Sample records for normal physiologic range

  1. Measurement of Physiologic Glucose Levels Using Raman Spectroscopy in a Rabbit Aqueous Humor Model

    NASA Technical Reports Server (NTRS)

    Lambert, J.; Storrie-Lombardi, M.; Borchert, M.

    1998-01-01

    We have elecited a reliable glucose signature in mammalian physiological ranges using near infrared Raman laser excitation at 785 nm and multivariate analysis. In a recent series of experiments we measured glucose levels in an artificial aqueous humor in the range from 0.5 to 13X normal values.

  2. Multiorgan insulin sensitivity in lean and obese subjects.

    PubMed

    Conte, Caterina; Fabbrini, Elisa; Kars, Marleen; Mittendorfer, Bettina; Patterson, Bruce W; Klein, Samuel

    2012-06-01

    To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m(2), mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m(2)) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. In obese subjects, palmitate and glucose R(a) in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose R(a) was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate R(a) (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate R(a) and glucose R(a) were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose R(d) was greater in lean than obese subjects across the entire physiological range of plasma insulin. Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.

  3. A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood.

    PubMed

    Lee, Chang-Joon; Ngo, Jennifer P; Kar, Saptarshi; Gardiner, Bruce S; Evans, Roger G; Smith, David W

    2017-08-01

    To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries, and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly, our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4-1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84-3.36%), and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2-4.8%). Under normal physiological conditions, blood Po 2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial Po 2 is predicted to fall most rapidly from Strahler order 4 , under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration, and some cardiovascular disease states. Copyright © 2017 the American Physiological Society.

  4. Electrocardiographic consequences of a peripatetic lifestyle in gray wolves (Canis lupus)

    USGS Publications Warehouse

    Constable, Peter; Hinchcliff, Ken; Demma, Nick; Callahan, Margaret; Dale, Bruce W.; Fox, Kevin; Adams, Layne G.; Wack, Ray; Kramer, Lynn

    1998-01-01

    Cardiac chamber enlargement and hypertrophy are normal physiologic responses to repetitive endurance exercise activity in human beings and domestic dogs. Whether similar changes occur in wild animals as a consequence of increased activity is unknown. We found that free-ranging gray wolves (Canis lupus, n=11), the archetypical endurance athlete, have electrocardiographic evidence of cardiac chamber enlargement and hypertrophy relative to sedentary captive gray wolves (n=20), as demonstrated by significant increases in QRS duration, QT interval, and QT interval corrected for heart rate, a tendency towards increased Q, R, and S wave voltages in all leads, and a significant decrease in heart rate. We conclude that exercise activity level and therefore lifestyle affects physiologic variables in wild animals. An immediate consequence of this finding is that physiologic measurements obtained from a captive wild-animal population with reduced exercise activity level may not accurately reflect the normal physiologic state for free-ranging members of the same species.

  5. A creatinine biosensor based on admittance measurement

    NASA Astrophysics Data System (ADS)

    Ching, Congo Tak-Shing; Sun, Tai-Ping; Jheng, Deng-Yun; Tsai, Hou-Wei; Shieh, Hsiu-Li

    2015-08-01

    Regular check of blood creatinine level is very important as it is a measurement of renal function. Therefore, the objective of this study is to develop a simple and reliable creatinine biosensor based on admittance measurement for precise determination of creatinine. The creatinine biosensor was fabricated with creatinine deiminase immobilized on screen-printed carbon electrodes. Admittance measurement at a specific frequency ranges (22.80 - 84.71 Hz) showed that the biosensor has an excellent linear (r2 > 0.95) response range (50 - 250 uM), which covers the normal physiological and pathological ranges of blood creatinine levels. Intraclass correlation coefficient (ICC) showed that the biosensor has excellent reliability and validity (ICC = 0.98). In conclusion, a simple and reliable creatinine biosensor was developed and it is capable of precisely determining blood creatinine levels in both the normal physiological and pathological ranges.

  6. Tissue Doppler Imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects

    PubMed Central

    Galanti, Giorgio; Toncelli, Loira; Del Furia, Francesca; Stefani, Laura; Cappelli, Brunello; De Luca, Alessio; Vono, Maria Concetta Roberta

    2009-01-01

    Background Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH. The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population. Methods we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 ± 19.7 vs 134.5 ± 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both. Results Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 ± 3.1 cm/sec; E/E' 7.8 ± 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 ± 2.4 cm/sec; E/E' 10.6 ± 3.2), and with E' and E/E' statistically different in the two groups (p < .001). Conclusion Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy. PMID:19845938

  7. Evaluating acoustic speaker normalization algorithms: evidence from longitudinal child data.

    PubMed

    Kohn, Mary Elizabeth; Farrington, Charlie

    2012-03-01

    Speaker vowel formant normalization, a technique that controls for variation introduced by physical differences between speakers, is necessary in variationist studies to compare speakers of different ages, genders, and physiological makeup in order to understand non-physiological variation patterns within populations. Many algorithms have been established to reduce variation introduced into vocalic data from physiological sources. The lack of real-time studies tracking the effectiveness of these normalization algorithms from childhood through adolescence inhibits exploration of child participation in vowel shifts. This analysis compares normalization techniques applied to data collected from ten African American children across five time points. Linear regressions compare the reduction in variation attributable to age and gender for each speaker for the vowels BEET, BAT, BOT, BUT, and BOAR. A normalization technique is successful if it maintains variation attributable to a reference sociolinguistic variable, while reducing variation attributable to age. Results indicate that normalization techniques which rely on both a measure of central tendency and range of the vowel space perform best at reducing variation attributable to age, although some variation attributable to age persists after normalization for some sections of the vowel space. © 2012 Acoustical Society of America

  8. Physiology and pathophysiology of potassium homeostasis.

    PubMed

    Palmer, Biff F; Clegg, Deborah J

    2016-12-01

    Total body potassium content and proper distribution of potassium across the cell membrane is of critical importance for normal cellular function. Potassium homeostasis is maintained by several different methods. In the kidney, total body potassium content is achieved by alterations in renal excretion of potassium in response to variations in intake. Insulin and beta-adrenergic tone play critical roles in maintaining the internal distribution of potassium under normal conditions. Despite homeostatic pathways designed to maintain potassium levels within the normal range, disorders of altered potassium homeostasis are common. The clinical approach to designing effective treatments relies on understanding the pathophysiology and regulatory influences which govern the internal distribution and external balance of potassium. Here we provide an overview of the key regulatory aspects of normal potassium physiology. This review is designed to provide an overview of potassium homeostasis as well as provide references of seminal papers to guide the reader into a more in depth discussion of the importance of potassium balance. This review is designed to be a resource for educators and well-informed clinicians who are teaching trainees about the importance of potassium balance. Copyright © 2016 the American Physiological Society.

  9. Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

    PubMed

    Kogan, Samuel; Sood, Aditya; Garnick, Mark S

    2017-04-01

    Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.

  10. Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging.

    PubMed

    Demirci, Emre; Sahin, Onur Erdem; Ocak, Meltem; Akovali, Burak; Nematyazar, Jamal; Kabasakal, Levent

    2016-11-01

    Ga-PSMA-11 is a novel PET tracer suggested to be used for imaging of advanced prostate cancer. In this study, we aimed to present a detailed biodistribution of Ga-PSMA-11, including physiological and benign variants of prostate-specific membrane antigen (PSMA) imaging. We carried out a retrospective analysis of 40 patients who underwent PSMA PET/computed tomography (CT) imaging and who had no evidence of residual or metastatic disease on the scans. In addition, 16 patients who underwent PSMA PET/CT imaging with any indication other than prostate cancer were included in the study to evaluate physiological uptake in the normal prostate gland. The median, minimum-maximum, and mean standardized uptake value (SUV) values were calculated for visceral organs, bone marrow and lymph nodes, and mucosal areas. Any physiological variants or benign lesions with Ga-PSMA-11 were also noted. Ga-PSMA-11 uptake was noted in the kidneys, parotid and submandibular glands, duodenum, small intestines, spleen, liver, and lacrimal glands, and mucosal uptake in the nasopharynx, vocal cords, pancreas, stomach, mediastinal blood pool, thyroid gland, adrenal gland, rectum, vertebral bone marrow, and testes. Celiac ganglia showed slight Ga-PSMA-11 uptake in 24 of 40 patients without the presence of any other pathologic lymph nodes in abdominal and pelvic areas. Variable uptake of Ga-PSMA-11 was observed in calcified choroid plexus, a thyroid nodule, an adrenal nodule, axillary lymph nodes and celiac ganglia, occasional osteophytes, and gallbladder. The patient group with PSMA PET/CT for indications other than prostate cancer (n=16) showed a slight radiotracer uptake in normal prostate gland (SUVmax: 5.5±1.6, range: 3.5-8.3). This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

  11. Sensitivity analysis of physiological factors in space habitat design

    NASA Technical Reports Server (NTRS)

    Billingham, J.

    1982-01-01

    The costs incurred by design conservatism in space habitat design are discussed from a structural standpoint, and areas of physiological research into less than earth-normal conditions that offer the greatest potential decrease in habitat construction and operating costs are studied. The established range of human tolerance limits is defined for those physiological conditions which directly affect habitat structural design. These entire ranges or portions thereof are set as habitat design constraints as a function of habitat population and degree of ecological closure. Calculations are performed to determine the structural weight and cost associated with each discrete population size and its selected environmental conditions, on the basis of habitable volume equivalence for four basic habitat configurations: sphere, cylinder with hemispherical ends, torus, and crystal palace.

  12. Normal range of human dietary sodium intake: a perspective based on 24-hour urinary sodium excretion worldwide.

    PubMed

    McCarron, David A; Kazaks, Alexandra G; Geerling, Joel C; Stern, Judith S; Graudal, Niels A

    2013-10-01

    The recommendation to restrict dietary sodium for management of hypertensive cardiovascular disease assumes that sodium intake exceeds physiologic need, that it can be significantly reduced, and that the reduction can be maintained over time. In contrast, neuroscientists have identified neural circuits in vertebrate animals that regulate sodium appetite within a narrow physiologic range. This study further validates our previous report that sodium intake, consistent with the neuroscience, tracks within a narrow range, consistent over time and across cultures. Peer-reviewed publications reporting 24-hour urinary sodium excretion (UNaV) in a defined population that were not included in our 2009 publication were identified from the medical literature. These datasets were combined with those in our previous report of worldwide dietary sodium consumption. The new data included 129 surveys, representing 50,060 participants. The mean value and range of 24-hour UNaV in each of these datasets were within 1 SD of our previous estimate. The combined mean and normal range of sodium intake of the 129 datasets were nearly identical to that we previously reported (mean = 158.3±22.5 vs. 162.4±22.4 mmol/d). Merging the previous and new datasets (n = 190) yielded sodium consumption of 159.4±22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d). Human sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries. As documented here, this range is determined by physiologic needs rather than environmental factors. Future guidelines should be based on this biologically determined range.

  13. Individual Colorimetric Observer Model

    PubMed Central

    Asano, Yuta; Fairchild, Mark D.; Blondé, Laurent

    2016-01-01

    This study proposes a vision model for individual colorimetric observers. The proposed model can be beneficial in many color-critical applications such as color grading and soft proofing to assess ranges of color matches instead of a single average match. We extended the CIE 2006 physiological observer by adding eight additional physiological parameters to model individual color-normal observers. These eight parameters control lens pigment density, macular pigment density, optical densities of L-, M-, and S-cone photopigments, and λmax shifts of L-, M-, and S-cone photopigments. By identifying the variability of each physiological parameter, the model can simulate color matching functions among color-normal populations using Monte Carlo simulation. The variabilities of the eight parameters were identified through two steps. In the first step, extensive reviews of past studies were performed for each of the eight physiological parameters. In the second step, the obtained variabilities were scaled to fit a color matching dataset. The model was validated using three different datasets: traditional color matching, applied color matching, and Rayleigh matches. PMID:26862905

  14. Baseline Physiologic and Psychosocial Characteristics of Transgender Youth Seeking Care for Gender Dysphoria

    PubMed Central

    Olson, Johanna; Schrager, Sheree M.; Belzer, Marvin; Simons, Lisa K.; Clark, Leslie F.

    2016-01-01

    Purpose The purpose of this study was to describe baseline characteristics of participants in a prospective observational study of transgender youth (aged 12–24 years) seeking care for gender dysphoria at a large, urban transgender youth clinic. Methods Eligible participants presented consecutively for care at between February 2011 and June 2013 and completed a computer-assisted survey at their initial study visit. Physiologic data were abstracted from medical charts. Data were analyzed by descriptive statistics, with limited comparisons between transmasculine and transfeminine participants. Results A total of 101 youth were evaluated for physiologic parameters, 96 completed surveys assessing psychosocial parameters. About half (50.5%) of the youth were assigned a male sex at birth. Baseline physiologic values were within normal ranges for assigned sex at birth. Youth recognized gender incongruence at a mean age of 8.3 years (standard deviation = 4.5), yet disclosed to their family much later (mean = 17.1; standard deviation = 4.2). Gender dysphoria was high among all participants. Thirty-five percent of the participants reported depression symptoms in the clinical range. More than half of the youth reported having thought about suicide at least once in their lifetime, and nearly a third had made at least one attempt. Conclusions Baseline physiologic parameters were within normal ranges for assigned sex at birth. Transgender youth are aware of the incongruence between their internal gender identity and their assigned sex at early ages. Prevalence of depression and suicidality demonstrates that youth may benefit from timely and appropriate intervention. Evaluation of these youth over time will help determine the impact of medical intervention and mental health therapy. PMID:26208863

  15. Baseline Physiologic and Psychosocial Characteristics of Transgender Youth Seeking Care for Gender Dysphoria.

    PubMed

    Olson, Johanna; Schrager, Sheree M; Belzer, Marvin; Simons, Lisa K; Clark, Leslie F

    2015-10-01

    The purpose of this study was to describe baseline characteristics of participants in a prospective observational study of transgender youth (aged 12-24 years) seeking care for gender dysphoria at a large, urban transgender youth clinic. Eligible participants presented consecutively for care at between February 2011 and June 2013 and completed a computer-assisted survey at their initial study visit. Physiologic data were abstracted from medical charts. Data were analyzed by descriptive statistics, with limited comparisons between transmasculine and transfeminine participants. A total of 101 youth were evaluated for physiologic parameters, 96 completed surveys assessing psychosocial parameters. About half (50.5%) of the youth were assigned a male sex at birth. Baseline physiologic values were within normal ranges for assigned sex at birth. Youth recognized gender incongruence at a mean age of 8.3 years (standard deviation = 4.5), yet disclosed to their family much later (mean = 17.1; standard deviation = 4.2). Gender dysphoria was high among all participants. Thirty-five percent of the participants reported depression symptoms in the clinical range. More than half of the youth reported having thought about suicide at least once in their lifetime, and nearly a third had made at least one attempt. Baseline physiologic parameters were within normal ranges for assigned sex at birth. Transgender youth are aware of the incongruence between their internal gender identity and their assigned sex at early ages. Prevalence of depression and suicidality demonstrates that youth may benefit from timely and appropriate intervention. Evaluation of these youth over time will help determine the impact of medical intervention and mental health therapy. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  16. A three-dimensional printed patient-specific scaphoid replacement: a cadaveric study.

    PubMed

    Honigmann, Philipp; Schumacher, Ralf; Marek, Romy; Büttner, Franz; Thieringer, Florian; Haefeli, Mathias

    2018-05-01

    We present our first cadaveric test results of a three-dimensional printed patient-specific scaphoid replacement with tendon suspension, which showed normal motion behaviour and preservation of a stable scapholunate interval during physiological range of motion.

  17. Extracellular calcium controls the expression of two different forms of ripple-like hippocampal oscillations.

    PubMed

    Aivar, Paloma; Valero, Manuel; Bellistri, Elisa; Menendez de la Prida, Liset

    2014-02-19

    Hippocampal high-frequency oscillations (HFOs) are prominent in physiological and pathological conditions. During physiological ripples (100-200 Hz), few pyramidal cells fire together coordinated by rhythmic inhibitory potentials. In the epileptic hippocampus, fast ripples (>200 Hz) reflect population spikes (PSs) from clusters of bursting cells, but HFOs in the ripple and the fast ripple range are vastly intermixed. What is the meaning of this frequency range? What determines the expression of different HFOs? Here, we used different concentrations of Ca(2+) in a physiological range (1-3 mM) to record local field potentials and single cells in hippocampal slices from normal rats. Surprisingly, we found that this sole manipulation results in the emergence of two forms of HFOs reminiscent of ripples and fast ripples recorded in vivo from normal and epileptic rats, respectively. We scrutinized the cellular correlates and mechanisms underlying the emergence of these two forms of HFOs by combining multisite, single-cell and paired-cell recordings in slices prepared from a rat reporter line that facilitates identification of GABAergic cells. We found a major effect of extracellular Ca(2+) in modulating intrinsic excitability and disynaptic inhibition, two critical factors shaping network dynamics. Moreover, locally modulating the extracellular Ca(2+) concentration in an in vivo environment had a similar effect on disynaptic inhibition, pyramidal cell excitability, and ripple dynamics. Therefore, the HFO frequency band reflects a range of firing dynamics of hippocampal networks.

  18. Anorectal physiology measurements are of no value in clinical practice. True or false?

    PubMed Central

    Carty, N. J.; Moran, B.; Johnson, C. D.

    1994-01-01

    This article examines whether there is any clinical value in anorectal physiology measurements. The function of the human rectum is poorly understood and the factors which affect function of the anal sphincters are complex. Several laboratories have reported results of anorectal physiology measurements, but there is extensive variation between normal values in different laboratories. It is argued that anorectal physiology measurements fail to meet the criteria of a useful clinical test: 1. It is not widely available to clinicians; 2. It is not possible to establish a reproducible normal range; 3. Abnormal measurements do not correlate with disease entities or explain symptoms; 4. The results are often unhelpful in diagnosis and management; 5. Clinical outcome after intervention does not correlate with alteration in the measurements obtained. On the other hand it can be argued that anorectal physiology measurements do provide information that assists in the management of conditions such as constipation, anismus, Hirschsprung's disease, faecal incontinence and tenesmus. Management based on biofeedback modification of physiological responses requires these techniques as part of the biofeedback system. There is evidence that this may be appropriate in anismus and solitary rectal ulcer syndrome. However, the assessment of these difficult conditions and the interpretation of the results are probably at present best confined to specialist units. PMID:8074392

  19. Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

    PubMed

    Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

    2014-01-01

    There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to human evolution, physiology and disease.

  20. Relating normalization to neuronal populations across cortical areas.

    PubMed

    Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

    2016-09-01

    Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

  1. Contrasting physiological plasticity in response to environmental stress within different cnidarians and their respective symbionts

    NASA Astrophysics Data System (ADS)

    Hoadley, Kenneth D.; Pettay, Daniel. T.; Dodge, Danielle; Warner, Mark E.

    2016-06-01

    Given concerns surrounding coral bleaching and ocean acidification, there is renewed interest in characterizing the physiological differences across the multiple host-algal symbiont combinations commonly found on coral reefs. Elevated temperature and CO2 were used to compare physiological responses within the scleractinian corals Montipora hirsuta ( Symbiodinium C15) and Pocillopora damicornis ( Symbiodinium D1), as well as the corallimorph (a non-calcifying anthozoan closely related to scleractinians) Discosoma nummiforme ( Symbiodinium C3). Several physiological proxies were affected more by temperature than CO2, including photochemistry, algal number and cellular chlorophyll a. Marked differences in symbiont number, chlorophyll and volume contributed to distinctive patterns of chlorophyll absorption among these animals. In contrast, carbon fixation either did not change or increased under elevated temperature. Also, the rate of photosynthetically fixed carbon translocated to each host did not change, and the percent of carbon translocated to the host increased in the corallimorph. Comparing all data revealed a significant negative correlation between photosynthetic rate and symbiont density that corroborates previous hypotheses about carbon limitation in these symbioses. The ratio of symbiont-normalized photosynthetic rate relative to the rate of symbiont-normalized carbon translocation (P:T) was compared in these organisms as well as the anemone, Exaiptasia pallida hosting Symbiodinium minutum, and revealed a P:T close to unity ( D. nummiforme) to a range of 2.0-4.5, with the lowest carbon translocation in the sea anemone. Major differences in the thermal responses across these organisms provide further evidence of a range of acclimation potential and physiological plasticity that highlights the need for continued study of these symbioses across a larger group of host taxa.

  2. Fractal dynamics in physiology: Alterations with disease and aging

    PubMed Central

    Goldberger, Ary L.; Amaral, Luis A. N.; Hausdorff, Jeffrey M.; Ivanov, Plamen Ch.; Peng, C.-K.; Stanley, H. Eugene

    2002-01-01

    According to classical concepts of physiologic control, healthy systems are self-regulated to reduce variability and maintain physiologic constancy. Contrary to the predictions of homeostasis, however, the output of a wide variety of systems, such as the normal human heartbeat, fluctuates in a complex manner, even under resting conditions. Scaling techniques adapted from statistical physics reveal the presence of long-range, power-law correlations, as part of multifractal cascades operating over a wide range of time scales. These scaling properties suggest that the nonlinear regulatory systems are operating far from equilibrium, and that maintaining constancy is not the goal of physiologic control. In contrast, for subjects at high risk of sudden death (including those with heart failure), fractal organization, along with certain nonlinear interactions, breaks down. Application of fractal analysis may provide new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as to monitoring the aging process. Similar approaches show promise in assessing other regulatory systems, such as human gait control in health and disease. Elucidating the fractal and nonlinear mechanisms involved in physiologic control and complex signaling networks is emerging as a major challenge in the postgenomic era. PMID:11875196

  3. Temperature responses of exercizing dogs to infusion of electrolytes

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Kozlowski, S.; Nazar, K.; Kaciuba-Uscilko, H.; Brzezinska, Z.

    1974-01-01

    The effect of infusions with solutions of various ionic and osmotic composition on exercise temperature responses was studied in dogs who do not regulate their temperature by sweating. The results suggest an association between plasma Na+ and Ca++ level within the normal physiological range and the control of body temperature during exercise.

