatic ratio was not initially different between sexes, although males were heavier than females. In three generations, the outcome of the dive significantly changed from 33% to 67% asymptomatic rats, for both sexes. Interestingly, survival in females increased sooner than in males. Conclusions: This study offers evidence suggesting the inheritance of DCS resistance. Future research will focus on genetic and physiological comparisons between the initial strain and the new resistant population.

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Hockey Fans in Training: A Pilot Pragmatic Randomized Controlled Trial

Introduction: Hockey Fans in Training (Hockey FIT) is a gender-sensitized weight loss and healthy lifestyle program. We investigated 1) feasibility of recruiting and retaining overweight and obese men into a pilot pragmatic randomized controlled trial and 2) potential for Hockey FIT to lead to weight loss and improvements in other outcomes at 12 wk and 12 months. Methods: Male fans of two ice hockey teams (35–65 yr; body mass index ≥28 kg·m−2) located in Ontario (Canada) were randomized to intervention (Hockey FIT) or comparator (wait-list control). Hockey FIT includes a 12-wk active phase (weekly, coach-led group meetings including provision of dietary information, practice of behavior change techniques, and safe exercise sessions plus incremental pedometer walking) and a 40-wk minimally supported phase (smartphone app for sustaining physical activity, private online social network, standardized e-mails, booster session/reunion). Measurement at baseline and 12 wk (both groups) and 12 months (intervention group only) included clinical outcomes (e.g., weight) and self-reported physical activity, diet, and self-rated health. Results: Eighty men were recruited in 4 wk; trial retention was >80% at 12 wk and >75% at 12 months. At 12 wk, the intervention group lost 3.6 kg (95% confidence interval, −5.26 to −1.90 kg) more than the comparator group (P

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Beyond the Bottom of the Foot: Topographic Organization of the Foot Dorsum in Walking

Introduction: Sensory feedback from the foot dorsum during walking has only been studied globally by whole nerve stimulation. Stimulating the main nerve innervating the dorsal surface produces a functional stumble corrective response that is phase-dependently modulated. We speculated that effects evoked by activation of discrete skin regions on the foot dorsum would be topographically organized, as with the foot sole. Methods: Nonnoxious electrical stimulation was delivered to five discrete locations on the dorsal surface of the foot during treadmill walking. Muscle activity from muscles acting at the ankle, knee, hip, and shoulder were recorded along with ankle, knee, and hip kinematics and kinetic information from forces under the foot. All data were sorted on the basis of stimulus occurrence in 12 step cycle phases, before being averaged together within a phase for subsequent analysis. Results: Results reveal dynamic changes in reflex amplitudes and kinematics that are site specific and phase dependent. Most responses from discrete sites on the foot dorsum were seen in the swing phase suggesting function to conform foot trajectory to maintain stability of the moving limb. In general, responses from lateral stimulation differed from medial stimulation, and effects were largest from stimulation at the distal end of the foot at the metatarsals; that is, in anatomical locations where actual impact with an object in the environment is most likely during swing. Responses to stimulation extend to include muscles at the hip and shoulder. Conclusions: We reveal that afferent feedback from specific cutaneous locations on the foot dorsum influences stance and swing phase corrective responses. This emphasizes the critical importance of feedback from the entire foot surface in locomotor control and has application for rehabilitation after neurological injury and in footwear development.

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Pilot Trial of a Home-based Physical Activity Program for African American Women

Purpose: This study aimed to assess the feasibility of a Home-based, Individually-tailored Physical activity Print (HIPP) intervention for African American women in the Deep South. Methods: A pilot randomized trial of the HIPP intervention (N = 43) versus wellness contact control (N = 41) was conducted. Recruitment, retention, and adherence were examined, along with physical activity (7-d physical activity recalls, accelerometers) and related psychosocial variables at baseline and 6 months. Results: The sample included 84 overweight/obese African American women 50–69 yr old in Birmingham, AL. Retention was high at 6 months (90%). Most participants reported being satisfied with the HIPP program and finding it helpful (91.67%). There were no significant between-group differences in physical activity (P = 0.22); however, HIPP participants reported larger increases (mean of +73.9 min·wk−1 (SD 90.9)) in moderate-intensity or greater physical activity from baseline to 6 months compared with the control group (+41.5 min·wk−1 (64.4)). The HIPP group also reported significantly greater improvements in physical activity goal setting (P = 0.02) and enjoyment (P = 0.04) from baseline to 6 months compared with the control group. There were no other significant between-group differences (6-min walk test, weight, physical activity planning, behavioral processes, stage of change); however, trends in the data for cognitive processes, self-efficacy, outcome expectations, and family support for physical activity indicated small improvements for HIPP participants (P > 0.05) and declines for control participants. Significant decreases in decisional balance (P = 0.01) and friend support (P = 0.03) from baseline to 6 months were observed in the control arm and not the intervention arm. Conclusions: The HIPP intervention has great potential as a low-cost, high-reach method for reducing physical activity–related health disparities. The lack of improvement in some domains may indicate that additional resources are needed to help this target population reach national guidelines.

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Associations of Physical Activity Intensities with Markers of Insulin Sensitivity

Background: Objectively measured physical activity (PA) intensity has traditionally been categorized as light, moderate, and vigorous using laboratory calibrated cut points. The relative contribution of time spent across a spectrum of accelerometer-determined intensities on health outcomes is less clear. Purpose: This study aimed to assess the relationship between objectively measured PA intensity on a continuous scale and markers of insulin sensitivity (IS). Methods: Participants at high risk of type 2 diabetes mellitus were recruited from primary care (Leicestershire, UK). PA was measured using an ActiGraph accelerometer. Fasting and postchallenge glucose and insulin levels were assessed using an oral glucose tolerance test. IS was calculated using the Matsuda-IS and the HOMA-IS indices. Log-linear regression modeling was used to assess the relationship between PA intensity, in increments of 500 counts per minute, with markers of IS. Models were controlled for known confounders. Results: Complete data were available for 569 participants. PA intensity was favorably associated with fasting and 2 h of insulin and IS, with the association increasing in magnitude with each increment of 500 counts per minute. Differences in HOMA-IS per 10 min of PA ranged from 12.4% (95% confidence interval = 3.7%–21.8%) to 26.8% (11.0%–44.7%) within the moderate-intensity PA category (from 2000–2499 to 3500–3999 counts per minute). For Matsuda-IS, these differences were 22.0% (10.3%–34.9%) and 34.7% (13.9%–59.3%), respectively. Significant associations for fasting insulin were no longer observed after controlling for body mass index, whereas differences associated with 2-h insulin and IS were attenuated but still significant. Conclusion: PA of any intensity may positively influence glucose regulation and insulin sensitivity in individuals at high risk of type 2 diabetes mellitus in a dose–response manner. Further research is required to identify the intensity thresholds at which clinically relevant benefits occur in this population.

