Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function.

We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebral blood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients. Apnoea duration increased from 306 ± 62 s during hypoxaemic hypercapnia to 959 ± 201 s in hyperoxaemic hypercapnia (P ≤ 0.001). Apnoea generally increased global cerebral blood flow (all P ≤ 0.001) but was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose (P = 0.015-0.044). This was associated with a general net cerebral output (v > a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P = 0.046 vs. hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake (a > v) and global cerebral blood flow (P = 0.034 to <0.001 vs. hyperoxaemic hypercapnia), implying reduced consumption and delivery of nitric oxide consistent with elevated cerebral oxidative-nitrosative stress. In contrast, we failed to observe equidirectional gradients consistent with S-nitrosohaemoglobin consumption and plasma S-nitrosothiol delivery during apnoea (all P ≥ 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia in cerebral oxidative-nitrosative stress. KEY POINTS: Local sampling of blood across the cerebral circulation in ultra-elite apnoeists determined the extent to which severe end-apnoea hypoxaemic hypercapnia (prior normoxic normoventilation) and hyperoxaemic hypercapnia (prior hyperoxic hyperventilation) impact free radical-mediated nitric oxide bioavailability and global cerebral bioenergetic function. Apnoea generally increased the net cerebral output of free radicals and suppressed plasma nitrite consumption, thereby reducing delivery of nitric oxide consistent with elevated oxidative-nitrosative stress. The apnoea-induced elevation in global cerebral blood flow was insufficient to prevent a reduction in the cerebral metabolic rates of oxygen and glucose. Cerebral oxidative-nitrosative stress was greater during hypoxaemic hypercapnia compared with hyperoxaemic hypercapnia and coincided with a lower apnoea-induced elevation in global cerebral blood flow, highlighting a key catalytic role for hypoxaemia. This applied model of voluntary human asphyxia might have broader implications for the management and treatment of neurological diseases characterized by extremes of oxygen demand and carbon dioxide production.

HYSTERICAL APNEA IN THE WORK OF GALEN (CA 129 - 199 AD): GENDER EQUITY IN THE HISTORY OF PSYCHOSOMATIC MEDICINE.

OBJECTIVE: The aim: To presents clinical, epidemiological and pathophysiological aspects of the disease described by Galenos of Pergamon during the 2nd century AD and discusses its implications on contemporary discourse on gender equity and gender - based discrimination. PATIENTS AND METHODS: Materials and methods: The authors searched original medical texts written in Greek language and attributed to Galenos for records related to hysterical apnea. CONCLUSION: Conclusions: Galen attempted to interpret hysterical apnea by combining clinical and epidemiological observations with anatomical and functional lesions. His approach denounced the anatomically unsound notion of the wandering womb and availed the knowledge of his period in a rational manner. Investigating gender - related aspects of contemporary psychosomatic conditions related to fertility and pregnancy can help address gender - based discrimination in modern societies.

Association between Self-Perceived Periodic Limb Movement during Sleep and Excessive Daytime Sleepiness Depend on Restless Leg Symptoms in Korean Adolescents.

Although periodic limb movement during sleep (PLMS) and restless legs syndrome (RLS) are common in children and adolescents, they are relatively overlooked as a target of treatment. PLMS has been evaluated as having a lower clinical significance than RLS. This study examined the relationship of socio-behavioral factors of PLMS in Korean adolescents and checked whether PLMS is associated with excessive daytime sleepiness (EDS), depending on whether restless legs symptoms accompany it. In a cross-sectional study, 25,789 adolescents between 12 and 18 years of age (15.76 ± 1.73 years; female 51.49%) were evaluated using an online survey. Various self-report questionnaires were used to assess PLMS and RLS symptoms, EDS, sleep habits, and various socio-behavioral factors. The prevalence of self-perceived PLMS and restless legs symptoms were 903 (3.50%) and 1311 (5.08%), respectively. Of the 1311 participants, 399 had self-perceived PLMS. The odds ratios (ORs) for self-perceived PLMS in participants with restless legs symptoms were: males (OR = 1.528; 95% CI: 1.145-2.040), usually/always experienced apnea apnea (OR, 3.006; 95% CI, 1.954-4.624), increased proneness to Internet addiction (OR = 1.013; 95% CI: 1.001-1.025), sometimes/often consuming coffee (OR = 1.312; 95% CI: 1.015-1.695), EDS (OR = 0.826; 95% CI: 0.488-1.398), and perceived insufficient sleep (OR = 1.143; 95% CI: 0.835-1.565). The male gender, witness apnea, consuming coffee, and being prone to Internet addiction were identified as factors significantly associated with self-perceived PLMS in participants with restless legs symptoms. However, EDS and insufficient sleep were associated with self-perceived PLMS in the absence of restless legs symptoms.

