Respiratory Adaptation Research Articles

High or hot-Perspectives on altitude camps and heat-acclimation training as preparation for prolonged stage races.

Adaptation to heat stress and hypoxia are relevant for athletes participating in Tour de France or similar cycling races taking place during the summertime in landscapes with varying altitude. Both to minimize detrimental performance effects associated with arterial desaturation occurring at moderate altitudes in elite athletes, respectively, reduce the risk of hyperthermia on hot days, but also as a pre-competition acclimatization strategy to boost blood volume in already highly adapted athletes. The hematological adaptations require weeks of exposure to manifest, but are attractive as an augmented hemoglobin mass may improve arterial oxygen delivery and hence benefit prolonged performances. Altitude training camps have in this context a long history in exercise physiology and are still common practice in elite cycling. However, heat-acclimation training provides an attractive alternative for some athletes either as a stand-alone approach or in combination with altitude. The present paper provides an update and practical perspectives on the potential to utilize hypoxia and heat exposure to optimize hematological adaptations. Furthermore, we will consider temporal aspects both in terms of onset and decay of the adaptations relevant for improved thermoregulatory capacity and respiratory adaptations to abate arterial desaturation during altitude exposure. From focus on involved physiological mechanisms, time course, and responsiveness in elite athletes, we will provide guidance based on our experience from practical implementation in cyclists preparing for prolonged stage races such as the Tour de France.

Ecological, physiological and life-history traits correlate with genome sizes in decapod crustaceans

Crustaceans are characterized by some of the most variable genome sizes among animals. Significant relationships between genome size and specific eco-physiological and morphological features have been described in many crustacean taxa, such as Amphipoda, Ostracoda, Cladocera, and Copepoda. A consistent pattern of genome size variation is yet to be found, however, in one of the most specious order of crustaceans, the Decapoda. We investigated how genome size is related to selected eco-physiological and life-history traits in species belonging to this order. We analyzed the respiratory, excretory, and developmental adaptations of 179 decapod species inhabiting shallow marine, deep marine, freshwater, intertidal, and terrestrial habitats. Our results show that the genome size is significantly larger in decapods that have a direct development. Moreover, in Anomura, Astacidea, and Brachyura we found larger genome sizes in species (i) living in freshwater habitats, (ii) using gills as a strictly water-breathing organs, and (iii) presenting a direct development. While species that (i) live in shallow waters, and intertidal and terrestrial habitats, (ii) have some degrees of air-breathing adaptations, namely gills that can exchange oxygen with air if wet or branchiostegal lungs, and (iii) possess an indirect or extended development are characterized by significantly smaller genomes. Our analyses show that developmental complexity affects genome size in decapods, and that multiple eco-physiological and life-history traits correlate with genome size in Anomura, Astacidea, and Brachyura.

Mechanisms of mitochondrial respiratory adaptation.

Mitochondrial energetic adaptations encompass a plethora of conserved processes that maintain cell and organismal fitness and survival in the changing environment by adjusting the respiratory capacity of mitochondria. These mitochondrial responses are governed by general principles of regulatory biology exemplified by changes in gene expression, protein translation, protein complex formation, transmembrane transport, enzymatic activities and metabolite levels. These changes can promote mitochondrial biogenesis and membrane dynamics that in turn support mitochondrial respiration. The main regulatory components of mitochondrial energetic adaptation include: the transcription coactivator peroxisome proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC1α) and associated transcription factors; mTOR and endoplasmic reticulum stress signalling; TOM70-dependent mitochondrial protein import; the cristae remodelling factors, including mitochondrial contact site and cristae organizing system (MICOS) and OPA1; lipid remodelling; and the assembly and metabolite-dependent regulation of respiratory complexes. These adaptive molecular and structural mechanisms increase respiration to maintain basic processes specific to cell types and tissues. Failure to execute these regulatory responses causes cell damage and inflammation or senescence, compromising cell survival and the ability to adapt to energetically demanding conditions. Thus, mitochondrial adaptive cellular processes are important for physiological responses, including to nutrient availability, temperature and physical activity, and their failure leads to diseases associated with mitochondrial dysfunction such as metabolic and age-associated diseases and cancer.