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Greater Effect of East versus West Travel on Jet Lag, Sleep, and Team Sport Performance

Purpose: This study aimed to determine the recovery timeline of sleep, subjective jet lag and fatigue, and team sport physical performance after east and west long-haul travel. Methods: Ten physically trained men underwent testing at 0900 h and 1700 h local time on four consecutive days 2 wk before outbound travel (BASE), and the first 4 d after 21 h of outbound (WEST) and return (EAST) air travel across eight time zones between Australia and Qatar. Data collection included performance (countermovement jump, 20-m sprint, and Yo-Yo intermittent recovery level 1 [YYIR1] test) and perceptual (jet lag, motivation, perceived exertion, and physical feeling) measures. In addition, sleep was measured via wrist activity monitors and self-report diaries throughout the aforementioned data collection periods. Results: Compared with the corresponding day at BASE, the reduction in YYIR1 distance after EAST was significantly different from the increase in WEST on day 1 after travel (P

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Trends of Magnet Ingestion in Children, an Ironic Attraction.

Background and Objectives: Ingestion of rare earth magnets is a serious ongoing hazard for pediatric patients. Our study aims to investigate whether 2012 Consumer Product Safety Commission (CPSC) policy action, in coordination with efforts from consumer and physician advocacy groups, decreased the incidence of magnet ingestions in children in US since 2012. Methods: Data from the National Electronic Injury Surveillance System (NEISS) was used to evaluate trends in emergency department (ED) encounters with pediatric patients (

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Expression of TLR7 , TLR9 , JAK2 , and STAT3 genes in peripheral blood mononuclear cells from patients with systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a rare, chronic, multisystem autoimmune disease clinically characterized by progressive fibrosis of the skin and internal organs. The basic mechanism appears to involve endothelial cell injury, overproduction of extracellular matrix proteins, and aberrant immune activation. So far, there have been a few attempts to find genetic biomarkers for monitoring disease activity or for correlation with certain symptoms. In order to reveal reliable biomarkers, we analyzed the expression of four genes representing three important signaling pathways, TLR7, TLR9, and JAK2-STAT3. Using RT-qPCR technique, we analyzed the expression of TLR7, TLR9, JAK2, and STAT3 genes in peripheral blood mononuclear cells of 50 SSc patients and 13 healthy individuals. We detected significant upregulation of TLR7 gene expression in a group of SSc patients compared to non-SSc group. Receiver operating characteristic (ROC) analysis showed that TLR7 expression efficiently discriminates SSc cases from healthy individuals. High TLR7 expression positively correlated with the late form of disease, active SSc, and the presence of digital ulcers. Decreased levels of TLR9 and JAK2 mRNA were found in the patient's cohort in comparison to non-SSc individuals, but showed no correlation with specific clinical outcomes. The expression level of the STAT3 gene did not differ between the analyzed groups. This is the first study on the expression of TLR7, TLR9, and STAT3 genes in SSc patients. Our results show that TLR7, TLR9, and JAK2 genes are potential biomarkers for SSc. The results obtained in this study could contribute to better classification, monitoring, and outcome prediction of patients with SSc based on genetics.

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Cycling Efficiency and Energy Cost of Walking in Young and Older Adults

To determine whether age affects cycling efficiency and the energy cost of walking (Cw), 190 healthy adults, ages 18-81 yr, cycled on an ergometer at 50 W and walked on a treadmill at 1.34 m/s. Ventilation and gas exchange at rest and during exercise were used to calculate net Cw and net efficiency of cycling. Compared to the 18-40 yr age group (2.17 ± 0.33 J/kg/m), net Cw was not different in the 60-64 yr (2.20 ± 0.40 J/kg/m) and 65-69 yr (2.20 ± 0.28 J/kg/m) age groups, but was significantly (P < 0.03) higher in the >70 yr (2.37 ± 0.33 J/kg/m) age group. For subjects >60 yr, net Cw was significantly correlated with age (R2 = 0.123; P = 0.002). Cycling net efficiency was not different between 18-40 yr (23.5 ± 2.9%), 60-64 yr (24.5 ± 3.6%), 65-69 yr (23.3 ± 3.6%) and >70 yr (24.7 ± 2.7%) age groups. Repeat tests on a subset of subjects (walking, n = 43; cycling, n = 37) demonstrated high test-retest reliability (intraclass correlation coefficients, ICC, 0.74-0.86) for all energy outcome measures except cycling net energy expenditure (ICC = 0.54) and net efficiency (ICC = 0.50). Coefficients of variation for all variables ranged from 3.1-7.7%. Considerable individual variation in Cw and efficiency was evident, with a ~2-fold difference between the least and most economical/efficient subjects. We conclude that, between 18-81 yr, net Cw was only higher for ages >70 yr, and that cycling net efficiency was not different across age groups.

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Exercise induces muscle fiber type switching via transient receptor potential melastatin 2 (TRPM2)-dependent Ca2+ signaling

The aim of the present study was to examine whether transient receptor potential melastatin 2 (TRPM2) plays a role in muscle fiber type transition during exercise. Mice were trained at a speed of 12 m/min at a slope of 0 ° for 60 min 5 consecutive d/wk for 4-wk. Exhaustion tests were performed on the treadmill (the speed was set at 6 m/min at a slope of 0° and increased at a rate of 1 m/min every 6 min). Isolated primary skeletal muscle cells from TRPM2 knockout (KO) mice showed lower amplitudes of electrical stimuli (ES)-induced Ca²⁺ signals when compared to wild-type (WT) mice, due to a defect in Ca²⁺ influx. Moreover, TRPM2 KO mice had a higher proportion of fast-twitch skeletal muscle fibers and a lower proportion of slow-twitch muscle fibers before exercise than WT mice. After exercise, the expression of slow-twitch skeletal muscle fibers was increased only in WT mice, but not in TRPM2 KO mice. ES-induced nuclear translocation of the Ca²⁺-dependent transcription factor NFATc1 was significantly lower in TRPM2 KO mice than WT mice. TRPM2 KO mice also showed decreased mitochondrial Ca²⁺ and membrane potential. Lactate levels were higher in the skeletal muscle cells of TRPM2 KO mice before and after ES, compared to WT mice. Collectively, these data indicate that TRPM2-mediated Ca²⁺ signaling plays a critical role in the regulation of fiber type switching and mitochondrial function in skeletal muscle.

