Abstract: This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model for assessing predicted versus observed physiological responses. A group of individuals with diverse Science Technology Engineering Mathematics (STEM) backgrounds conducted a hypobaric training session to an altitude up to 22,000 ft (FL220) or 6,705 meters, where heart rate (HR), breathing rate (BR) and core temperature (Tc) were monitored with the use of a chest strap sensor pre and post HH exposure. A pulse oximeter registered levels of saturation of oxygen (SpO2), number and duration of desaturations during the HH chamber flight. Hypoxia symptoms as described by the SACs during the HH training session were also registered. This data allowed to generate a preliminary predictive model of the oxygen desaturation and O2 pressure curve for each subject, which consists of a sixth-order polynomial fit during exposure, and a fifth or fourth-order polynomial fit during recovery. Data analysis showed that HR and BR showed no significant differences between pre and post HH exposure in most of the SACs, while Tc measures showed slight but consistent decrement changes. All subjects registered SpO2 greater than 94% for the majority of their individual HH exposures, but all of them presented at least one clinically significant desaturation (SpO2 < 85% for more than 5 seconds) and half of the individuals showed SpO2 below 87% for at least 30% of their HH exposure time. Finally, real time collection of HH symptoms presented temperature somatosensory perceptions (SP) for 65% of individuals, and task-focus issues for 52.5% of individuals as the most common HH indications. 95% of the subjects experienced HH onset symptoms below FL180; all participants achieved full recovery of HH symptoms within 1 minute of donning their O2 mask. The current HH study performed on this group of individuals suggests a rapid and fully reversible physiologic response after HH exposure as expected and obtained in previous studies. Our data showed consistent results between predicted versus observed SpO2 curves during HH suggesting a mathematical function that may be used to model HH performance deficiencies. During the HH study, real-time HH symptoms were registered providing evidenced SP and task focusing as the earliest and most common indicators. Finally, an assessment of HH signs of symptoms in a group of heterogeneous, non-pilot individuals showed similar results to previous studies in homogeneous populations of pilots.
Abstract: Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of the present study is to characterize different physiologic variables in a population of STEM practitioners during an aerobatic flight. Cardiovascular and pulmonary responses were determined in Science Astronaut Candidates (SACs) during unusual attitude aerobatic flight indoctrination. Physiologic data recordings from 20 subjects participating in high-G flight training were analyzed. These recordings were registered by wearable sensor-vest that monitored electrocardiographic tracings (ECGs), signs of dysrhythmias or other electric disturbances during all the flight. The same cardiovascular parameters were also collected approximately 10 min pre-flight, during each high-G/unusual attitude maneuver and 10 min after the flights. The ratio (pre-flight/in-flight/post-flight) of the cardiovascular responses was calculated for comparison of inter-individual differences. The resulting tracings depicting the cardiovascular responses of the subjects were compared against the G-loads (Gs) during the aerobatic flights to analyze cardiovascular variability aspects and fluid/pressure shifts due to the high Gs. In-flight ECG revealed cardiac variability patterns associated with rapid Gs onset in terms of reduced heart rate (HR) and some scattered dysrhythmic patterns (15% premature ventricular contractions-type) that were considered as triggered physiological responses to high-G/unusual attitude training and some were considered as instrument artifact. Variation events were observed in subjects during the +Gz and –Gz maneuvers and these may be due to preload and afterload, sudden shift. Our data reveal that aerobatic flight influenced the breathing rate of the subject, due in part by the various levels of energy expenditure due to the increased use of muscle work during these aerobatic maneuvers. Noteworthy was the high heterogeneity in the different physiological responses among a relatively small group of SACs exposed to similar aerobatic flights with similar Gs exposures. The cardiovascular responses clearly demonstrated that SACs were subjected to significant flight stress. Routine ECG monitoring during high-G/unusual attitude flight training is recommended to capture pathology underlying dangerous dysrhythmias in suborbital flight safety. More research is currently being conducted to further facilitate the development of robust medical screening, medical risk assessment approaches, and suborbital flight training in the context of the evolving commercial human suborbital spaceflight industry. A more mature and integrative medical assessment method is required to understand the physiology state and response variability among highly diverse populations of prospective suborbital flight participants.