Overexpression of MRX9 impairs processing of RNAs encoding mitochondrial oxidative phosphorylation factors COB and COX1 in yeast

Mitochondrial translation is a highly regulated process, and newly synthesized mitochondrial products must first associate with several nuclear-encoded auxiliary factors to form oxidative phosphorylation complexes. The output of mitochondrial products should therefore be in stoichiometric equilibrium with the nuclear-encoded products to prevent unnecessary energy expense or the accumulation of pro-oxidant assembly modules. In the mitochondrial DNA of Saccharomyces cerevisiae, COX1 encodes subunit 1 of the cytochrome c oxidase and COB the central core of the cytochrome bc1 electron transfer complex; however, factors regulating the expression of these mitochondrial products are not completely described. Here, we identified Mrx9p as a new factor that controls COX1 and COB expression. We isolated MRX9 in a screen for mitochondrial factors that cause poor accumulation of newly synthesized Cox1p and compromised transition to the respiratory metabolism. Northern analyses indicated lower levels of COX1 and COB mature mRNAs accompanied by an accumulation of unprocessed transcripts in the presence of excess Mrx9p. In a strain devoid of mitochondrial introns, MRX9 overexpression did not affect COX1 and COB translation or respiratory adaptation, implying Mrx9p regulates processing of COX1 and COB RNAs. In addition, we found Mrx9p was localized in the mitochondrial inner membrane, facing the matrix, as a portion of it cosedimented with mitoribosome subunits and its removal or overexpression altered Mss51p sedimentation. Finally, we showed accumulation of newly synthesized Cox1p in the absence of Mrx9p was diminished in cox14 null mutants. Taken together, these data indicate a regulatory role of Mrx9p in COX1 RNA processing.

RARE-14. Newborn with hypothalamic hamartoma and Pallister-Hall syndrome

A female full-term newborn of 41 + 2 weeks gestational age with a respiratory adaptation disorder and hypercapnia was transferred from an external maternity clinic to our pediatric intensive care unit. The child is the second child of healthy, non-consanguineous parents. Multiple dysmorphias were noticed at arrival. We identified a choanal atresia/stenosis on both sides in the respiratory tract, a high palate, a submucous cleft palate, a bifid uvula, a laryngeal cleft and a bronchus suis. The child required intubation and ventilation. In addition, we recognized brachydactyly of the hands and feet. The phalanges were not visibly separable. There was nail hypoplasia and rocker bottom feet on both sides. Furthermore, we saw an anal atresia. In routine laboratory work-up, a hypoglycemia and not measurable low TSH serum concentration was noticed. Extended endocrinological laboratory diagnostics revealed a complete pituitary insufficiency. On cranial MRI, a large, iso- to slightly hyperintense space-occupying mass (3.8x3.7x2.5 cm3), originating from the hypothalamus was observed. The brainstem was displaced posteriorly by the mass. The imaging is consistent with a hypothalamic hamartoma. With regard to the present findings, we assumed an underlying genetic cause of the congenital malformations. As a clinical diagnosis, a Pallister-Hall syndrome was suspected. As described in our case, we saw the characteristic features: dysmorphia of the hands and feet, upper respiratory tract, anal atresia, and hypothalamic hamartomas. The Pallister-Hall syndrome is caused by mutations in the GLI3 gene on the 7p13 chromosome. It is inherited in an autosomal dominant manner and its prevalence is unknown. In our patient, a heterozygous, probably pathogenic variant in the GLI3-Gene was proven by Next Generation Sequencing (NGS).

Management Practices During Perinatal Respiratory Transition of Very Premature Infants.