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Specific force of the vastus lateralis in adults with Achondroplasia

Achondroplasia is a clinical condition defined by shorter stature and disproportionate limb length. Force production in able-bodied individuals (controls) is proportional to muscle size, but given the disproportionate nature of Achondroplasia, normalising to anatomical cross sectional area (ACSA) is inappropriate. The aim of this study was to assess specific force of the vastus lateralis (VL) in 10 adults with Achondroplasia (22 ±3 yrs) and 18 gender matched controls (22 ±2 yrs). Isometric torque (iMVC) of the dominant knee extensors (KE) and in vivo measures of VL muscle architecture, volume, activation and patella tendon moment arm were used to calculate VL physiological CSA (PCSA), fascicle force and specific force in both groups. Achondroplasia muscle volume was 53% smaller than controls (284 ±36 vs 604 ±102 cm³, P < 0.001). KE iMVC was 63% lower in Achondroplasia compared to controls (95 ±24 vs 256 ±47 N•m, P < 0.001). Activation and moment arm length were similar between groups (P > 0.05), but coactivation of Achondroplasia bicep femoris was 70% more than controls (43 ±20 vs 13 ±5%, P < 0.001). Achondroplasia had 58% less PCSA (43 ±10 vs 74.7 ±14 cm², P < 0.001), 29% lower fascicle force (702 ±235 vs 1704 ±303 N, P < 0.001) and 29% lower specific force than controls (17 ±6 vs 24 ±6 N•cm^-2, P = 0.012). The smaller VL specific force in Achondroplasia may be attributed to infiltration of fat and connective tissue, rather than to any difference in myofilament function.

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Looking beyond macro-ventilatory parameters and re-thinking ventilator-induced lung injury

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Asymmetric distribution of CRUMBS polarity complex proteins from compacted 8-cell to blastocyst stage during mouse preimplantation development

Publication date: Available online 15 November 2017
Source:Gene Expression Patterns
Author(s): Xinlong Jiang, Wenzhong An, Xiao Yang, Jieye Lin, Shiliang Ma, Dajia Wang, Shuang Tang
During mouse preimplantation development, blastomeres are equipotent until polarity establishment at compacted 8-cell stage. The intrinsic nature of polarity is the asymmetric distribution of polarity proteins between inside and outside blastomeres along the direction of apical-basal axis. This study investigated the early developmental temporal and spatial expression of the main CRUMBS polarity complex proteins in the mouse preimplantation embryo. We observed that Crb3, Pals1, Patj and Mpdz are transcribed in the mouse preimplantation embryo. However, the asymmetric distribution of these polarity proteins is not established until the compacted 8-cell stage. From compaction and thereafter, CRB3 and PALS1 are progressively enriched in the apical membrane, while PATJ and MPDZ are discretely localized at both tight junctions and the apical membrane adjacent to tight junctions. These temporal and spatial distribution patterns suggest that CRUMBS polarity complex might be involved in the cell polarity establishment in the early mouse embryo and reinforce the viewpoint that developmentally spatial asymmetries are first set up at the compaction stage. The present study provides a foundation for further investigation on the functions of CRUMBS polarity complex in trophectoderm specification and blastocyst morphogenesis.



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Correction to: The Content of c-Fos-Positive Neurons in the Cerebral Cortex and Striatum and Behavioral Characteristics in Rats on Cutaneous Application of Antiseptic Dorogov’s Stimulator Paste

To the article "The Content of c-Fos-Positive Neurons in the Cerebral Cortex and Striatum and Behavioral Characteristics in Rats on Cutaneous Application of Antiseptic Dorogov's Stimulator Paste," by G. A. P'yavchenko, V. A. Pugach, N. S. Novikova, L. I. Shmarkova, E. A. Korneva, and V. I. Nozdrin.

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Comparison of ChIP-seq Data and a Reference Motif Set for Human KRAB C2H2 Zinc Finger Proteins

KRAB C2H2 zinc finger proteins (KZNFs) are the largest and most diverse family of human transcription factors, likely due to diversifying selection driven by novel endogenous retroelements (EREs), but the vast majority lack binding motifs or functional data. Two recent studies analyzed a majority of the human KZNFs using either ChIP-seq (60 proteins) or ChIP-exo (221 proteins) in the same cell type (HEK293). The ChIP-exo paper did not describe binding motifs, however. Thirty-nine proteins are represented in both studies, enabling the systematic comparison of the data sets presented here. Typically, only a minority of peaks overlap, but the two studies nonetheless display significant similarity in ERE binding for 32/39, and yield highly similar DNA binding motifs for 23 and related motifs for 34 (MoSBAT similarity score > 0.5 and > 0.2, respectively). Thus, there is overall (albeit imperfect) agreement between the two studies. For the 242 proteins represented in at least one study, we selected a highest-confidence motif for each protein, utilizing several motif-derivation approaches, and evaluating motifs within and across data sets. Peaks for the majority (158) are enriched (96% with AUC > 0.6 predicting peak vs non-peak) for a motif that is supported by the C2H2 "recognition code", consistent with intrinsic sequence specificity driving DNA binding in cells. An additional 63 yield motifs enriched in peaks, but not supported by the recognition code, which could reflect indirect binding. Altogether, these analyses validate both data sets, and provide a reference motif set with associated quality metrics.

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microRNA Tissue Atlas of the Malaria Mosquito Anopheles gambiae

Anopheles gambiae mosquitoes transmit the human malaria parasite Plasmodium falciparum, which causes the majority of fatal malaria cases worldwide. The hematophagous life style defines the mosquito reproductive biology and is exploited by P. falciparum for its own sexual reproduction and transmission. The two main phases of the mosquito reproductive cycle, pre-vitellogenic (PV) and post-blood meal (PBM) shape its capacity to transmit malaria. Transition between these phases is tightly coordinated to ensure homeostasis between mosquito tissues and successful reproduction. One layer of control is provided by microRNAs, well known regulators of blood meal digestion and egg development in Aedes mosquitoes. Here, we report a global overview of tissue-specific miRNA expression during the PV and PBM phases and identify miRNAs regulated during PV to PBM transition. The observed coordinated changes in the expression levels of a set of miRNAs in the energy-storing tissues suggest a role in the regulation of blood meal-induced metabolic changes.

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Are We Highly Dependent on Critical Care for Scoliosis Surgery?

BACKGROUND: At Sheffield Children's Hospital (SCH), based on a previously presented audit, scoliosis patients are postoperatively cared for on the general spinal ward (S3) if they satisfy the following criteria:

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Investigating the Impact of BMI, Age, and Gender on the Severity of the Main Curve in Adolescent Idiopathic Scoliosis

BACKGROUND: Adolescent Idiopathic Scoliosis (AIS) is a common condition with a wide spectrum of severity. However, the factors affecting curve severity are poorly understood. Existing research has yielded sparse and contradictory information regarding the impact of demographic factors such as body mass index (BMI), age, and gender on the severity of scoliotic curves in AIS.