  4. The physiology of spacecraft and space suit atmosphere selection

    NASA Astrophysics Data System (ADS)

    Waligora, J. M.; Horrigan, D. J.; Nicogossian, A.

    The majority of the environmental factors which comprise the spacecraft and space suit environments can be controlled at "Earth normal" values, at optimum values, or at other values decided upon by spacecraft designers. Factors which are considered in arriving at control values and control ranges of these parameters include physiological, engineering, operational cost, and safety considerations. Several of the physiologic considerations, including hypoxia and hyperoxia, hypercapnia, temperature regulation, and decompression sickness are identified and their impact on space craft and space suit atmosphere selection are considered. The past experience in controlling these parameters in U.S. and Soviet spacecraft and space suits and the associated physiological responses are reviewed. Current areas of physiological investigation relating to environmental factors in spacecraft are discussed, particularly decompression sickness which can occur as a result of change in pressure from Earth to spacecraft or spacecraft to space suit. Physiological considerations for long-term lunar or Martian missions will have different impacts on atmosphere selection and may result in the selection of atmospheres different than those currently in use.

  5. Physiological and psychological effects of forest therapy on middle-aged males with high-normal blood pressure.

    PubMed

    Ochiai, Hiroko; Ikei, Harumi; Song, Chorong; Kobayashi, Maiko; Takamatsu, Ako; Miura, Takashi; Kagawa, Takahide; Li, Qing; Kumeda, Shigeyoshi; Imai, Michiko; Miyazaki, Yoshifumi

    2015-02-25

    Time spent walking and relaxing in a forest environment ("forest bathing" or "forest therapy") has well demonstrated anti-stress effects in healthy adults, but benefits for ill or at-risk populations have not been reported. The present study assessed the physiological and psychological effects of forest therapy (relaxation and stress management activity in the forest) on middle-aged males with high-normal blood pressure. Blood pressure and several physiological and psychological indices of stress were measured the day before and approximately 2 h following forest therapy. Both pre- and post-treatment measures were conducted at the same time of day to avoid circadian influences. Systolic and diastolic blood pressure (BP), urinary adrenaline, and serum cortisol were all significantly lower than baseline following forest therapy (p<0.05). Subjects reported feeling significantly more "relaxed" and "natural" according to the Semantic Differential (SD) method. Profile of Mood State (POMS) negative mood subscale scores for "tension-anxiety," "confusion," and "anger-hostility," as well as the Total Mood Disturbance (TMD) score were significantly lower following forest therapy. These results highlight that forest is a promising treatment strategy to reduce blood pressure into the optimal range and possibly prevent progression to clinical hypertension in middle-aged males with high-normal blood pressure.

  6. Thermal Stress

    DTIC Science & Technology

    2011-01-01

    can have a significant impact on normal physiological functioning if precipitous increases in core temperature are not adequately controlled with...anterior hypothalamusIntroduction Thermal stress can have a significant impact on normal physiological functioning if precipitous increases in core...fat and skin). The regulation of a relatively constant internal temperature is critical for normal physiological functioning of tissues and cells, as

  7. Autoimmune thyroid disease in pregnancy: a review.

    PubMed

    Galofre, Juan C; Davies, Terry F

    2009-11-01

    The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%-15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T(4)) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L.

  8. Autoimmune Thyroid Disease in Pregnancy: A Review

    PubMed Central

    Galofre, Juan C.

    2009-01-01

    Abstract The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%–15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T4) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L. PMID:19951221

  9. Phenotypic plasticity in the range-margin population of the lycaenid butterfly Zizeeria maha

    PubMed Central

    2010-01-01

    Background Many butterfly species have been experiencing the northward range expansion and physiological adaptation, probably due to climate warming. Here, we document an extraordinary field case of a species of lycaenid butterfly, Zizeeria maha, for which plastic phenotypes of wing color-patterns were revealed at the population level in the course of range expansion. Furthermore, we examined whether this outbreak of phenotypic changes was able to be reproduced in a laboratory. Results In the recently expanded northern range margins of this species, more than 10% of the Z. maha population exhibited characteristic color-pattern modifications on the ventral wings for three years. We physiologically reproduced similar phenotypes by an artificial cold-shock treatment of a normal southern population, and furthermore, we genetically reproduced a similar phenotype after selective breeding of a normal population for ten generations, demonstrating that the cold-shock-induced phenotype was heritable and partially assimilated genetically in the breeding line. Similar genetic process might have occurred in the previous and recent range-margin populations as well. Relatively minor modifications expressed in the tenth generation of the breeding line together with other data suggest a role of founder effect in this field case. Conclusions Our results support the notion that the outbreak of the modified phenotypes in the recent range-margin population was primed by the revelation of plastic phenotypes in response to temperature stress and by the subsequent genetic process in the previous range-margin population, followed by migration and temporal establishment of genetically unstable founders in the recent range margins. This case presents not only an evolutionary role of phenotypic plasticity in the field but also a novel evolutionary aspect of range expansion at the species level. PMID:20718993

  10. Functionality of empirical model-based predictive analytics for the early detection of hemodynamic instabilty.

    PubMed

    Summers, Richard L; Pipke, Matt; Wegerich, Stephan; Conkright, Gary; Isom, Kristen C

    2014-01-01

    Background. Monitoring cardiovascular hemodynamics in the modern clinical setting is a major challenge. Increasing amounts of physiologic data must be analyzed and interpreted in the context of the individual patient’s pathology and inherent biologic variability. Certain data-driven analytical methods are currently being explored for smart monitoring of data streams from patients as a first tier automated detection system for clinical deterioration. As a prelude to human clinical trials, an empirical multivariate machine learning method called Similarity-Based Modeling (“SBM”), was tested in an In Silico experiment using data generated with the aid of a detailed computer simulator of human physiology (Quantitative Circulatory Physiology or “QCP”) which contains complex control systems with realistic integrated feedback loops. Methods. SBM is a kernel-based, multivariate machine learning method that that uses monitored clinical information to generate an empirical model of a patient’s physiologic state. This platform allows for the use of predictive analytic techniques to identify early changes in a patient’s condition that are indicative of a state of deterioration or instability. The integrity of the technique was tested through an In Silico experiment using QCP in which the output of computer simulations of a slowly evolving cardiac tamponade resulted in progressive state of cardiovascular decompensation. Simulator outputs for the variables under consideration were generated at a 2-min data rate (0.083Hz) with the tamponade introduced at a point 420 minutes into the simulation sequence. The functionality of the SBM predictive analytics methodology to identify clinical deterioration was compared to the thresholds used by conventional monitoring methods. Results. The SBM modeling method was found to closely track the normal physiologic variation as simulated by QCP. With the slow development of the tamponade, the SBM model are seen to disagree while the simulated biosignals in the early stages of physiologic deterioration and while the variables are still within normal ranges. Thus, the SBM system was found to identify pathophysiologic conditions in a timeframe that would not have been detected in a usual clinical monitoring scenario. Conclusion. In this study the functionality of a multivariate machine learning predictive methodology that that incorporates commonly monitored clinical information was tested using a computer model of human physiology. SBM and predictive analytics were able to differentiate a state of decompensation while the monitored variables were still within normal clinical ranges. This finding suggests that the SBM could provide for early identification of a clinical deterioration using predictive analytic techniques. predictive analytics, hemodynamic, monitoring.

  11. ATM activation in normal human tissues and testicular cancer.

    PubMed

    Bartkova, Jirina; Bakkenist, Christopher J; Rajpert-De Meyts, Ewa; Skakkebaek, Niels E; Sehested, Maxwell; Lukas, Jiri; Kastan, Michael B; Bartek, Jiri

    2005-06-01

    The ATM kinase is a tumor suppressor and key regulator of biological responses to DNA damage. Cultured cells respond to genotoxic insults that induce DNA double-strand breaks by prompt activation of ATM through its autophosphorylation on serine 1981. However, whether ATM-S1981 becomes phosphorylated in vivo, for example during physiological processes that generate DSBs, is unknown. Here we produced phospho-specific monoclonal antibodies against S1981-phosphorylated ATM (pS-ATM), and applied them to immunohistochemical analyses of a wide range of normal human tissues and testicular tumors. Our data show that regardless of proliferation and differentiation, most human tissues contain only the S1981-nonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in the adult testes, cell types in which DSBs are generated during physiological V(D)J recombination and meiotic recombination, respectively. Among testicular germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in embryonal carcinomas, less in seminomas, and only modestly in teratomas and the pre-invasive carcinoma-in-situ stage. Compared with pS-ATM, phosphorylated histone H2AX (gammaH2AX), another DNA damage marker and ATM substrate, was detected in a higher proportion of cancer cells, and also in normal fetal gonocytes, and a wider range of adult spermatocyte differentiation stages. Collectively, our results strongly support the physiological relevance of the recently proposed model of ATM autoactivation, and provide further evidence for constitutive activation of the DNA damage machinery during cancer development. The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies.

  12. Mechanics of the Unusual Basilar Membrane in Gerbil

    NASA Astrophysics Data System (ADS)

    Kapuria, Santosh; Steele, Charles R.; Puria, Sunil

    2011-11-01

    The basilar membrane in gerbil differs from most other mammals, since its width and thickness show little variation from base to apex, and tympanic fiber layer in the pectinate zone forms a pronounced arch. Measurements indicate a quadratically increasing stiffness under point loading, which is contrary to the expected behavior of an arch. The plateau value has been considered to be the physiologically relevant stiffness, but it only occurs after 10-25 μm of deflection, whereas the normal physiological deflection is in the submicron range. The present work aims to resolve these contradictions by considering the mechanics of the geometric configuration.

  13. Glucose Counterregulatory Responses to Hypoglycemia

    PubMed Central

    Sprague, Jennifer E.; Arbeláez, Ana María

    2013-01-01

    The brain relies almost exclusively on glucose for fuel. Therefore, adequate uptake of glucose from the plasma is key for normal brain function and survival. Despite wide variations in glucose flux (i.e. fed state, fasting state, etc), blood glucose is maintained in a very narrow range. This is accomplished by a series of hormonal and physiologic responses. As a result, hypoglycemia is a rare occurrence in normal individuals. However, glucose counterregulatory responses are altered in patients with diabetes treated with insulin especially after repeated hypoglycemia or antecedent exercise. PMID:22783644

  14. Things Don’t Just Go Back to Normal: The Implications of Antenatal and Postpartum Physiology and Morphology for the Resumption of Fitness Testing

    DTIC Science & Technology

    2015-04-08

    September 2014 - April 2015 Things Don’t Just Go Back to Normal: The Implications of Antenatal and Postpartum Physiology and Morphology for the...physiology; morphology Unclassified Unclassified Unclassified UU 56 Marine Corps University/Command a (703) 784-3330 (Admin Office) United States Marine...MASTER OF MILITARY STUDIES Things Don’t Just Go Back to Normal: The Implications of Antenatal and Postpartum Physiology and Morphology for the

  15. Short-duration respirometry underestimates metabolic rate for discontinuous breathers.

    PubMed

    Winwood-Smith, Hugh S; White, Craig R

    2018-06-07

    Metabolic rate is commonly estimated from rates of gas exchange. An underappreciated factor that can influence estimates is patterns of pulmonary respiration. Amphibians display discontinuous respiratory patterns, often including long apnoeas, in addition to cutaneous gas exchange. The contribution of cutaneous exchange increases at low temperatures when metabolic rate is low. Due to the relatively low permeability of skin, measurements that disproportionately capture cutaneous exchange can produce underestimates of metabolic rate. The permeability of amphibian skin to CO 2 is greater than O 2 , therefore calculating the ratio of whole-animal CO 2 emission to O 2 uptake (the respiratory exchange ratio, RER) can be used to avoid underestimates of metabolic rate by ensuring that observed values of RER fall within the normal physiological range (∼0.7 to 1). Using data for cane toads Rhinella marina we show that short-duration measurements lead to underestimates of metabolic rate and overestimates of RER. At low temperatures this problem is exacerbated, requiring over 12 hours for RER to fall within the normal physiological range. Many published values of metabolic rate in animals that utilise cutaneous exchange may be underestimates. © 2018. Published by The Company of Biologists Ltd.

  16. Biodistribution of [(68)Ga]PSMA-HBED-CC in Patients with Prostate Cancer: Characterization of Uptake in Normal Organs and Tumour Lesions.

    PubMed

    Prasad, Vikas; Steffen, Ingo G; Diederichs, Gerd; Makowski, Marcus R; Wust, Peter; Brenner, Winfried

    2016-06-01

    The aim of this study was to determine the physiological and pathophysiological biodistribution of [(68)Ga]PSMA-HBED-CC (PSMA-11) ([(68)Ga]PSMA) in patients with prostate cancer (PCA) to establish the range of normal uptake in relevant organs and primary prostate tumours, locally recurrent PCA, lymph and bone metastases and other metastatic lesions. Additionally, we aimed to determine a cut-off uptake value for differentiation of primary tumours from normal prostate tissue. Overall, [(68)Ga]PSMA positron emission tomography/x-ray computed tomography (PET/CT) of 101 patients (mean age 69.1 years) with PCA was analysed retrospectively. For assessment of tracer biodistribution, maximum standardized uptake values (SUVmax) were calculated for various normal organs, as well as for primary tumours (PT) and/or metastases. Results are presented as median, interquartile range (IQR; 25th quantil-75th quantil) and range (minimum-maximum). [(68)Ga]PSMA PET/CT was performed 50 min (range 30-126) after injection of 109 MBq (range 84-158). Regarding biodistribution, highest uptake (median/IQR/range) of the tracer was found in the kidneys (49.6/40.7-57.6/2.7-97.0) followed by the submandibular glands (17.3/13.7-21.2/7.5-30.4), parotid glands (16.1/12.2-19.8/5.5-30.9) and duodenum (13.8/10.5-17.2/5.8-26.9). The best cut-off value for differentiating physiological uptake in the primary tumour from that in the prostate was found to be an SUVmax of 3.2. The median SUVmax in the PT (n = 35), locally recurrent PCA (n = 8), lymph node (n = 166), bone (n = 157) and other metastases (n = 3) were 10.2, 5.9, 6.2, 7.4 and 3.8, respectively. The best cut-off values for differentiating non-pathological uptake in lymph nodes and bones from tumour uptake were found to be SUVmax of 3.2 and 1.9, respectively. Patients with PSA <2 had significantly lower SUVmax in bone metastases as compared to patients with PSA ≥2 (p < 0.01). This biodistribution study provided a broad range of uptake data of [(68)Ga]PSMA-11 for normal organs/tissues, primary prostate tumours and metastatic lesions based on a large patient cohort. Both PT and small metastatic lesions were detectable due to their high tracer uptake. Four-times-higher median uptake in PT in comparison to normal prostate stroma resulted in a high diagnostic accuracy that could potentially be used for multimodal image-guided biopsy with dedicated reconstruction software.

  17. Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

    PubMed Central

    Hanson, M. A.; Gluckman, P. D.

    2014-01-01

    Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

  18. Sleep and the Cardiovascular System in Children.

    PubMed

    Paul, Grace R; Pinto, Swaroop

    2017-06-01

    Subspecialty pediatric practice provides comprehensive medical care for a range of ages, from premature infants to children, and often includes adults with complex medical and surgical issues that warrant multidisciplinary care. Normal physiologic variations involving different body systems occur during sleep and these vary with age, stage of sleep, and underlying health conditions. This article is a concise review of the cardiovascular (CV) physiology and pathophysiology in children, sleep-disordered breathing (SDB) contributing to CV morbidity, congenital and acquired CV pathology resulting in SDB, and the relationship between SDB and CV morbidity in different clinical syndromes and systemic diseases in the expanded pediatric population. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Abnormal aldosterone physiology and cardiometabolic risk factors.

    PubMed

    Vaidya, Anand; Underwood, Patricia C; Hopkins, Paul N; Jeunemaitre, Xavier; Ferri, Claudio; Williams, Gordon H; Adler, Gail K

    2013-04-01

    Abnormal aldosterone physiology has been implicated in the pathogenesis of cardiometabolic diseases. Single aldosterone measurements capture only a limited range of aldosterone physiology. New methods of characterizing aldosterone physiology may provide a more comprehensive understanding of its relationship with cardiometabolic disease. We evaluated whether novel indices of aldosterone responses to dietary sodium modulation, the sodium-modulated aldosterone suppression-stimulation index (SASSI for serum and SAUSSI for urine), could predict cardiometabolic risk factors. We performed cross-sectional analyses on 539 subjects studied on liberal and restricted sodium diets with serum and urinary aldosterone measurements. SASSI and SAUSSI were calculated as the ratio of aldosterone on liberal (maximally suppressed aldosterone) to the aldosterone on restricted (stimulated aldosterone) diets and associated with risk factors using adjusted regression models. Cardiometabolic risk factors associated with either impaired suppression of aldosterone on liberal diet, or impaired stimulation on restricted diet, or both; in all of these individual cases, these risk factors associated with higher SASSI or SAUSSI. In the context of abnormalities that constitute the metabolic syndrome, there was a strong positive association between the number of metabolic syndrome components (0-4) and both SASSI and SAUSSI (P<0.0001) that was independent of known aldosterone secretagogues (angiotensin II, corticotropin, potassium). SASSI and SAUSSI exhibited a high sensitivity in detecting normal individuals with zero metabolic syndrome components (86% for SASSI and 83% for SAUSSI). Assessing the physiological range of aldosterone responses may provide greater insights into adrenal pathophysiology. Dysregulated aldosterone physiology may contribute to, or result from, early cardiometabolic abnormalities.

  20. Evaluation and management of bradycardia in neonates and children.

    PubMed

    Baruteau, Alban-Elouen; Perry, James C; Sanatani, Shubhayan; Horie, Minoru; Dubin, Anne M

    2016-02-01

    Heart rate is commonly used in pediatric early warning scores. Age-related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Bradycardia is defined as a heart rate below the lowest normal value for age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. As a result of several different etiologies, it may occur in an entirely structurally normal heart or in association with concomitant congenital heart disease. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited sinus node dysfunction or progressive cardiac conduction disorders. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. The simplest aspect of severe bradycardia management is reflected in the Pediatric and Advanced Life Support (PALS) guidelines. Early diagnosis and appropriate management are critical in many cases in order to prevent sudden death, and this review critically assesses our current practice for evaluation and management of bradycardia in neonates and children. Bradycardia is defined as a heart rate below the lowest normal value for age. Age related changes in the anatomy and physiology of infants and children produce normal ranges for electrocardiogram features that differ from adults and vary with age. Pediatric bradycardia most commonly manifests as sinus bradycardia, junctional bradycardia, or atrioventricular block. Management and eventual prognosis of bradycardia in the young are entirely dependent upon the underlying cause. Bradycardia may occur in a structurally normal heart or in association with congenital heart disease. Genetic variants in multiple genes have been described. Reasons to intervene for bradycardia are the association of related symptoms and/or the downstream risk of heart failure or pause-dependent tachyarrhythmia. Early diagnosis and appropriate management are critical in order to prevent sudden death.

  1. Understanding the physiology and adaptation of staphylococci: a post-genomic approach.

    PubMed

    Becker, Karsten; Bierbaum, Gabriele; von Eiff, Christof; Engelmann, Susanne; Götz, Friedrich; Hacker, Jörg; Hecker, Michael; Peters, Georg; Rosenstein, Ralf; Ziebuhr, Wilma

    2007-11-01

    Staphylococcus aureus as well as coagulase-negative staphylococci are medically highly important pathogens characterized by an increasing resistance rate toward many antibiotics. Although normally being skin and mucosa commensals, some staphylococcal species and strains have the capacity to cause a wide range of infectious diseases. Many of these infections affect immunocompromised patients in hospitals. However, community-acquired staphylococcal infections due to resistant strains are also currently on the rise. In the light of this development, there is an urgent need for novel anti-staphylococcal therapeutic and prevention strategies for which a better understanding of the physiology of these bacteria is an essential prerequisite. Within the past years, staphylococci have been in the focus of genomic research, resulting in the determination and publication of a range of full-genome sequences of different staphylococcal species and strains which provided the basis for the design and application of DNA microarrays and other genomic tools. Here we summarize the results of the project group 'Staphylococci' within the research network 'Pathogenomics' giving new insights into the genome structure, molecular epidemiology, physiology, and genetic adaptation of both S. aureus and coagulase-negative staphylococci.

  2. Cardiac anatomy and physiology: a review.

    PubMed

    Gavaghan, M

    1998-04-01

    This article reviews the normal anatomy and physiology of the heart. Understanding the normal anatomic and physiologic relationships described in this article will help perioperative nurses care for patients who are undergoing cardiac procedures. Such knowledge also assists nurses in educating patients about cardiac procedures and about activities that can prevent, reverse, or improve cardiac illness.

  3. Factors influencing brain natriuretic peptide levels in healthy pregnant women.

    PubMed

    Mayama, Michinori; Yoshihara, Masato; Uno, Kaname; Tano, Sho; Takeda, Takehiko; Ukai, Mayu; Kishigami, Yasuyuki; Oguchi, Hidenori

    2017-02-01

    The normal range of plasma brain natriuretic peptide (BNP) in pregnant women is still unclear. Moreover, pregnant women experience dynamic body weight changes and suffer from anemia, but effects on maternal BNP have not been investigated. This study aimed to reveal the normal plasma BNP range and examine the effects of physiological changes on BNP among pregnant women. Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58 non-pregnant control women and in 773 normal pregnant women at late pregnancy, early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95% confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, p<0.001) at late pregnancy, 42.5 (0-112.6, p<0.001) early postpartum and 16.1 (0-43.9, p=0.001) 1-month postpartum. Multiple regression analysis revealed that pre-delivery BNP levels were negatively correlated with BMI (p<0.001) and hemoglobin (p=0.002) and positively correlated with creatinine (p<0.001). Post-delivery BNP was positively associated with body weight change during pregnancy (p=0.001) and post-delivery creatinine (p=0.010) but negatively associated with body weight loss at delivery (p<0.001) and post-delivery hemoglobin (p=0.004). Even normal pregnancy affects plasma BNP, particularly in the early postpartum period, indicative of cardiac stress. Plasma BNP levels are affected by BMI, body weight changes, creatinine and hemoglobin levels; therefore, these factors should be considered when analysing cardiac function and the physiological implications of BNP levels in pregnant women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Functional buckling behavior of silicone rubber shells for biomedical use.