Physiology, pathophysiology and (mal)adaptations to chronic apnoeic training: a state-of-the-art review.

Breath-hold diving is an activity that humans have engaged in since antiquity to forage for resources, provide sustenance and to support military campaigns. In modern times, breath-hold diving continues to gain popularity and recognition as both a competitive and recreational sport. The continued progression of world records is somewhat remarkable, particularly given the extreme hypoxaemic and hypercapnic conditions, and hydrostatic pressures these athletes endure. However, there is abundant literature to suggest a large inter-individual variation in the apnoeic capabilities that is thus far not fully understood. In this review, we explore developments in apnoea physiology and delineate the traits and mechanisms that potentially underpin this variation. In addition, we sought to highlight the physiological (mal)adaptations associated with consistent breath-hold training. Breath-hold divers (BHDs) are evidenced to exhibit a more pronounced diving-response than non-divers, while elite BHDs (EBHDs) also display beneficial adaptations in both blood and skeletal muscle. Importantly, these physiological characteristics are documented to be primarily influenced by training-induced stimuli. BHDs are exposed to unique physiological and environmental stressors, and as such possess an ability to withstand acute cerebrovascular and neuronal strains. Whether these characteristics are also a result of training-induced adaptations or genetic predisposition is less certain. Although the long-term effects of regular breath-hold diving activity are yet to be holistically established, preliminary evidence has posed considerations for cognitive, neurological, renal and bone health in BHDs. These areas should be explored further in longitudinal studies to more confidently ascertain the long-term health implications of extreme breath-holding activity.

Phenotype and genotype characteristics of 58 patients showing a prolonged effect of succinylcholine: A four-year experience.

INTRODUCTION: This study sought to describe the phenotype and genotype characteristics of patients referred to our laboratory to undergo further assessment due to a suspicion of a prolonged effect of suxamethonium attributed to BChE deficiency. METHODS: All patients referred to our laboratory from January 2016 to December 2019 due to the suspicion of a prolonged effect of suxamethonium were included in this study. The determination of BChE activity and genotyping using complete nucleotide sequencing of the entire complementary DNA-coding region with flanking intron-exon boundaries were completed. RESULTS: During this four-year period, 58 patients were referred to our laboratory for the investigation of prolonged neuromuscular block due to BChE deficiency. Among them, 52 showed a BChE deficiency related to BCHE gene mutations. The most commonly detected genotype was compound homozygous atypical variant (p.Asp98Gly)/homozygous Kalow variant (p.Ala569Thr) (p.[Asp98Gly;Ala567Thr];[p.Asp98Gly;Ala567Thr]). Further, we recorded four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea: p.(Trp205Cys), p.(Leu222His), p.(Glu469Gln), and p.(Lys276Ter). CONCLUSION: During a four-year period, among the 58 patients referred to our laboratory, we have found four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea (p.(Trp205Cys), p.(Leu22His), p.(Glu469Gln), and p.(Lys276Ter)).

Relation between coffee consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy.

OBJECTIVE: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown. METHODS: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO2 ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO2 < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both. RESULTS: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042). SIGNIFICANCE: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect.

Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation.

Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

Changes in PUFA and eicosanoid metabolism during/after apnea diving: a prospective single-center study.