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An NIHR Approved Two-Year Observational Study on Magnetically Controlled Growth Rods

AIMS: The primary aim of this work was to undertake an NIHR approved study to evaluate the performance and safety of Magnetically Controlled Growth Rods (MCGR). The secondary aims were: (1) Evaluation of clinical outcome, (2) Assess impact on re-operation rate, (3) Evaluate complication rates and (4) Evaluate durability of correction.

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The Efficacy of Multi-Modal Intra-Operative Spinal Cord Monitoring (IOM) in Preventing Neurological Injury during Spinal Deformity Surgery

OBJECTIVE: The purpose of this study was to present the diagnostic characteristics of multi-modal IOM in spinal deformity surgery. Also, to define and categorize the neuro-monitoring events, as well as develop an algorithm of action.

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Return to Activity and Sports Following Posterior Correction and Fusion for Adolescent Idiopathic Scoliosis

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is largely asymptomatic preoperatively. Sport offers physical benefits and psychosocial wellbeing to developing individuals. Scoliosis is not a contraindication to participating in sport. Literature would suggest that patients with AIS who exercise regularly have less psychosocial or body image disturbance. There are no agreed guidelines for patients to return to sports following surgery for AIS. Fear of litigation in a medicolegal culture can lead to an overcautious approach.

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Advancing the Management of Adolescent Idiopathic Scoliosis: the Alder Hey Scan Jacket

INTRODUCTION: Brace management of scoliosis is known to be an effective means of controlling flexible and reducing the risk of curve progression. Traditionally braces have been cumbersome and poorly tolerated however recent innovations have allowed for the development of patient specific braces that are both cosmetically and functionally better. We present our experience with the Alder Hey Scan Jacket Brace.

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Anterior Vertebral Body Tethering for Adolescent Idiopathic Scoliosis: One-Year Results on the First 17 Patients

METHODS: Retrospective analysis of clinical and radiographic data of anterior vertebral body tethering for adolescent idiopathic scoliosis with a minimum follow up (FU) of 1-year.

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Editorial Board

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Are Supine Bending Films Absolutely Essential in Preoperative Assessment and Deciding Fusion Levels in AIS ?

INTRODUCTION: Analysis of preoperative flexibility in adolescent idiopathic scoliosis (AIS) is essential to classify the curves, determine their structurality, and select the fusion levels during preoperative planning. Side-bending supine x-rays are the gold standard for the analysis of preoperative flexibility. The objective of this study was to examine two groups of patients with AIS group I (supine bending films) and AIS group II (supine films) and to determine the feasibility of supine images in assessing curve flexibility and determining fusion levels in AIS.

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Selection of Duchenne Muscular Dystrophy Patients for Spinal Surgery in Great Ormond Street Hospital. Have We Got It Right?

BACKGROUND: Children with Duchenne muscular dystrophy (DMD) develop progressive weakness, loss of ambulation and worsening spinal deformity, which can lead to pain, deteriorating respiratory function and quality of life. It remains controversial whether spinal surgery has benefits on delaying progression of respiratory dysfunction, on survival and whether these outweigh the recognised perioperative complications.

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A Novel Modified Posterior Surgical Approach for Neuromuscular Scoliosis

BACKGROUND: Standard midline posterior approach is established corridor for treatment of neuromuscular scoliosis. This approach however in the lower part of deformity becomes contaminated as it is included in napee since most of these patients are having double incontinence, leading to potential threat for surgical site infections (SSI).

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Anterior Column Reconstruction in Primary Adult Degenerative Scoliosis Correction Surgery: Restoring Lordosis and Achieving Indirect Decompression With Minimally Invasive Lateral Cages

BACKGROUND: Patients with degenerative scoliosis often present with leg pain, back pain and issues with sagittal balance. Complications following open correction surgery can be high and sagittal balance correction poor using a posterior only technique. We present a case series demonstrating that multiple anterior cages inserted via a minimally invasive lateral or anterior technique is an effective way of correcting the coronal deformity and restoring sagittal balance. Additionally, it provides indirect decompression of neural structures.

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A United Kingdom Single Centre Review of the Impact of Extended Waiting Times in Scoliosis: The Effect of a Delay to Surgical Treatment of Greater Than 12 Months

INTRODUCTION: Timely intervention in scoliosis is necessary to ensure optimal outcome. Surgical delays can lead to patient harm as a result of deteriorating physical function, reduced pulmonary function or a change in planned surgery. The extent that pulmonary development is impaired by surgical delay is difficult to quantify.

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Direct Vertebral Derotation: Does It Work?

BACKGROUND: Adolescent idiopathic scoliosis (AIS) affects around 1.2% of the population. The current treatment for those requiring operative intervention is posterior instrumented correction (PIC). Correction is either by translation or direct vertebral derotation (DVDR). At surgery any residual rib cage deformity is addressed by means of thoracoplasty which is not without complications. This study reports the outcomes of the two methods in a single center.

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The Operative Management of Early Onset Scoliosis Using VEPTR: The Complete Patient Journey

STUDY DESIGN: A retrospective study of patients treated operatively with vertical expandable prosthetic titanium rib (VEPTR) for early onset scoliosis.

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Ultrasonography Compared to Radiographs in the Assessment of Extension of Magnetically Controlled Growing Rods

BACKGROUND: Magnetically controlled growing rods (MCGR) are used in the management of early onset scoliosis. Unlike traditional growing rod spinal systems the theoretical advantage is the fact that the extension of the rod can be conducted in clinic without the need for repeat surgery. This requires repeated radiographs to assess rod extension increasing patient's ionizing radiation exposure. Ultrasound may offer a safe non-invasive alternative. The purpose of this study is to investigate ultrasongraphic measurement of rod extension and compare it to radiographic assessment.

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The Use of Magnetically-Controlled Growth Rods (MCGR) and Traditional Growth Rods (TGR) in a Paediatric Population

BACKGROUND: We conducted a single-centre prospective study comparing magnetically controlled growth rods (MCGR) and traditional growth rods (TGR) in a paediatric scoliosis population. The purpose was to evaluate clinical outcomes in both cohorts.

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Cyanotic Congenital Cardiac Disease and Scoliosis: Preoperative Assessment, Surgical Treatment and Outcome

ABSTRACT: Congenital heart disease (CHD) affects 1% of live births (10% cyanotic CHD). There is well-recognised association between CHD and scoliosis. Improvements in cardiac care have extended survivorship with increase in the need for deformity correction. There is limited information on the spinal care of these patients. In patients with univentricular heart it has been recommended that surgery is performed earlier in life to prevent bleeding complications. We present 3 patients with CHD who underwent scoliosis correction and review the literature on this rare condition.

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The Rate of Disc Degeneration on MRI in Preoperative Adolescent Idiopathic Scoliosis

INTRODUCTION: Surgical goals in the management of Adolescent Idiopathic Scoliosis (AIS) include deformity correction as well as preservation of caudal motion segments. In the region of 7% of patients have radiographic markers of significant disc degeneration ten years after surgery for AIS. However, quoted rates of disc degeneration preoperatively are in relation to the normal paediatric population not the AIS population. Currently the rate of preoperative disc degeneration in the AIS population is not clearly defined.