Abstract: The aim of this study is to assesses the lifting capabilities of persons experiencing hypoxia. It also examines the behavior of the physiological response induced through the lifting process related to changing in the hypoxia and lifting frequency variables. For this purpose, the study performed two consecutive tests by using; (1) training and acclimatization; and (2) an actual collection of data. A total of 10 male students from King Saud University, Kingdom of Saudi Arabia, were recruited in the study. A two-way repeated measures design, with two independent variables (ambient oxygen (15%, 18% and 21%)) and lifting frequency (1 lift/min and 4 lifts/min) and four dependent variables i.e., maximum acceptable weight of lift (MAWL), Electromyography (EMG) of four muscle groups (anterior deltoid, trapezius, biceps brachii, and erector spinae), rating of perceived exertion (RPE), and rating of oxygen feeling (ROF) were used in this study. The results show that lifting frequency has significantly impacted the MAWL and muscles’ activities. The oxygen content had a significant effect on the RPE and ROE. The study has revealed that acclimatization and training sessions significantly reduce the effect of the hypoxia on the human physiological parameters during the manual materials handling tasks.
Abstract: Human soft tissue is loaded and deformed by any
activity, an effect known as a stress-strain relationship, and is often
described by a load and tissue elongation curve. Several advances
have been made in the fields of biology and mechanics of soft human
tissue. However, there is limited information available on in vivo
tissue mechanical characteristics and behavior. Confident mechanical
properties of human soft tissue cannot be extrapolated from e.g.
animal testing. Thus, there is need for non invasive methods to
analyze mechanical characteristics of soft human tissue. In the present
study, the internal mechanical conditions of the lower limb, which
is subject to an external load, is studied by use of the finite element
method. A detailed finite element model of the lower limb is made
possible by use of MRI scans. Skin, fat, bones, fascia and muscles
are represented separately and the material properties for them are
obtained from literature. Previous studies have been shown to address
macroscopic deformation features, e.g. indentation depth, to a large
extent. However, the detail in which the internal anatomical features
have been modeled does not reveal the critical internal strains that
may induce hypoxia and/or eventual tissue damage. The results of the
present study reveals that lumped material models, i.e. averaging of
the material properties for the different constituents, does not capture
regions of critical strains in contrast to more detailed models.
Abstract: Kidney cancer is the most lethal urological cancer
accounting for 3% of adult malignancies. VHL, a tumor-suppressor
gene, is best known to be associated with renal cell carcinoma
(RCC). The VHL functions as negative regulator of hypoxia inducible
factors. Recent sequencing efforts have identified several novel
frequent mutations of histone modifying and chromatin remodeling
genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The
PBRM1 gene encodes the BAF180 protein, which involved in
transcriptional activation and repression of selected genes. SETD2
encodes a histone methyltransferase, which may play a role in
suppressing tumor development. In this study, RNAs of 30 paired
tumor and normal samples that were grouped according to the types
of kidney cancer and clinical characteristics of patients, including
gender and average age were examined by RT-PCR, SSCP and
sequencing techniques. VHL, PBRM1 and SETD2 expressions were
relatively down-regulated. However, statistically no significance was
found (Wilcoxon signed rank test, p>0.05). Interestingly, no mutation
was observed on the contrary of previous studies. Understanding the
molecular mechanisms involved in the pathogenesis of RCC has
aided the development of molecular-targeted drugs for kidney cancer.
Further analysis is required to identify the responsible genes rather
than VHL, PBRM1 and SETD2 in kidney cancer.
Abstract: Multipotent mesenchymal stromal cells (MSCs)
possess immunomodulatory properties. The effect of MSCs on the
crucial cellular immunity compartment – T-cells is of a special
interest. It is known that MSC tissue niche and expected milieu of
their interaction with T- cells are characterized by low oxygen
concentration, whereas the in vitro experiments usually are carried
out at a much higher ambient oxygen (20%). We firstly evaluated
immunomodulatory effects of MSCs on T-cells at tissue-related
oxygen (5%) after interaction implied cell-to-cell contacts and
paracrine factors only. It turned out that MSCs under reduced oxygen
can effectively suppress the activation and proliferation of PHAstimulated
T-cells and can provoke decrease in the production of
proinflammatory and increase in anti-inflammatory cytokines. In
hypoxia some effects were amplified (inhibition of proliferation, antiinflammatory
cytokine profile shift). This impact was more evident
after direct cell-to-cell interaction; lack of intercellular contacts could
revoke the potentiating effect of hypoxia.