    PubMed

    van der Houwen, E B; Kuiper, L H; Burgerhof, J G M; van der Laan, B F A M; Verkerke, G J

    2013-12-01

    The use of soft elastic biomaterials in medical devices enables substantial function integration. The consequent increased simplification in design can improve reliability at a lower cost in comparison to traditional (hard) biomaterials. Functional bi-stable buckling is one of the many new mechanisms made possible by soft materials. The buckling behavior of shells, however, is typically described from a structural failure point of view: the collapse of arches or rupture of steam vessels, for example. There is little or no literature about the functional elastic buckling of small-sized silicone rubber shells, and it is unknown whether or not theory can predict their behavior. Is functional buckling possible within the scale, material and pressure normally associated with physiological applications? An automatic speech valve is used as an example application. Silicone rubber spherical shells (diameter 30mm) with hinged and double-hinged boundaries were subjected to air pressure loading. Twelve different geometrical configurations were tested for buckling and reverse buckling pressures. Data were compared with the theory. Buckling pressure increases linearly with shell thickness and shell height. Reverse buckling shows these same relations, with pressures always below normal buckling pressure. Secondary hinges change normal/reverse buckling pressure ratios and promote symmetrical buckling. All tested configurations buckled within or closely around physiological pressures. Functional bi-stable buckling of silicone rubber shells is possible with adjustable properties in the physiological pressure range. Results can be predicted using the proposed relations and equations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Neonatal stomach volume and physiology suggest feeding at 1-h intervals.

    PubMed

    Bergman, Nils J

    2013-08-01

    There is insufficient evidence on optimal neonatal feeding intervals, with a wide range of practices. The stomach capacity could determine feeding frequency. A literature search was conducted for studies reporting volumes or dimensions of stomach capacity before or after birth. Six articles were found, suggesting a stomach capacity of 20 mL at birth. A stomach capacity of 20 mL translates to a feeding interval of approximately 1 h for a term neonate. This corresponds to the gastric emptying time for human milk, as well as the normal neonatal sleep cycle. Larger feeding volumes at longer intervals may therefore be stressful and the cause of spitting up, reflux and hypoglycaemia. Outcomes for low birthweight infants could possibly be improved if stress from overfeeding was avoided while supporting the development of normal gastrointestinal physiology. Cycles between feeding and sleeping at 1-h intervals likely meet the evolutionary expectations of human neonates. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  6. Altered Sleep Patterns and Physiologic Characteristics in Spontaneous Dwarf Rats

    PubMed Central

    Andersen, Monica L; Lee, Kil S; Guindalini, Camila; Leite, Waldemarks A; Bignotto, Magda; Tufik, Sergio

    2009-01-01

    Spontaneous dwarf rats are a useful experimental model for studying various biologic events associated with pituitary dwarfism. Dwarf rats occurred serendipitously in our colony of Wistar rats during experimental breeding. This study aimed to describe the sleep pattern and physiologic characteristics of these rats compared with normal-sized adult rats. Because growth hormone can attenuate the upregulation of ceruloplasmin expression caused by acute inflammation, we also assessed the basal levels of serum ceruloplasmin in these animals. At 90 d of age, body weight and length were significantly lower in dwarf rats relative to normal rats. Dwarves had lower concentrations of serum testosterone and growth hormone, but progesterone was unchanged. Corticosterone levels did not differ between groups. During the light period, the percentage of sleep time recorded and duration of slow-wave sleep did not differ between groups. However, compared with controls, dwarf rats had marked fragmentation of sleep and less paradoxical sleep. During the dark phase, sleep patterns in dwarf rats were within the normal range. Immunoblotting data showed that the levels of ceruloplasmin in serum were lower in dwarf rats. Our findings provide insight into pathologic processes related to growth hormone deficiency. PMID:19712574

  7. A prospective randomized trial of two solutions for intrapartum amnioinfusion: effects on fetal electrolytes, osmolality, and acid-base status.

    PubMed

    Pressman, E K; Blakemore, K J

    1996-10-01

    Our purpose was to compare the effects of intrapartum amnioinfusion with normal saline solution versus lactated Ringer's solution plus physiologic glucose on neonatal electrolytes and acid-base balance. Patients undergoing amnioinfusion for obstetric indications were randomized to receive normal saline solution or lactated Ringer's solution plus physiologic glucose at standardized amnioinfusion rates. Data were collected prospectively on maternal demographics, course of labor, and maternal and neonatal outcome. Arterial cord blood was obtained for analysis of electrolytes, glucose, osmolality, lactic acid, and blood gases. Control subjects with normal fetal heart rate patterns, and clear amniotic fluid not receiving amnioinfusion were studied concurrently. Data were collected on 59 patients (21 normal saline solution, 18 lactated Ringer's solution plus physiologic glucose, and 20 controls). Maternal demographics, course of labor, and neonatal outcome were similar in all three groups. Cesarean sections were performed more often in the amnioinfusion groups (33.3% for normal saline solution, 38.9% for lactated Ringer's solution plus physiologic glucose) than in the control group (5.0%), p < 0.05. Cord arterial electrolytes, glucose, osmolality, lactic acid, and blood gases were not altered by amnioinfusion with either solution. Intrapartum amnioinfusion with normal saline solution or lactated Ringer's solution plus physiologic glucose has no effect on neonatal electrolytes or acid-base balance.

  8. Synthetic lipids and their role in defining macromolecular assemblies.

    PubMed

    Parrill, Abby L

    2015-10-01

    Lipids have a variety of physiological roles, ranging from structural and biophysical contributions to membrane functions to signaling contributions in normal and abnormal physiology. This review highlights some of the contributions made by Robert Bittman to our understanding of lipid assemblies through the production of synthetic lipid analogs in the sterol, sphingolipid, and glycolipid classes. His contributions have included the development of a fluorescent cholesterol analog that shows strong functional analogies to cholesterol that has allowed live imaging of cholesterol distribution in living systems, to stereospecific synthetic approaches to both sphingolipid and glycolipid analogs crucial in defining the structure-activity relationships of lipid biological targets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. ABNORMAL ALDOSTERONE PHYSIOLOGY AND CARDIO-METABOLIC RISK FACTORS

    PubMed Central

    Vaidya, Anand; Underwood, Patricia C.; Hopkins, Paul N.; Jeunemaitre, Xavier; Ferri, Claudio; Williams, Gordon H.; Adler, Gail K.

    2013-01-01

    Abnormal aldosterone physiology has been implicated in the pathogenesis of cardio-metabolic diseases. Single aldosterone measurements capture only a limited range of aldosterone physiology. New methods of characterizing aldosterone physiology may provide a more comprehensive understanding of its relationship with cardio-metabolic disease. We evaluated whether novel indices of aldosterone responses to dietary sodium modulation, the Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI for serum and SAUSSI for urine), could predict cardio-metabolic risk factors. We performed cross-sectional analyses on 539 subjects studied on liberal (LIB) and restricted (RES) sodium diets with serum and urinary aldosterone measurements. SASSI and SAUSSI were calculated as the ratio of aldosterone on LIB (maximally suppressed aldosterone) to aldosterone on RES (stimulated aldosterone) diets, and associated with risk factors using adjusted regression models. Cardio-metabolic risk factors associated with either impaired suppression of aldosterone on LIB diet, or impaired stimulation on RES diet, or both; in all of these individual cases, these risk factors associated with higher SASSI or SAUSSI. In the context of abnormalities that comprise the metabolic syndrome (MetS), there was a strong positive association between the number of MetS components (0–4) and both SASSI and SAUSSI (P<0.0001) that was independent of known aldosterone secretagogues (angiotensin II, corticotropin, potassium). SASSI and SAUSSI exhibited a high sensitivity in detecting normal individuals with zero MetS components (86% for SASSI and 83% for SAUSSI). Assessing the physiologic range of aldosterone responses may provide greater insights into adrenal pathophysiology. Dysregulated aldosterone physiology may contribute to, and/or result from, early cardio-metabolic abnormalities. PMID:23399714

  10. The TRPM2 channel: A thermo-sensitive metabolic sensor.

    PubMed

    Kashio, Makiko; Tominaga, Makoto

    2017-09-03

    Living organisms continually experience changes in ambient temperature. To detect such temperature changes for adaptive behavioral responses, we evolved the ability to sense temperature. Thermosensitive transient receptor potential (TRP) channels, so-called thermo-TRPs, are involved in many physiologic functions in diverse organisms and constitute important temperature sensors. One of the important roles of thermo-TRPs is detecting ambient temperature in sensory neurons. Importantly, the functional expression of thermo-TRPs is observed not only in sensory neurons but also in tissues and cells that are not exposed to drastic temperature changes, indicating that thermo-TRPs are involved in many physiologic functions within the body's normal temperature range. Among such thermo-TRPs, this review focuses on one thermo-sensitive metabolic sensor in particular, TRPM2, and summarizes recent progress to clarify the regulatory mechanisms and physiologic functions of TRPM2 at body temperature under various metabolic states.

  11. Nonlinear dynamics applied to the study of cardiovascular effects of stress

    NASA Astrophysics Data System (ADS)

    Anishchenko, T. G.; Igosheva, N. B.

    1998-03-01

    We study cardiovascular responses to emotional stresses in humans and rats using traditional physiological parameters and methods of nonlinear dynamics. We found that emotional stress results in significant changes of chaos degree of ECG and blood pressure signals, estimated using a normalized entropy. We demonstrate that the normalized entropy is a more sensitive indicator of the stress-induced changes in cardiovascular systems compared with traditional physiological parameters Using the normalized entropy we discovered the significant individual differences in cardiovascular stress-reactivity that was impossible to obtain by traditional physiological methods.

  12. Physiological Ranges of Matrix Rigidity Modulate Primary Mouse Hepatocyte Function In Part Through Hepatocyte Nuclear Factor 4 Alpha

    PubMed Central

    Desai, Seema S.; Tung, Jason C.; Zhou, Vivian X.; Grenert, James P.; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M.; Chang, Tammy T.

    2016-01-01

    Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of hepatic-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150Pa and increased to 1–6kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α) whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase (FAK). In addition, blockade of the Rho/Rho-associated protein kinase (ROCK) pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/ROCK pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. PMID:26755329

  13. Phosphorescent nanosensors for in vivo tracking of histamine levels.

    PubMed

    Cash, Kevin J; Clark, Heather A

    2013-07-02

    Continuously tracking bioanalytes in vivo will enable clinicians and researchers to profile normal physiology and monitor diseased states. Current in vivo monitoring system designs are limited by invasive implantation procedures and biofouling, limiting the utility of these tools for obtaining physiologic data. In this work, we demonstrate the first success in optically tracking histamine levels in vivo using a modular, injectable sensing platform based on diamine oxidase and a phosphorescent oxygen nanosensor. Our new approach increases the range of measurable analytes by combining an enzymatic recognition element with a reversible nanosensor capable of measuring the effects of enzymatic activity. We use these enzyme nanosensors (EnzNS) to monitor the in vivo histamine dynamics as the concentration rapidly increases and decreases due to administration and clearance. The EnzNS system measured kinetics that match those reported from ex vivo measurements. This work establishes a modular approach to in vivo nanosensor design for measuring a broad range of potential target analytes. Simply replacing the recognition enzyme, or both the enzyme and nanosensor, can produce a new sensor system capable of measuring a wide range of specific analytical targets in vivo.

  14. Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

    PubMed

    Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

    2017-09-01

    Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

  15. Biomonitoring of physiological status and cognitive performance of underway submariners undergoing a novel watch-standing schedule

    NASA Astrophysics Data System (ADS)

    Duplessis, C. A.; Cullum, M. E.; Crepeau, L. J.

    2005-05-01

    Submarine watch-standers adhere to a 6 hour-on, 12 hour-off (6/12) watch-standing schedule, yoking them to an 18-hr day, engendering circadian desynchronization and chronic sleep deprivation. Moreover, the chronic social crowding, shift work, and confinement of submarine life provide additional stressors known to correlate with elevated secretory immunoglobulin A (sIgA) and cortisol levels, reduced performance, immunologic dysfunction, malignancies, infections, gastrointestinal illness, coronary disease, anxiety, and depression. We evaluated an alternative, compressed, fixed work schedule designed to enhance circadian rhythm entrainment, sleep hygiene, performance, and health on 10 underway submariners, who followed the alternative and 6/12 schedules for approximately 2 weeks each. We measured subjects" sleep, cognitive performance, and salivary biomarker levels. Pilot analysis of the salivary data on one subject utilizing ELISA suggests elevated biomarker levels of stress. Average PM cortisol levels were 0.2 μg/L (normal range: nondetectable - 0.15 μg/L), and mean sIgA levels were 562 μg/ml (normal range: 100-500 μg/ml). Future research exploiting real-time salivary bioassays, via fluorescent polarimetry technology, identified by the Office of Naval Research (ONR) as a future Naval requirement, allows researchers to address correlations between stress-induced elaboration of salivary biomarkers with physiological and performance decrements, thereby fostering insight into the underway submariner"s psychoimmunological status. This may help identify strategies that enhance resilience to stressors. Specifically, empirically-based modeling can identify optimal watch-standing schedules and stress-mitigating procedures -- within the operational constraints of the submarine milieu and the mission --that foster improved circadian entrainment and reduced stress reactivity, enhancing physiological health, operational performance, safety, and job satisfaction.

  16. Are vaginal symptoms ever normal? a review of the literature.

    PubMed

    Anderson, Matthew; Karasz, Alison; Friedland, Sarah

    2004-11-22

    Vaginal symptoms such as discharge, odor, and itch are among the most common presenting complaints in primary care. We undertook to determine if the symptoms associated with vaginitis (discharge, odor, irritation) occur in normal women. To answer this question, we performed a literature review. We conducted a Medline search using the following terms: "vagina," "vaginal discharge," "secretion," "odors," discharge," "pruritus," "normal," "irritation," "itch," "physical examination," "healthy," "asymptomatic," "quantity," and "physiology." To find additional references we reviewed textbooks in gynecology, primary care, and physical diagnosis and contacted authors. There are few primary studies, and most are not of high quality. Existing data show that the quantity and quality of vaginal discharge in healthy women vary considerably both across individuals and in the same individual during the menstrual cycle. Most studies indicate that discharge is greatest at midcycle. Vaginal fluid contains malodorants, and one study of intact vaginal fluid found it to be malodorous. Two studies found that normal women reported irritative symptoms in the course of their menstrual cycle. The primary literature indicates that there is a wide variation in the normal vagina and that some of the symptoms associated with vaginal abnormality are found in well women. Both clinicians and their patients would benefit from a better understanding of the range of normal as well as what constitutes a meaningful departure from that range.

  17. Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures.

    PubMed

    Yang, Dong-Ping; Robinson, P A

    2017-04-01

    A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

  18. Critical dynamics of Hopf bifurcations in the corticothalamic system: Transitions from normal arousal states to epileptic seizures

    NASA Astrophysics Data System (ADS)

    Yang, Dong-Ping; Robinson, P. A.

    2017-04-01

    A physiologically based corticothalamic model of large-scale brain activity is used to analyze critical dynamics of transitions from normal arousal states to epileptic seizures, which correspond to Hopf bifurcations. This relates an abstract normal form quantitatively to underlying physiology that includes neural dynamics, axonal propagation, and time delays. Thus, a bridge is constructed that enables normal forms to be used to interpret quantitative data. The normal form of the Hopf bifurcations with delays is derived using Hale's theory, the center manifold theorem, and normal form analysis, and it is found to be explicitly expressed in terms of transfer functions and the sensitivity matrix of a reduced open-loop system. It can be applied to understand the effect of each physiological parameter on the critical dynamics and determine whether the Hopf bifurcation is supercritical or subcritical in instabilities that lead to absence and tonic-clonic seizures. Furthermore, the effects of thalamic and cortical nonlinearities on the bifurcation type are investigated, with implications for the roles of underlying physiology. The theoretical predictions about the bifurcation type and the onset dynamics are confirmed by numerical simulations and provide physiologically based criteria for determining bifurcation types from first principles. The results are consistent with experimental data from previous studies, imply that new regimes of seizure transitions may exist in clinical settings, and provide a simplified basis for control-systems interventions. Using the normal form, and the full equations from which it is derived, more complex dynamics, such as quasiperiodic cycles and saddle cycles, are discovered near the critical points of the subcritical Hopf bifurcations.

  19. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation

    PubMed Central

    2014-01-01

    The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis. There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease. In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation. PMID:24661309

  20. Friction and lubrication of pleural tissues.

    PubMed

    D'Angelo, Edgardo; Loring, Stephen H; Gioia, Magda E; Pecchiari, Matteo; Moscheni, Claudia

    2004-08-20

    The frictional behaviour of rabbit's visceral pleura sliding against parietal pleura was assessed in vitro while oscillating at physiological velocities and amplitudes under physiological normal forces. For sliding velocities up to 3 cm s(-1) and normal compressive loads up to 12 cm H2O, the average value of the coefficient of kinetic friction (mu) was constant at 0.019 +/- 0.002 (S.E.) with pleural liquid as lubricant. With Ringer-bicarbonate solution, mu was still constant, but significantly increased (Deltamu = 0.008 +/- 0.001; P < 0.001). Under these conditions, no damage of the sliding pleural surfaces was found on light and electron microscopy. Additional measurements, performed also on peritoneum, showed that changes in nominal contact area or strain of the mesothelia, temperature in the range 19-39 degrees C, and prolonged sliding did not affect mu. Gentle application of filter paper increased mu approximately 10-fold and irreversibly, suggesting alteration of the mesothelia. With packed the red blood cells (RBC) between the sliding mesothelia, mu increased appreciably but reversibly on removal of RBC suspension, whilst no ruptures of RBC occurred. In conclusion, the results indicate a low value of sliding friction in pleural tissues, partly related to the characteristics of the pleural liquid, and show that friction is independent of velocity, normal load, and nominal contact area, consistent with boundary lubrication.

  1. Multiscale entropy analysis of human gait dynamics

    NASA Astrophysics Data System (ADS)

    Costa, M.; Peng, C.-K.; L. Goldberger, Ary; Hausdorff, Jeffrey M.

    2003-12-01

    We compare the complexity of human gait time series from healthy subjects under different conditions. Using the recently developed multiscale entropy algorithm, which provides a way to measure complexity over a range of scales, we observe that normal spontaneous walking has the highest complexity when compared to slow and fast walking and also to walking paced by a metronome. These findings have implications for modeling locomotor control and for quantifying gait dynamics in physiologic and pathologic states.

  2. Chloride concentrations in human hepatic cytosol and mitochondria are a function of age

    PubMed Central

    Jahn, Stephan C.; Rowland-Faux, Laura; Stacpoole, Peter W.; James, Margaret O.

    2015-01-01

    We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7 – 365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9 – 22.2 mM). These results suggest a possible explanation for clinical observations seen in patients treated with dichloroacetate, whereby children metabolize the drug more rapidly than adults following repeated doses, and also provide information that may influence our understanding of normal liver physiology. PMID:25748576

  3. Chloride concentrations in human hepatic cytosol and mitochondria are a function of age.

    PubMed

    Jahn, Stephan C; Rowland-Faux, Laura; Stacpoole, Peter W; James, Margaret O

    2015-04-10

    We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7-365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9-22.2 mM). These results suggest a possible explanation for clinical observations seen in patients treated with dichloroacetate, whereby children metabolize the drug more rapidly than adults following repeated doses, and also provide information that may influence our understanding of normal liver physiology. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Ecological comparison of cellular stress responses among populations - normalizing RT-qPCR values to investigate differential environmental adaptations.

    PubMed

    Koenigstein, Stefan; Pöhlmann, Kevin; Held, Christoph; Abele, Doris

    2013-05-16

    Rising temperatures and other environmental factors influenced by global climate change can cause increased physiological stress for many species and lead to range shifts or regional population extinctions. To advance the understanding of species' response to change and establish links between individual and ecosystem adaptations, physiological reactions have to be compared between populations living in different environments. Although changes in expression of stress genes are relatively easy to quantify, methods for reliable comparison of the data remain a contentious issue. Using normalization algorithms and further methodological considerations, we compare cellular stress response gene expression levels measured by RT-qPCR after air exposure experiments among different subpopulations of three species of the intertidal limpet Nacella. Reference gene assessment algorithms reveal that stable reference genes can differ among investigated populations and / or treatment groups. Normalized expression values point to differential defense strategies to air exposure in the investigated populations, which either employ a pronounced cellular stress response in the inducible Hsp70 forms, or exhibit a comparatively high constitutive expression of Hsps (heat shock proteins) while showing only little response in terms of Hsp induction. This study serves as a case study to explore the methodological prerequisites of physiological stress response comparisons among ecologically and phylogenetically different organisms. To improve the reliability of gene expression data and compare the stress responses of subpopulations under potential genetic divergence, reference gene stability algorithms are valuable and necessary tools. As the Hsp70 isoforms have been shown to play different roles in the acute stress responses and increased constitutive defenses of populations in their different habitats, these comparative studies can yield insight into physiological strategies of adaptation to environmental stress and provide hints for the prudent use of the cellular stress response as a biomarker to study environmental stress and stress adaptation of populations under changing environmental conditions.

  5. Effect of halo-vest components on stabilizing the injured cervical spine.

    PubMed

    Ivancic, Paul C; Beauchman, Naseem N; Tweardy, Lisa

    2009-01-15

    An in vitro biomechanical study. The objectives were to develop a new biofidelic skull-neck-thorax model capable of quantifying motion patterns of the cervical spine in the presence of a halo-vest; to investigate the effects of vest loosening, superstructure loosening, and removal of the posterior uprights; and to evaluate the ability of the halo-vest to stabilize the neck within physiological motion limits. Previous clinical and biomechanical studies have investigated neck motion with the halo-vest only in the sagittal plane or only at the injured spinal level. No previous studies have quantified three-dimensional intervertebral motion patterns throughout the injured cervical spine stabilized with the halo-vest or studied the effect of halo-vest components on these motions. The halo-vest was applied to the skull-neck-thorax model. Six osteoligamentous whole cervical spine specimens (occiput through T1 vertebra) were used that had sustained multiplanar ligamentous injuries at C3/4 through C7-T1 during a previous protocol. Flexibility tests were performed with normal halo-vest application, loose vest, loose superstructure, and following removal of the posterior uprights. Average total range of motion for each experimental condition was statistically compared (P < 0.05) with the physiologic rotation limit for each spinal level. Cervical spine snaking was observed in both the sagittal and frontal planes. The halo-vest, applied normally, generally limited average spinal motions to within average physiological limits. No significant increases in average spinal motions above physiologic were observed due to loose vest, loose superstructure, or removal of the posterior uprights. However, a trend toward increased motion at C6/7 in lateral bending was observed due to loose superstructure. The halo-vest, applied normally, effectively immobilized the cervical spine. Sagittal or frontal plane snaking of the cervical spine due to the halo-vest may reduce its immobilization capability at the upper cervical spine and cervicothoracic junction.