Background: The popularity of apneic diving is continually growing. As apnea diving substantially burdens the cardiovascular system, special focus is warranted. Regarding inflammation processes and associated inflammatory-related diseases (e.g., cardiovascular diseases), eicosanoids play an important role. This study aims to investigate polyunsaturated fatty acids (PUFAs) and eicosanoids in voluntary apnea divers, and so to further improve understanding of pathophysiological processes focusing on proinflammatory effects of temporarily hypercapnic hypoxia.. Methods: The concentration of PUFAs and eicosanoids were investigated in EDTA plasma in apnea divers (n=10) before and immediately after apnea, 0.5 hour and four hours later, applying liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Mean age was 41±10 years, and divers performed a mean breath-hold time of 317±111 seconds. PUFAs, eicosanoids and related lipids could be classified in four different kinetical reaction groups following apnea. The first group (e.g., Ω-6 and Ω-3-PUFAs) showed an immediate concentration increase followed by a decrease below baseline four hours after apnea. The second group (e.g., thromboxane B2) showed a slower increase, with its maximum concentration 0.5 hour post-apnea followed by a decrease four hours post-apnea. Group 3 (9- and 13-hydroxyoctadecadienoic acid) is characterized by two concentration increase peaks directly after apnea and four hours afterward compared to baseline. Group 4 (e.g., prostaglandin D2) shows no clear response. Conclusion: Changes in the PUFA metabolism after even a single apnea revealed different kinetics of pro- and anti-inflammatory regulations and changes for oxidative stress levels. Due to the importance of these mediators, apnea diving should be evaluated carefully and be performed only with great caution against the background of cardiovascular diseases and inflammation processes.

Myofunctional therapy (oropharyngeal exercises) for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is a syndrome characterised by episodes of apnoea (complete cessation of breathing) or hypopnoea (insufficient breathing) during sleep. Classical symptoms of the disease - such as snoring, unsatisfactory rest and daytime sleepiness - are experienced mainly by men; women report more unspecific symptoms such as low energy or fatigue, tiredness, initial insomnia and morning headaches. OSA is associated with an increased risk of occupational injuries, metabolic diseases, cardiovascular diseases, mortality, and being involved in traffic accidents. Continuous positive airway pressure (CPAP) - delivered by a machine which uses a hose and mask or nosepiece to deliver constant and steady air pressure- is considered the first treatment option for most people with OSA. However, adherence to treatment is often suboptimal. Myofunctional therapy could be an alternative for many patients. Myofunctional therapy consists of combinations of oropharyngeal exercises - i.e. mouth and throat exercises. These combinations typically include both isotonic and isometric exercises involving several muscles and areas of the mouth, pharynx and upper respiratory tract, to work on functions such as speaking, breathing, blowing, sucking, chewing and swallowing. OBJECTIVES: To evaluate the benefits and harms of myofunctional therapy (oropharyngeal exercises) for the treatment of obstructive sleep apnoea. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 1 May 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs that recruited adults and children with a diagnosis of OSA. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were daytime sleepiness, morbidity and mortality. MAIN RESULTS: We found nine studies eligible for inclusion in this review and nine ongoing studies. The nine included RCTs analysed a total of 347 participants, 69 of them women and 13 children. The adults' mean ages ranged from 46 to 51, daytime sleepiness scores from eight to 14, and severity of the condition from mild to severe OSA. The studies' duration ranged from two to four months. None of the studies assessed accidents, cardiovascular diseases or mortality outcomes. We sought data about adverse events, but none of the included studies reported these. In adults, compared to sham therapy, myofunctional therapy: probably reduces daytime sleepiness (Epworth Sleepiness Scale (ESS), MD (mean difference) -4.52 points, 95% Confidence Interval (CI) -6.67 to -2.36; two studies, 82 participants; moderate-certainty evidence); may increase sleep quality (MD -3.90 points, 95% CI -6.31 to -1.49; one study, 31 participants; low-certainty evidence); may result in a large reduction in Apnoea-Hypopnoea Index (AHI, MD -13.20 points, 95% CI -18.48 to -7.93; two studies, 82 participants; low-certainty evidence); may have little to no effect in reduction of snoring frequency but the evidence is very uncertain (Standardised Mean Difference (SMD) -0.53 points, 95% CI -1.03 to -0.03; two studies, 67 participants; very low-certainty evidence); and probably reduces subjective snoring intensity slightly (MD -1.9 points, 95% CI -3.69 to -0.11 one study, 51 participants; moderate-certainty evidence). Compared to waiting list, myofunctional therapy may: reduce daytime sleepiness (ESS, change from baseline MD -3.00 points, 95% CI -5.47 to -0.53; one study, 25 participants; low-certainty evidence); result in little to no difference in sleep quality (MD -0.70 points, 95% CI -2.01 to 0.61; one study, 25 participants; low-certainty evidence); and reduce AHI (MD -6.20 points, 95% CI -11.94 to -0.46; one study, 25 participants; low-certainty evidence). Compared to CPAP, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.30 points, 95% CI -1.65 to 2.25; one study, 54 participants; low-certainty evidence); and may increase AHI (MD 9.60 points, 95% CI 2.46 to 16.74; one study, 54 participants; low-certainty evidence). Compared to CPAP plus myofunctional therapy, myofunctional therapy alone may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.56 to 2.96; one study, 49 participants; low-certainty evidence) and may increase AHI (MD 10.50 points, 95% CI 3.43 to 17.57; one study, 49 participants; low-certainty evidence). Compared to respiratory exercises plus nasal dilator strip, myofunctional therapy may result in little to no difference in daytime sleepiness (MD 0.20 points, 95% CI -2.46 to 2.86; one study, 58 participants; low-certainty evidence); probably increases sleep quality slightly (-1.94 points, 95% CI -3.17 to -0.72; two studies, 97 participants; moderate-certainty evidence); and may result in little to no difference in AHI (MD -3.80 points, 95% CI -9.05 to 1.45; one study, 58 participants; low-certainty evidence). Compared to standard medical treatment, myofunctional therapy may reduce daytime sleepiness (MD -6.40 points, 95% CI -9.82 to -2.98; one study, 26 participants; low-certainty evidence) and may increase sleep quality (MD -3.10 points, 95% CI -5.12 to -1.08; one study, 26 participants; low-certainty evidence). In children, compared to nasal washing alone, myofunctional therapy and nasal washing may result in little to no difference in AHI (MD 3.00, 95% CI -0.26 to 6.26; one study, 13 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Compared to sham therapy, myofunctional therapy probably reduces daytime sleepiness and may increase sleep quality in the short term. The certainty of the evidence for all comparisons ranges from moderate to very low, mainly due to lack of blinding of the assessors of subjective outcomes, incomplete outcome data and imprecision. More studies are needed. In future studies, outcome assessors should be blinded. New trials should recruit more participants, including more women and children, and have longer treatment and follow-up periods.

