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3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The β‑methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT

We aimed to compare cardiopulmonary exercise test (CPET) parameters, cardiac adaptations, and proportion of responders after different aerobic training programs amongst women and men with coronary heart disease (CHD). Patients with CHD were evaluated with a CPET and echocardiography before and after 3 months of aerobic exercise training. Peak oxygen uptake exercise training response was assessed according to the median peak oxygen uptake change for post- versus pretraining in the whole cohort (stratification non/low responders (NLR) vs. high-responders) and normalized for lean body mass (LBM). Eighty-three CHD patients were included (19 women, 64 men; 27 patients with interval, 19 with continuous, and 37 with combination exercises). Peak oxygen uptake, peak workload normalized for LBM, pulmonary variables (i.e., ventilation and oxygen uptake efficiency slope), and O2 pulse were significantly lower in women versus men. These parameters improved similarly with training in both sexes (p < 0.05). There were no differences in the proportion of NLR among women and men with CHD (7/19 (37%) vs. 35/64 (55%), p = 0.1719). Left ventricular ejection fraction and mean peak early diastolic mitral annulus velocity improved similarly with training in both sexes (p < 0.05). Women and men with CHD have a similar exercise training response regarding key CPET and echocardiographic parameters. The proportion of responders is similar. ClinicalTrials.gov: NCT03414996, NCT02048696, NCT03443193. Novelty: Cardiopulmonary adaptations to exercise training are similar among CHD men and women. Proportion of peak oxygen uptake for non/low/high responders is similar in CHD men and women. Left ventricular systolic and diastolic function improved similarly after exercise training in CHD men and women.

Rationale 4-Thio-substituted phenylalkylamines such as 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and 2,5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) produce psychedelic effects in humans and have been distributed as recreational drugs. Objectives The present studies were conducted to examine the structure–activity relationships (SAR) of a series of 4-thio-substituted phenylalkylamines using the head twitch response (HTR), a 5-HT2A receptor-mediated behavior induced by psychedelic drugs in mice. The HTR is commonly used as a behavioral proxy in rodents for human psychedelic effects and can be used to discriminate hallucinogenic and non-hallucinogenic 5-HT2A agonists. Methods HTR dose–response studies with twelve different 4-thio-substituted phenylalkylamines were conducted in male C57BL/6 J mice. To detect the HTR, head movement was recorded electronically using a magnetometer coil and then head twitches were identified in the recordings using a validated method based on artificial intelligence. Results 2C-T, the parent compound of this series, had relatively low potency in the HTR paradigm, but adding an α-methyl group increased potency fivefold. Potency was also increased when the 4-methylthio group was extended by one to three methylene units. Fluorination of the 4-position alkylthio chain, however, was detrimental for activity, as was the presence of a 4-allylthio substituent versus a propylthio group. 2C-T analogs containing a 4-benzylthio group showed little or no effect in the HTR paradigm, which is consistent with evidence that bulky 4-substituents can dampen agonist efficacy at the 5-HT2A receptor. Binding and functional studies confirmed that the compounds have nanomolar affinity for 5-HT2 receptor subtypes and act as partial agonists at 5-HT2A. Conclusions In general, there were close parallels between the HTR data and the known SAR governing activity of phenylalkylamines at the 5-HT2A receptor. These findings further support the classification of 2C-T compounds as psychedelic drugs.

Introduction and objectives We compared the effects of 12 weeks of low-volume high-intensity interval training (LV-HIIT) vs moderate-intensity continuous exercise training (MICET) on cardiopulmonary exercise test parameters and the proportion of non/low responders (NLR) to exercise training in post-acute coronary syndrome (ACS) patients. Methods Patients with a recent ACS were randomized to LV-HIIT, MICET, or a usual care group. LV-HIIT consisted of 2 to 3 sets of 6 to 10 minutes with repeated bouts of 15 to 30 seconds at 100% of peak workload alternating with 15 to 30 seconds of passive recovery. Cardiopulmonary exercise test parameters were assessed, and key exercise variables were calculated. Training response was assessed according to the median VO2peak change post vs pretraining in the whole cohort (stratification NLR vs high response). Results Fifty patients were included in the analysis (LV-HIIT, n = 23; MICET, n = 18; usual care, n = 9) and 74% were male. The proportion of NLR was higher in the LV-HIIT group than in the MICET group (LV-HIIT 61%, MICET 21%, and usual care 80%; P = .0040). VO2peak-dependent variables (VO2peak, percent-predicted VO2peak) improved in both training groups (P = .002 and P Conclusions In patients with a recent ACS, several prognostic VO2peak-dependent variables were improved after LV-HIIT, but the improvement was more pronounced or only found after MICET. Low-volume HIIT resulted in a higher proportion of NLR than isocaloric MICET. Clinical trialsregistered at ClinicalTrials.gov (Identifiers: NCT03414996 and NCT02048696)