  6. Ecological comparison of cellular stress responses among populations – normalizing RT-qPCR values to investigate differential environmental adaptations

    PubMed Central

    2013-01-01

    Background Rising temperatures and other environmental factors influenced by global climate change can cause increased physiological stress for many species and lead to range shifts or regional population extinctions. To advance the understanding of species’ response to change and establish links between individual and ecosystem adaptations, physiological reactions have to be compared between populations living in different environments. Although changes in expression of stress genes are relatively easy to quantify, methods for reliable comparison of the data remain a contentious issue. Using normalization algorithms and further methodological considerations, we compare cellular stress response gene expression levels measured by RT-qPCR after air exposure experiments among different subpopulations of three species of the intertidal limpet Nacella. Results Reference gene assessment algorithms reveal that stable reference genes can differ among investigated populations and / or treatment groups. Normalized expression values point to differential defense strategies to air exposure in the investigated populations, which either employ a pronounced cellular stress response in the inducible Hsp70 forms, or exhibit a comparatively high constitutive expression of Hsps (heat shock proteins) while showing only little response in terms of Hsp induction. Conclusions This study serves as a case study to explore the methodological prerequisites of physiological stress response comparisons among ecologically and phylogenetically different organisms. To improve the reliability of gene expression data and compare the stress responses of subpopulations under potential genetic divergence, reference gene stability algorithms are valuable and necessary tools. As the Hsp70 isoforms have been shown to play different roles in the acute stress responses and increased constitutive defenses of populations in their different habitats, these comparative studies can yield insight into physiological strategies of adaptation to environmental stress and provide hints for the prudent use of the cellular stress response as a biomarker to study environmental stress and stress adaptation of populations under changing environmental conditions. PMID:23680017

  7. 24-Hour colonic manometry in pediatric slow transit constipation shows significant reductions in antegrade propagation.

    PubMed

    King, Sebastian K; Catto-Smith, Anthony G; Stanton, Michael P; Sutcliffe, Jonathan R; Simpson, Dianne; Cook, Ian; Dinning, Phil; Hutson, John M; Southwell, Bridget R

    2008-08-01

    The physiological basis of slow transit constipation (STC) in children remains poorly understood. We wished to examine pan-colonic motility in a group of children with severe chronic constipation refractory to conservative therapy. We performed 24 h pan-colonic manometry in 18 children (13 boys, 11.6 +/- 0.9 yr, range 6.6-18.7 yr) with scintigraphically proven STC. A water-perfused, balloon tipped, 8-channel, silicone catheter with a 7.5 cm intersidehole distance was introduced through a previously formed appendicostomy. Comparison data were obtained from nasocolonic motility studies in 16 healthy young adult controls and per-appendicostomy motility studies in eight constipated children with anorectal retention and/or normal transit on scintigraphy (non-STC). Antegrade propagating sequences (PS) were significantly less frequent (P < 0.01) in subjects with STC (29 +/- 4 per 24 h) compared to adult (53 +/- 4 per 24 h) and non-STC (70 +/- 14 per 24 h) subjects. High amplitude propagating sequences (HAPS) were of a normal frequency in STC subjects. Retrograde propagating sequences were significantly more frequent (P < 0.05) in non-STC subjects compared to STC and adult subjects. High amplitude retrograde propagating sequences were only identified in the STC and non-STC pediatric groups. The normal increase in motility index associated with waking and ingestion of a meal was absent in STC subjects. Prolonged pancolonic manometry in children with STC showed significant impairment in antegrade propagating motor activity and failure to respond to normal physiological stimuli. Despite this, HAPS occurred with normal frequency. These findings suggest significant clinical differences between STC in children and adults.

  8. Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease

    NASA Technical Reports Server (NTRS)

    Peng, C. K.; Havlin, S.; Hausdorff, J. M.; Mietus, J. E.; Stanley, H. E.; Goldberger, A. L.

    1995-01-01

    Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.

  9. Application of Markov chain model to daily maximum temperature for thermal comfort in Malaysia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nordin, Muhamad Asyraf bin Che; Hassan, Husna

    2015-10-22

    The Markov chain’s first order principle has been widely used to model various meteorological fields, for prediction purposes. In this study, a 14-year (2000-2013) data of daily maximum temperatures in Bayan Lepas were used. Earlier studies showed that the outdoor thermal comfort range based on physiologically equivalent temperature (PET) index in Malaysia is less than 34°C, thus the data obtained were classified into two state: normal state (within thermal comfort range) and hot state (above thermal comfort range). The long-run results show the probability of daily temperature exceed TCR will be only 2.2%. On the other hand, the probability dailymore » temperature within TCR will be 97.8%.« less

  10. Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development.

    PubMed

    Schaer, Dominik J; Vinchi, Francesca; Ingoglia, Giada; Tolosano, Emanuela; Buehler, Paul W

    2014-01-01

    Hemolysis, which occurs in many disease states, can trigger a diverse pathophysiologic cascade that is related to the specific biochemical activities of free Hb and its porphyrin component heme. Normal erythropoiesis and concomitant removal of senescent red blood cells (RBC) from the circulation occurs at rates of approximately 2 × 10(6) RBCs/second. Within this physiologic range of RBC turnover, a small fraction of hemoglobin (Hb) is released into plasma as free extracellular Hb. In humans, there is an efficient multicomponent system of Hb sequestration, oxidative neutralization and clearance. Haptoglobin (Hp) is the primary Hb-binding protein in human plasma, which attenuates the adverse biochemical and physiologic effects of extracellular Hb. The cellular receptor target of Hp is the monocyte/macrophage scavenger receptor, CD163. Following Hb-Hp binding to CD163, cellular internalization of the complex leads to globin and heme metabolism, which is followed by adaptive changes in antioxidant and iron metabolism pathways and macrophage phenotype polarization. When Hb is released from RBCs within the physiologic range of Hp, the potential deleterious effects of Hb are prevented. However, during hyper-hemolytic conditions or with chronic hemolysis, Hp is depleted and Hb readily distributes to tissues where it might be exposed to oxidative conditions. In such conditions, heme can be released from ferric Hb. The free heme can then accelerate tissue damage by promoting peroxidative reactions and activation of inflammatory cascades. Hemopexin (Hx) is another plasma glycoprotein able to bind heme with high affinity. Hx sequesters heme in an inert, non-toxic form and transports it to the liver for catabolism and excretion. In the present review we discuss the components of physiologic Hb/heme detoxification and their potential therapeutic application in a wide range of hemolytic conditions.

  11. Endurance Exercise: Normal Physiology and Limitations Imposed by Pathological Processes (Part 1).

    ERIC Educational Resources Information Center

    Frontera, Walter R.; Adams, Richard P.

    1986-01-01

    The physiologic and metabolic adjustments of the body to a single endurance exercise session are analyzed in terms of the respiratory system, the cardiovascular system, and oxygen delivery to the muscles. Patients with cardiorespiratory and neuromuscular diseases are compared to normal individuals. (Author/MT)

  12. Neck motion due to the halo-vest in prone and supine positions.

    PubMed

    Ivancic, Paul C; Telles, Connor J

    2010-05-01

    An in vitro biomechanical study of the effectiveness of halo-vest fixation. The objective was to evaluate motion of the injured cervical spine with normal halo-vest application and vest loose in the prone and supine positions. Snaking motion of the neck is defined as rotation in opposing directions throughout the cervical spine. Previous clinical studies have suggested snaking neck motion due to the halo-vest may lead to inadequate healing or nonunion. The halo-vest was applied to a Human Model of the Neck, which consisted of a cervical spine specimen mounted to the torso of an anthropometric test dummy and carrying a surrogate head. The model was transitioned from prone, to upright, to supine with the halo-vest applied normally and with the vest loose. Average peak spinal motions were computed in the prone and supine positions and contrasted with the physiologic rotation range, obtained from the intact flexibility test, and statistically compared (P < 0.05) between normal halo-vest application and vest loose. Snaking motion of the neck was observed in the prone and supine positions, consisting of extension at head/C1 and C1/2 and flexion at the inferior spinal levels. The intervertebral rotation peaks generally exceeded the physiologic range throughout the cervical spine due to the loose vest in the prone position. Significant increases in the extension peaks at head/C1 (16.9 degrees vs. 5.7 degrees) and flexion peaks at C4/5 (6.9 degrees vs. 3.6 degrees) and C7-T1 (5.2 degrees vs. 0.7 degrees) were observed in the prone position due to the loose vest, as compared to normal halo-vest application. Axial neck separation was consistently observed in the prone and supine positions. The present results, which document snaking motion of the cervical spine due to the halo-vest, indicate that an inadequately fitting or loose vest may significantly diminish its immobilization capacity leading to delayed healing or nonunion.

  13. Elevated left ventricular outflow tract velocities on exercise stress echocardiography may be a normal physiologic response in healthy youth.

    PubMed

    Wittlieb-Weber, Carol A; Cohen, Meryl S; McBride, Michael G; Paridon, Stephen M; Morrow, Robert; Wasserman, Melissa; Wang, Yan; Stephens, Paul

    2013-12-01

    Children with heart disease are at risk for sudden death during exercise, yet decisions regarding sports participation are often based on resting data. Acceleration across the left ventricular outflow tract (LVOT) assessed on stress echocardiography may suggest a diagnosis of hypertrophic cardiomyopathy in patients in whom it is not otherwise obvious. However, the range of peak velocities across the LVOT in healthy youth is unknown. The aim of this study was to describe LVOT velocities with maximal exercise in this age group. Subjects up to 18 years old were prospectively enrolled if they had normal results on resting echocardiography and were undergoing exercise testing for other reasons. Subjects with significant comorbidities, suspected cardiomyopathy, or family histories of cardiomyopathy were excluded. Peak LVOT velocities were measured in the upright position using continuous-wave Doppler immediately after maximal exercise. Fifty subjects (mean age, 13.8 ± 2.8 years) were included. Twenty-eight (56%) were male, and 40 (80%) were Caucasian. The median peak LVOT velocity measured immediately after exercise was 2.5 m/sec (range, 1.3-5.9 m/sec). Sixteen subjects (32%) developed peak LVOT velocities of ≥3 m/sec. Twelve of the 16 (75%) with elevated velocities had a dynamic outflow tract Doppler pattern, of whom eight had evidence of intracavitary narrowing on two-dimensional echocardiography. The development of significant exercise-induced LVOT velocities may be a normal physiologic finding in healthy youth. The measurement of LVOT velocities alone with maximal exercise may not help distinguish patients with hypertrophic cardiomyopathy from healthy children. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  14. Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.

    PubMed

    Desai, Seema S; Tung, Jason C; Zhou, Vivian X; Grenert, James P; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M; Chang, Tammy T

    2016-07-01

    Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275). © 2016 by the American Association for the Study of Liver Diseases.

  15. Development of sensitive holographic devices for physiological metal ion detection

    NASA Astrophysics Data System (ADS)

    Sabad-e.-Gul; Martin, Suzanne; Cassidy, John; Naydenova, Izabela

    2017-08-01

    The development of selective alkali metal ions sensors in particular is a subject of significant interest. In this respect, the level of blood electrolytes, particularly H+, Na+, K+ and Cl- , is widely used to monitor aberrant physiologies associated with pulmonary emphysema, acute and chronic renal failure, heart failure, diabetes. The sensors reported in this paper are created by holographic recording of surface relief structures in a self-processing photopolymer material. The structures are functionalized by ionophores dibenzo-18-crown-6 (DC) and tetraethyl 4-tert-butylcalix[4]arene (TBC) in plasticised polyvinyl chloride (PVC) matrix. Interrogation of these structures by light allows indirect measurements of chemical analytes' concentration in real time. We present results on the optimisation and testing of the holographic sensor. A self-processing acrylamide-based photopolymer was used to fabricate the required photonic structures. The performance of the sensors for detection of K+ and Na+ was investigated. It was observed that the functionalisation with DC provides a selective response of the devices to K+ over Na+ and TBC coated surface structures are selectively sensitive to Na+. The sensor responds to Na+ within the physiological ranges. Normal levels of Na+ and K+ in human serum lie within the ranges 135-148mM and 3.5-5.3 mM respectively.

  16. Phosphorus Imaging as a Tool for Studying the pH Metabolism in Living Insects

    NASA Astrophysics Data System (ADS)

    Skibbe, U.; Christeller, J. T.; Eccles, C. D.; Laing, W. A.; Callaghan, P. T.

    1995-09-01

    Comparative 31P NMR and 1H NMR imaging experiments at submillimeter pixel resolution were carried out, using a specially constructed solenoidal RF coil. Chemical-shift imaging is used to provide pH maps from the midgut of a Lepidopteran larvae and to demonstrate physiological dependence in the resulting images, The titration curve of pH versus chemical shift for inorganic phosphate is extended beyond the "normal" biological range to the strong alkaline limit.

  17. Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

    NASA Astrophysics Data System (ADS)

    Khokhlova, Maria D.; Lyubin, Eugeny V.; Zhdanov, Alexander G.; Rykova, Sophia Yu.; Sokolova, Irina A.; Fedyanin, Andrey A.

    2012-02-01

    Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.

  18. Role of cholesterol and lipid organization in disease

    NASA Astrophysics Data System (ADS)

    Maxfield, Frederick R.; Tabas, Ira

    2005-12-01

    Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.

  19. Luminal glucose concentrations in the gut under normal conditions.

    PubMed

    Ferraris, R P; Yasharpour, S; Lloyd, K C; Mirzayan, R; Diamond, J M

    1990-11-01

    Luminal glucose (Glc) concentrations in the small intestine (SI) are widely assumed to be 50-500 mM. These values have posed problems for interpreting SI luminal osmolality and absorptive capacity, Glc transporter Michaelis-Menten constants (Km), and the physiological role of active Glc transport and its regulation. Hence we measured luminal contents, osmolality, and Glc, Na+, and K+ concentrations in normally feeding rats, rabbits, and dogs. Measured Glc concentrations were compatible with the portion of measured osmolality not accounted for by Na+ and K+ salts, amino acids, and peptides. Mean SI luminal osmolalities were less than or equal to 100 mosmol/kg hypertonic. For animals on the most nearly physiological diets, SI Glc concentrations averaged 0.4-24 mM and ranged with time and SI region from 0.2 to a maximum of 48 mM. The older published very high values are artifacts of direct infusion of concentrated Glc solutions into the gut, nonspecific Glc assays, and failure to test for quantitative recovery or to centrifuge samples in the cold. By storing food after meals and releasing it between meals, rat stomach greatly damps diurnal fluctuations in quantity and osmolality of food reaching the SI and hence also damps fluctuations in absorption rates. These new values for luminal Glc have five important physiological implications: the problem of accounting for apparently very hypertonic SI contents in the face of high osmotic water permeability disappears; the effective Km of the SI Glc transporter is now comparable to prevailing Glc concentrations; the SI no longer appears to have enormous excess absorptive capacity for Glc; regulation of Glc transport by dietary intake now makes functional sense; and the claim that high luminal Glc concentrations permit solvent drag to become the major mode of Glc absorption under normal conditions is undermined.

  20. Influence of Total Knee Arthroplasty on Patellar Kinematics and Patellofemoral Pressure.

    PubMed

    Tanikawa, Hidenori; Tada, Mitsunori; Harato, Kengo; Okuma, Kazunari; Nagura, Takeo

    2017-01-01

    Patellofemoral complications are one of the main problems after total knee arthroplasty (TKA). The design of the TKA component may affect the patellar biomechanics, which may be associated with this postoperative complication. The purpose of this study was to assess the influence of TKA and prosthesis designs on the patellar kinematics and patellofemoral pressure. Using fresh-frozen cadavers, we measured the patellofemoral pressure, patella offset, and patella tilt in the following 4 conditions: normal knee (patella replacement only), cruciate-retaining TKA, condylar-stabilizing TKA, and posterior-stabilized TKA. The patellofemoral pressure increased significantly after the cruciate-retaining TKA and condylar-stabilizing TKA compared with the normal knee. The patella offset in the normal knee decreased with increasing knee flexion angles, while the patella offset in the TKA knees did not change significantly through the full range of motion. The amount of lateral patella tilt in the normal knee was significantly larger than the TKA knees in the full range of motion. Although the femoral components are designed to reproduce an anatomical patellar tracking, the physiological patellar kinematics were not observed. Relatively high patellofemoral pressure and kinematic change after TKA may be associated with postoperative complications such as the anterior knee pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. THE RHYTHMIC RANGE OF THE WHITE BLOOD CELLS IN HUMAN, PATHOLOGICAL LEUCOPENIC AND LEUCOCYTIC STATES, WITH A STUDY OF THIRTY-TWO HUMAN BONE MARROWS

    PubMed Central

    Doan, Charles A.; Zerfas, Leon G.

    1927-01-01

    In a study of twenty clinical cases with a wide range of diagnoses, repeated total counts of the white cells at 15 minute intervals reveal a large fluctuation at various levels comparable to that found for the normal (1, 2). The granulocytes seem to follow a more or less hourly rhythm, the most marked shift to the left in the Ameth pattern and the moment of greatest percentage of motility coinciding with the peaks. The independence found existing between the peripheral blood concentrations of individual strains of white cells and the red cells, as determined by total and differential counts, their differential response to pathological and pharmacological stimuli, and their normal relative relations, all indicate some separate physiological mechanism of control for each type of cell, either working through, or independently of, their sources of origin. The many factors to which the circulation of the blood, as such, is subject, the complexity of the influences on origin, maturation, delivery, longevity, and destruction of each cell group, the limitations inherent in the present involved, indirect technics of counting, combine to make any single observation subject to grave misinterpretation. The value to the clinician must come in repeated observations, at times when the diagnosis or a therapeutic procedure is in doubt, at frequent intervals, at other times over longer or shorter periods, but always with the relation between consecutive counts, rather than the absolute values, the important point for consideration. Both the red and the white cells probably change their relative concentrations in the peripheral blood from time to time over a considerable range that is quite within normal physiological limits, so that, in theoretical considerations and in practical functional estimations, a zonal concept with adequate individual extremes should always be kept in mind for both physiological and pathological states. A cytological analysis of thirty-two bone marrows from human biopsy and autopsy material shows the striking reciprocity found to exist between the myelocytes and the mature polymorphonuclear leucocytes. This, together with the observed focal uniformity of maturation found in bone marrow, and the periodicity of the fluctuations of the neutrophils in the peripheral blood, leads to the formulation of the hypothesis of a constant functional withdrawal of granulocytes from the peripheral blood with a periodic delivery of new cells from the marrow, which in leucopenia and in leucocytosis represents a depression or a stimulation, respectively, of the normal mechanism. The nature and degree of the response are an approximate index of the cellular factor in the complex of the "resistance" of the particular individual. PMID:19869352

  2. Tissue Physiology and Pathology of Aromatase

    PubMed Central

    Stocco, Carlos

    2011-01-01

    Summary Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies. PMID:22108547

  3. Distinguishing hyperhidrosis and normal physiological sweat production: new data and review of hyperhidrosis data for 1980-2013.

    PubMed

    Thorlacius, Linnea; Gyldenløve, Mette; Zachariae, Claus; Carlsen, Berit C

    2015-10-01

    Hyperhidrosis is a condition in which the production of sweat is abnormally increased. No objective criteria for the diagnosis of hyperhidrosis exist, mainly because reference intervals for normal physiological sweat production at rest are unknown. The main objective of this study was to establish reference intervals for normal physiological axillary and palmar sweat production. Gravimetric testing was performed in 75 healthy control subjects. Subsequently, these results were compared with findings in a cohort of patients with hyperhidrosis and with the results derived from a review of data on hyperhidrosis published between 1980 and 2013. Approximately 90% of the controls had axillary and palmar sweat production rates of below 100 mg/5 min. In all except one of the axillary and palmar hyperhidrosis studies reviewed, average sweat production exceeded 100 mg/5 min. A sweat production rate of 100 mg/5 min as measured by gravimetric testing may be a reasonable cut-off value for distinguishing axillary and palmar hyperhidrosis from normal physiological sweat production. © 2015 The International Society of Dermatology.

  4. Aging and memory: corrections for age, sex and education for three widely used memory tests.

    PubMed

    Zappalà, G; Measso, G; Cavarzeran, F; Grigoletto, F; Lebowitz, B; Pirozzolo, F; Amaducci, L; Massari, D; Crook, T

    1995-04-01

    The associate learning subtest from the Wechsler Memory Scale; Benton's Visual Retention test and a Controlled Word Association Task (FAS) were administered to a random sample of normal, healthy individuals whose age ranged from 20 to 79 years, recruited within the Italian peninsula. The neuropsychological examination took place on a mobile unit and the tests were given by the same team of neuropsychologists to reduce variability among examiners. The Research Project was known as Progetto Memoria. Corrections to the scores of these tests were calculated for age, sex, and education. These corrected values will allow clinicians to screen for memory impairment with greater precision among normally aging individuals, thus improving differential diagnosis between physiologic and pathologic deterioration of cognitive functions.

  5. First-Year Medical Students' Naïve Beliefs about Respiratory Physiology

    ERIC Educational Resources Information Center

    Badenhorst, Elmi; Mamede, Silvia; Abrahams, Amaal; Bugarith, Kishor; Friedling, Jacqui; Gunston, Geney; Kelly-Laubscher, Roisin; Schmidt, Henk G.