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Does Magnesium Sulphate Infusion in the Perioperative Period Reduce the Requirement for Postoperative Opioid Analgesia in Posterior Surgical Correction of AIS

BACKGROUND TO THE STUDY: Postoperative muscle spasm is an important cause of post-operative pain. Magnesium is an effective calcium antagonist and is able to attenuate calcium-induced muscle contraction reducing muscle spasm. This is a retrospective study that explores the use of magnesium sulphate as an analgesic adjunct in patients undergoing scoliosis correction.

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Clinical outcome of portal vein thrombosis in patients with digestive cancers: a large AGEO multicenter study

Management of portal vein thrombosis (PVT) in cancer patients remains discussed.

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The effect of increased intracranial EEG sampling rates in clinical practice

For the ∼1/3 of epilepsy patients who are not controlled by medications alone, epilepsy surgery or the possibility of implantable devices to treat their seizures may be the only therapeutic option. However, the success rates of epilepsy surgery vary broadly from 40-80%(Cohen-Gadol et al., 2006; Lee et al., 2005; Mohammed et al., 2012; de Tisi et al., 2011), and these numbers have not changed in many years. It is clear that the standard practice of evaluating epilepsy surgical candidates needs improvement.

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Cognitive impairment measured by event-related potentials during early and late postoperative period following intravenous or inhalation anaesthesia

Postoperative cognitive impairment, known as POCD (postoperative cognitive dysfunction), is not a diagnosis, but rather a clinical phenomenon. Development of POCD has not yet been clearly and unequivocally elucidated due to a lack of formal criteria for assessment and diagnosis. Some clinicians have challenged the importance of POCD because cognitive impairment seems to be transient, and long-term effects are unknown. It is likely that the cause of POCD is multifactorial and may include the preoperative health status of patients, perioperative events related to the surgery itself, and possible neurotoxic effects of anaesthetic agents (Machado et al.

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Correlating motor unit morphology with bioelectrical activity – a simulation study

Simulation studies on motor unit potentials (MUPs), apart from clinical experience, are important in understanding how the morphological features such as number of fibers, their diameters and distribution within the motor unit area influence the MUP waveform (Dumitru et al., 1997; Nandedkar et al., 1988b; Nandedkar and Sanders, 1989; Stålberg and Karlsson, 2000, 2001; Zalewska et al., 2004). Simulation enables the relationship between motor unit morphology and MUP shape variability to be determined.

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Clinical outcome of portal vein thrombosis in patients with digestive cancers: a large AGEO multicenter study

Management of portal vein thrombosis (PVT) in cancer patients remains discussed.

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Ambulatory anterior cervical discectomy and fusion is associated with a higher risk of revision surgery and perioperative complications: an analysis of a large nationwide database

With the changing landscape of healthcare, outpatient spine surgery is being more commonly performed to reduce cost and improve efficiency. Anterior cervical discectomy and fusion (ACDF) is one of the most common spine surgeries performed and demand is expected to increase with an aging population.

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Predictors before and after multimodal rehabilitation for pain acceptance and engagement in activities at a one-year follow-up for patients with whiplash associated disorders, WAD – a study based on the swedish quality registry for pain rehabilitation (SQRP)

Studies have shown that pain acceptance strategies related to psychological flexibility are important in the presence of chronic musculoskeletal pain. However, the predictors of these strategies have not been studied extensively in patients with Whiplash Associated Disorders (WAD).

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Health outcomes and costs of acute traumatic spinal injury in New South Wales, Australia

Traumatic spinal injuries are often associated with both long-term disability, higher frequency of hospital readmissions and high medical costs for individuals of all ages. Age differences in terms of injury profile and health outcomes among those who sustain a spinal cord injury have been identified. However, factors that may influence health outcomes among those with a spinal injury have not been extensively examined at a population-level.

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Outpatient elective posterior lumbar fusions appear to be safely considered for appropriately selected patients

There has been growing interest in performing posterior lumbar fusions (PLFs) in the outpatient setting to optimize patient satisfaction and reduce cost. Although still done in only a small percentage of cases, this has been more possible due to advances in surgical techniques and anesthesia. However, data on the perioperative course of outpatient compared to inpatient PLF in a large sample size is scarce.

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Freehand technique for C2 pedicle and pars screw placement: safe or not?

During placement of C2 pedicle and pars screws, intraoperative fluoroscopy is used so that neurovascular complications can be avoided, and screws can be placed in the proper position. However, this method is time consuming and increases radiation exposure. Furthermore, it does not guarantee completely safe and accurate screw placement.

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Body mass index predicts risk of complications in lumbar spine surgery based on surgical invasiveness

Obesity as a comorbidity in spine pathology may increase the risk of complications following surgical treatment. The BMI threshold at which obesity becomes clinically relevant, and the exact nature of that effect, remains poorly understood.

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Operations Manager/Chief - Lifeguard Ambulance

Job Description As a provider of emergency medical services in Northwest Mississippi we look to hire a forward thinking and proactive Operations Manager for our 911 oriented base in Batesville, MS. To succeed in the position you'll need to be a leader that promotes and executes operational excellence in the base. You must be an excellent communicator, promoter, detail oriented, business driver with ...

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Standing on slopes – how current microprocessor-controlled prosthetic feet support transtibial and transfemoral amputees in an everyday task

Conventional prosthetic feet like energy storage and return feet provide only a limited range of ankle motion compared to human ones. In order to overcome the poor rotational adaptability, prosthetic manufactu...

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Iowa county donates AEDs to public sites

People at each location will be trained to use the devices, according to Wapello County Public Health director Lynelle Diers

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Frontal infraslow activity marks the motor spasms of anti-LGI1 encephalitis

Publication date: January 2018
Source:Clinical Neurophysiology, Volume 129, Issue 1
Author(s): Richard Wennberg, Claude Steriade, Robert Chen, Danielle Andrade
ObjectiveThe clinical and electrographic features of seizures in anti-LGI1 encephalitis are distinct from those seen in other autoimmune encephalitides or non-encephalitic epilepsies. One electroclinical phenomenon specific to the condition consists of lateralized motor spasms, known as faciobrachial dystonic seizures (FBDS). An electrodecremental pattern overriding a "DC shift" has been described as the EEG correlate of these spasms. We sought to further characterize this pre-spasm infraslow activity (ISA).MethodsContinuous video-EEG recordings were acquired in four patients with anti-LGI1 encephalitis: each had frequent motor spasms/FBDS as well as frequent subclinical temporal lobe seizures (an independent indicator of anti-LGI1 encephalitis).ResultsIn artifact-free recordings obtained using clinical amplifiers equipped with a low frequency analog filter of 0.07 Hz, ISA reliably preceded clinical onset of the motor spasms by ∼1.2 s and preceded the electrodecremental pattern by ∼700 ms. Pre-spasm ISA was invariably recorded contralateral to FBDS, with a voltage topographic maximum over the mid frontal region. The pre-movement ISA differed from the Bereitschaftspotential in timing and topography and was an order of magnitude higher in amplitude. Sporadic FBDS that occurred in association with temporal lobe seizures were preceded by identical ISA.ConclusionsThe motor spasms of anti-LGI1 encephalitis are preceded by frontal ISA. A paucity of data at the microscale level precludes mechanistic explanations at the macroscale level, or even determination of the relative contributions of neurons and glia in the generation of the ISA.SignificanceAlthough fundamental cellular mechanisms await elucidation, the pre-spasm ISA represents a singular and readily identifiable EEG response to this autoimmune brain disorder.