The present review considers some controversial management practices during extremely premature perinatal transition. We focus on perinatal prevention and treatment of respiratory distress syndrome (RDS) in immature infants. New concerns regarding antenatal corticosteroid management have been raised. Many fetuses are only exposed to potential adverse effects of the drug. Hence, the formulation and the dosage may need to be modified. Another challenge is to increase the fraction of the high-risk fetuses that benefit from the drug and to minimize the harmful effects of the drug. On the other hand, boosting anti-inflammatory and anti-microbial properties of surfactant requires further attention. Techniques of prophylactic surfactant administration to extremely immature infants at birth may be further refined. Also, new findings suggest that prophylactic treatment of patent ductus arteriosus (PDA) of a high-risk population rather than later selective closure of PDA may be preferred. The TREOCAPA trial (Prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen) evaluates, whether early intravenous paracetamol decreases the serious cardiorespiratory consequences following extremely premature birth. Lastly, is inhaled nitric oxide (iNO) used in excess? According to current evidence, iNO treatment of uncomplicated RDS is not indicated. Considerably less than 10% of all very premature infants are affected by early persistence of pulmonary hypertension (PPHN). According to observational studies, effective ventilation combined with early iNO treatment are effective in management of this previously fatal disease. PPHN is associated with prolonged rupture of fetal membranes and birth asphyxia. The lipopolysaccharide (LPS)-induced immunotolerance and hypoxia-reperfusion-induced oxidant stress may inactivate NO-synthetases in pulmonary arterioles and terminal airways. Prospective trials on iNO in the management of PPHN are indicated. Other pulmonary vasodilators may be considered as comparison drugs or adjunctive drugs. The multidisciplinary challenge is to understand the regulation of pregnancy duration and the factors participating the onset of extremely premature preterm deliveries and respiratory adaptation. Basic research aims to identify deficiencies in maternal and fetal tissues that predispose to very preterm births and deteriorate the respiratory adaptation of immature infants. Better understanding on causes and prevention of extremely preterm births would eventually provide effective antenatal and neonatal management practices required for the intact survival.

In Transgenic Erythropoietin Deficient Mice, an Increase in Respiratory Response to Hypercapnia Parallels Abnormal Distribution of CO2/H+-Activated Cells in the Medulla Oblongata.

Erythropoietin (Epo) and its receptor are expressed in central respiratory areas. We hypothesized that chronic Epo deficiency alters functioning of central respiratory areas and thus the respiratory adaptation to hypercapnia. The hypercapnic ventilatory response (HcVR) was evaluated by whole body plethysmography in wild type (WT) and Epo deficient (Epo-TAgh) adult male mice under 4%CO2. Epo-TAgh mice showed a larger HcVR than WT mice because of an increase in both respiratory frequency and tidal volume, whereas WT mice only increased their tidal volume. A functional histological approach revealed changes in CO2/H+-activated cells between Epo-TAgh and WT mice. First, Epo-TAgh mice showed a smaller increase under hypercapnia in c-FOS-positive number of cells in the retrotrapezoid nucleus/parafacial respiratory group than WT, and this, independently of changes in the number of PHOX2B-expressing cells. Second, we did not observe in Epo-TAgh mice the hypercapnic increase in c-FOS-positive number of cells in the nucleus of the solitary tract present in WT mice. Finally, whereas hypercapnia did not induce an increase in the c-FOS-positive number of cells in medullary raphe nuclei in WT mice, chronic Epo deficiency leads to raphe pallidus and magnus nuclei activation by hyperacpnia, with a significant part of c-FOS positive cells displaying an immunoreactivity for serotonin in the raphe pallidus nucleus. All of these results suggest that chronic Epo-deficiency affects both the pattern of ventilatory response to hypercapnia and associated medullary respiratory network at adult stage with an increase in the sensitivity of 5-HT and non-5-HT neurons of the raphe medullary nuclei leading to stimulation of f R for moderate level of CO2.

Factors impacting performance on the 6-minute walk test by people with late-onset Pompe disease.

Pompe disease is a progressive myopathy that combines motor, respiratory, and cardiac impairments. The 6-min walk test is the gold standard for assessing disease severity at the motor level. The objective of this study was to better determine the parameters that influence the total distance covered in patients with Pompe disease. We performed a retrospective review of 15 patients with late-onset Pompe disease who were followed regularly at a single referral center. Logistic regression was used to investigate the links between motor, respiratory and cardiac variables and 6-min walk test performance. When considering baseline clinical and demographic variables, a seven-step backward elimination regression analysis yielded a model with two predictors (age and the use of an assistive device) that explained 85.5% of the variance. When considering the cardiorespiratory variables monitored during gait, a three-step backward elimination regression analysis showed that two predictors (heart rate recovery and the baseline partial pressure of carbon dioxide) explained 42.2% of the variance. Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability) during the 6-min walk test in patients with Pompe disease. Further studies of larger cohorts are necessary to validate the model, which might enable investigators to determine whether intra-individual fluctuations in 6-min walk test performance are related to physiological parameters and/or to other variables such as the patient's level of motivation during the test.

Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth.