    2016-01-01

    The present study explored the nature and frequency of physiology naïve beliefs by investigating novices' understanding of the respiratory system. Previous studies have shown considerable misconceptions related to physiology but focused mostly on specific physiological processes of normal respiration. Little is known about novices' broader…

  6. Reduced G tolerance associated with supplement use.

    PubMed

    Barker, Patrick D

    2011-02-01

    High G forces encountered in tactical military aviation and aerobatic flight produce a host of physiologic responses aimed at preserving cerebral perfusion. The military has instituted measures to augment the physiologic response in order to avoid G-induced loss of consciousness (G-LOC) because of its potential to cause a catastrophic mishap. The case presented here details a Naval Aviator who experienced reduced G tolerance over two successive flights with a temporal relationship of starting a new supplement. Two components of the supplement, coenzyme Q10 and niacin, are highlighted here for their hemodynamic effects. After stopping the supplement the aviator regained his normal G tolerance and had no further issues in flight. There are several factors that can reduce G tolerance and supplement use has to be considered here because of the potential for altering the normal physiological response to increased G force. Our discussion reviews the physiological effects of increased G force, the spectrum of signs of decompensation under the stress of G force, and the potential effects this supplement had on the normal physiological response to increased G force, thus reducing the aviator's G tolerance.

  7. A stochastic differential equation model of diurnal cortisol patterns

    NASA Technical Reports Server (NTRS)

    Brown, E. N.; Meehan, P. M.; Dempster, A. P.

    2001-01-01

    Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems.

  8. Use of ambient light in remote photoplethysmographic systems: comparison between a high-performance camera and a low-cost webcam.

    PubMed

    Sun, Yu; Papin, Charlotte; Azorin-Peris, Vicente; Kalawsky, Roy; Greenwald, Stephen; Hu, Sijung

    2012-03-01

    Imaging photoplethysmography (PPG) is able to capture useful physiological data remotely from a wide range of anatomical locations. Recent imaging PPG studies have concentrated on two broad research directions involving either high-performance cameras and or webcam-based systems. However, little has been reported about the difference between these two techniques, particularly in terms of their performance under illumination with ambient light. We explore these two imaging PPG approaches through the simultaneous measurement of the cardiac pulse acquired from the face of 10 male subjects and the spectral characteristics of ambient light. Measurements are made before and after a period of cycling exercise. The physiological pulse waves extracted from both imaging PPG systems using the smoothed pseudo-Wigner-Ville distribution yield functional characteristics comparable to those acquired using gold standard contact PPG sensors. The influence of ambient light intensity on the physiological information is considered, where results reveal an independent relationship between the ambient light intensity and the normalized plethysmographic signals. This provides further support for imaging PPG as a means for practical noncontact physiological assessment with clear applications in several domains, including telemedicine and homecare. © 2012 Society of Photo-Optical Instrumentation Engineers (SPIE).

  9. What goes on behind closed doors: physiological vs. pharmacological steroid hormone actions

    PubMed Central

    Simons, S. Stoney

    2009-01-01

    Summary Steroid hormone-activated receptor proteins are among the best understood class of factors for altering gene transcription in cells. Steroid receptors are of major importance in maintaining normal human physiology by responding to circulating concentrations of steroid in the nM range. Nonetheless, most studies of steroid receptor action have been conducted using the supra-physiological conditions of saturating concentrations (≥100 nM) of potent synthetic steroid agonists. Here we summarize the recent developments arising from experiments using two clinically relevant conditions: subsaturating concentrations of agonist (to mimic the circulating concentrations in mammals) and saturating concentrations of antagonists (which are employed in endocrine therapies to block the actions of endogenous steroids). These studies have revealed new facets of steroid hormone action that could not be uncovered by conventional experiments with saturating concentrations of agonist steroids, such as a plethora of factors/conditions for the differential control of gene expression by physiological levels of steroid, a rational approach for examining the gene-specific variations in partial agonist activity of antisteroids, and a dissociation of steroid potency and efficacy that implies the existence of separate, and possibly novel, mechanistic steps and cofactors. PMID:18623071

  10. Use of ambient light in remote photoplethysmographic systems: comparison between a high-performance camera and a low-cost webcam

    NASA Astrophysics Data System (ADS)

    Sun, Yu; Papin, Charlotte; Azorin-Peris, Vicente; Kalawsky, Roy; Greenwald, Stephen; Hu, Sijung

    2012-03-01

    Imaging photoplethysmography (PPG) is able to capture useful physiological data remotely from a wide range of anatomical locations. Recent imaging PPG studies have concentrated on two broad research directions involving either high-performance cameras and or webcam-based systems. However, little has been reported about the difference between these two techniques, particularly in terms of their performance under illumination with ambient light. We explore these two imaging PPG approaches through the simultaneous measurement of the cardiac pulse acquired from the face of 10 male subjects and the spectral characteristics of ambient light. Measurements are made before and after a period of cycling exercise. The physiological pulse waves extracted from both imaging PPG systems using the smoothed pseudo-Wigner-Ville distribution yield functional characteristics comparable to those acquired using gold standard contact PPG sensors. The influence of ambient light intensity on the physiological information is considered, where results reveal an independent relationship between the ambient light intensity and the normalized plethysmographic signals. This provides further support for imaging PPG as a means for practical noncontact physiological assessment with clear applications in several domains, including telemedicine and homecare.

  11. Zinc: physiology, deficiency, and parenteral nutrition.

    PubMed

    Livingstone, Callum

    2015-06-01

    The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN. © 2015 American Society for Parenteral and Enteral Nutrition.

  12. Metabolic physiology of the Humboldt squid, Dosidicus gigas: Implications for vertical migration in a pronounced oxygen minimum zone

    NASA Astrophysics Data System (ADS)

    Rosa, Rui; Seibel, Brad A.

    2010-07-01

    The Humboldt (or jumbo) squid, Dosidicus gigas, is an active predator endemic to the Eastern Pacific that undergoes diel vertical migrations into a pronounced oxygen minimum layer (OML). Here, we investigate the physiological mechanisms that facilitate these migrations and assess the associated costs and benefits. Exposure to hypoxic conditions equivalent to those found in the OML (∼10 μM O 2 at 10 °C) led to a significant reduction in the squid’s routine metabolic rate (RMR), from 8.9 to 1.6 μmol O 2 g -1 h -1 ( p < 0.05), and a concomitant increase in mantle muscle octopine levels (from 0.50 to 5.24 μmol g -1 tissue, p < 0.05). Enhanced glycolitic ATP production accounted for only 7.0% and 2.8% at 10 °C and 20 °C, respectively, of the energy deficit that resulted from the decline in aerobic respiration. The observed metabolic suppression presumably extends survival time in the OML by conserving the finite stores of fermentable substrate and avoiding the accumulation of the deleterious anaerobic end products in the tissues. RMR increased significantly with temperature ( p < 0.05), from 8.9 (at 10 °C) to 49.85 μmol O 2 g -1 h -1 (at 25 °C) which yielded a Q10 of 2.0 between 10 and 20 °C and 7.9 between 20 and 25 °C ( p < 0.05). These results suggest that 25 °C, although within the normal surface temperature range in the Gulf of California, is outside this species’ normal temperature range. By following the scattering layer into oxygen-enriched shallow water at night, D. gigas may repay any oxygen debt accumulated during the daytime. The dive to deeper water may minimize exposure to stressful surface temperatures when most prey have migrated to depth during the daytime. The physiological and ecological strategies demonstrated here may have facilitated the recent range expansion of this species into northern waters where expanding hypoxic zones prohibit competing top predators.

  13. The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium.

    PubMed

    Milani-Nejad, Nima; Canan, Benjamin D; Elnakish, Mohammad T; Davis, Jonathan P; Chung, Jae-Hoon; Fedorov, Vadim V; Binkley, Philip F; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2015-12-15

    Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization (P < 0.05), indicating the expected pathological myocardium in the right ventricles. We found that there exists a length-dependent regulation of cross-bridge cycling kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P < 0.05) equally; there were no major differences between nonfailing and failing myocardium at each respective length (P > 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients. Copyright © 2015 the American Physiological Society.

  14. Normative aging of the respiratory system.

    PubMed

    Zeleznik, Jomarie

    2003-02-01

    An absolute quantified normal rate of change and normal range of functions of the respiratory system applicable to all older adults as they age is elusive. Like life expectancy, which is dependent on a cohort effect, the norms of respiratory system function are related to the birth cohort to which a given individual belongs and the age at which the parameter is assessed. No single rate of change can express normal across all age ranges even for those individuals in apparently good health [29]. Analogous to defining risk factors for a disease, determining that a change in anatomy or physiology is not disease requires stringent prospective evaluation for the absence of occult disease and known risk factors for disease prior to concluding that the alteration is inevitable with the normal aging process [19,31]. Additional limitations in quantifying the norms of respiratory function with age are the lack of participation of the oldest adults in studies and the lack of precision and accuracy in these performance-based measurements. The data, although limited, do support a qualitative emphysematous change in lung histology and lung-thorax mechanics. This change plus altered lung volumes influence oxygenation and oxygen consumption. There is no evidence that the changes in the respiratory system with aging impact day-to-day function of older adults, but they may become evident under circumstances when physiologic demand reaches the limits of supply. Despite changes in cholinergic and adrenergic receptor functioning, there is no evidence to suggest altering prescribing these classes of medications for older people. Pioneer physiologists asked the original question "Is there a difference in this measurement for older people?" Researchers in pulmonary medicine, pathology, radiology, epidemiology, and public health have continued to revise the question toward the clinical implications while studying the aging process from their respective viewpoints. Clinicians who need to develop an integrated care plan should neither rely on formulas to "normalize" a measurement for age nor assume that a established predictive value of a diagnostic test done in young adults can be automatically applied to geriatric patients [4]. Rather, the clinical situation should consider that the variability in normal is greater with older age and that all diagnostic tests and care plans should be considered in the context of the patient's symptoms [5].

  15. Group management influences reproductive function of the male cheetah (Acinonyx jubatus).

    PubMed

    Koester, Diana C; Freeman, Elizabeth W; Wildt, David E; Terrell, Kimberly A; Franklin, Ashley D; Meeks, Karen; Crosier, Adrienne E

    2017-03-01

    Although the free-ranging cheetah is generally socially solitary, as many as 60% of males live in same-sex (usually sibling) coalitions. Under ex situ conditions, the cheetah experiences low reproductive success with only ~18% of males having ever produced young. Most male cheetahs (85%) are managed in captivity in coalitions, but with no data on the influence of social grouping on reproductive parameters. We examined the influence of singleton versus coalition management on various male cheetah physiological traits, including ejaculate quality and gonadal and adrenal hormone metabolite concentrations. We also assessed behaviour within coalitions for evidence of social hierarchy through initiation of interactions with group mates and relatedness to physiological traits. Ejaculate quality (including total motile and structurally normal spermatozoa per ejaculate) and androgen concentration profiles were higher (P<0.05) in coalition compared with singleton males. These results support the conclusion that testis function in the cheetah, specifically related to the development of normal, motile spermatozoa and androgen production, is influenced by management with same-sex conspecifics. The findings have implications for ex situ conservation breeding programs by suggesting that reproductive quality can be enhanced through group maintenance of cheetah males.

  16. Exploration of a physiologically-inspired hearing-aid algorithm using a computer model mimicking impaired hearing.

    PubMed

    Jürgens, Tim; Clark, Nicholas R; Lecluyse, Wendy; Meddis, Ray

    2016-01-01

    To use a computer model of impaired hearing to explore the effects of a physiologically-inspired hearing-aid algorithm on a range of psychoacoustic measures. A computer model of a hypothetical impaired listener's hearing was constructed by adjusting parameters of a computer model of normal hearing. Absolute thresholds, estimates of compression, and frequency selectivity (summarized to a hearing profile) were assessed using this model with and without pre-processing the stimuli by a hearing-aid algorithm. The influence of different settings of the algorithm on the impaired profile was investigated. To validate the model predictions, the effect of the algorithm on hearing profiles of human impaired listeners was measured. A computer model simulating impaired hearing (total absence of basilar membrane compression) was used, and three hearing-impaired listeners participated. The hearing profiles of the model and the listeners showed substantial changes when the test stimuli were pre-processed by the hearing-aid algorithm. These changes consisted of lower absolute thresholds, steeper temporal masking curves, and sharper psychophysical tuning curves. The hearing-aid algorithm affected the impaired hearing profile of the model to approximate a normal hearing profile. Qualitatively similar results were found with the impaired listeners' hearing profiles.

  17. [Results of a dynamic study on the status of health and nutrition of a Siberian vegan settlement].

    PubMed

    Medkova, I L; Mosiakina, L I; Biriukova, L S

    2001-01-01

    In 1996 for the first time a study of state of health, living conditions and nutrition status of 84 persons from the Siberian settlement of the rigorous vegetarians--vegans and 26 aboriginal inhabitants who feed on a traditional mixed diet was carried out. The clinical and laboratory investigations are kept. The positive influencing vegan ration on a serum lipids, body weight, state of cardiovascular system was showed. The contents of vitamin B12 and serum iron in vegans was in normal physiological range. The level of blood calcium was reduced in comparison with control. Increased contents of copper and zinc in blood was marked both in vegans and in control group. The repeated examination of 77 vegans of the same settlement in 1999 has revealed positive alterations in serum lipids: augmentation of cholesterol of high density lipoproteins on the average on 54.3%, that result in a reliable decrease of atherogenicity coefficient. The decrease to normal amounts of blood copper and zinc, and also increase of blood calcium on the average on 16% was marked. However level of calcium remained below than physiological values.

  18. Sex-Based Differences in Physiology: What Should We Teach in the Medical Curriculum?

    ERIC Educational Resources Information Center

    Blair, Martha L.

    2007-01-01

    An abundance of recent research indicates that there are multiple differences between males and females both in normal physiology and in the pathophysiology of disease. The Refresher Course on Gender Differences in Physiology, sponsored by the American Physiological Society Education Committee at the 2006 Experimental Biology Meeting in San…

  19. Vital signs and other observations used to detect deterioration in pregnant women: an analysis of vital sign charts in consultant-led UK maternity units.

    PubMed

    Smith, G B; Isaacs, R; Andrews, L; Wee, M Y K; van Teijlingen, E; Bick, D E; Hundley, V

    2017-05-01

    Obstetric early warning systems are recommended for monitoring hospitalised pregnant and postnatal women. We decided to compare: (i) vital sign values used to define physiological normality; (ii) symptoms and signs used to escalate care; (iii) type of chart used; and (iv) presence of explicit instructions for escalating care. One-hundred-and-twenty obstetric early warning charts and escalation protocols were obtained from consultant-led maternity units in the UK and Channel Islands. These data were extracted: values used to determine normality for each maternal vital sign; chart colour-coding; instructions following early warning system triggering; other criteria used as triggers. There was considerable variation in the charts, warning systems and escalation protocols. Of 120 charts, 89.2% used colour; 69.2% used colour-coded escalation systems. Forty-one (34.2%) systems required the calculation of weighted scores. Seventy-five discrete combinations of 'normal' vital sign ranges were found, the most common being: heart rate=50-99beats/min; respiratory rate=11-20breaths/min; blood pressure, systolic=100-149mmHg, diastolic ≤89mmHg; SpO 2 =95-100%; temperature=36.0-37.9°C; and Alert-Voice-Pain-Unresponsive assessment=Alert. Most charts (90.8%) provided instructions about who to contact following triggering, but only 41.7% gave instructions about subsequent observation frequency. The wide range of 'normal' vital sign values in different systems suggests a lack of equity in the processes for detecting deterioration and escalating care in hospitalised pregnant and postnatal women. Agreement regarding 'normal' vital sign ranges is urgently required and would assist the development of a standardised obstetric early warning system and chart. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. A closed-loop hybrid physiological model relating to subjects under physical stress.

    PubMed

    El-Samahy, Emad; Mahfouf, Mahdi; Linkens, Derek A

    2006-11-01

    The objective of this research study is to derive a comprehensive physiological model relating to subjects under physical stress conditions. The model should describe the behaviour of the cardiovascular system, respiratory system, thermoregulation and brain activity in response to physical workload. An experimental testing rig was built which consists of recumbent high performance bicycle for inducing the physical load and a data acquisition system comprising monitors and PCs. The signals acquired and used within this study are the blood pressure, heart rate, respiration, body temperature, and EEG signals. The proposed model is based on a grey-box based modelling approach which was used because of the sufficient level of details it provides. Cardiovascular and EEG Data relating to 16 healthy subject volunteers (data from 12 subjects were used for training/validation and the data from 4 subjects were used for model testing) were collected using the Finapres and the ProComp+ monitors. For model validation, residual analysis via the computing of the confidence intervals as well as related histograms was performed. Closed-loop simulations for different subjects showed that the model can provide reliable predictions for heart rate, blood pressure, body temperature, respiration, and the EEG signals. These findings were also reinforced by the residual analyses data obtained, which suggested that the residuals were within the 90% confidence bands and that the corresponding histograms were of a normal distribution. A higher intelligent level was added to the model, based on neural networks, to extend the capabilities of the model to predict over a wide range of subjects dynamics. The elicited physiological model describing the effect of physiological stress on several physiological variables can be used to predict performance breakdown of operators in critical environments. Such a model architecture lends itself naturally to exploitation via feedback control in a 'reverse-engineering' fashion to control stress via the specification of a safe operating range for the psycho-physiological variables.

  1. Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep.

    PubMed

    Huupponen, E; Maksimow, A; Lapinlampi, P; Särkelä, M; Saastamoinen, A; Snapir, A; Scheinin, H; Scheinin, M; Meriläinen, P; Himanen, S-L; Jääskeläinen, S

    2008-02-01

    Dexmedetomidine, a selective alpha(2)-adrenoceptor agonist, induces a unique, sleep-like state of sedation. The objective of the present work was to study human electroencephalogram (EEG) sleep spindles during dexmedetomidine sedation and compare them with spindles during normal physiological sleep, to test the hypothesis that dexmedetomidine exerts its effects via normal sleep-promoting pathways. EEG was continuously recorded from a bipolar frontopolar-laterofrontal derivation with Entropy Module (GE Healthcare) during light and deep dexmedetomidine sedation (target-controlled infusions set at 0.5 and 3.2 ng/ml) in 11 healthy subjects, and during physiological sleep in 10 healthy control subjects. Sleep spindles were visually scored and quantitatively analyzed for density, duration, amplitude (band-pass filtering) and frequency content (matching pursuit approach), and compared between the two groups. In visual analysis, EEG activity during dexmedetomidine sedation was similar to physiological stage 2 (S2) sleep with slight to moderate amount of slow-wave activity and abundant sleep spindle activity. In quantitative EEG analyses, sleep spindles were similar during dexmedetomidine sedation and normal sleep. No statistically significant differences were found in spindle density, amplitude or frequency content, but the spindles during dexmedetomidine sedation had longer duration (mean 1.11 s, SD 0.14 s) than spindles in normal sleep (mean 0.88 s, SD 0.14 s; P=0.0014). Analysis of sleep spindles shows that dexmedetomidine produces a state closely resembling physiological S2 sleep in humans, which gives further support to earlier experimental evidence for activation of normal non-rapid eye movement sleep-promoting pathways by this sedative agent.

  2. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

    PubMed

    Smith, Carli J; Emge, Jacob R; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M; Sousa, Andrew J; Reardon, Colin; Sherman, Philip M; Barrett, Kim E; Gareau, Mélanie G

    2014-10-15

    The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. Copyright © 2014 the American Physiological Society.

  3. Scale-Free Neural and Physiological Dynamics in Naturalistic Stimuli Processing

    PubMed Central

    Lin, Amy

    2016-01-01

    Abstract Neural activity recorded at multiple spatiotemporal scales is dominated by arrhythmic fluctuations without a characteristic temporal periodicity. Such activity often exhibits a 1/f-type power spectrum, in which power falls off with increasing frequency following a power-law function: P(f)∝1/fβ, which is indicative of scale-free dynamics. Two extensively studied forms of scale-free neural dynamics in the human brain are slow cortical potentials (SCPs)—the low-frequency (<5 Hz) component of brain field potentials—and the amplitude fluctuations of α oscillations, both of which have been shown to carry important functional roles. In addition, scale-free dynamics characterize normal human physiology such as heartbeat dynamics. However, the exact relationships among these scale-free neural and physiological dynamics remain unclear. We recorded simultaneous magnetoencephalography and electrocardiography in healthy subjects in the resting state and while performing a discrimination task on scale-free dynamical auditory stimuli that followed different scale-free statistics. We observed that long-range temporal correlation (captured by the power-law exponent β) in SCPs positively correlated with that of heartbeat dynamics across time within an individual and negatively correlated with that of α-amplitude fluctuations across individuals. In addition, across individuals, long-range temporal correlation of both SCP and α-oscillation amplitude predicted subjects’ discrimination performance in the auditory task, albeit through antagonistic relationships. These findings reveal interrelations among different scale-free neural and physiological dynamics and initial evidence for the involvement of scale-free neural dynamics in the processing of natural stimuli, which often exhibit scale-free dynamics. PMID:27822495

  4. A brain imaging repository of normal structural MRI across the life course: Brain Images of Normal Subjects (BRAINS).

    PubMed

    Job, Dominic E; Dickie, David Alexander; Rodriguez, David; Robson, Andrew; Danso, Sammy; Pernet, Cyril; Bastin, Mark E; Boardman, James P; Murray, Alison D; Ahearn, Trevor; Waiter, Gordon D; Staff, Roger T; Deary, Ian J; Shenkin, Susan D; Wardlaw, Joanna M

    2017-01-01

    The Brain Images of Normal Subjects (BRAINS) Imagebank (http://www.brainsimagebank.ac.uk) is an integrated repository project hosted by the University of Edinburgh and sponsored by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaborators. BRAINS provide sharing and archiving of detailed normal human brain imaging and relevant phenotypic data already collected in studies of healthy volunteers across the life-course. It particularly focusses on the extremes of age (currently older age, and in future perinatal) where variability is largest, and which are under-represented in existing databanks. BRAINS is a living imagebank where new data will be added when available. Currently BRAINS contains data from 808 healthy volunteers, from 15 to 81years of age, from 7 projects in 3 centres. Additional completed and ongoing studies of normal individuals from 1st to 10th decades are in preparation and will be included as they become available. BRAINS holds several MRI structural sequences, including T1, T2, T2* and fluid attenuated inversion recovery (FLAIR), available in DICOM (http://dicom.nema.org/); in future Diffusion Tensor Imaging (DTI) will be added where available. Images are linked to a wide range of 'textual data', such as age, medical history, physiological measures (e.g. blood pressure), medication use, cognitive ability, and perinatal information for pre/post-natal subjects. The imagebank can be searched to include or exclude ranges of these variables to create better estimates of 'what is normal' at different ages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. [Peculiarities of cerebral structures functioning in adolescents with achondroplasia].