Impact of the odors of vanilla extract and breast milk on the frequency of apnea in preterm neonates.

AIM: We developed this study using an experimental design to determine the impact of the odors of vanilla extract and breast milk on apnea frequency in preterm neonates. MATERIALS AND METHODS: We obtained the study data from 42 preterm neonates (16 vanilla, 13 breast milk, 13 control group) who had been admitted to the Neonatal Intensive Care Unit of Istanbul University meeting the case selection criteria. All groups were monitored on the first day without any intervention. On the second and third days, breast milk was placed in the incubators of the babies in the breast milk group and the sterile gauze that was vanilla-impregnated was placed in the incubators of the babies in the vanilla group. On the fourth day, the babies were watched without any interference. RESULTS: On the second, third and fourth days of the study, we determined that apnea frequency in the vanilla group neonates was significantly lower (P < .00) as compared to the breast milk and control groups. CONCLUSION: Using vanilla extract in neonates suffering from apnea to reduce its frequency is an effective method.

A criança com Brief Resolved Unexplained Event no primeiro ano de vida: intervenção especializada de enfermagem / The child with Brief Resolved Unexplained Event in the first year of life: specialized nursing intervention

Desde sempre que os eventos adversos no 1º ano de vida constituem um desafio para profissionais de saúde e são motivo de ansiedade para os cuidadores de um lactente. Na década de 1960, estes eventos designavam-se Sudden Infant Death Syndrome e possuíam uma conotação de fatalidade sem prenúncio. Posteriormente, na década de 1980 transitaram para Apparent Life-Threatening Event, sugerindo uma ameaça à vida e desprovido de objetividade, necessária à elaboração de um diagnóstico. Desta necessidade emergiu o Brief Resolved Unexplained Event (BRUE) em 2016, cuja natureza mais específica permitiu a categorização do risco de recorrência de eventos num algoritmo, o qual constitui um importante instrumento de trabalho para os profissionais de saúde que prestam cuidados a estes lactentes. Devido ao seu carácter recente, a enfermagem destaca a importância de se globalizar a transição de ALTE para BRUE, de ser usado este conceito em detrimento do seu antecessor e de fomentar a atualização das equipas de profissionais de saúde, assim como os ensinos aos cuidadores do lactente, potenciando a intervenção especializada de enfermagem sobre o lactente e respetiva estrutura familiar. O objetivo deste relatório é descrever, de modo reflexivo, analítico e crítico, as atividades desenvolvidas em contexto clínico de serviço de urgência de pediatria e cuidados intensivos neonatais, que deram resposta aos objetivos gerais no processo de aquisição e desenvolvimento de competências comuns de Enfermeiro Especialista e especializadas de Enfermeiro Especialista na área de Pessoa em Situação Crítica, nomeadamente à criança com BRUE no 1º ano de vida. No Modelo de Dreyfus adaptado à enfermagem ancorou-se o desenvolvimento das áreas de perícia de saberes e competências científicas, técnicas e humanas na prestação de cuidados de enfermagem especializados de elevada qualidade ao cliente crítico, estando atento às suas necessidades de forma holística, não esquecendo a família como vetor de informação e potencial cuidador. Este processo formativo foi sustentado pela Teoria de Sistemas de Betty Neuman, assim como pelo Modelo de Parceria de Cuidados de Anne Casey, ambos ancorados nos pilares da enfermagem pediátrica.

Adverse events in early childhood has been a challenge for pediatric healthcare professionals and a torment for parents and caregivers, since a long time. In the 60's, these events were called Sudden Infant Death Syndrome, which imprinted a sense of fatality that could not be predicted. Later on, in the 80's, the Apparent Life-Threatening Event emerged, suggesting a threat to a child's life and had no objectivity, which is required to perform a diagnosis. Therefore, in 2016, based on this necessity, the Brief Resolved Unexplained Event (BRUE) was created, possessing a more specific nature, that allowed the stratification of the risk category of recurrence of these events in an algorithm, as an important work tool for healthcare professionals that assist these infants. Due to the fact that it's a very recent concept, Nursing highlights the need for ALTE's transition into BRUE to be globalized, advocates for the use of BRUE's concept instead of ALTE's and fosters the healthcare professionals update as well as caregivers' education, promoting specialized nursing interventions in an infant and his family. The purpose of this report is to describe, in a reflective, analytic and critical way, the developed activities in the pediatric emergency department and neonatal intensive care unit internships, that fulfilled the general objectives outlined in the process of acquiring and developing common and specific skills of the Specialized Nurse in Critical Care Patients area of expertise, namely to the child who experiences a BRUE in the first year of life. The development of knowledge proficiency and scientific, technical and human skills in specialized nursing healthcare of high quality to the critical patient, were based on Dreyfus Model, adapted by Benner to Nursing, requiring constant awareness to human needs in a holistic manner, always considering family as an information vector and potential caregivers. This academic practice was built on Betty Neuman's Systems Model, as on Anne Casey's Partnership Model of Nursing Care, both anchored in Nursing Pediatrics foundations.

Análisis fenoménico de la técnica neuromuscular funcional como tratamiento para el SAOS / Phenomenical Analysis of the Functional Neuromuscular Technique as a Treatment for OSA