Resumen Introduccion y objetivos Se comparo los efectos de 12 semanas de ejercicio intervalico de alta intensidad y de bajo volumen (EIAI-BV) frente a un ejercicio continuo de intensidad moderada (ECIM), sobre los parametros de la prueba de esfuerzo cardiopulmonar y la proporcion de no respondedores o con baja respuesta (NBR) al ejercicio fisico en pacientes que sufrieron un sindrome coronario agudo (SCA). Metodos Se aleatorizo a pacientes con un SCA reciente a EIAI-BV, ECIM y a cuidados habituales. EIAI-BV consto de 2 a 3 sesiones de 6-10 minutos con periodos de repeticion de 15 a 30 s al 100% de la carga de trabajo alternados con 15-30 segundos de recuperacion pasiva. Los parametros de la prueba de ejercicio cardiopulmonar se evaluaron y se calcularon las variables claves. La respuesta al ejercicio se evaluo con la mediana de VO2 pico de cambio (post- frente a preejercicio) en toda la cohorte estratificada en NBR al ejercicio frente a alta respuesta. Resultados Se incluyo a 50 pacientes en el analisis (EIAI-BV, n = 23; ECIM, n = 18; cuidados habituales, n = 9), el 74% eran varones. La proporcion de NBR fue mayor en el EIAI-BV en comparacion con el grupo ECIM y el grupo de cuidados habituales (el 61 frente al 21 y el 80%, respectivamente; p = 0,0040). Las variables dependientes del VO2 (VO2 pico y porcentaje VO2 pico predicho) mejoraron en ambos grupos de entrenamiento (p = 0,002 y p Conclusiones En pacientes con un SCA reciente, varias variables pronosticas dependientes del VO2 pico mejoraron despues de EIAI-BV, pero la mejora fue mas pronunciada o bien mejoro unicamente despues de ECIM. El EIAI-BV resulto en una mayor proporcion de NBR en comparacion con el ECIM isocalorico. Ensayos registrados en ClinicalTrials.gov (Identificadores: NCT03414996 and NCT02048696)

Laryngeal and respiratory reflexes are vitally important defense mechanisms against foreign body aspiration, safeguarding airway patency, and ventilation. These highly preserved automatisms easily overrule external influences like willpower or (anesthetic) medication. Prevention and anticipation are, therefore, the essential strategies to avoid adverse events and damage, and treatment is most effective in the early stage of the reflex response. The physiology and pathophysiology of the various defensive reflexes as well as a comprehensive anesthetic approach to prevention and treatment are outlined in this review.

Background Apnea of prematurity cannot be reliably measured with current monitoring techniques. Instead, indirect parameters such as oxygen desaturation or bradycardia are captured. We propose a Kalman filter-based detection of respiration activity and hence apnea using multichannel esophageal signals in neonatal intensive care unit patients. Methods We performed a single-center observational study with moderately preterm infants. Commercially available nasogastric feeding tubes containing multiple electrodes were used to capture signals with customized software. Multichannel esophageal raw signals were manually annotated, processed using extended Kalman filter, and compared with standard monitoring data including chest impedance to measure respiration activity. Results Out of a total of 405.4 h captured signals in 13 infants, 100 episodes of drop in oxygen saturation or heart rate were examined. Median (interquartile range) difference in respiratory rate was 0.04 (−2.45 to 1.48)/min between esophageal measurements annotated manually and with Kalman filter and −3.51 (−7.05 to −1.33)/min when compared to standard monitoring, suggesting an underestimation of respiratory rate when using the latter. Conclusions Kalman filter-based estimation of respiratory activity using multichannel esophageal signals is safe and feasible and results in respiratory rate closer to visual annotation than that derived from chest impedance of standard monitoring.

Various developmental aspects of respiratory physiology put infants and young children at an increased risk of respiratory failure, which is associated with a higher rate of critical incidents during anesthesia. The immaturity of control of breathing in infants is reflected by prolonged central apneas and periodic breathing, and an increased risk of apneas after anesthesia. The physiology of the pediatric upper and lower airways is characterized by a higher flow resistance and airway collapsibility. The increased chest wall compliance and reduced gas exchange surface of the lungs reduce the pulmonary oxygen reserve vis-à-vis a higher metabolic oxygen demand, which causes more rapid oxygen desaturation when ventilation is compromised. This review describes the various developmental aspects of respiratory physiology and summarizes anesthetic implications.