    PubMed

    Skripnikov, A A; Dolganova, T I; Aranovich, A M

    2013-01-01

    Complex neurophysiological examination (rheoencephalography, electroencephalography) was carried out in 12 adolescents 12 to 18 years old in order to reveal the peculiarities of cerebral structures functioning in adolescents with achondroplasia. Some deviations from the normal values were found out: reduced blood filling of the brain vessels in the pools of a. carotis interna and a. vertebralis, rheoencephalographic signs of intracranial hypertension of mild degree and brain cycling characterized by moderate and significant amplitude increase, presence of pathological types (delta-, theta-) of the rhythmics and the reduction of the physiological ones (alpha-, beta-). At the same time the peculiarities of rheoencephalographic indices were observed while functional testings (hypercapnia, hyperoxia). Brain cycling differed from normal values by weaker response to the weight-bearing, mainly in alpha- and beta-ranges.

  6. An Extended Normalization Model of Attention Accounts for Feature-Based Attentional Enhancement of Both Response and Coherence Gain

    PubMed Central

    Krishna, B. Suresh; Treue, Stefan

    2016-01-01

    Paying attention to a sensory feature improves its perception and impairs that of others. Recent work has shown that a Normalization Model of Attention (NMoA) can account for a wide range of physiological findings and the influence of different attentional manipulations on visual performance. A key prediction of the NMoA is that attention to a visual feature like an orientation or a motion direction will increase the response of neurons preferring the attended feature (response gain) rather than increase the sensory input strength of the attended stimulus (input gain). This effect of feature-based attention on neuronal responses should translate to similar patterns of improvement in behavioral performance, with psychometric functions showing response gain rather than input gain when attention is directed to the task-relevant feature. In contrast, we report here that when human subjects are cued to attend to one of two motion directions in a transparent motion display, attentional effects manifest as a combination of input and response gain. Further, the impact on input gain is greater when attention is directed towards a narrow range of motion directions than when it is directed towards a broad range. These results are captured by an extended NMoA, which either includes a stimulus-independent attentional contribution to normalization or utilizes direction-tuned normalization. The proposed extensions are consistent with the feature-similarity gain model of attention and the attentional modulation in extrastriate area MT, where neuronal responses are enhanced and suppressed by attention to preferred and non-preferred motion directions respectively. PMID:27977679

  7. On the continuity of mean total normal stress in geometrical multiscale cardiovascular problems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blanco, Pablo J., E-mail: pjblanco@lncc.br; INCT-MACC, Instituto Nacional de Ciência e Tecnologia em Medicina Assistida por Computação Científica, Petrópolis; Deparis, Simone, E-mail: simone.deparis@epfl.ch

    2013-10-15

    In this work an iterative strategy to implicitly couple dimensionally-heterogeneous blood flow models accounting for the continuity of mean total normal stress at interface boundaries is developed. Conservation of mean total normal stress in the coupling of heterogeneous models is mandatory to satisfy energetic consistency between them. Nevertheless, existing methodologies are based on modifications of the Navier–Stokes variational formulation, which are undesired when dealing with fluid–structure interaction or black box codes. The proposed methodology makes possible to couple one-dimensional and three-dimensional fluid–structure interaction models, enforcing the continuity of mean total normal stress while just imposing flow rate data or evenmore » the classical Neumann boundary data to the models. This is accomplished by modifying an existing iterative algorithm, which is also able to account for the continuity of the vessel area, when required. Comparisons are performed to assess differences in the convergence properties of the algorithms when considering the continuity of mean normal stress and the continuity of mean total normal stress for a wide range of flow regimes. Finally, examples in the physiological regime are shown to evaluate the importance, or not, of considering the continuity of mean total normal stress in hemodynamics simulations.« less

  8. Brassinosteroids

    PubMed Central

    Clouse, Steven D.

    2011-01-01

    Brassinosteroids (BRs) are endogenous plant hormones essential for the proper regulation of multiple physiological processes required for normal plant growth and development. Since their discovery more than 30 years ago, extensive research on the mechanisms of BR action using biochemistry, mutant studies, proteomics and genome-wide transcriptome analyses, has helped refine the BR biosynthetic pathway, identify the basic molecular components required to relay the BR signal from perception to gene regulation, and expand the known physiological responses influenced by BRs. These mechanistic advances have helped answer the intriguing question of how BRs can have such dramatic pleiotropic effects on a broad range of diverse developmental pathways and have further pointed to BR interactions with other plant hormones and environmental cues. This chapter briefly reviews historical aspects of BR research and then summarizes the current state of knowledge on BR biosynthesis, metabolism and signal transduction. Recent studies uncovering novel phosphorelays and gene regulatory networks through which BR influences both vegetative and reproductive development are examined and placed in the context of known BR physiological responses including cell elongation and division, vascular differentiation, flowering, pollen development and photomorphogenesis. PMID:22303275

  9. Two Oral Midazolam Preparations in Pediatric Dental Patients: A Prospective Randomised Clinical Trial

    PubMed Central

    Kamranzadeh, Shaqayegh; Kousha, Maryam; Shaeghi, Shahnaz; AbdollahGorgi, Fatemeh

    2015-01-01

    Pharmacological sedation is an alternative behavior management strategy in pediatric dentistry. The aim of this study was to compare the behavioral and physiologic effects of “commercially midazolam syrup” versus “orally administered IV midazolam dosage form (extemporaneous midazolam (EF))” in uncooperative pediatric dental patients. Eighty-eight children between 4 to 7 years of age received 0.2–0.5 mg/kg midazolam in this parallel trial. Physiologic parameters were recorded at baseline and every 15 minutes. Behavior assessment was conducted objectively by Houpt scale throughout the sedation and North Carolina at baseline and during injection and cavity preparation. No significant difference in behavior was noted by Houpt or North Carolina scale. Acceptable behavior (excellent, very good, and good) was observed in 90.9% of syrup and 79.5% of EF subjects, respectively. Physiological parameters remained in normal range without significant difference between groups and no adverse effect was observed. It is concluded that EF midazolam preparation can be used as an acceptable alternative to midazolam syrup. PMID:26120325

  10. Insulin-producing cells could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells

    PubMed Central

    2013-01-01

    Objective The aim of this study was to compare the difference between insulin-producing cells (IPCs) and normal human pancreatic beta cells both in physiological function and morphological features in cellular level. Methods The levels of insulin secretion were measured by enzyme-linked immunosorbent assay. The insulin gene expression was determined by real-time quantitative polymerase chain reaction. The morphological features were detected by atomic force microscopy (AFM) and laser confocal scanning microscopy. Results IPCs and normal human pancreatic beta cells were similar to each other under the observation in AFM with the porous structure features in the cytoplasm. Both number of membrane particle size and average roughness of normal human beta cells were higher than those of IPCs. Conclusions Our results firstly revealed that the cellular ultrastructure of IPCs was closer to that of normal human pancreatic beta cells, but they still could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. PMID:23421382

  11. A comparison of a novel testosterone bioadhesive buccal system, striant, with a testosterone adhesive patch in hypogonadal males.

    PubMed

    Korbonits, Márta; Slawik, Marc; Cullen, Derek; Ross, Richard J; Stalla, Günter; Schneider, Harald; Reincke, Martin; Bouloux, Pierre M; Grossman, Ashley B

    2004-05-01

    A novel delivery system has been developed for testosterone replacement. This formulation, COL-1621 (Striant), a testosterone-containing buccal mucoadhesive system, has been shown in preliminary studies to replace testosterone at physiological levels when used twice daily. Therefore, the current study compared the steady-state pharmacokinetics and tolerability of the buccal system with a testosterone-containing skin patch (Andropatch or Androderm) in an international multicenter study of a group of hypogonadal men. Sixty-six patients were randomized into two groups; one applied the buccal system twice daily, whereas the other applied the transdermal patch daily, in each case for 7 d. Serum total testosterone and dihydrotestosterone concentrations were measured at d 1, 3 or 4, and 6, and serially over the last 24 h of the study. Pharmacokinetic parameters for each formulation were calculated, and the two groups were compared. The tolerability of both formulations was also evaluated. Thirty-three patients were treated with the buccal preparation, and 34 were treated with the transdermal patch. The average serum testosterone concentration over 24 h showed a mean of 18.74 nmol/liter (SD =; 5.90) in the buccal system group and 12.15 nmol/liter (SD =; 5.55) in the transdermal patch group (P < 0.01). Of the patients treated with the buccal system, 97% had average steady-state testosterone concentrations within the physiological range (10.41-36.44 nmol/liter), whereas only 56% of the transdermal patch patients achieved physiological total testosterone concentrations (P < 0.001 between groups). Testosterone concentrations were within the physiological range in the buccal system group for a significantly greater portion of the 24-h treatment period than in the transdermal patch group (mean, 84.9% vs. 54.9%; P < 0.001). Testosterone/dihydrotestosterone ratios were physiological and similar in both groups. Few patients experienced major adverse effects from either treatment. No significant local tolerability problems were noted with the buccal system, other than a single patient withdrawal. We conclude that this buccal system is superior to the transdermal patch in achieving testosterone concentrations within the normal range. It may, therefore, be a valuable addition to the range of choices for testosterone replacement therapy.

  12. Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

    NASA Technical Reports Server (NTRS)

    Alperin, Noam; Barr, Yael; Lee, Sang H.; Mason,Sara; Bagci, Ahmet M.

    2015-01-01

    Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed in a subject with VIIP signs. Study limitations include a slightly longer landing-to-MRI scan period for the short-duration cohort and limited sensitivity of the subjective discrete ordinal CPG scale. This limitation can be overcome by using imaging based parametric measures of VIIP severity such as globe deformation measures.

  13. Quantitative, simultaneous, and collinear eye-tracked, high dynamic range optical coherence tomography at 850 and 1060 nm

    NASA Astrophysics Data System (ADS)

    Mooser, Matthias; Burri, Christian; Stoller, Markus; Luggen, David; Peyer, Michael; Arnold, Patrik; Meier, Christoph; Považay, Boris

    2017-07-01

    Ocular optical coherence tomography at the wavelengths ranges of 850 and 1060 nm have been integrated with a confocal scanning laser ophthalmoscope eye-tracker as a clinical commercial-class system. Collinear optics enables an exact overlap of the different channels to produce precisely overlapping depth-scans for evaluating the similarities and differences between the wavelengths to extract additional physiologic information. A reliable segmentation algorithm utilizing Graphcuts has been implemented and applied to automatically extract retinal and choroidal shape in cross-sections and volumes. The device has been tested in normals and pathologies including a cross-sectional and longitudinal study of myopia progress and control with a duplicate instrument in Asian children.

  14. Abnormal pulmonary function in adults with sickle cell anemia.

    PubMed

    Klings, Elizabeth S; Wyszynski, Diego F; Nolan, Vikki G; Steinberg, Martin H

    2006-06-01

    Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 +/- 14.7% predicted) and DLCO (64.5 +/- 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DLCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function.

  15. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    NASA Astrophysics Data System (ADS)

    Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

    2013-06-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

  16. Near-Infrared Fluorescent Nanoprobes for Revealing the Role of Dopamine in Drug Addiction.

    PubMed

    Feng, Peijian; Chen, Yulei; Zhang, Lei; Qian, Cheng-Gen; Xiao, Xuanzhong; Han, Xu; Shen, Qun-Dong

    2018-02-07

    Brain imaging techniques enable visualizing the activity of central nervous system without invasive neurosurgery. Dopamine is an important neurotransmitter. Its fluctuation in brain leads to a wide range of diseases and disorders, like drug addiction, depression, and Parkinson's disease. We designed near-infrared fluorescence dopamine-responsive nanoprobes (DRNs) for brain activity imaging during drug abuse and addiction process. On the basis of light-induced electron transfer between DRNs and dopamine and molecular wire effect of the DRNs, we can track the dynamical change of the neurotransmitter level in the physiological environment and the releasing of the neurotransmitter in living dopaminergic neurons in response to nicotine stimulation. The functional near-infrared fluorescence imaging can dynamically track the dopamine level in the mice midbrain under normal or drug-activated condition and evaluate the long-term effect of addictive substances to the brain. This strategy has the potential for studying neural activity under physiological condition.

  17. Nutritional support of the elderly cancer patient: the role of the nurse.

    PubMed

    Hopkinson, Jane B

    2015-04-01

    Cancer in the geriatric population is a growing problem. Malnutrition is common in cancer. A number of factors increase the risk for malnutrition in older people with cancer, including chronic comorbid conditions and normal physiological changes of aging. Nurses have an important role in the nutritional support of older cancer patients. To contribute to the improvement of nutritional support of these patients, nurses need appropriate training to be able to identify risk for malnutrition and offer a range of interventions tailored to individual need. Factors to consider in tailoring interventions include disease status, cancer site, cancer treatment, comorbidity, physiological age, method of facilitating dietary change, and family support. This article identifies ways in which nurses can contribute to the nutritional support of older cancer patients and thus help mitigate the effects of malnutrition. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    NASA Technical Reports Server (NTRS)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  19. Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

    PubMed

    Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

    2016-05-01

    Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Stability of auditory discrimination and novelty processing in physiological aging.

    PubMed

    Raggi, Alberto; Tasca, Domenica; Rundo, Francesco; Ferri, Raffaele

    2013-01-01

    Complex higher-order cognitive functions and their possible changes with aging are mandatory objectives of cognitive neuroscience. Event-related potentials (ERPs) allow investigators to probe the earliest stages of information processing. N100, Mismatch negativity (MMN) and P3a are auditory ERP components that reflect automatic sensory discrimination. The aim of the present study was to determine if N100, MMN and P3a parameters are stable in healthy aged subjects, compared to those of normal young adults. Normal young adults and older participants were assessed using standardized cognitive functional instruments and their ERPs were obtained with an auditory stimulation at two different interstimulus intervals, during a passive paradigm. All individuals were within the normal range on cognitive tests. No significant differences were found for any ERP parameters obtained from the two age groups. This study shows that aging is characterized by a stability of the auditory discrimination and novelty processing. This is important for the arrangement of normative for the detection of subtle preclinical changes due to abnormal brain aging.

  1. Thermal sensation and climate: a comparison of UTCI and PET thresholds in different climates

    NASA Astrophysics Data System (ADS)

    Pantavou, Katerina; Lykoudis, Spyridon; Nikolopoulou, Marialena; Tsiros, Ioannis X.

    2018-06-01

    The influence of physiological acclimatization and psychological adaptation on thermal perception is well documented and has revealed the importance of thermal experience and expectation in the evaluation of environmental stimuli. Seasonal patterns of thermal perception have been studied, and calibrated thermal indices' scales have been proposed to obtain meaningful interpretations of thermal sensation indices in different climate regions. The current work attempts to quantify the contribution of climate to the long-term thermal adaptation by examining the relationship between climate normal annual air temperature (1971-2000) and such climate-calibrated thermal indices' assessment scales. The thermal sensation ranges of two thermal indices, the Universal Thermal Climate Index (UTCI) and the Physiological Equivalent Temperature Index (PET), were calibrated for three warm temperate climate contexts (Cfa, Cfb, Csa), against the subjective evaluation of the thermal environment indicated by interviewees during field surveys conducted at seven European cities: Athens (GR), Thessaloniki (GR), Milan (IT), Fribourg (CH), Kassel (DE), Cambridge (UK), and Sheffield (UK), under the same research protocol. Then, calibrated scales for other climate contexts were added from the literature, and the relationship between the respective scales' thresholds and climate normal annual air temperature was examined. To maintain the maximum possible comparability, three methods were applied for the calibration, namely linear, ordinal, and probit regression. The results indicated that the calibrated UTCI and PET thresholds increase with the climate normal annual air temperature of the survey city. To investigate further climates, we also included in the analysis results of previous studies presenting only thresholds for neutral thermal sensation. The average increase of the respective thresholds in the case of neutral thermal sensation was about 0.6 °C for each 1 °C increase of the normal annual air temperature for both indices, statistically significant only for PET though.

  2. Effect of environmental parameters on habitat structural weight and cost

    NASA Technical Reports Server (NTRS)

    Bock, E.; Lambrou, F., Jr.; Simon, M.

    1979-01-01

    Space-settlement conceptual designs were previously accomplished using earth-normal physiological conditions. The habitat weight and cost penalties associated with this conservative design approach are quantified. These penalties are identified by comparison of conservative earth-normal designs with habitats designed to less than earth-normal conditions. Physiological research areas are also recommended as a necessary prerequisite to realizing these potential weight and cost savings. Major habitat structural elements, that is, pressure shell and radiation shielding, for populations of 100, 10,000, and 1,000,000, are evaluated for effects of atmospheric pressure, pseudogravity level, radiation shielding thickness, and habitat configuration.

  3. Neutropenia - infants

    MedlinePlus

    ... Bliss JM, Mariscalco MM. Normal and abnormal neutrophil physiology in the newborn. In: Polin RA, Abman SH, ... Benitz WE, Fox WW, eds. Fetal and Neonatal Physiology . 5th ed. Philadelphia, PA: Elsevier; 2017:chap 126. ...

  4. Autonomic physiological data associated with simulator discomfort

    NASA Technical Reports Server (NTRS)

    Miller, James C.; Sharkey, Thomas J.; Graham, Glenna A.; Mccauley, Michael E.

    1993-01-01

    The development of a physiological monitoring capability for the Army's advanced helicopter simulator facility is reported. Additionally, preliminary physiological data is presented. Our objective was to demonstrate the sensitivity of physiological measures in this simulator to self-reported simulator sickness. The data suggested that heart period, hypergastria, and skin conductance level were more sensitive to simulator sickness than were vagal tone and normal electrogastric activity.

  5. The significance of oxygen during contact lens wear.

    PubMed

    Papas, Eric B

    2014-12-01

    In order to establish the relevance of oxygen to contemporary contact lens practice, a review of the literature was conducted. The results indicate that there are a number of processes occurring in the normal healthy eye where oxygen is required and which are potentially affected by the presence of a contact lens. These activities appear to take place at all corneal levels, as well as at the limbus. Evidence from laboratory, clinical and modelling studies indicates that what constitutes normal oxygenation (normoxia) depends on, among other things, the physiological system under consideration, corneal location and the state of eye closure. This diversity is reflected in the wide range of minimum lens oxygen transmissibility (Dk/t) requirements that are present in a literature. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  6. Serum Creatinine: Not So Simple!

    PubMed

    Delanaye, Pierre; Cavalier, Etienne; Pottel, Hans

    2017-01-01

    Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range). © 2017 S. Karger AG, Basel.

  7. Serum creatine kinase after exercise: drawing the line between physiological response and exertional rhabdomyolysis.

    PubMed

    Kenney, Kimbra; Landau, Mark E; Gonzalez, Rodney S; Hundertmark, Julie; O'Brien, Karen; Campbell, William W

    2012-03-01

    In this investigation we assessed the spectrum of creatine kinase (CK) responses in military recruits undergoing basic training. Musculoskeletal examination data, questionnaire findings, and CK levels were obtained from 499 recruits at days 0, 3, 7, and 14 of training. Correlations of CK with ethnicity, age, body mass index, exercise, muscle pain, and climate were obtained. None of the subjects developed clinical exertional rhabdomyolysis (ER). The mean/median serum CK values were 223/157, 734/478, 1226/567, and 667/486 IU/L at days 0, 3, 7, and 14, respectively, with a wide overall range (34-35,056 IU/L). African-American subjects had higher mean CK levels. CK elevations and muscle pain are common during basic training. Widely accepted laboratory diagnostic values for ER are routinely exceeded in this military recruits, suggesting that CK levels >50 times the upper limit of normal are more specific. The findings support using CK as a marker for ER. Normal laboratory reference ranges for CK should be published by ethnicity. Copyright © 2011 Wiley Periodicals, Inc.

  8. Determination of glutathione in human plasma using high-performance liquid chromatography with electrochemical detection with a carbon-epoxy resin composite electrode chemically modified with cobalt phthalocyanine.

    PubMed

    Wring, S A; Hart, J P; Birch, B J

    1989-12-01

    High-performance liquid chromatography with electrochemical detection (LCEC), incorporating a novel carbon-epoxy resin working electrode modified with cobalt phthalocyanine, has been employed for preliminary studies directed towards the determination of normal circulating levels of reduced glutathione (GSH) in human plasma. The mobile phase consisted of 0.05 M phosphate buffer (pH 3) containing 0.1% m/m ethylenediaminetetraacetic acid (EDTA); the calibration graph was linear in the range 0.24-30.7 ng of GSH injected. The mean recovery of GSH added to a control serum over the physiological concentration range (0.38-3.07 ng ml-1) was 99%; this was achieved following a simple sample pre-treatment method, prior to LCEC, involving chelation of divalent cations with EDTA and subsequent acidification with orthophosphoric acid. Using the LCEC method, the mean circulating level of GSH in plasma, found in three normal subjects, was 2.69 microM, GSH; this indicates that the method might be applicable to the determination of depressed circulating levels of GSH.

  9. Multiple functions of BCL-2 family proteins.

    PubMed

    Hardwick, J Marie; Soane, Lucian

    2013-02-01

    BCL-2 family proteins are the regulators of apoptosis, but also have other functions. This family of interacting partners includes inhibitors and inducers of cell death. Together they regulate and mediate the process by which mitochondria contribute to cell death known as the intrinsic apoptosis pathway. This pathway is required for normal embryonic development and for preventing cancer. However, before apoptosis is induced, BCL-2 proteins have critical roles in normal cell physiology related to neuronal activity, autophagy, calcium handling, mitochondrial dynamics and energetics, and other processes of normal healthy cells. The relative importance of these physiological functions compared to their apoptosis functions in overall organismal physiology is difficult to decipher. Apoptotic and noncanonical functions of these proteins may be intertwined to link cell growth to cell death. Disentanglement of these functions may require delineation of biochemical activities inherent to the characteristic three-dimensional shape shared by distantly related viral and cellular BCL-2 family members.