SummaryInvaginations of the mitochondrial inner membrane, termed cristae, are hubs for oxidative phosphorylation. The mitochondrial contact site and cristae organizing system (MICOS) and the dimeric F1Fo-ATP synthase play important roles in controlling cristae architecture. A fraction of the MICOS core subunit Mic10 is found in association with the ATP synthase, yet it is unknown whether this interaction is of relevance for mitochondrial or cellular functions. Here, we established conditions to selectively study the role of Mic10 at the ATP synthase. Mic10 variants impaired in MICOS functions stimulate ATP synthase oligomerization like wild-type Mic10 and promote efficient inner membrane energization, adaptation to non-fermentable carbon sources, and respiratory growth. Mic10's functions in respiratory growth largely depend on Mic10ATPsynthase, not on Mic10MICOS. We conclude that Mic10 plays a dual role as core subunit of MICOS and as partner of the F1Fo-ATP synthase, serving distinct functions in cristae shaping and respiratory adaptation and growth.

Clinical and laboratory evaluation of premature goat kids with and without antenatal corticotherapy

ABSTRACT: This article evaluated the vital parameters, blood gas measurements, cortisol values and radiological findings of goat kids born at term and prematurely during the first 48 hours of life. For this purpose, 24 kids from 24 goats were used and assigned to groups as follows: Group I, eight kids born through cesarean sections performed at 149 days of gestation; Group II, eight kids born through cesarean sections performed at 143 days of gestation; Group III, eight kids born through cesarean sections performed at 143 days of gestation, whose mothers received 20 mg of dexamethasone. Group I had lower heart rate values than the other groups at 60 minutes after birth. In terms of temperature, there was no difference between the groups. The pH values were reduced shortly after birth, rising at 24 and 48 hours in all animals studied. In terms of the cortisol levels, the values increased significantly at birth (M0), with the highest values obtained in animals in group II. These values decreased at 48 hours after birth in the evaluated goats. The animals belonging to group I showed better radiographic aspects, and throughout the 48 hours of evaluation, all newborns exhibited adequate respiratory adaptation. It can be concluded that antenatal dexamethasone administered at 143 days of gestation did not influence neonatal viability, metabolic or radiographic parameters. The metabolic changes found are consistent with the extrauterine adaptation period that animals in this stage of life.

Chapter 4 - Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia

This chapter reviews cardiorespiratory adaptations to chronic hypoxia (CH) experienced at high altitude and cardiorespiratory pathologies elicited by chronic intermittent hypoxia (CIH) occurring with obstructive sleep apnea (OSA). Short-term CH increases breathing (ventilatory acclimatization to hypoxia) and blood pressure (BP) through carotid body (CB) chemo reflex. Hyperplasia of glomus cells, alterations in ion channels, and recruitment of additional excitatory molecules are implicated in the heightened CB chemo reflex by CH. Transcriptional activation of hypoxia-inducible factors (HIF-1 and 2) is a major molecular mechanism underlying respiratory adaptations to short-term CH. High-altitude natives experiencing long-term CH exhibit blunted hypoxic ventilatory response (HVR) and reduced BP due to desensitization of CB response to hypoxia and impaired processing of CB sensory information at the central nervous system. Ventilatory changes evoked by long-term CH are not readily reversed after return to sea level. OSA patients and rodents subjected to CIH exhibit heightened CB chemo reflex, increased hypoxic ventilatory response, and hypertension. Increased generation of reactive oxygen species (ROS) is a major cellular mechanism underlying CIH-induced enhanced CB chemo reflex and the ensuing cardiorespiratory pathologies. ROS generation by CIH is mediated by nontranscriptional, disrupted HIF-1 and HIF-2-dependent transcriptions as well as epigenetic mechanisms.

Perinatal inflammation and gestational intermittent hypoxia disturbs respiratory rhythm generation and long-term facilitation in vitro: Partial protection by acute minocycline