Background Lung disease can develop within the first year of life in infants with cystic fibrosis (CF). However, the frequency and severity of respiratory symptoms in infancy are not known. Methods We assessed respiratory symptoms in 50 infants with CF and 50 healthy matched controls from two prospective birth cohort studies. Respiratory symptoms and respiratory rate were documented by standardized weekly interviews throughout the first year. Infants performed multiple breath washout in the first weeks of life. Results We analyzed 4552 data points (2217 in CF). Respiratory symptoms (either mild or severe) were not more frequent in infants with CF (OR:1.1;95% CI:[0.76, 1.59]; p=0.6). Higher lung clearance index and higher respiratory rate in infants with CF were not associated with respiratory symptoms. Conclusions We found no difference in respiratory symptoms between healthy and CF infants. These data indicate that early CF lung disease may not be captured by clinical presentation alone.

Linear aerobic training periodisation (LP) is recommended for patients with coronary heart disease (CHD). However, the effects of training periodisation on the right heart mechanics in patients with CHD have never been examined. This study aimed to explore the effects of LP and non-linear periodisation (NLP) on right heart mechanics. We prospectively randomised CHD patients to 12 weeks of aerobic training with LP or NLP. While there was a weekly increase in energy expenditure with LP, there was a steeper increase during the first 3 weeks, followed by a decrease in the fourth week with NLP. Echocardiography was performed at baseline and after the training period to assess the right ventricular free wall (RVFW) and right atrial strain. Thirty patients with CHD were included (NLP, n = 16; LP, n = 14). The traditional right and left heart parameters showed no significant time effects. There was a decrease of RVFW strain with time in both groups (+1.3 ± 0.9% with NLP, and +1.5 ± 0.8% with LP; p = 0.033). Mid-ventricular RVFW strain changed significantly with time (+2.0 ± 1.3% with NLP, and from +2.3 ± 1.2% with LP; p = 0.025). There was no time effect on the right atrial strain. In stable CHD patients, LP and NLP resulted in right ventricular strain decrements with a segment-specific pattern. This study was registered at ClinicalTrials.gov (identifier number: NCT03414996). Novelty: In stable coronary heart disease patients, both linear and non-linear aerobic training periodisation programs result in right ventricular strain decrements with time, particularly in the mid-ventricular segment. Traditional right and left heart parameters and right atrial strain showed no significant time effect in both 12 weeks aerobic training periodisation programs.

Background Aerobic exercise training is associated with beneficial ventricular remodeling and an improvement in cardiac biomarkers in chronic stable heart failure. High‐intensity interval training (HIIT) is a time‐efficient method to improve V˙O2peak in stable coronary heart disease patients. This pilot study aimed to compare the effect of HIIT on ventricular remodeling in patients with a recent acute myocardial infarction (AMI). Methods Nineteen post‐AMI patients were randomized to either HIIT (n = 9) or usual care (n = 10). A cardiopulmonary exercise test (CPET), transthoracic echocardiography, and cardiac biomarker assessment (ie, N‐terminal pro B‐type natriuretic peptide levels and G protein‐coupled receptor kinase 2 expression) were performed before and after a 12‐week training intervention. CPET parameters including oxygen uptake efficiency slope (OUES) and V˙O2 at the first ventilatory threshold (V˙O2 VT1) were calculated. left ventricular (LV) structural and functional echocardiographic parameters including myocardial strain imaging were assessed. Results V˙O2peak and OUES improved solely in the HIIT group (P

Many ring-substituted phenethylamines exert psychedelic effects that are thought to be primarily mediated by interactions with serotonergic 5-hydroxytryptamine 2 (5-HT2A) receptors. The 2,5-dimethoxyphenethylamine (2C derivative) core structure with small lipophilic substituents at the 4-position seems to be particularly favorable for psychedelic effects. In contrast, 2C derivatives with bulky lipophilic substituents at the 4-position of the phenyl ring tend to display antagonist behavior at serotonin 5-HT2 receptor sites. To gain a better understanding of agonist and antagonist behavior of substituted phenethylamines, binding affinities and functional activation and inhibition of a series of 4'-aryl substituted 2,5-dimethoxyphenethylamine (2C-BI derivatives) at various monoamine receptors were determined. In addition, the interactions of the compounds with monoamine transporters were assessed. Various 2C-BI derivatives potently bound to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. Additionally, 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations. 2C-BI-1 and 2C-BI-7 were the only 2C-BI derivatives to activate human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted with monoamine transporters but with low overall potency. In conclusion, the tested 2C-BI derivatives displayed diverse pharmacological profiles. The relatively high affinities of various 2C-BI derivatives at the serotonin 5-HT2A receptor indicate a high steric tolerance of the binding pocket. Potent partial activation of the serotonin 5-HT2A receptor by 2C-BI-8 and 2C-BI-12 suggests that these substances may potentially exert psychedelic effects similar to other compounds of the 2C family.