  10. Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

    PubMed Central

    Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

    2013-01-01

    Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

  11. Rectal intussusception and unexplained faecal incontinence: findings of a proctographic study.

    PubMed

    Collinson, R; Cunningham, C; D'Costa, H; Lindsey, I

    2009-01-01

    The aetiology of faecal incontinence is multifactorial, yet there remains an approach to assessment and treatment that focusses on the sphincter. Rectal intussusception (RI) is underdiagnosed and manifests primarily as obstructed defecation. Yet greater than 50% of these patients admit to faecal incontinence on closer questioning. We aimed to evaluate the incidence of RI at evacuation proctography selectively undertaken in the evaluation of patients with faecal incontinence. Patients with faecal incontinence seen in a pelvic floor clinic were evaluated with anorectal physiology and ultrasound. Where the faecal incontinence was not fully explained by physiology and ultrasound, evacuation proctography was undertaken. Studies were classified as 'normal', 'low-grade RI' (recto-rectal), 'high-grade RI' (recto-anal) or 'anismus'. Forty patients underwent evacuation proctography (33 women, 83%). Median age was 63 years (range 34-77 years). Seven patients (17%) had a normal proctogram. Three (8%) had recto-rectal RI. Twenty-five (63%) demonstrated recto-anal RI. Five patients (12%) had anismus. Recto-anal intussusception is common in patients undergoing selective evacuation proctography for investigation of faecal incontinence. The role of recto-anal intussusception in the multifactorial aetiology of faecal incontinence has been largely overlooked. Evacuation proctography should be considered as part of routine work-up of patients with faecal incontinence.

  12. PHYSIOLOGICAL EFFECTS OF DEUTERIUM ON DOGS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Czajka, D.M.; Finkel, A.J.; Fischer, C.S.

    1961-08-01

    The physiological consequences of the deuterium isotope effect in lange mammals were studied in two dogs, one of which was maintained at 20% concentration of D/sub 2/0 in the bcdy fluids for 50 days, and the other at the toxic range of 33-35% for a brief pericd. Deuteration of the dcgs was effected by replacement of ordinary water with deuterium oxide in both focd and drink. Hemoglobin, hematocrit, and red blood cell count dropped but the white blood cell count was essentially unaffected although there was a progressive lymphopenia and granulocytosis. Serum glucose was decreased, especially at higher deuterium levels.more » Total serum cholesterol values were also diminished although the esters were essentially unchanged. Serum sodium and both NPN and BUN were within normal limits except for a terminal elevation of the latter. Serum potassium was slightly lowered for a brief period after 3 weeks. Electrocardiograms showed ST segment coving and elevation and an increase in the QT ratio that suggested nonspecific myocardial damage; these changes reverted to normal while the dog was still deuterated at a level of 20%. Both dogs exhibited neuromuscular disturbances, in one case definite weakness of the hind legs and in the other, fine muscle tremors. (auth)« less

  13. Nonvisualization of the ovaries on pelvic ultrasound: does MRI add anything?

    PubMed

    Lisanti, Christopher J; Wood, Jonathan R; Schwope, Ryan B

    2014-02-01

    The purpose of our study is to assess the utility of pelvic magnetic resonance imaging (MRI) in the event that either one or both ovaries are not visualized by pelvic ultrasound. This HIPAA-compliant retrospective study was approved by our local institutional review board and informed consent waived. 1926 pelvic MRI examinations between March 2007 and December 2011 were reviewed and included if a combined transabdominal and endovaginal pelvic ultrasound had been performed in the preceding 6 months with at least one ovary nonvisualized. Ovaries not visualized on pelvic ultrasound were assumed to be normal and compared with the pelvic MRI findings. MRI findings were categorized as concordant or discordant. Discordant findings were divided into malignant, non-malignant physiologic or non-malignant non-physiologic. The modified Wald, the "rule of thirds", and the binomial distribution probability tests were performed. 255 pelvic ultrasounds met inclusion criteria with 364 ovaries not visualized. 0 malignancies were detected on MRI. 6.9% (25/364) of nonvisualized ovaries had non-malignant discordant findings on MRI: 5.2% (19/364) physiologic, 1.6% (6/364) non-physiologic. Physiologic findings included: 16 functional cysts and 3 hemorrhagic cysts. Non-physiologic findings included: 3 cysts in post-menopausal women, 1 hydrosalpinx, and 2 broad ligament fibroids. The theoretical risk of detecting an ovarian carcinoma on pelvic MRI when an ovary is not visualized on ultrasound ranges from 0 to 1.3%. If an ovary is not visualized on pelvic ultrasound, it can be assumed to be without carcinoma and MRI rarely adds additional information.

  14. Glial-released proteins in clonal cultures and their modulation by hydrocortisone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arenander, A.T.; de Vellis, J.

    Rat glial C6 cells release into the culture medium a reproducible spectrum of soluble proteins of 12 major peaks over a broad molecular weight range as determined by fractionation on SDS-gel electrophoresis. Exposing C6 monolayers to hydrocortisone (HC) results in a selective alteration in the pattern of glial-released protein (GRP). The selective HC-induced increase or decrease in GRP peaks is specific to HC in that 17 ..beta..-estradiol, dibutyryl cyclic AMP, isoproterenol, and melatonin exert either no detectable or a qualitatively different influence on the GRP pattern. The HC influence is dose dependent over a physiological range of concentrations from 10/supmore » -9/ to 10/sup -6/ M. Differences in culture age and in subclones of C6 can influence both the normal and the HC-induced pattern of GRP. The origin of the GRP is unknown, but pattern reproducibility, viability tests, surface labelling studies, and metabolic labelling studies of soluble and particulate compartment proteins and glycoproteins support the position that cell lysis is not an important source of GRP. More importantly, these studies indicate that GRP and HC-induced changes in GRP pattern are physiologically significant aspects of glial cell behavior.« less

  15. In Vitro Study of Flow Regulation for Pulmonary Insufficiency

    PubMed Central

    Camp, T. A.; Stewart, K. C.; Figliola, R. S.; McQuinn, T.

    2007-01-01

    Given the tolerance of the right heart circulation to mild regurgitation and gradient, we study the potential of using motionless devices to regulate the pulmonary circulation. In addition, we document the flow performance of two mechanical valves. A motionless diode, a nozzle, a mechanical bileaflet valve, and a tilting disk valve were tested in a pulmonary mock circulatory system over the normal human range of pulmonary vascular resistance (PVR). For the mechanical valves, regurgitant fractions (RFs) and transvalvular pressure gradients were found to be weak functions of PVR. On the low end of normal PVR, the bileaflet and tilting disk valves fluttered and would not fully close. Despite this anomaly, the regurgitant fraction of either valve did not change significantly. The values for RF and transvalvular gradient measured varied from 4 to 7% and 4 to 7 mm Hg, respectively, at 5 lpm for all tests. The diode valve was able to regulate flow with mild regurgitant fraction and trivial gradient but with values higher than either mechanical valve tested. Regurgitant fraction ranged from 2 to 17% in tests extending from PVR values of 1 to 4.5 mm Hg/lpm at 5 lpm and with concomitant increases in gradient up to 17 mm Hg. The regurgitant fraction for the nozzle increased from 2 to 23% over the range of PVR with gradients increasing to 18 mm Hg. The significant findings were: (1) the mechanical valves controlled regurgitation at normal physiological cardiac output and PVR even though they failed to close at some normal values of PVR and showed leaflet flutter; and (2) it may be possible to regulate the pulmonary circulation to tolerable levels using a motionless pulmonary valve device. PMID:17408334

  16. Is Physiology the Locus of Health/Health Promotion?

    ERIC Educational Resources Information Center

    Zbilut, Joseph P.

    2008-01-01

    A current trend in physiology education involves the use of clinical vignettes to demonstrate the importance of knowing normal physiology to appreciate pathophysiology. Although laudable, in effect, such tactics promote the so-called "disease" model of medicine while at the same time suggesting that the only utility for the knowledge of physiology…

  17. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    NASA Astrophysics Data System (ADS)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-04-01

    Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

  18. Metabolomic strategies to map functions of metabolic pathways.

    PubMed

    Mulvihill, Melinda M; Nomura, Daniel K

    2014-08-01

    Genome sequencing efforts have revealed a strikingly large number of unannotated and uncharacterized genes that fall into metabolic enzymes classes, likely indicating that our current knowledge of biochemical pathways in normal physiology, let alone in disease states, remains largely incomplete. This realization presents a daunting challenge for post-genomic-era scientists in deciphering the biochemical and (patho)physiological roles of these enzymes and their metabolites and metabolic networks. This is further complicated by many recent studies showing a rewiring of normal metabolic networks in disease states to give rise to unique pathophysiological functions of enzymes, metabolites, and metabolic pathways. This review focuses on recent discoveries made using metabolic mapping technologies to uncover novel pathways and metabolite-mediated posttranslational modifications and epigenetic alterations and their impact on physiology and disease. Copyright © 2014 the American Physiological Society.

  19. Abnormal Pulmonary Function in Adults with Sickle Cell Anemia

    PubMed Central

    Klings, Elizabeth S.; Wyszynski, Diego F.; Nolan, Vikki G.; Steinberg, Martin H.

    2006-01-01

    Rationale: Pulmonary complications of sickle cell anemia (Hb-SS) commonly cause morbidity, yet few large studies of pulmonary function tests (PFTs) in this population have been reported. Objectives: PFTs (spirometry, lung volumes, and diffusion capacity for carbon monoxide [DLCO]) from 310 adults with Hb-SS were analyzed to determine the pattern of pulmonary dysfunction and their association with other systemic complications of sickle cell disease. Methods: Raw PFT data were compared with predicted values. Each subject was subclassified into one of five groups: obstructive physiology, restrictive physiology, mixed obstructive/restrictive physiology, isolated low DLCO, or normal. The association between laboratory data of patients with decreased DLCO or restrictive physiology and those of normal subjects was assessed by multivariate linear regression. Measurements and Main Results: Normal PFTs were present in only 31 of 310 (10%) patients. Overall, adults with Hb-SS were characterized by decreased total lung capacities (70.2 ± 14.7% predicted) and DlCO (64.5 ± 19.9%). The most common PFT patterns were restrictive physiology (74%) and isolated low DlCO (13%). Decreased DLCO was associated with thrombocytosis (p = 0.05), with hepatic dysfunction (elevated alanine aminotransferase; p = 0.07), and a trend toward renal dysfunction (elevated blood urea nitrogen and creatinine; p = 0.05 and 0.07, respectively). Conclusions: Pulmonary function is abnormal in 90% of adult patients with Hb-SS. Common abnormalities include restrictive physiology and decreased DLCO. Decreased DLCO may indicate more severe sickle vasculopathy characterized by impaired hepatic and renal function. PMID:16556694

  20. Inhibition of intracellular proteolysis in muscle cultures by multiplication-stimulating activity

    NASA Technical Reports Server (NTRS)

    Janeczko, Richard A.; Etlinger, Joseph D.

    1984-01-01

    The effects of the insulin-like growth factor, multiplication-stimulating activity (MSA), on chick myotube cultures are studied. The results indicate that MSA is an effective anabolic agent regulating protein metabolism and amino acid uptake, but not sugar transport. Similar size effects on protein metabolism and amino acid uptake in serum-free media were observed in parallel studies with insulin, although insulin levels well in excess of the normal physiological range are required to produce significant effects. It is suggested that there is a generally low insulin sensitivity in cultured chick myotubes relative to adult tissues.

  1. [Prescribing monitoring in clinical practice: from enlightened empiricism to rational strategies].

    PubMed

    Buclin, Thierry; Herzig, Lilli

    2013-05-15

    Monitoring of a medical condition is the periodic measurement of one or several physiological or biological variables to detect a signal regarding its clinical progression or its response to treatment. We distinguish different medical situations between diagnostic, clinical and therapeutic process to apply monitoring. Many clinical, variables can be used for monitoring, once their intrinsic properties (normal range, critical difference, kinetics, reactivity) and external validity (pathophysiological importance, predictive power for clinical outcomes) are established. A formal conceptualization of monitoring is being developed and should support the rational development of monitoring strategies and their validation through appropriate clinical trials.

  2. Modeling and control of a brushless DC axial flow ventricular assist device.

    PubMed

    Giridharan, Guruprasad A; Skliar, Mikhail; Olsen, Donald B; Pantalos, George M

    2002-01-01

    This article presents an integrated model of the human circulatory system that incorporates circulatory support by a brushless DC axial flow ventricular assist device (VAD), and a feedback VAD controller designed to maintain physiologically sufficient perfusion. The developed integrated model combines a network type model of the circulatory system with a nonlinear dynamic model of the brushless DC pump We show that maintaining a reference differential pressure between the left ventricle and aorta leads to adequate perfusion for different pathologic cases, ranging from normal heart to left heart asystole, and widely varying physical activity scenarios from rest to exercise.

  3. Effects of Varied Housing Density on a Hybrid Mouse Strain Followed for 20 Months

    PubMed Central

    Currer, Joanne M.

    2016-01-01

    To evaluate the effect of increased housing density in a hybrid mouse strain, we evaluated a panel of physiological and behavioral traits in animals that were housed in groups of 3, 5, 8, or 12, using cages that provide 78.1 in2 of floor space. Such groupings resulted in cage densities that ranged from half to almost twice the density recommended by the Guide for the Care and Use of Laboratory Animals. While previous studies have investigated physiological effects of increased housing density using inbred mouse strains, including C57BL/6J and 129S1/SvImJ, this study tested an F1 hybrid population of C57BL/6J x 129S1/SvImJ for changes resulting from either decreased or increased housing density. Mice were followed until they were 20 months old, a substantially longer duration than has been used in previous density studies. We evaluated mortality, growth, home cage behavior, blood pressure, body composition, clinical plasma chemistries, immune function, and organ weights (heart, kidney, adrenal glands, and testes) as endpoints of chronic stress that may arise from sub-optimal housing conditions. Few statistically different parameters were observed in this study, none of which describe chronic stress and all within normal physiological ranges for research mice, suggesting that this hybrid strain was not adversely affected by housing at twice the density currently recommended. PMID:26900840

  4. Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.

    PubMed

    Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

    2012-07-01

    The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.

  5. Size-dependent physiological responses of the branching coral Pocillopora verrucosa to elevated temperature and PCO2.

    PubMed

    Edmunds, Peter J; Burgess, Scott C

    2016-12-15

    Body size has large effects on organism physiology, but these effects remain poorly understood in modular animals with complex morphologies. Using two trials of a ∼24 day experiment conducted in 2014 and 2015, we tested the hypothesis that colony size of the coral Pocillopora verrucosa affects the response of calcification, aerobic respiration and gross photosynthesis to temperature (∼26.5 and ∼29.7°C) and P CO 2  (∼40 and ∼1000 µatm). Large corals calcified more than small corals, but at a slower size-specific rate; area-normalized calcification declined with size. Whole-colony and area-normalized calcification were unaffected by temperature, P CO 2 , or the interaction between the two. Whole-colony respiration increased with colony size, but the slopes of these relationships differed between treatments. Area-normalized gross photosynthesis declined with colony size, but whole-colony photosynthesis was unaffected by P CO 2 , and showed a weak response to temperature. When scaled up to predict the response of large corals, area-normalized metrics of physiological performance measured using small corals provide inaccurate estimates of the physiological performance of large colonies. Together, these results demonstrate the importance of colony size in modulating the response of branching corals to elevated temperature and high P CO 2 . © 2016. Published by The Company of Biologists Ltd.

  6. Extensions, Validation, and Clinical Applications of a Feedback Control System Simulator of the Hypothalamo-Pituitary-Thyroid Axis

    PubMed Central

    Samuels, Mary; DiStefano, Joseph J.

    2008-01-01

    Background We upgraded our recent feedback control system (FBCS) simulation model of human thyroid hormone (TH) regulation to include explicit representation of hypothalamic and pituitary dynamics, and updated TH distribution and elimination (D&E) parameters. This new model greatly expands the range of clinical and basic science scenarios explorable by computer simulation. Methods We quantified the model from pharmacokinetic (PK) and physiological human data and validated it comparatively against several independent clinical data sets. We then explored three contemporary clinical issues with the new model: combined triiodothyronine (T3)/thyroxine (T4) versus T4-only treatment, parenteral levothyroxine (L-T4) administration, and central hypothyroidism. Results Combined T3/T4 therapy—In thyroidectomized patients, the L-T4–only replacement doses needed to normalize plasma T3 or average tissue T3 were 145 μg L-T4/day or 165 μgL-T4/day, respectively. The combined T4 + T3 dosing needed to normalize both plasma and tissue T3 levels was 105 μg L-T4 + 9 μgT3 per day. For all three regimens, simulated mean steady-state plasma thyroid-stimulating hormone (TSH), T3, and T4 was within normal ranges (TSH: 0.5–5 mU/L; T4: 5–12 μg/dL; T3: 0.8–1.9 ng/mL). Parenteral T4 administration—800 μg weekly or 400 μg twice weekly normalized average tissue T3 levels both for subcutaneous (SC) and intramuscular (IM) routes of administration. TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM). Central hypothyroidism—We simulated steady-state plasma T3,T4, and TSH concentrations in response to varying degrees of central hypothyroidism, reducing TSH secretion from 50% down to 0.1% of normal. Surprisingly, TSH, T3, and T4 plasma concentrations remained within normal ranges for TSH secretion as low as 25% of normal. Conclusions Combined T3/T4 treatment—Simulated standard L-T4–only therapy was sufficient to renormalize average tissue T3 levels and maintain normal TSH, T3, and T4 plasma levels, supporting adequacy of standard L-T4–only treatment. Parenteral T4 administration—TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM), supporting these therapeutic alternatives for patients with compromised L-T4 gut absorption. Central hypothyroidism—These results highlight how highly nonlinear feedback in the hypothalamic-pituitary-thyroid axis acts to maintain normal hormone levels, even with severely reduced TSH secretion. PMID:18844475

  7. Pulp-dentin biology in restorative dentistry. Part 1: normal structure and physiology.

    PubMed

    Mjör, I A; Sveen, O B; Heyeraas, K J

    2001-06-01

    Considerable knowledge has accumulated over the years on the structure and function of the dental pulp and dentin. Some of this knowledge has important clinical implications. This review, which is the first of seven articles, will be limited to those parts of the normal structure and physiology of the pulp and dentin that have been shown to result in, or are likely lead to, tissue reactions associated with the clinical treatment of these tissues. Although certain normal structures will be highlighted in some detail, a basic knowledge of pulpal and dentinal development and structure is a prerequisite for an understanding of this text.

  8. Evaluation and Management of Refractory Acne Vulgaris in Adolescent and Adult Men.

    PubMed

    McCarty, Morgan

    2016-04-01

    Acne vulgaris alters the normal skin physiology, impairing stratum corneum and transepidermal water loss. A male's normal skin physiologic state is different than a female's and may have implications when choosing treatment when the skin is altered in a disease state. Transepidermal water loss, pH, and sebum production are different between the sexes. Several underlying conditions present in male acne patients at several ages that may require a more in-depth evaluation. As knowledge of the pathogenesis of acne expands, the differences in skin physiology between the sexes may alter the manner in which male patients with acne medications are approached. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. THE METABOLIC RESPONSE TO RADIATION IN THE PRIMATE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hunter, C.G.

    1959-10-31

    At present there is little information available concerning the metabolism of man following exposure to ionizing radiation in the lethal range. Reference is made in vague terms to the maintenance of fluid and electrolytes, the administration of a bland diet, intravenous glucose, salines etc., with little experimental evidence from primate studies to indicate the benefit of these modes of therapy. It is felt, therefore, that results of metabolic studies made in sub-human primates will be of therapeutic interest. Adult monkeys of both sexes were exposed to whole-body irradiation with x and gamma rays. The absorbed doses were in the sub-lethalmore » and lower lethal range for monkeys (400 to 500 r), and were administered at rates varying from 7 to 124 r/min. Observations were made on eleven monkeys that were kept in metabolic cages before and after irradiation. The derangement of metabolism consequent to irradiation was studied. After physioiogical recovery of eight surviving animals, the experiment was repeated using identical dietary intake and experimental technique but omitting irradiation. Comparisons were then raade between the results of the irradiation study and those obtained after physiological recovery. Data are presented on the clinical physiology of representative animals, including data on body weights, food and fluid intakes, urine and faecal outputs, insensible losses, metabolic rates, balances of water, nitrogen and electrolytes, nitrogen utilization, and caloric intakes. It is concluded that the metabolic response to radiation injury in the lethal range does not differ qualitatively in the primate from that of any injury and that the irradiated primate is not at a disadvantage until the time of anabolic response. At that time the tissues responsible for normal reparative processes, themselves injured by the radiation, are no longer able to perform normal restorative functions, the resultant catabolism being in excess of that from equivalent injury from other causes. The implications of these studies on the clinical nutrition of the human exposed to sublethal doses of radiation are considered. (C.H.)« less

  10. Bioactivities in the tamarind seed extracts: A preliminary study

    NASA Astrophysics Data System (ADS)

    Garg, Sukant; Muangman, Thanchanok; Huifu, He; Ling, Li; Kaul, Sunil C.; Wadhwa, Renu

    2018-01-01

    Stress is a state that triggers change in normal physiology and recognized by human body and brain as an unfavorable event causing concern, worry or anxiety. It may vary from physical, metabolic, physiological or emotional often culminating into wide range of ailments that may range from common cold, decline in functional efficacy of body systems or even cancer. Skin is the largest tissue of the body and makes the first interface with the environment. Skin color and characteristics are highly influenced by environment stress. A variety of natural compounds have been used for anti-stress and disease preventive potentials in worldwide traditional home medicine systems. They have recently attracted attention in research laboratories to dissect their mode of action to promote safe and economic drug development. We have earlier identified anti-stress and anti-aging activities in Withania somnifera, Helicteres angustifolia and honeybee propolis using human cultured normal and cancer cells. In the present study, we explored the effect of tamarind seed extracts prepared in water or 95% ethanol. In cell-based assays, we found that the extracts were safe to use in viable cells (in the range of 0.01-1.0%, for at least 4 weeks). Consistently, molecular studies revealed no effect on the expression/activity of cancer promoting proteins. We recruited oxidative stress models, such as, hydrogen peroxide (H2O2), ultraviolet radiation (UV) and diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (OAG). Investigation on anti-stress potential of the extracts revealed that they do not offer remarkable protection against stress caused by either H2O2 or UV, however, significantly compromised OAG-induced melanogenesis. The preliminary data warrant further investigations on the active components and mechanism of action to develop useful natural compounds/extracts for manipulation of melanogenesis that plays important role in response of cells to UV and its consequences including DNA damage, oxidative stress and related diseases.