Abstract: Upper gastrointestinal endoscopy is a commonly performed diagnostic and therapeutic procedure and has many adverse effects like cardiopulmonary complications, complications related to sedation, infectious complications, bleeding and perforation. So this study was undertaken to evaluate important variables like patient’s age, gender and stage of the procedure in relation to the cardiopulmonary changes during diagnostic upper gastrointestinal endoscopy by monitoring oxygen saturation, blood pressure, heart rate and electrocardiogram. This is a prospective longitudinal hospital based study involving a total of 140 consecutive patients, at Sri. B. M. Patil Medical College, Hospital and Research Centre. Cardiopulmonary changes during upper gastrointestinal endoscopy are more common in the age groups of 51-60 years, with equal frequency in both male and female. Oxygen saturation levels decreased by about 4% in both sexes during introduction of endoscopy. Mild to moderate hypoxia was found in 32% of the study group. Severe hypoxia was found in 5% of the patients, mostly in those patients who are above 50 years of age. Tachycardia was noted in 88% of the study group patients. Blood pressure increased to hypertension levels in 22 patients (15.7%) which returned to normal within few minutes after the procedure. S-T depression was noticed in 4% of patients and T wave inversion in 8% of patients during upper gastrointestinal endoscopy. All these changes disappeared after 10 minutes after the endoscopy. Cardiopulmonary changes are common during upper gastrointestinal endoscopy. Maximum changes in oxygen saturation, heart rate and blood pressure occurred immediately after the introduction of endoscope. The cardiopulmonary changes did not manifest into any identifiable clinical symptoms. The rate of recovery was faster in younger age groups and women.
Abstract: Hypoxia has negative effects on growth and crop yield, its severity is so varied depending on crop growth stages, duration of hypoxia and crop species. The objective was to evaluate the sensitive growth stage and the duration of hypoxia negatively affecting growth and yield of waxy corn. Pot experiment was conducted using a split plot in randomized complete block with 3 growth stages: V3 (3-4 true leaves), V7 (7-8 true leaves) and R1 (silking stage), and 3 hypoxic durations: 6, 9 and 12 days, in an open –ended outdoor greenhouse during January to March 2013. The results revealed that different growth stages had significantly (p < 0.5) different responses to hypoxia, seeing that the sensitive growth stage affecting plant height, yield and yield components was mostly detected in V7 growth stage whereas leaf greenness and days to silking were sensitive to hypoxia at R1 growth stage. Different hypoxic durations significantly affected yield and yield components, hypoxic duration of 12 days showed the most negative effect greater than the others. In this present study, it can be concluded that waxy corn plants were waterlogged at V7 growth stage for 12 days had the most negative effect on yield and yield components.
Abstract: Human genome is not only the evolutionary
summation of all advantageous events, but also houses lesions of
deleterious foot prints. A single gene mutation sometimes may
express multiple consequences in numerous tissues and a linear
relationship of the genotype and the phenotype may often be obscure.
ß Thalassemia minor, a transfusion independent mild anaemia,
coupled with environment among other factors may articulate into
phenotypic pleotropy with Hypocholesterolemia, Vitamin D
deficiency, Tissue hypoxia, Hyper-parathyroidism and Psychological
alterations. Occurrence of Pancreatic insufficiency, resultant
steatorrhoea, Vitamin-D (25-OH) deficiency (13.86 ngm/ml) with
Hypocholesterolemia (85mg/dl) in a 30 years old male ß Thal-minor
patient (Hemoglobin 11mg/dl with Fetal Hemoglobin 2.10%, Hb A2
4.60% and Hb Adult 84.80% and altered Hemogram) with increased
Para thyroid hormone (62 pg/ml) & moderate Serum Ca+2
(9.5mg/ml) indicate towards a cascade of phenotypic pleotropy
where the ß Thalassemia mutation ,be it in the 5’ cap site of the
mRNA , differential splicing etc in heterozygous state is effecting
several metabolic pathways. Compensatory extramedulary
hematopoiesis may not coped up well with the stressful life style of
the young individual and increased erythropoietic stress with high
demand for cholesterol for RBC membrane synthesis may have
resulted in Hypocholesterolemia.Oxidative stress and tissue hypoxia
may have caused the pancreatic insufficiency, leading to Vitamin D
deficiency. This may in turn have caused the secondary
hyperparathyroidism to sustain serum Calcium level. Irritability and
stress intolerance of the patient was a cumulative effect of the vicious
cycle of metabolic compromises. From these findings we propose
that the metabolic deficiencies in the ß Thalassemia mutations may
be considered as the phenotypic display of the pleotropy to explain
the genetic epidemiology.
According to the recommendations from the NIH Workshop on
Gene-Environment Interplay in Common Complex Diseases: Forging
an Integrative Model, study design of observations should be
informed by gene-environment hypotheses and results of a study
(genetic diseases) should be published to inform future hypotheses.
Variety of approaches is needed to capture data on all possible
aspects, each of which is likely to contribute to the etiology of
disease. Speakers also agreed that there is a need for development of
new statistical methods and measurement tools to appraise
information that may be missed out by conventional method where
large sample size is needed to segregate considerable effect.
A meta analytic cohort study in future may bring about significant
insight on to the title comment.