Objective: To compare the effects of high-intensity interval training versus moderate-intensity continuous training on risk markers of arrhythmic death in patients who recently suffered from an acute coronary syndrome. Design: Double-blind (patient and evaluator) randomized controlled trial. Setting: Cardiovascular Prevention and Rehabilitation Centre (EPIC Centre) of the Montreal Heart Institute, Montreal, Canada. Subjects: A total of 43 patients were randomized following an acute coronary syndrome. Interventions: Patients were assigned to either high-intensity interval training (n = 18) or isocaloric moderate-intensity continuous training (n = 19), three times a week for a total of 36 sessions. Main measures: Heart rate recovery for 5 minutes, heart rate variability for 24 hours, occurrence of ventricular arrhythmias, and QT dispersion were measured before and after the 36 sessions of training. Results: Among the 43 patients randomized, 6 participants in the high-intensity interval training group stopped training for reasons unrelated to exercise training and were excluded from the analyses. Heart rate recovery improved solely in the high-intensity interval training group, particularly at the end of recovery period ( p < 0.05). There were no differences in heart rate variability, occurrence of ventricular arrhythmias, or QT dispersion parameters between the groups at study end. Conclusion: Despite the lack of power to detect any large difference between the two interventions with respect to risk markers of arrhythmic death, high-intensity interval training appears safe and may be more effective at improving heart rate recovery relative to moderate-intensity continuous training in our patients following acute coronary syndrome.

Zusammenfassung. Rund jedes zehnte Kind schnarcht habituell, etwa ein Viertel davon hat ein obstruktives Schlafapnoesyndrom (OSAS). Während ein OSAS aufgrund der negativen Auswirkungen auf das Verhalten und die kognitive Entwicklung als ernstzunehmendes medizinisches Problem auch im Kindesalter mittlerweile anerkannt ist, bleibt die gesundheitliche Bedeutung des habituellen Schnarchens kontrovers. Schlafassoziierte obstruktive Ventilationsstörungen bleiben im Kindesalter unterschätzt und unterdiagnostiziert, u.a. aufgrund der gegenüber Erwachsenen variableren Klinik. Dies trifft besonders zu auf Kinder mit syndromalen Erkrankungen wie beispielsweise einer Trisomie 21. In dieser Übersicht werden die essenziellen Wissenspunkte dargestellt.

A Child's Sleep: A Book with Seven Seals? A Guide to Systematic Problem Identification and Solution Abstract. The sleep of a child can be influenced and sometimes disturbed by many, often development-associated, phenomena. This results not only in a burden for the child, but regularly also for the parents, who in their need for help, often seek the advice of the attending physician. The child- and adolescent-specific questionnaire BEARS, which was developed by J. Owens and K. Mindell, allows the first diagnostic steps and classifications based on the most important symptoms such as bedtime problems, excessive daytime sleepiness, waking up at night, problems with regularity and sleep duration as well as nocturnal breathing disorders. The aim of this article is to show that important conclusions can be drawn in the everyday practice as to which symptoms need to be clarified how and how urgently, and which belong in the hands of a specialized sleep center.

We compared the impacts of linear (LP) and nonlinear (NLP) aerobic training periodizations on left ventricular (LV) function and geometry in coronary artery disease (CAD) patients. Thirty-nine CAD patients were randomized to either a 3-month isoenergetic supervised LP or NLP. All underwent standard echocardiography with assessment of 3D LV ejection fraction (LVEF), diastolic function, strain (global longitudinal, radial, and circumferential), and strain rate at baseline and study end. Training was performed 3 times/week and included high-intensity interval and moderate-intensity continuous training sessions. Training load was progressively increased in the LP group, while it was deeply increased and intercepted with a recovery week each fourth week in the NLP group. For the 34 analyzed patients, we found similar improvements for 3D LVEF (effect size (ES): LP, 0.29; NLP, 0.77), radial strain (ES: LP, 0.58; NLP, 0.48), and radial strain rate (ES: LP, 0.87; NLP, 0.17) in both groups (time for all: p ≤ 0.01). All other parameters of cardiac function remained similar. In conclusion, NLP and LP led to similar improvements in 3D LVEF and radial strain, suggesting a favourable positive cardiac remodelling through myofibers reorganization. These findings must be investigated in patients with more severe cardiac dysfunction. The study was registered on ClinicalTrials.gov (NCT03443193). Novelty: Linear and nonlinear periodization programs improved radial strain, accompanied by improvement of ejection fraction. Both aerobic periodization programs did not negatively impact cardiac function in coronary artery disease patients.