Introducción: el objetivo de este estudio es develar si la técnica Neuromuscular Funcional (NMF) puede ser considerada como opción de tratamiento en el Síndrome de Apnea Obstructiva de Sueño (SAOS) y si se complementa con la Terapia Miofun-cional Orofacial o hace parte de ella.Métodos: la fenomenología trascendental de Husserl es el enfoque metodoló-gico que se adoptó para este estudio, siguiendo la ruta para su desarrollo: epojé, reducción trascendental fenomenológica y síntesis. El contenido real se obtuvo mediante dos entrevistas semiestructuradas, aplicadas a un informante clave que contó con los criterios de inclusión presupuestados. Resultados: en la primera etapa se identificaron 10 noesis y 266 noemas, que fue-ron relacionados entre sí; en la fase de reducción trascendental las noesis se redujeron a 5 y los noemas a 14. Análisis y discusión: el Método Chiavaro como fenómeno se decanta en las di-mensiones: (a) Enfoque Sistémico, (b) Técnica Neuromuscular Funcional y (c) Téc-nica Respiratoria. La prioridad del fenómeno NMF es la explicación de la alteración dentro del enfoque sistémico a partir de la lógica Función-Estructura-Función, de esta manera el SAOS se considera una manifestación de esas relaciones y como tal se le cataloga como adaptación o como función en disfunción.Conclusiones: la Técnica NMF hace parte de la neurorrehabilitación mientras que la TMO para intervenir el SAOS se inscribe en la fisiología del ejercicio

Introduction: the objective of this study is to reveal if the Functional Neuromuscu-lar technique (In Spanish: NMF) can be considered as a treatment option for OSA. Additionally, this paper seeks to assess if the aforementioned is derived from, a por-tion of or if it is complemented by Orofacial Myofunctional Therapy (OMT). Methods: Husserl's transcendental phenomenology is the methodological approach that was adopted for this study, following the path to its development: epoché, phenomenologi-cal transcendental reduction and synthesis. The actual content was obtained through two semi-structured interviews applied to a key informant who met the preconceived inclusion criteria.Results: in the first stage 10 noesis and 266 noems , which were related to each other, were identified; in the phase of transcendental reduction, the noesis were reduced to 5 and the noems to 14. Analysis and discussion: the Chiavaro Method as a phenomenon is composed of three dimensions: (a) Systemic Approach, (b) Functional Neuromuscular Technique and (c) Respi-ratory Technique. The priority of the NMF phenomenon is the explanation of the alteration within the systemic approach based on the Function-Structure-Function logic, ergo the OSA is considered a manifestation of these relationships and as such it is classified as adaptation or as a function in dysfunction.Conclusions: the NMF technique is a part of neurorehabilitation whilst OMT for the in-tervention of OSA is subscribed to the physiology of exercise.

Optimizing neural networks for medical data sets: A case study on neonatal apnea prediction.

OBJECTIVE: The neonatal period of a child is considered the most crucial phase of its physical development and future health. As per the World Health Organization, India has the highest number of pre-term births [1], with over 3.5 million babies born prematurely, and up to 40% of them are babies with low birth weights, highly prone to a multitude of diseases such as Jaundice, Sepsis, Apnea, and other Metabolic disorders. Apnea is the primary concern for caretakers of neonates in intensive care units. The real-time medical data is known to be noisy and nonlinear and to address the resultant complexity in classification and prediction of diseases; there is a need for optimizing learning models to maximize predictive performance. Our study attempts to optimize neural network architectures to predict the occurrence of apneic episodes in neonates, after the first week of admission to Neonatal Intensive Care Unit (NICU). The primary contribution of this study is the formulation and description of a set of generic steps involved in selecting various model-specific, training and hyper-parametric optimization algorithms, as well as model architectures for optimal predictive performance on complex and noisy medical datasets. METHODS: The data used for the study being inherently complex and noisy, Kernel Principal Component Analysis (PCA) is used to reduce dataset dimensionality for the analysis such as interpretations and visualization of the dataset. Hyper-parametric and parametric optimization, in different categories, are considered, including learning rate updater algorithms, regularization methods, activation functions, gradient descent algorithms and depth of the network, based on their performance on the validation set, to obtain a holistically optimized neural network, that best model the given complex medical dataset. Deep Neural Network Architectures such as Deep Multilayer Perceptron's, Stacked Auto-encoders and Deep Belief Networks are employed to model the dataset, and their performance is compared to the optimized neural network obtained from the parametric exploration. Further, the results are compared with Support Vector Machine (SVM), K Nearest Neighbor, Decision Tree (DT) and Random Forest (RF) algorithms. RESULTS: The results indicate that the optimized eight layer Multilayer Perceptron (MLP) model, with Adam Decay and Stochastic Gradient Descent (AUC 0.82) can outperform the conventional machine learning models, and perform comparably to the Deep Auto-encoder model (AUC 0.83) in predicting the presence of apnea in neonates. CONCLUSION: The study shows that an MLP model can undergo significant improvements in predictive performance, by the proposed step-wise optimization. The optimized MLP is proved to be as accurate as deep neural network models such as Deep Belief Networks and Deep Auto-encoders for noisy and nonlinear data sets, and outperform all conventional models like Support Vector Machine (SVM), Decision Tree (DT), K Nearest Neighbor and Random Forest (RF) algorithms. The generic nature of the proposed step-wise optimization provides a framework to optimize neural networks on such complex nonlinear datasets. The investigated models can help neonatologists as a diagnostic tool.