Perinatal inflammation triggers breathing disturbances early in life and affects the respiratory adaptations to challenging conditions, including the generation of amplitude long-term facilitation (LTF) by acute intermittent hypoxia (AIH). Some of these effects can be avoided by anti-inflammatory treatments like minocycline. Since little is known about the effects of perinatal inflammation on the inspiratory rhythm generator, located in the preBötzinger complex (preBötC), we tested the impact of acute lipopolysaccharide (LPS) systemic administration (sLPS), as well as gestational LPS (gLPS) and gestational chronic IH (gCIH), on respiratory rhythm generation and its long-term response to AIH in a brainstem slice preparation from neonatal mice. We also evaluated whether acute minocycline administration could influence these effects. We found that perinatal inflammation induced by sLPS or gLPS, as well as gCIH, modulate the frequency, signal-to-noise ratio and/or amplitude (and their regularity) of the respiratory rhythm recorded from the preBötC in the brainstem slice. Moreover, all these perinatal conditions inhibited frequency LTF and amplitude long-term depression (LTD); gCIH even induced frequency LTD of the respiratory rhythm after AIH. Some of these alterations were not observed in slices pre-treated in vitro with minocycline, when compared with slices obtained from naïve pups, suggesting that ongoing inflammatory conditions affect respiratory rhythm generation and its plasticity. Thus, it is likely that alterations in the inspiratory rhythm generator and its adaptive responses could contribute to the respiratory disturbances observed in neonates that suffered from perinatal inflammatory challenges.

Reference Values of Forced Vital Capacity and Expiratory Flow in High-Level Cyclists

Several studies have demonstrated that spirometric theoretical values may not be applicable to the high-level sports population. No reference values exist for high-level professional cyclists. We aimed to establish predictive spirometric values by reference equations. One hundred and forty-five French Caucasian high-level professional cyclists, aged 18–38, performed basic anthropometric assessment and spirometry during the medical evaluation at the beginning of the sport season. Measured values were compared with theoretical values. Predictive equations were established from anthropometric parameters to explain variations of spirometric parameters. High-level cyclists had significantly higher spirometric values than the theoretical values established from a general population, except for forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and forced expiratory flow (FEF) at 25% of FVC. Only FVC and FEV1 were well predicted from body height. The FVC variation of 43.5% is explained by body height and weight. The FEV1 variation of 25.8% is explained only by body height. High-level cycling is associated with important respiratory adaptations depending on the body height and the sport specificity: intensive and prolonged endurance training. These findings are interesting for clinical individual application to diagnose obstructive disease and test reversibility with bronchodilator drugs.

SARS-CoV-2 Antibody Response among Women Infected during Pregnancy.

Novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus has been declared a pandemic by the World Health Organization as of March 11, 2020. Pregnant women naturally have a reduced immune system due to immunological changes and decreased lung capacity due to respiratory adaptations, making them more susceptible to coronavirus complications. Within the Mount Sinai Health system, more than 15,000 deliveries are performed annually. We began to care for pregnant women with known COVID-19 infections in late March of 2020. In early April 2020, a policy was implemented to perform universal COVID-19 testing for all women planning to deliver within the Mount Sinai Health system. We examined the antibody response of postpartum women who delivered at Mount Sinai Hospital with a SARS-CoV-2 infection between the study intervals during March 15, 2020, through April 30, 2020. This was a prospective observational study examining the immune response of pregnant women who delivered at Mount Sinai Hospital with a polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection. Women with a SARS-CoV-2 infection were contacted via phone to discuss participation in the study. Patients who consented were scheduled for a phlebotomy visit to assess their antibody titer levels to COVID-19. The COVID-19 enzyme-linked immunosorbent assay (ELISA) immunoglobulin (Ig)-G antibody test was used to evaluate the patients' antibody titers. The assay detects IgG antibodies for the detection of IgG seroconversion in patients following a known recent SARS-CoV-2 infection. A total of 120 patients were identified with a documented SARS-CoV-2 infection who delivered within the prespecified time frame. Of those patients, 25 women agreed to participate and were included. Of them, 64.00% were Caucasian with a mean age of 35 years. The mean body mass index (BMI) was 30 kg/m2 and the majority of patients had commercial insurance (88.00%). The majority of women were asymptomatic for COVID-19 at the time of admission (80.00%) and the average gestational age of delivery and diagnosis of COVID-19 was 39 weeks' gestation. The later the gestational age at the time of diagnosis, the lower the antibody titer response. When examining the interval from diagnosis to antibody titer analysis, patients with the highest titers (2,880) tended to have a shorter interval between their COVID-19 diagnosis and the time at which the titer level was drawn. Patients with symptoms on admission had similar antibody titer levels when compared with women who were asymptomatic. The antibody response among women infected with COVID-19 during pregnancy appears to be greater when the patients are diagnosed at an earlier gestational age. · COVID-19 antibody status appears to be greater when diagnosed at an earlier gestational age.. · Asymptomatic and symptomatic pregnant women had similar antibody responses.. · Patients with the highest titers tended to have a shorter interval between their COVID-19 diagnoses..