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Contraction response to muscle percussion: A reappraisal of the mechanism of this bedside test

Publication date: January 2018
Source:Clinical Neurophysiology, Volume 129, Issue 1
Author(s): Christoph Czarnetzki, André Truffert, Abdelhafid Mekideche, Antoine Poncet, Christopher Lysakowski, Martin R. Tramèr, Michel R. Magistris
ObjectiveTo study whether the contraction evoked by muscle percussion stems from the excitation of the muscle or of the nerve and to discuss the changes of this response in neuromuscular disorders.MethodsIn 30 neurologically healthy patients undergoing surgery (for ear, nose, or throat problems unrelated to the study) under general anesthesia with propofol and sufentanil we measured with an electrogoniometer the maximal dorsiflexion of the ankle evoked by reflex hammer percussion of the tibialis anterior muscle before and under neuromuscular junction blockade with rocuronium bromide. In 3 additional healthy volunteers we searched for F-waves to disclose whether percussion excites axons within the muscle.ResultsResponses from 28 neurologically healthy patients (15 women) were analyzed after exclusion of 2 due to technical problems. Mean age (SD) was 28 (9) years. Maximal dorsiflexion of the ankle was not significantly modified by neuromuscular junction blockade (mean difference 0.01 mV [95%CI, −0.07 to 0.08], p=0.879). Muscle percussion evoked F-waves in the 3 healthy volunteers tested.ConclusionsMaximal contraction response to muscle percussion has a muscular rather than a neural origin. However, percussion also excites axons within the muscle.SignificanceThese findings may provide clues to understand the changes observed in neuromuscular disorders.



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Structural rearrangements of the RNA polymerase III machinery during tRNA transcription initiation

Publication date: Available online 15 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ewan Phillip Ramsay, Alessandro Vannini
RNA polymerase III catalyses the synthesis of tRNAs in eukaryotic organisms. Through combined biochemical and structural characterisation, multiple auxiliary factors have been identified alongside RNA Polymerase III as critical in both facilitating and regulating transcription. Together, this machinery forms dynamic multi-protein complexes at tRNA genes which are required for polymerase recruitment, DNA opening and initiation and elongation of the tRNA transcripts. Central to the function of these complexes is their ability to undergo multiple conformational changes and rearrangements that regulate each step. Here, we discuss the available biochemical and structural data on the structural plasticity of multi-protein complexes involved in RNA Polymerase III transcriptional initiation and facilitated re-initiation during tRNA synthesis. Increasingly, structural information is becoming available for RNA polymerase III and its functional complexes, allowing for a deeper understanding of tRNA transcriptional initiation. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.



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Paramedic starts viral campaign to spread EMS positivity

By EMS1 Staff BRIERLEY HILL, England — Amidst recent stories of EMS abuse, a paramedic invited colleagues to share positive community experiences. BBC reported that West Midlands Ambulance Service paramedic Rob Moore created the campaign #BlueLightHappy to remind everyone of the positivity EMS providers experience. With so much negativity out there, Birmingham Paramedic @wmasRobMoore decided to ...

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Dallas fire dept. rolls out new 911 system

The new system cuts out the practice of "over triaging calls" and uses an algorithm to suggest to dispatchers what resources are needed

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Uranium mobility across annual growth rings in three deciduous tree species

Publication date: Available online 15 November 2017
Source:Journal of Environmental Radioactivity
Author(s): Kelly C. McHugh, Elisabeth Widom, Henry B. Spitz, Gregory C. Wiles, Sam E. Glover
Black walnut (Juglans nigra), slippery elm (Ulmus rubra), and white ash (Fraxinus americana) trees were evaluated as potential archives of past uranium (U) contamination. Like other metals, U mobility in annual growth rings of trees is dependent on the tree species. Uranium concentrations and isotopic compositions (masses 234, 235, 236, and 238) were analyzed by thermal ionization mass spectrometry to test the efficacy of using tree rings to retroactively monitor U pollution from the FFMPC, a U purification facility operating from 1951 to 1989. This study found non-natural U (depleted U and detectable ²³⁶U) in growth rings of all three tree species that pre-dated the start of operations at FFMPC and compositional trends that did not correspond with known contamination events. Therefore, the annual growth rings of these tree species cannot be used to reliably monitor the chronology of U contamination.



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137Cs in mushrooms from Croatia sampled 15–30 years after Chernobyl

Publication date: Available online 15 November 2017
Source:Journal of Environmental Radioactivity
Author(s): Ivana Tucaković, Delko Barišić, Željko Grahek, Ante Kasap, Ivan Širić
The aim of this study was to select species with higher potential to accumulate ¹³⁷Cs among the available mushroom species, by determining the activity concentrations of ¹³⁷Cs in mushrooms collected along north and north-western part of Croatia. A total of 55 samples of 14 different species were analyzed and the potential of mycorrhizal and saprotrophic species to accumulate ¹³⁷Cs was compared. A wide range of the dry weight activity concentrations of ¹³⁷Cs was detected, ranging from 0.95 to 1210 Bq/kg (154 Bq/kg mean value; 52.3 Bq/kg geometric mean) in mycorrhizal and 1.05–36.8 Bq/kg (8.90 Bq/kg mean value; 5.49 Bq/kg geometric mean) in saprotrophic species. Statistical analyses showed that mycorrhizal species accumulate significantly higher concentrations of ¹³⁷Cs and thus could perform better as long-term bioindicators of environmental pollution by radiocaesium then saprotrophic species. The comparison of Boletus sp. and Hydnum repandum (both mycorrhizal species commonly found in Croatia) showed, in general order of magnitude, higher accumulation in Hydnum repandum. Clearly, mushrooms, especially mycorrhizal species, can be used as significant indicators even decades after the occurrence of any serious ¹³⁷Cs contamination event. However, as a wide range of values indicates that various parameters may influence the total uptake of the ¹³⁷Cs into the mushroom fruit bodies, it is necessary to emphasize that ¹³⁷Cs activity detected in a single mushroom sample is very site-specific.