A lower heart rate (HR) during heat exposure is a classic marker of heat acclimation (HA), although it remains unclear whether this adaptation occurs secondary to reduced thermal strain and/or improvements in cardiac function. We evaluated the hypothesis that short-term passive HA reduces HR and improves cardiac function during passive heating. Echocardiography was performed under thermoneutral and hyperthermic conditions in 10 healthy adults (9 men/1 woman, 29 ± 6 yr old), pre and post 7 days of controlled hyperthermia. HR (P = 0.61), stroke volume (P = 0.99), and cardiac output (P = 0.99), were similar on days 1 and 7 of HA. Core (pre: 38.17 ± 0.42, post: 38.15 ± 0.27°C, P = 0.95) and mean skin (pre: 38.24 ± 0.41, post: 38.51 ± 0.29°C, P = 0.17) temperatures were similar during hyperthermic echocardiographic assessments. Cardiac systolic function was unaffected by HA (P ≥ 0.10). HA attenuated the decrease in end-diastolic volume (pre: -18 ± 18, post: -12 ± 19 mL, P = 0.05), accentuated the greater atrial contribution to diastolic filling (pre: +11 ± 5, post: +14 ± 5%, P = 0.02), and attenuated the increase in left atrial reservoir strain rate (pre: +1.5 ± 1.2, post: +0.8 ± 0.8 1/s, P = 0.02) during heating. Nonetheless, there were no differences in HR (pre: 106 ± 12, post: 104 ± 12 beats/min, P = 0.50), stroke volume (pre: 65 ± 15, post: 68 ± 13 mL, P = 0.55), or cardiac output (pre: 6.9 ± 2.0, post: 7.1 ± 1.7 L/min, P = 0.70) during passive heating. Short-term controlled hyperthermia HA results in limited adaptations of cardiac function during passive heating.NEW & NOTEWORTHY A lower heart rate during heat exposure is a classic marker of heat acclimation (HA). It remains unknown if improved cardiac function contributes to this response. A 7-day passive HA protocol did not alter cardiac systolic function during passive heating, whereas it improved some indexes of diastolic function in young adults. Nonetheless, heart rate during heating was unaffected by HA. These results suggest that passive HA induces limited adaptations in cardiac function during passive heating.

Background We aimed to compare: (1) two different periodized aerobic training protocols (linear (LP) versus non-linear (NLP)) on the cardiopulmonary exercise response in patients with coronary heart disease; (2) the proportion of responders between both training protocols. Design A randomized controlled trial. Methods A total of 39 coronary heart disease patients completed either LP ( n = 20, 65 ± 10 years) or NLP ( n = 19, 66 ± 5 years). All patients completed a cardiopulmonary exercise testing with gas exchange measurements. Patients underwent a 12-week supervised exercise program including an isoenergetic aerobic periodized training and a similar resistance training program, 3 times/week. Weekly energy expenditure was constantly increased in the LP group for the aerobic training, while it was deeply increased and intercepted with a recovery week each fourth week in the NLP group. Peak oxygen uptake (peak V̇O2), oxygen uptake efficiency slope, ventilatory efficiency slope (V̇E/V̇CO2 slope), V̇O2 at the first (VT1) and second (VT2) ventilatory thresholds, and oxygen pulse (O2 pulse) were measured. Responders were determined according the median value of the Δpeak V̇O2 (mL.min−1.kg−1). Results We found similar improvement for peak V̇O2 (LP: +8.1%, NLP: +5.3%, interaction: p = 0.37; time: p 1, VT2 and O2 pulse in both groups (interaction: p > 0.05; time: p Conclusion In contrast to the athletes, more variation (NLP) does not seem necessary for greater cardiopulmonary adaptations in coronary heart disease patients.