Eight weeks of static apnea training increases spleen volume but not acute spleen contraction.

Splenic contraction is an important response to acute apnea causing the release of red blood cells into blood circulation. Current literature shows higher spleen volumes and greater spleen contractions in trained apnea divers compared to untrained individuals, but the influence of training is presently unknown. Thirteen subjects daily performed five static apneas for 8 weeks. Before, halfway through and after the apnea training period, subjects performed five maximal breath-holds at the laboratory. Baseline values for and changes in splenic volume and hemoglobin ([Hb]) were assessed. Although baseline spleen volume had increased (from 241 ±â€¯55 mL PRE to 299 ±â€¯51 mL POST training, p = 0.007), the absolute spleen contraction (142 ±â€¯52 mL PRE and 139 ±â€¯34 mL POST training, p = 0.868) and the acute increase in [Hb] remained unchanged. The present study shows that apnea training can increase the size of the spleen but that eight weeks of training is not sufficient to elicit significant training adaptations on the acute response.

Ambiguous Genitalia Associated with an Extremely Rare Syndrome: A Case Report of XLAG Syndrome and Review of the Literature.

X-linked lissencephaly, absent corpus callosum, and epilepsy of neonatal onset with ambiguous genitalia comprises the XLAG syndrome and only 15 cases have been reported in literature. Due to its rarity, the exact clinical course and outcome are not known. Exact associations of this disease are also elusive. Hereby we are reporting this extremely rare entity and we searched the English literature extensively to get consolidated knowledge regarding this entity that would help the readers. Pre-natal radiological work-up can detect these malformations, which should be followed by medical termination, counseling and karyotyping. Till date the longest survival noted was 4 years only.

Breath-Holding Spells in Pediatrics: A Narrative Review of the Current Evidence.

BACKGROUND: Breath-holding spells are common, frightening, but fortunately benign events. Familiarity with this condition is important so that an accurate diagnosis can be made. OBJECTIVE: To familiarize physicians with the clinical manifestations, diagnosis, evaluation, and management of children with breath-holding spells. METHODS: A PubMed search was completed in Clinical Queries using the key term "breath-holding spells". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. RESULTS: Breath-holding spells affect 0.1 to 4.6% of otherwise healthy young children. The onset is usually between 6 and 18 months of age. The etiopathogenesis is likely multifactorial and includes autonomic nervous system dysregulation, vagally-mediated cardiac inhibition, delayed myelination of the brain stem, and iron deficiency anemia. Breath-holding spells may be cyanotic or pallid. The former are usually precipitated by anger or frustration while the latter are more often precipitated by pain or fear. In the cyanotic type, the child usually emits a short, loud cry, which leads to a sudden involuntary holding of the breath in forced expiration. The child becomes cyanosed, rigid or limp, followed by a transient loss of consciousness, and a long-awaited inspiration and resolution of the spell. In the pallid type, crying may be minimal or "silent". The apneic period in the pallid type is briefer than that in the cyanotic type prior to the loss of consciousness and posture. The episode in the pallid type then proceeds in the same manner as a cyanotic spell except that the child in the pallid type develops pallor rather than cyanosis. In both types, the entire episode lasts approximately 10 to 60 seconds. The spells usually disappear spontaneously by 5 years of age. CONCLUSION: Although breath-holding spells are benign, they can be quite distressing to the parents. Confident reassurance and frank explanation are the cornerstones of treatment. Underlying cause, if present, should be treated. Interventions beyond iron supplementation may be considered for children with severe and frequent breath-holding spells which have a strong impact on the lifestyle of both the child and family.