Graphical abstract

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Comparative genomic analysis of Lactobacillus plantarum GB-LP4 and identification of evolutionarily divergent genes in high-osmolarity environment

Abstract

Lactobacillus plantarum is one of the widely-used probiotics and there have been a large number of advanced researches on the effectiveness of this species. However, the difference between previously reported plantarum strains, and the source of genomic variation among the strains were not clearly specified. In order to understand further on the molecular basis of L. plantarum on Korean traditional fermentation, we isolated the L. plantarum GB-LP4 from Korean fermented vegetable and conducted whole genome assembly. With comparative genomics approach, we identified the candidate genes that are expected to have undergone evolutionary acceleration. These genes have been reported to associate with the maintaining homeostasis, which are generally known to overcome instability in external environment including low pH or high osmotic pressure. Here, our results provide an evolutionary relationship between L. plantarum species and elucidate the candidate genes that play a pivotal role in evolutionary acceleration of GB-LP4 in high osmolarity environment. This study may provide guidance for further studies on L. plantarum.

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Correction to: A comparison of isomaltulose versus maltodextrin ingestion during soccer-specific exercise

Abstract

The article "A comparison of isomaltulose versus maltodextrin ingestion during soccer-specific exercise", written by "Emma J. Stevenson, Anthony Watson, Stephan Theis, Anja Holz,·Liam D. Harper, Mark Russell", was originally published Online First without open access. After publication in volume [117], issue [11], page.

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FDA clears nerve stimulator to aid recovery from opioids

The nerve stimulator is the first device to treat such symptoms including joint pain, anxiety, stomach aches and insomnia

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Good Samaritan, officer help revive woman in crash

Officer Jared Yaris was working at a construction site when passerby Edward Rocha alerted him to the crash

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A Randomized Controlled Study of the Efficacy of Pregabalin in the Treatment of Opiate Withdrawal Syndrome

Objective. To study the efficacy and safety of pregabalin (Lyrica) in the complex therapy of opioid withdrawal syndrome (OWS). Materials and methods. The study design was a randomized, symptom-controlled, simple, blind study with active controls. A total of 34 patients with OWS were randomized to two groups. Patients of group 1 (19 subjects) received pregabalin at a dose of up to 600 mg/day as the main substance for treating OWS, in combination with symptomatic treatment (basal and symptom-triggered). Patients of group 2 (15 subjects) received clonidine (Clofelin, up to 600 mg/day) as the main treatment agent, in combination with basal and symptom-triggered treatment. The severity of OWS, cravings for opiates, sleep disorders, anxiety, depression, and side effects were assessed daily using international validated quantified assessment scales. Results. In group 1, 15 patients (79%) completed OWS treatment, compared with seven (47%) in group 2 (p = 0.05, Fisher's exact test). There were no statistically significant differences between groups in terms of the dynamics of the severity of OWS (perhaps because of the limited number of patients). In the pregabalin-treated group, measures of the intensity of opiate cravings decreased during treatment as compared with group 2 (p = 0.05), and similar changes were seen in relation to anxiety (p = 0.05) and depression (p < 0.05); self-assessments of wellbeing increased (p < 0.05). There were no significant between-group differences in the overall incidence of side effects, though treatment tolerance was better in group 1. Conclusions. The treatment scheme including pregabalin was effective and safe and was well tolerated by patients, providing more successful completion of detoxification programs.

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A Therapeutic Target for Inhibition of Neurodegeneration: Autophagy

The role of autophagy in supporting cellular survival and inhibiting neurodegeneration in Alzheimer's disease, Parkinson's disease, and Huntington's disease, which are accompanied by the accumulation of the proteins β-amyloid, α-synuclein, and huntingtin, is discussed. Autophagy undergoes various degrees of weakening in these diseases, and also decreases in aging. Removal of accumulated toxic proteins and structures is mediated by the mechanisms of autophagy (chaperone-mediated autophagy, macroautophagy, mitophagy) in interactions with the ubiquitin-proteasome system. In many cases, activation of mTOR-dependent autophagy and mTOR-independent pathways for its regulation leads to the therapeutic effect of inhibiting neurodegeneration in cell cultures and animal models of diseases. A number of autophagy activators (resveratrol, metformin, rilmenidine, lithium, cucurmin, etc.) are in the stage of clinical trials.

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Correlation between the Functional Connectivity of Brain Areas Active in the Resting State with Behavioral and Psychological Indicators

Recent years have seen extensive data on continuous recording of brain activity in the state of restful waking. This activity is particularly reflected in spatial maps of brain activity obtained using functional MRI scanning (fMRI) and termed resting state networks (RSN). RSN have stable spatial structure which is reproducible over time in healthy subjects, but can be significantly different from normal in the presence of clinical pathology. One important parameter of this type of brain activity is the functional connectivity (FC) of individual elements within the network or between RSN. This review describes results from studies of the interaction of behavioral parameters and FC in brain areas active in the state of restful waking. Data on the reproducibility of RSN parameters over time in healthy subjects are presented, along with data on changes in the FC of networks depending on individual experience.

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Sustained cardiac programming by short-term juvenile exercise training in male rats

Abstract

The aim of this study was to investigate if endurance training during juvenile life 'reprograms' the heart and leads to sustained improvements in the structure, function, and morphology of the adult heart. Male Wistar Kyoto rats were exercise trained 5 days/week for four weeks in either juvenile (5–9 weeks of age), adolescent (11–15 weeks of age) or adult life (20–24 weeks of age). Juvenile exercise training, when compared to 24 week old sedentary rats, led to sustained increases in left ventricle (LV) mass (+18%; P < 0.05), wall thickness (+11%; P < 0.05), the longitudinal area of binucleated cardiomyocytes (P < 0.05), cardiomyocyte number (+36%; P < 0.05), and doubled the proportion of mononucleated cardiomyocytes (P < 0.05), with a less pronounced effect of exercise during adolescent life. Adult exercise training also increased LV mass (+11%; P < 0.05), wall thickness (+6%; P < 0.05) and the longitudinal area of binucleated cardiomyocytes (P < 0.05), despite no change in cardiomyocyte number or the proportion of mono and binucleated cardiomyocytes. Resting cardiac function, LV chamber dimensions and fibrosis levels were not altered by juvenile or adult exercise training. At 9 weeks of age juvenile exercise significantly reduced the expression of microRNA-208b, which is a known regulator of cardiac growth but this was not sustained to 24 weeks of age. In conclusion, juvenile exercise leads to physiological cardiac hypertrophy that is sustained into adulthood long after exercise training has ceased. Furthermore, this cardiac reprogramming is largely due to a 36% increase in cardiomyocyte number, which results in an additional 20 million cardiomyocytes in adulthood.