Background: 2,4,5-Trimethoxyamphetamine (TMA-2) is a potent psychedelic compound. Structurally related 4-alkyloxy-substituted 2,5-dimethoxyamphetamines and phenethylamine congeners (2C-O derivatives) have been described but their pharmacology is mostly undefined. Therefore, we examined receptor binding and activation profiles of these derivatives at monoamine receptors and transporters. Methods: Receptor binding affinities were determined at the serotonergic 5-HT1A, 5-HT2A, and 5-HT2C receptors, trace amine-associated receptor 1 (TAAR1), adrenergic α1 and α2 receptors, dopaminergic D2 receptor, and at monoamine transporters, using target-transfected cells. Additionally, activation of 5-HT2A and 5-HT2B receptors and TAAR1 was determined. Furthermore, we assessed monoamine transporter inhibition. Results: Both the phenethylamine and amphetamine derivatives (K i = 8–1700 nM and 61–4400 nM, respectively) bound with moderate to high affinities to the 5-HT2A receptor with preference over the 5-HT1A and 5-HT2C receptors (5-HT2A/5-HT1A = 1.4–333 and 5-HT2A/5-HT2C = 2.1–14, respectively). Extending the 4-alkoxy-group generally increased binding affinities at 5-HT2A and 5-HT2C receptors but showed mixed effects in terms of activation potency and efficacy at these receptors. Introduction of a terminal fluorine atom into the 4-ethoxy substituent by trend decreased, and with progressive fluorination increased affinities at the 5-HT2A and 5-HT2C receptors. Little or no effect was observed at the 5-HT1A receptor for any of the substances tested (K i ≥ 2700 nM). Phenethylamines bound more strongly to the TAAR1 (K i = 21–3300 nM) compared with their amphetamine analogs (K i = 630–3100 nM). Conclusion: As seen with earlier series investigated, the 4-alkyloxy-substituted 2,5-dimethoxyamphetamines and phenethylamines share some trends with the many other phenethylamine pharmacophore containing compounds, such as when increasing the size of the 4-substituent and increasing the lipophilicity, the affinities at the 5-HT2A/C subtype also increase, and only weak 5-HT2A/C subtype selectivities were achieved. At least from the binding data available (i.e., high affinity binding at the 5-HT2A receptor) one may predict mainly psychedelic-like effects in humans, at least for some of the compound investigated herein.

Introduction: Several diagnostic tests are used in children suspected for asthma, but the accuracy of these tests to diagnose asthma is unclear. Aim: We aimed to assess the diagnostic accuracy of reported respiratory symptoms and clinical tests to diagnose asthma in school-aged children under investigation for asthma. Methods: We studied cross-sectionally children aged 6-16 years referred to 2 pulmonary outpatient clinics with suspicion of asthma. All children underwent clinical evaluation including spirometry, fractional exhaled nitric oxide (FeNO), skin prick tests, and bronchial provocation tests (BPT) by exercise, methacholine, and mannitol. Symptoms were reported in a parental questionnaire. Asthma was diagnosed by the physicians based on medical history, clinical examination, and all clinical test results. We calculated sensitivity, specificity, positive and negative predictive value and area under the curve to assess the diagnostic accuracy of symptoms and clinical tests. Results: Of the 111 participants, 68 (61%) were diagnosed with asthma. The combined sensitivity and specificity to diagnose asthma was highest for wheeze without colds ((sensitivity/specificity) 0.76/0.65), wheeze (0.87/0.51), wheeze triggered by pollen (0.59/0.79) and more than 3 attacks of wheeze (0.49/0.88). Of the diagnostic tests, the area under the curve was highest for FeNO (0.81) and BPT by exercise (0.79) and lowest for FEV1 (0.52) and FEV1/FVC (0.58). Conclusion: This study, which needs validation in a larger sample, suggests that specific questions about triggers and severity of wheeze, FeNO and BPT by exercise are more useful to diagnose asthma in school-aged children than spirometry, skin prick tests and other BPTs.

Congenital lung anomalies are a group of rare malformations, often diagnosed during the prenatal period. Guidelines on how to manage these patients are currently under debate, especially with regard to prophylactic surgery in asymptomatic patients, or how to proceed with conservative follow-up. Currently, there is no clear consensus on management strategies. A Swiss congenital lung anomaly national database and biobank was created in 2016 to enable data recording and collection of surgical lung samples in order to help define the most appropriate management strategies. This national observational cohort study represents an important step towards a better understanding of the pathophysiology and clinical course of the diseases included under congenital lung anomalies, especially in the context of a small country like Switzerland.