The antibiotic use by pregnant mice was a reason of lung pathology of their offspring

The inappropriate antibiotic usage in human and animal treating is a main reason of the antibiotic resistance, spreading wider and wider all over the world. It was proved that the use of antibiotic induces the changes in microbiota profile as well as the protective properties of the intestinal mucosal barrier, determining the level of the bacterial translocation to the distant loci of the body. Pneumonia in newborns is one of the severe pathologies that cause increased neonatal morbidity and mortality. During the newborn period, pneumonia develops much more often than in other age periods. It is considered that main reason of respiratory adaptation disorders and newborns’ pneumonia is the intrauterine infection and the development of the inflammatory process. In animal husbandry we can see that a non- specific bronchopneumonia is one of the main causes of mass mortality of young cattle. There is no any confirmed reason of the growing level of the mortality of cattle. Here we present the results of our investigation which allow suggesting a role of antibiotic use by pregnant females as a basis for the following bacterial translocation to the fetus and a non- specific bronchopneumonia.

Pediatric Hypothermia: An Ambiguous Issue.

Hypothermia in pediatrics is mainly about small body size. The key thermal factor here is the large surface-to-volume ratio. Although small mammals, including human infants and children, are adapted to higher heat losses through their elevated metabolic rate and thermogenic capacity, they are still at risk of hypothermia because of a small regulatory range and an impending metabolic exhaustion. However, some small mammalian species (hibernators) use reduced metabolic rates and lowered body temperatures as adaptations to impaired energy supply. Similar to nature, hypothermia has contradictory effects in clinical pediatrics as well: In neonates, it is a serious risk factor affecting respiratory adaptation in term and developmental outcome in preterm infants. On the other hand, it is an important self-protective response to neonatal hypoxia and an evidence-based treatment option for asphyxiated babies. In children, hypothermia first enabled the surgical repair of congenital heart defects and promotes favorable outcome after ice water drowning. Yet, it is also a major threat in various prehospital and clinical settings and has no proven therapeutic benefit in pediatric critical care. All in all, pediatric hypothermia is an ambiguous issue whose harmful or beneficial effects strongly depend on the particular circumstances.

Three-dimensional form and function of the nasal cavity and nasopharynx in humans and chimpanzees.

The facial differences between recent Pan troglodytes and Homo sapiens can be used as a proxy for the reduction of facial prognathism that happened during evolutionary transition between Australopithecines and early Homo. The projecting nasal morphology of Homo has been considered both a passive consequence of anatomical reorganization related to brain and integrated craniofacial evolution as well as an adaptation related to air-conditioning during physiological and behavioral shifts in human evolution. Yet, previous research suggested impaired air-conditioning in Homo challenging respiratory adaptations based on computational fluid dynamics (CFD) and airflow simulations. Here we improved CFD model at the inflow region and also carried out three-dimensional (3D) geometric morphometrics to address the hypothesis of impaired air-conditioning in humans and species differences in airway shape. With the new CFD model we simulated pressure, velocity, and temperature changes in airflow of six adult humans and six chimpanzees and analyzed 164 semi-landmarks of 10 humans and 10 chimpanzees for 3D size and shape comparisons. Our finding shows significantly different internal 3D nasal airways. Also, species means of pressure, velocity, and temperature differed statistically significantly. However, form-related differences in temperature exchanges seem subtle and may question adaptive disadvantages. We rather support a hypothesis of craniofacial changes in the Australopithecus-Homo transition that are related to brain evolution and craniofacial integration with facial and nasal modifications that contribute to maintain respiratory adaptations related to air conditioning.