This article is protected by copyright. All rights reserved

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Human cerebral blood flow control during hypoxia: focus on chronic pulmonary obstructive disease and obstructive sleep apnea

The brain is a vital organ that relies on a constant and adequate blood flow to match oxygen and glucose delivery with the local metabolic demands of active neurons. Thus exquisite regulation of cerebral blood flow (CBF) is particularly important under hypoxic conditions to prevent a detrimental decrease in the partial pressure of oxygen within the brain tissues. Cerebrovascular sensitivity to hypoxia, assessed as the change in CBF during a hypoxic challenge, represents the capacity of cerebral vessels to respond to, and compensate for, a reduced oxygen supply, and has been shown to be impaired or blunted in a number of conditions. For instance, this is observed with aging, and in clinical conditions such as untreated obstructive sleep apnea (OSA) and in healthy humans exposed to intermittent hypoxia. This review will 1) provide a brief overview of cerebral blood flow regulation and results of pharmacological intervention studies which we have performed to better elucidate the basic mechanisms of cerebrovascular regulation in humans; and 2) present data from studies in clinical and healthy populations, using a translational physiology approach, to investigate human CBF control during hypoxia. Results from studies in patients with chronic obstructive pulmonary disease and OSA will be presented to identify the effects of the disease processes on cerebrovascular sensitivity to hypoxia. Data emerging from experimental human models of intermittent hypoxia during wakefulness will also be reviewed to highlight the effects of intermittent hypoxia on the brain.

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Acute oxygen sensing by the carotid body: from mitochondria to plasma membrane

Maintaining oxygen homeostasis is crucial to the survival of animals. Mammals respond acutely to changes in blood oxygen levels by modulating cardiopulmonary function. The major sensor of blood oxygen that regulates breathing is the carotid body (CB), a small chemosensory organ located at the carotid bifurcation. When arterial blood oxygen levels drop in hypoxia, neuroendocrine cells in the CB called glomus cells are activated to signal to afferent nerves that project to the brain stem. The mechanism by which hypoxia stimulates CB sensory activity has been the subject of many studies over the past 90 years. Two discrete models emerged that argue for the seat of oxygen sensing to lie either in the plasma membrane or mitochondria of CB cells. Recent studies are bridging the gap between these models by identifying hypoxic signals generated by changes in mitochondrial function in the CB that can be sensed by plasma membrane proteins on glomus cells. The CB is important for physiological adaptation to hypoxia, and its dysfunction contributes to sympathetic hyperactivity in common conditions such as sleep-disordered breathing, chronic heart failure, and insulin resistance. Understanding the basic mechanism of oxygen sensing in the CB could allow us to develop strategies to target this organ for therapy. In this short review, I will describe two historical models of CB oxygen sensing and new findings that are integrating these models.

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Epigenomics and human adaptation to high altitude

Over the past decade, major technological and analytical advancements have propelled efforts toward identifying the molecular mechanisms that govern human adaptation to high altitude. Despite remarkable progress with respect to the identification of adaptive genomic signals that are strongly associated with the "hypoxia-tolerant" physiological characteristics of high-altitude populations, many questions regarding the fundamental biological processes underlying human adaptation remain unanswered. Vital to address these enduring questions will be determining the role of epigenetic processes, or non-sequence-based features of the genome, that are not only critical for the regulation of transcriptional responses to hypoxia but heritable across generations. This review proposes that epigenomic processes are involved in shaping patterns of adaptation to high altitude by influencing adaptive potential and phenotypic variability under conditions of limited oxygen supply. Improved understanding of the interaction between genetic, epigenetic, and environmental factors holds great promise to provide deeper insight into the mechanisms underlying human adaptive potential, and clarify its implications for biomedical research.

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On the existence of a central respiratory oxygen sensor

A commonly held view that dominates both the scientific and educational literature is that in terrestrial mammals the central nervous system lacks a physiological hypoxia sensor capable of triggering increases in lung ventilation in response to decreases in Po₂ of the brain parenchyma. Indeed, a normocapnic hypoxic ventilatory response has never been observed in humans following bilateral resection of the carotid bodies. In contrast, almost complete or partial recovery of the hypoxic ventilatory response after denervation/removal of the peripheral respiratory oxygen chemoreceptors has been demonstrated in many experimental animals when assessed in an awake state. In this essay we review the experimental evidence obtained using in vitro and in vivo animal models, results of human studies, and discuss potential mechanisms underlying the effects of CNS hypoxia on breathing. We consider experimental limitations and discuss potential reasons why the recovery of the hypoxic ventilatory response has not been observed in humans. We review recent experimental evidence suggesting that the lower brain stem contains functional oxygen sensitive elements capable of stimulating respiratory activity independently of peripheral chemoreceptor input.

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Determinants of hypoxia-inducible factor activity in the intestinal mucosa

The intestinal mucosa is exposed to fluctuations in oxygen levels due to constantly changing rates of oxygen demand and supply and its juxtaposition with the anoxic environment of the intestinal lumen. This frequently results in a state of hypoxia in the healthy mucosa even in the physiologic state. Furthermore, pathophysiologic hypoxia (which is more severe and extensive) is associated with chronic inflammatory diseases including inflammatory bowel disease (IBD). The hypoxia-inducible factor (HIF), a ubiquitously expressed regulator of cellular adaptation to hypoxia, is central to both the adaptive and the inflammatory responses of cells of the intestinal mucosa in IBD patients. In this review, we discuss the microenvironmental factors which influence the level of HIF activity in healthy and inflamed intestinal mucosae and the consequences that increased HIF activity has for tissue function and disease progression.

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Oxygen metabolism and innate immune responses in the gut

Epithelial cells of the mucosa provide a first line of defense to prevent the inappropriate translocation of luminal antigens, and therefore contribute significantly to nonspecific innate immunity. In the gastrointestinal (GI) tract, barrier is provided by multiple components of the mucosa, including mucus production, epithelial junctional complexes, and the production of antimicrobial molecules. In recent years, it is better appreciated that tissue oxygen metabolism is key to homeostasis in the mucosa. The intestine, for example, maintains a low baseline Po₂ level due to high rates of metabolism, countercurrent blood flow, and the presence of a steep oxygen gradient across the luminal aspect of tissue surface. As a result, hypoxia and hypoxia-inducible factor (HIF)-dependent signaling exists even in the healthy, unperturbed intestinal mucosa. In a number of examples, HIF has been demonstrated both to promote barrier function during homeostasis and to promote resolution of active inflammation. Hypoxia-elicited factors that contribute to innate responses in the mucosa include the transcriptional regulation of mucin genes, junction proteins, and autophagic flux. Here, we review current literature related to hypoxia and innate immunity in health and during mucosal inflammation.

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