INTRODUCTION The contribution of clinical investigations to prediction of long-term outcomes of children investigated for asthma is unclear. AIM We performed a broad range of clinical tests and investigated whether they helped to predict long-term wheeze among children referred for evaluation of possible asthma. METHODS We studied children aged 6 to 16 years referred to two Swiss pulmonary outpatient clinics with a history of wheeze, dyspnea, or cough in 2007. The initial assessment included spirometry, fractional exhaled nitric oxide, skin prick tests, and bronchial provocation tests by exercise, methacholine, and mannitol. Respiratory symptoms were assessed with questionnaires at baseline and at follow-up 7 years later. Associations between baseline factors and wheeze at follow-up were investigated by logistic regression. RESULTS At baseline, 111 children were examined in 2007. After 7 years, 85 (77%) completed the follow-up questionnaire, among whom 61 (72%) had wheeze at baseline, while at follow-up 39 (46%) reported wheeze. Adjusting for age and sex, the following characteristics predicted wheeze at adolescence: wheeze triggered by pets (odds ratio, 4.2; 95% CI, 1.2-14.8), pollen (2.8, 1.1-7.0), and exercise (3.1, 1.2-8.0). Of the clinical tests, only a positive exercise test (3.2, 1.1-9.7) predicted wheeze at adolescence. CONCLUSION Reported exercise-induced wheeze and wheeze triggered by pets or pollen were important predictors of wheeze persistence into adolescence. None of the clinical tests predicted wheeze more strongly than reported symptoms. Clinical tests might be important for asthma diagnosis but medical history is more helpful in predicting prognosis in children referred for asthma.

We compared the effects of 12 weeks of low-volume high-intensity interval training (LV-HIIT) vs moderate-intensity continuous exercise training (MICET) on cardiopulmonary exercise test parameters and the proportion of non/low responders (NLR) to exercise training in post-acute coronary syndrome (ACS) patients.Patients with a recent ACS were randomized to LV-HIIT, MICET, or a usual care group. LV-HIIT consisted of 2 to 3 sets of 6 to 10minutes with repeated bouts of 15 to 30seconds at 100% of peak workload alternating with 15 to 30seconds of passive recovery. Cardiopulmonary exercise test parameters were assessed, and key exercise variables were calculated. Training response was assessed according to the median VOFifty patients were included in the analysis (LV-HIIT, n=23; MICET, n=18; usual care, n=9) and 74% were male. The proportion of NLR was higher in the LV-HIIT group than in the MICET group (LV-HIIT 61%, MICET 21%, and usual care 80%; P=.0040). VOIn patients with a recent ACS, several prognostic VO

Rationale: Damage control is a staged surgical approach to manage polytraumatized patients. The damage control approach comprises three steps. First, bleeding is controlled and fractures are stabilized temporarily; second, vital parameters are stabilized and the child is rewarmed in the intensive care unit; and third, the child is reoperated for definitive repair of injuries. We aimed to describe the feasibility of the damage control orthopedic approach in a child. Patient concerns: An 8-year-old girl fell from the balcony of the 5th floor onto concrete pavement and was admitted to our accident and emergency ward in a stable cardiorespiratory state, but with gross deformity of the lower limbs, left thigh, and forearm. Diagnoses: The child had sustained multiple injuries with severe bilateral lung contusion, pneumothorax, fracture of first rib, liver laceration, stable spine fractures, transforaminal fracture of sacrum, pelvic ring fracture, displaced baso-cervical femoral neck fracture, displaced bilateral multifragmental growth plate fractures of both tibiae, fractures of both fibulae, displaced fracture of left forearm, and displaced supracondylar fracture of the humerus. Intervention: In the initial operation, we performed closed reduction and K-wire fixation of the right tibia, closed reduction and external fixation of the left tibia, open reduction and screw osteosynthesis of the femoral neck fracture, closed reduction and K-wire fixation of the radius, and closed reduction of the supracondylar fracture. Subsequently, we transferred the girl to the pediatric intensive care unit for hemodynamic stabilization, respiratory therapy, rewarming, and treatment of crush syndrome. In a third step, 10 days after the injury, we managed the supracondylar fracture of the humerus by closed reduction and K-wire fixation. Outcomes: Growth arrest of the left distal tibial growth plate and osteonecrosis of the femoral head and neck, slipped capital femoris epiphysis (SCFE), and coxa vara of the right femur led to balanced leg length inequality 2 years after the injury. The lesion of the left sciatic nerve improved over time and the girl walked without walking aids and took part in school sports but avoided jumping exercises. Lessons: We emphasize the importance of damage control principles when managing polytraumatized children.