A pilot study of limb stimulation for the treatment of neonatal apnea.

This study explored the feasibility effect and safety of the limb stimulation (LS) for the treatment of neonatal apnea (NAP).The cases of 30 eligible premature infants with NAP were included in this retrospective study. These cases were equally divided into an intervention group (n = 15) and a control group (n = 15). The infants in both groups received caffeine treatment. Moreover, cases in the intervention group also received LS for a total 30 hours, while the subjects in the control group did not receive LS during this period. The primary outcome included apnea frequency (number of episodes per 24 hours), and apnea rate. The secondary outcomes consisted of desaturation (number of episodes per 24 hours), and heart rate (beats per minute). Additionally, adverse events were also documented during the treatment period.After treatment, LS did not show better outcomes in apnea frequency (P = .48), apnea rate (P = .33), desaturation (P = .55), and heart rate (P = .41). Furthermore, no significant differences of all adverse events were found between 2 groups.The results of this pilot study demonstrated that LS might be not efficacious for premature infants with NAP.

A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent cause of intellectual disability in girls and there is currently no cure for the disease. The finding that the deficits caused by the loss of Mecp2 are reversible in the mouse has bolstered interest in gene therapy as a cure for RTT. In order to assess the feasibility of gene therapy in a RTT mouse model, and in keeping with translational goals, we investigated the efficacy of a self-complementary AAV9 vector expressing a codon-optimized version of Mecp2 (AAV9-MCO) delivered via a systemic approach in early symptomatic Mecp2-deficient (KO) mice. Our results show that AAV9-MCO administered at a dose of 2×1011 viral genome (vg)/mouse was able to significantly increase survival and weight gain, and delay the occurrence of behavioral deficits. Apneas, which are one of the core RTT breathing deficits, were significantly decreased to WT levels in Mecp2 KO mice after AAV9-MCO administration. Semi-quantitative analysis showed that AAV9-MCO administration in Mecp2 KO mice resulted in 10 to 20% Mecp2 immunopositive cells compared to WT animals, with the highest Mecp2 expression found in midbrain regions known to regulate cardio-respiratory functions. In addition, we also found a cell autonomous increase in tyrosine hydroxylase levels in the A1C1 and A2C2 catecholaminergic Mecp2+ neurons in treated Mecp2 KO mice, which may partly explain the beneficial effect of AAV9-MCO administration on apneas occurrence.

Clinical Outcomes Associated with a Failed Infant Car Seat Challenge.

OBJECTIVE: To assess comorbid conditions and clinical outcomes among late preterm and low birth weight term infants (<2.5 kg) who failed the Infant Car Seat Challenge (ICSC) on the Mother-Baby Unit. STUDY DESIGN: This was a retrospective chart review of consecutive infants who failed ICSC on the Mother-Baby Unit and were subsequently admitted to the neonatal intensive care unit at Prentice Women's Hospital between January 1, 2009, and December 31, 2015. Regression models were used to estimate risk differences (RDs) with 95% CIs for factors related to length of stay. RESULTS: A total of 148 infants were studied (43% male; 37% delivered via cesarean). ICSC failure in the Mother-Baby Unit was due to desaturation, bradycardia, and tachypnea in 59%, 37%, and 4% of infants, respectively. During monitoring on the neonatal intensive care unit, 39% of infants experienced apnea (48% in preterm vs 17% in term infants) in the supine position, 19% received phototherapy, and 2% and 6.8% received nasogastric and thermoregulatory support, respectively. Univariate predictors of increased duration of stay (days) were younger gestational age, apnea, nasogastric support, intravenous fluids, and antibiotics (all P < .05). In multivariable analysis adjusted for gestational age and discharge weight, only apnea (RD, 4.87; 95% CI, 2.99-6.74; P < .001), administration of antibiotics (RD, 3.25; 95% CI, 0.29-6.21; P < .032), and intravenous fluid support (RD, 4.87; 95% CI, 0.076-9.66; P < .047) remained independent predictors of a longer duration of stay. CONCLUSION: Infants who failed ICSC were at risk for comorbid conditions that prolonged hospital stay beyond the neonatal intensive care unit observation period. Almost one-half of late preterm infants who failed ICSC had apnea events in the supine position.