Autonomic and cardiac evaluation upon sub-therapeutic doxorubicin administration

Abstract Doxorubicin (DOX) is a chemotherapeutic agent that improves the survival and quality of life of patients with solid tumours. However, these improvements are counterbalanced by various dose-dependent side effects including cardiac dysfunction, which may occur in a subset of patients leading to treatment discontinuation. In addition, despite overall insufficiently studied, available data clearly show that women are more susceptible to drugs toxicity due to sex differences in drug metabolism or sensitivity. Regarding doxorubicin, apart its acute toxicity, women are also more vulnerable to late cardiotoxicity. Currently, there are no robust clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline and, despite treatment personalization, subclinical signs of toxicity are not yet well identified. Thus, in the present work, we sought to characterize the toxic effects of a sub-therapeutic dose of doxorubicin upon cardiovascular and autonomic function. For that, adult healthy female wistar rats (n=14), aged >3 months, were intraperitoneally treated with doxorubicin (2 mg/kg) at weekly intervals for up to 4 weeks. A control (Ctrl, n=7) group received saline solution 0,9% NaCl as a vehicle. Rats underwent an echocardiographic evaluation at 4 weeks. Blood pressure, heart rate and respiratory frequency were assessed in an acute experiment. Cardiovascular variability studies in the time-frequency domain (LF, HF and LF/HF calculation) and cardiorespiratory reflexes assessment were performed. T-Student test for paired observations was applied (level significance p<0.05) DOX-treated animals showed a severe bradypnea and hypotension, significant decrease in ejection fraction and fractional shortening, sympatho-inhibition and reduced baroreceptor reflex gain and chemoreflex sensitivity. Our functional results might be due to cellular respiratory dysfunction and vascular adaptations induced by doxorubicin via TNF alpha actions at central nervous system (CNS) and peripheral level. In fact, peripheral TNF alpha release elicits NO production, which through vasodilation will induce hypotension and baroreceptor reflex adjustments. Reinforcing these actions, and despite doxorubicin low ability to pass BBB, TNF alpha acting at CNS induces neuronal apoptosis and impairment of mitochondrial function which might also contribute to affect autonomic and respiratory function, expressed by a decreased chemoreflex sensitivity and sympathetic tone. In conclusion, sub-therapeutic doses of doxorubicin are able to produce per se the impairment of autonomic and cardiac functions. Thus, a tight monitoring of these functions in patients treated with therapeutic doses of doxorubicin is highly recommended. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fundação para a Ciência e a Tecnologia

Assessment of the Adequacy of Amateur Sports by the Functional Status of Students

Background: In the right dose, physical activity can bring health benefits. Objectives: To assess indicators of health and physical development of students engaged in amateur sports. Materials and methods: The study involved 30 male students aged 23.8 ± 0.3 years. We established their daily energy expenditures, integral indices characterizing their physical development, such as body weight, Pignet, strength, vitality, and Kerdo vegetative indices, endurance rate, circulatory efficiency, and the index of functional changes. We also analyzed cardiovascular system parameters including heart rate, systolic and diastolic blood pressure at rest, after exercise and after exercise recovery. Results of the biochemical blood test taken the next morning after workout were used to evaluate the status of functions and systems of the body. Results: Energy expenditures amounted to 3,665.5 ± 37.3 kcal. Students were physically strong, their functional capabilities of the respiratory system and adaptation to sports (according to the activity of the parasympathetic autonomic nervous system) were found satisfactory while their physical activity was assessed as high (hard work). In the body, catabolic processes prevailed, and the level of cortisol exceeding the norm in 50.0 % of the subjects indicated stress. Inadequacy of physical exercises was evidenced by the index of functional changes (in 57.7 % of the students adaptation was in the state of functional stress); reaction of the cardiovascular system (endurance and heart rates, circulatory efficiency, creatine kinase MB, troponin-1, ALT, and LDH); increased erythropoiesis; hormonal changes (cortisol, testosterone); changes in the metabolism of proteins (total protein, urea, uric acid), fats (total cholesterol, high- and low-density lipoproteins), and hormones (cortisol, testosterone); signs of an early stage of anemia (erythrocytes, total protein, ferritin). Conclusion: The use of the methodology for assessing the functional status of the human body by integral and biochemical criteria during recovery period after exercise enables pre-nosology diagnostics and prevention of health disorders during active sports.

Prognosticul fetal în operația cezariană

When deciding on a caesarean section, perinatologists should consider the consequences for the newborn. Studies show that caesarean section modifies adaptation to extrauterine life and is associated with risks of neonatal complications. Other determining factors for the condition and future of the newborn (gestational age, the existence of labor before cesarean section, anesthesia etc.) are not to be neglected. This article reviews the elements of the neonatal respiratory adaptation physiology, which are essential to understanding the clinical complications attributed to the mode of birth, and proposes a reconsideration of neonatal morbimortality after cesarean section.