Sleep-Disordered Breathing in Childhood Abstract. One out of ten healthy children is a habitual snorer, and one fourth of snoring children suffer from obstructive sleep apnea syndrome (OSAS). While OSAS is widely recognized as a relevant social and health problem due to its negative impact on behavior and neurocognitive development, the medical significance of habitual snoring remains debated. Sleep-disordered breathing remains underestimated and underdiagnosed in childhood, in part due to the variability of clinical manifestations. This is particularly true for children with an underlying syndromal morbidity such as Down syndrome or Prader-Willi syndrome. This review summarizes the essential key points of Sleep-Disordered Breathing (SDB) in childhood.Zusammenfassung. Rund jedes zehnte Kind schnarcht habituell, etwa ein Viertel davon hat ein obstruktives Schlafapnoesyndrom (OSAS). Während ein OSAS aufgrund der negativen Auswirkungen auf das Verhalten und die kognitive Entwicklung als ernstzunehmendes medizinisches Problem auch im Kindesalter mittlerweile anerkannt ist, bleibt die gesundheitliche Bedeutung des habituellen Schnarchens kontrovers. Schlafassoziierte obstruktive Ventilationsstörungen bleiben im Kindesalter unterschätzt und unterdiagnostiziert, u.a. aufgrund der gegenüber Erwachsenen variableren Klinik. Dies trifft besonders zu auf Kinder mit syndromalen Erkrankungen wie beispielsweise einer Trisomie 21. In dieser Übersicht werden die essenziellen Wissenspunkte dargestellt.

A Child's Sleep: A Book with Seven Seals? A Guide to Systematic Problem Identification and Solution Abstract. The sleep of a child can be influenced and sometimes disturbed by many, often development-associated, phenomena. This results not only in a burden for the child, but regularly also for the parents, who in their need for help, often seek the advice of the attending physician. The child- and adolescent-specific questionnaire BEARS, which was developed by J. Owens and K. Mindell, allows the first diagnostic steps and classifications based on the most important symptoms such as bedtime problems, excessive daytime sleepiness, waking up at night, problems with regularity and sleep duration as well as nocturnal breathing disorders. The aim of this article is to show that important conclusions can be drawn in the everyday practice as to which symptoms need to be clarified how and how urgently, and which belong in the hands of a specialized sleep center.Zusammenfassung. Der Schlaf eines Kindes kann durch viele, oft entwicklungsassoziierte Phänomene, verändert und teils auch gestört sein. Daraus resultiert nicht nur eine Belastung für das Kind, sondern häufig auch für die Eltern, die dann in ihrer Not den Rat des/der behandelnden Arztes/Ärztin erfragen. Der kinder- und jugendspezifische Fragebogen BEARS, der von J. Owens und K. Mindell entwickelt wurde, erlaubt es, anhand der wichtigsten Kardinalsymptome Bettzeitprobleme, exzessive Tagesschläfrigkeit, nächtliches Aufwachen, Probleme in der Regelmässigkeit und Schlafdauer sowie nächtliche Atemstörungen erste diagnostische Schritte und Zuordnungen zu machen. Ziel dieses Artikels ist es, dass daraus im Praxisalltag wichtige Schlüsse gezogen werden können, welche Symptome wodurch und mit welcher Dringlichkeit abgeklärt werden müssen, und welche in die Hände eines spezialisierten Schlafzentrums gehören.

An 8-year-old girl developed severe acute lung injury after irrigation of a pelvic aneurysmal bone cyst with H2O2 and filling with bone cement. Sudden profound oxygen desaturation occurred on the operating table when the patient was turned from the prone to the supine position. After a brief improvement in her oxygenation, the girl developed rapidly progressing severe respiratory failure necessitating reintubation and hour-long manual ventilation, while copious amounts of hemorrhagic frothy fluids were aspirated through the endotracheal tube. The patient started to improve after 24 hours and eventually made a full recovery. We hypothesize that the incident was caused by gas embolization and pulmonary endothelial damage by H2O2.

Respiratory adverse events are one of the major causes of morbidity and mortality in paediatric anaesthesia. Aside from predisposing conditions associated with an increased risk of respiratory incidents in children such as concurrent infections and chronic airway irritation, there are adverse respiratory events directly attributable to the impact of anaesthesia on the respiratory system. Anaesthesia can negatively affect respiratory drive, ventilation/perfusion (V/Q) matching and tidal breathing, all resulting in potentially devastating hypoxaemia. Understanding paediatric respiratory physiology and its changes during anaesthesia will enable anaesthetists to anticipate, recognize and prevent deterioration that can lead to respiratory failure. This review aims to give a comprehensive overview of the effects of anaesthesia on respiration in children. It focuses on the impact of the different components of anaesthesia, patient positioning and procedure-related changes on respiratory physiology.