  11. Physiological joint line total knee arthroplasty designs are especially sensitive to rotational placement - A finite element analysis.

    PubMed

    Moewis, Philippe; Checa, Sara; Kutzner, Ines; Hommel, Hagen; Duda, Georg N

    2018-01-01

    Mechanical and kinematical aligning techniques are the usual positioning methods during total knee arthroplasty. However, alteration of the physiological joint line and unbalanced medio-lateral load distribution are considered disadvantages in the mechanical and kinematical techniques, respectively. The aim of this study was to analyse the influence of the joint line on the strain and stress distributions in an implanted knee and their sensitivity to rotational mal-alignment. Finite element calculations were conducted to analyse the stresses in the PE-Inlay and the mechanical strains at the bone side of the tibia component-tibia bone interface during normal positioning of the components and internal and external mal-rotation of the tibial component. Two designs were included, a horizontal and a physiological implant. The loading conditions are based on internal knee joint loads during walking. A medialization of the stresses on the PE-Inlay was observed in the physiological implant in a normal position, accompanied by higher stresses in the mal-rotated positions. Within the tibia component-tibia bone interface, similar strain distributions were observed in both implant geometries in the normal position. However, a medialization of the strains was observed in the physiological implant in both mal-rotated conditions with greater bone volume affected by higher strains. Although evident changes due to mal-rotation were observed, the stresses do not suggest a local plastic deformation of the PE-Inlay. The strains values within most of the tibia component-tibia bone interface were in the physiological strain zone and no significant bone changes would be expected. The physiological cut on the articular aspect showed no detrimental effect compared to the horizontal implant.

  12. Birth weight and prematurity in infants with single ventricle physiology: pediatric heart network infant single ventricle trial screened population.

    PubMed

    Williams, Richard V; Ravishankar, Chitra; Zak, Victor; Evans, Frank; Atz, Andrew M; Border, William L; Levine, Jami; Li, Jennifer S; Mahony, Lynn; Mital, Seema; Pearson, Gail D; Prakash, Ashwin; Hsu, Daphne T

    2010-01-01

    Although congenital heart disease is associated with low birth weight and prematurity, there is little information about these birth outcomes in infants with single ventricle physiology. We describe the birth outcomes (i.e., gestational age and birth weight) in neonates with single ventricle physiology screened for enrollment in the Pediatric Heart Network's Infant Single Ventricle Trial, compare these outcomes with US norms, and examine the association of birth outcomes with anatomic diagnosis and race. All neonates with single ventricle physiology presenting to Infant Single Ventricle Trial centers were screened for enrollment. Demographic data and anatomic diagnoses were obtained from medical records. A total of 1245 neonates with single ventricle physiology were screened at 10 centers (63 to 266 per center). Diagnoses included hypoplastic left heart syndrome in 49%, unbalanced atrioventricular septal defect in 12%, and tricuspid atresia in 9%. Preterm birth occurred in 16% of neonates with single ventricle physiology vs. 12% in normal neonates (P < .001), low birth weight (<2.5 kg) in 18% vs. 8% in normals (P < .001), and small for gestational age (<10th percentile by definition) in 22% vs. 10% in normals (P < .001). A genetic syndrome was reported in 8%. The percentage of preterm birth, low birth weight, and small for gestational age was similar between screened neonates with and without hypoplastic left heart syndrome. In this large, contemporary cohort of neonates with single ventricle physiology, rates of preterm birth, low birth weight, and small for gestational age were higher than in the general population, but similar between screened neonates with and without hypoplastic left heart syndrome.

  13. The temporal representation of speech in a nonlinear model of the guinea pig cochlea

    NASA Astrophysics Data System (ADS)

    Holmes, Stephen D.; Sumner, Christian J.; O'Mard, Lowel P.; Meddis, Ray

    2004-12-01

    The temporal representation of speechlike stimuli in the auditory-nerve output of a guinea pig cochlea model is described. The model consists of a bank of dual resonance nonlinear filters that simulate the vibratory response of the basilar membrane followed by a model of the inner hair cell/auditory nerve complex. The model is evaluated by comparing its output with published physiological auditory nerve data in response to single and double vowels. The evaluation includes analyses of individual fibers, as well as ensemble responses over a wide range of best frequencies. In all cases the model response closely follows the patterns in the physiological data, particularly the tendency for the temporal firing pattern of each fiber to represent the frequency of a nearby formant of the speech sound. In the model this behavior is largely a consequence of filter shapes; nonlinear filtering has only a small contribution at low frequencies. The guinea pig cochlear model produces a useful simulation of the measured physiological response to simple speech sounds and is therefore suitable for use in more advanced applications including attempts to generalize these principles to the response of human auditory system, both normal and impaired. .

  14. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics

    PubMed Central

    Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B.; Janmey, Paul A.; Wells, Rebecca G.

    2016-01-01

    Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G’ and G” and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver. PMID:26735954

  15. Right Ventricular Tissue Doppler in Space Flight

    NASA Technical Reports Server (NTRS)

    Garcia, Kathleen M.; Hamilton, Douglas R.; Sargsyan, Ashot E.; Ebert, Douglas; Martin, David S.; Barratt, Michael R.; Martin, David S.; Bogomolov, Valery V.; Dulchavsky, Scott A.; Duncan, J. Michael

    2010-01-01

    The presentation slides review normal physiology of the right ventricle in space, general physiology of the right ventricle; difficulties in imaging the heart in space, imaging methods, tissue Doppler spectrum, right ventricle tissue Doppler, and Rt Tei Index.

  16. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism.

    PubMed

    Das, K C; Mukherjee, M; Sarkar, T K; Dash, R J; Rastogi, G K

    1975-02-01

    Qualitative and quantitative studies of erythropoiesis in 23 patients with hypothyroidism and 21 patients with hyperthryoidism included routine hematologic evaluation, bone marrow morphology, status of serum iron, B12 and folate red blood cell mass and plasma volume by radioisotope methods, erythrokinetics and radiobioassay of plasma erythropoietin. A majority of patients with the hypothyroid state had significant reduction in red blood cell mas per kg of body weight. The presence of anemia in many of these patients was not evident from hemoglobin and hematocrit values due to concomitant reduction of plasma volume. The erythrokinetic data in hypothyroid patients provided evidence of significant decline of the erythropoietic activity of the bone marrow. Erythroid cells in the marrow were depleted and also showed reduced proliferative activity as indicated by lower 3H-thymidine labeling index. Plasma erythropoietin levels were reduced, often being immeasurable by the polycythemic mouse bioassay technique. These changes in erythropoiesis in the hypothyroid state appear to be a part of physiological adjustment to the reduced oxygen requirement of the tissues due to diminished basal metabolic rate. Similar investigations revealed mild erythrocytosis in a significant proportion of patients with hyperthyroidism. Failure of erythrocytosis to occur in other patients of this group was associated with impaired erythropoiesis due to a deficiency of hemopoietic nutrients such as iron, vitamin B12 and folate. The mean plasma erythropoietin level of these patients was significantly elevated; in 4 patients the levels were in the upper normal range whereas in the rest, the values were above the normal range. The bone marrow showed erythyroid hyperplasia in all patients with hyperthyroidism. The mean 3H-thymidine labeling index of the erythroblasts was also significantly higher than normal in hyperthyroidism; in 8 patients the index was within the normal range whereas in the remaining 13 it was above the normal range. Erythrokinetic studies also provided evidences of increased erythropoietic activity in the bone marrow. It is postulated that thyroid hormones stimulate erythropoiesis, sometimes leading to erythrocytosis provided there is no deficiency of hemopoietic nutrients. Stimulation of erythropoiesis by thryoid hormones appears to be mediated through erythropoietin.

  17. Nociceptive threshold, blood constituents and physiological values in 213 cows with locomotion scores ranging from normal to severely lame.

    PubMed

    Tadich, N; Tejeda, C; Bastias, S; Rosenfeld, C; Green, L E

    2013-08-01

    The aim of this study was to investigate associations between mechanical nociceptive threshold, blood constituents, physiological measurements and locomotion score (LS) in dairy cattle with a range of LS from 1 (normal) to 5 (severely lame). The study used 213 Friesian/Friesian cross dairy cows from 12 farms. There were 40-50 cows each with LS 1-4 and 22 cows with LS 5. Each cow was restrained and her temperature and respiratory and cardiac rates were measured. Nociceptive threshold, plasma concentrations of haptoglobin, β-hydroxybutyrate (β-HB), cortisol, glucose, lactate, creatinine kinase activity, packed cell volume and white blood cell counts were determined. Mixed effect models were used to investigate associations between the variables measured and LS. Parity and stage of lactation were forced into all analyses and the model fit was checked by investigation of residuals. After accounting for parity and stage of lactation, nociceptive threshold was significantly lower in cattle with LS 3-5 compared with LS 1 in a dose response manner, indicating increasing hyperalgesia with increasing LS. Haptoglobin concentration was raised in all cattle with LS>1, demonstrating an inflammatory response with all levels of lameness. Cortisol and glucose concentrations were lower and β-HB concentrations higher in cows with LS 2 compared with cows with other scores, possibly signifying metabolic challenge. Heart and respiratory rate and rectal temperature were significantly higher only in cows with LS 5, suggesting that these measurements were insensitive measures of pain or stress. It was concluded that hyperalgesia increases with increasing severity of lameness and that nociceptive pressure and haptoglobin were sensitive measures of pain from lameness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Tachycardia

    MedlinePlus

    ... normal while at rest. It's normal for your heart rate to rise during exercise or as a physiological ... the heart or both while at rest. Your heart rate is controlled by electrical signals sent across heart ...

  19. The Advantages of Normalizing Electromyography to Ballistic Rather than Isometric or Isokinetic Tasks.

    PubMed

    Suydam, Stephen M; Manal, Kurt; Buchanan, Thomas S

    2017-07-01

    Isometric tasks have been a standard for electromyography (EMG) normalization stemming from anatomic and physiologic stability observed during contraction. Ballistic dynamic tasks have the benefit of eliciting maximum EMG signals for normalization, despite having the potential for greater signal variability. It is the purpose of this study to compare maximum voluntary isometric contraction (MVIC) to nonisometric tasks with increasing degrees of extrinsic variability, ie, joint range of motion, velocity, rate of contraction, etc., to determine if the ballistic tasks, which elicit larger peak EMG signals, are more reliable than the constrained MVIC. Fifteen subjects performed MVIC, isokinetic, maximum countermovement jump, and sprint tasks while EMG was collected from 9 muscles in the quadriceps, hamstrings, and lower leg. The results revealed the unconstrained ballistic tasks were more reliable compared to the constrained MVIC and isokinetic tasks for all triceps surae muscles. The EMG from sprinting was more reliable than the constrained cases for both the hamstrings and vasti. The most reliable EMG signals occurred when the body was permitted its natural, unconstrained motion. These results suggest that EMG is best normalized using ballistic tasks to provide the greatest within-subject reliability, which beneficially yield maximum EMG values.

  20. Inhibition of physiological growth hormone secretion by atropine.

    PubMed

    Taylor, B J; Smith, P J; Brook, C G

    1985-04-01

    We have investigated the effects of atropine (specific muscarinic cholinergic inhibition) on the nocturnal secretion of GH during the first cycle of stage IV sleep in six normal volunteers and three tall adolescents. Atropine was administered orally in a dose of 0.6 mg (n = 8) or 1.8 mg (n = 4) 30 min before expected sleep and the sampling repeated. Peak GH level without atropine was 45.3 mU/l (range 5.7 to 92.0): both doses of atropine abolished sleep associated GH secretion. Spontaneous daytime GH secretion was demonstrated during five 6 h sampling periods in three normal adults. There was a significant decrease in spontaneous daytime GH secretion when the sampling was repeated after atropine 0.6 mg or 1.8 mg. We conclude that inhibition of GH secretion using anticholinergic drugs should be further investigated in the management of excessive growth hormone secretion.

  1. Cardiovascular Adjustments to Gravitational Stress

    NASA Technical Reports Server (NTRS)

    Blomqvist, C. Gunnar; Stone, H. Lowell

    1991-01-01

    The effects of gravity on the cardiovascular system must be taken into account whenever a hemodynamic assessment is made. All intravascular pressure have a gravity-dependent hydrostatic component. The interaction between the gravitational field, the position of the body, and the functional characteristics of the blood vessels determines the distribution of intravascular volume. In turn this distribution largely determines cardiac pump function. Multiple control mechanisms are activated to preserve optimal tissue perfusion when the magnitude of the gravitational field or its direction relative to the body changes. Humans are particularly sensitive to such changes because of the combination of their normally erect posture and the large body mass and blood volume below the level of the heart. Current aerospace technology also exposes human subjects to extreme variations in the gravitational forces that range from zero during space travel to as much an nine-times normal during operation of high-performance military aircraft. This chapter therefore emphasizes human physiology.

  2. Individual differences in normal body temperature: longitudinal big data analysis of patient records.

    PubMed

    Obermeyer, Ziad; Samra, Jasmeet K; Mullainathan, Sendhil

    2017-12-13

    To estimate individual level body temperature and to correlate it with other measures of physiology and health. Observational cohort study. Outpatient clinics of a large academic hospital, 2009-14. 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (-0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: -0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg 2 , P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Individuals' baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Individual differences in normal body temperature: longitudinal big data analysis of patient records

    PubMed Central

    Samra, Jasmeet K; Mullainathan, Sendhil

    2017-01-01

    Abstract Objective To estimate individual level body temperature and to correlate it with other measures of physiology and health. Design Observational cohort study. Setting Outpatient clinics of a large academic hospital, 2009-14. Participants 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Main outcome measures Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. Results In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (–0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: –0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg2, P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Conclusions Individuals’ baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality. PMID:29237616

  4. Engineering mechanical gradients in next generation biomaterials - Lessons learned from medical textile design.

    PubMed

    Ng, Joanna L; Collins, Ciara E; Knothe Tate, Melissa L

    2017-07-01

    Nonwoven and textile membranes have been applied both externally and internally to prescribe boundary conditions for medical conditions as diverse as oedema and tissue defects. Incorporation of mechanical gradients in next generation medical membrane design offers great potential to enhance function in a dynamic, physiological context. Yet the gradient properties and resulting mechanical performance of current membranes are not well described. To bridge this knowledge gap, we tested and compared the mechanical properties of bounding membranes used in both external (compression sleeves for oedema, exercise bands) and internal (surgical membranes) physiological contexts. We showed that anisotropic compression garment textiles, isotropic exercise bands and surgical membranes exhibit similar ranges of resistance to tension under physiologic strains. However, their mechanical gradients and resulting stress-strain relationships show differences in work capacity and energy expenditure. Exercise bands' moduli of elasticity and respective thicknesses allow for controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. In contrast, the gradients intrinsic to compression sleeve design exhibit gaps in the middle range (1-5N) of physiological strains and also inconsistencies along the length of the sleeve, resulting in less than optimal performance of these devices. These current shortcomings in compression textile and garment design may be addressed in the future through implementation of novel approaches. For example, patterns, fibre compositions, and fibre anisotropy can be incorporated into biomaterial design to achieve seamless mechanical gradients in structure and resulting dynamic function, which would be particularly useful in physiological contexts. These concepts can be applied further to biomaterial design to deliver pressure gradients during movement of oedematous limbs (compression garments) and facilitate transport of molecules and cells during tissue genesis within tissue defects (surgical membranes). External and internal biomaterial membranes prescribe boundary conditions for treatment of medical disorders, from oedema to tissue defects. Studies are needed to guide the design of next generation biomaterials and devices that incorporate gradient engineering approaches, which offer great potential to enhance function in a dynamic and physiological context. Mechanical gradients intrinsic to currently implemented biomaterials such as medical textiles and surgical interface membranes are poorly understood. Here we characterise quantitatively the mechanics of textile and nonwoven biomaterial membranes for external and internal use. The lack of seamless gradients in compression medical textiles contrasts with the graded mechanical effects achieved by elastomeric exercise bands, which are designed to deliver controlled, incremental increases in loading to facilitate healing as injured tissues return to normal structure and function. Engineering textiles with a prescient choice of fibre composition/size, type of knit/weave and inlay fibres, and weave density/anisotropy will enable creation of fabrics that can deliver spatially and temporally controlled mechanical gradients to maintain force balances at tissue boundaries, e.g. to treat oedema or tissue defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Human albumin: old, new, and emerging applications.

    PubMed

    Rozga, Jacek; Piątek, Tomasz; Małkowski, Piotr

    2013-05-10

    Human serum albumin has been widely used in an array of clinical settings for nearly 7 decades. Although there is no evidence to support the use of albumin rather than crystalloid in acute volume resuscitation, many clinicians continue to use albumin because it has other important physiologic effects besides the oncotic function. In keeping with the improved understanding of albumin physiology and pathophysiology of many acute and chronic diseases, use of albumin for medical applications has increased in recent years. This, along with increased costs of manufacturing and lower production volume of medical-grade albumin, has lead to an ongoing shortage and rapid increase in albumin prices. This review is based on the analysis of major publications, related to albumin chemistry, physiology, and medical uses including guidelines developed by professional and governmental organizations. Results reflect current knowledge about the role of albumin in health and disease and relevance of albumin therapy in specific clinical settings. Albumin therapy is currently recommended in spontaneous bacterial peritonitis with ascites, refractory ascites not responsive to diuretics, large-volume paracentesis, post-paracentesis syndrome, and the treatment of hepatorenal syndrome as an adjunct to vasoconstrictors. New indications for albumin therapy are linked to the antioxidant activity of albumin and its effects on capillary integrity. In recent years, large-pore hemofiltration and albumin exchange have emerged as promising liver support therapies for liver failure and other toxic syndromes. They are designed to remove a broad range of blood-borne toxins and to restore normal functions of the circulating albumin by replacing defective forms of albumin and albumin molecules saturated with toxins with normal albumin. In view of the ongoing worldwide shortage and high cost of human albumin (native and recombinant), new usage criteria, protocols, and guidelines for appropriate utilization of albumin are needed.

  6. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlation with salt sensitivity in normal subjects.

    PubMed

    ter Maaten, J C; Bakker, S J; Serné, E H; ter Wee, P M; Donker, A J; Gans, R O

    1999-10-01

    Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.

  7. Seasonal variation and meteotropism in various self-rated psychological and physiological features of a normal couple

    NASA Astrophysics Data System (ADS)

    Maes, Michael; de Meyer, Frans; Peeters, Dirk; Meltzer, Herbert; Cosyns, Paul; Schotte, Chris

    1992-12-01

    Recently, true seasonal variation with significant periodicities (circannual, semiannual, circatrimensual, circabimensual) and a significant meteotropism have been observed in a number of self-rated characteristics of normal man (arousal, mood, physiology and social behaviour). In order to replicate these findings, two normal controls (a married couple) were asked daily to complete a self-rating scale concerned with the characteristics mentioned above during one calendar year. By means of time series analysis, significant rhythmicities with recurrent cycles in the autorhythmometric data of all of the above characteristics were found. An important part of the variance in these characteristics was found, using multiple regression, to be related to various weather variables, such as mean atmospheric pressure, temperature, relative humidity, wind speed, minutes of sunlight/day and precipitation/day. These results support the hypothesis that temporal variations in human psychological and physiological characteristics may be dictated by the composite effects of past and present atmospheric activity.

  8. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

    PubMed

    Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

  9. Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma

    PubMed Central

    Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero

    2015-01-01

    Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

  10. A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

    PubMed Central

    Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

    2017-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of xenobiotic administration that eliminates physiological alterations associated with other methods of delivery. PMID:27094606

  11. A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

    PubMed

    Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

    2016-01-01

    Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of xenobiotic administration that eliminates physiological alterations associated with other methods of delivery. Copyright © 2016. Published by Elsevier Inc.

  12. Modulation of Wolframin Expression in Human Placenta during Pregnancy: Comparison among Physiological and Pathological States

    PubMed Central

    Perna, Angelica; Iannaccone, Alessandro; Cobellis, Luigi; De Luca, Antonio

    2014-01-01

    The WFS1 gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of the WFS1 gene in mice causes progressive β-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ. PMID:24588001

  13. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice

    PubMed Central

    Smith, Carli J.; Emge, Jacob R.; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M.; Sousa, Andrew J.; Reardon, Colin; Sherman, Philip M.; Barrett, Kim E.

    2014-01-01

    The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1−/− mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. PMID:25190473

  14. Physiologic Inter-eye Differences in Monkey Optic Nerve Head Architecture and Their Relation to Changes in Early Experimental Glaucoma

    PubMed Central

    Yang, Hongli; Downs, J. Crawford; Burgoyne, Claude F.

    2009-01-01

    Purpose To characterize physiologic inter-eye differences in optic nerve head (ONH) architecture within six normal rhesus monkeys and compare them to inter-eye differences within three previously-reported cynomolgus monkeys with early experimental glaucoma (EEG). Methods Trephinated ONH and peripapillary sclera from both eyes of six normal monkeys were serial sectioned, 3D reconstructed, 3D delineated and parameterized. For each normal animal, and each parameter, physiologic inter-eye difference (PID) was calculated (both overall and regionally) by converting all OS data to OD configuration and subtracting the OS from the OD value and Physiologic Inter-eye Percent Difference (PIPD) was calculated as the PID divided by the measurement mean of the two eyes. For each EEG monkey, inter-eye (EEG minus normal) differences and percent differences for each parameter overall and regionally were compared to the PID and PIPD Maximums. Results For all parameters the PID Maximums were relatively small overall. Compared to overall PID maximums, overall inter-eye differences in EEG monkeys were greatest for laminar deformation and thickening, posterior scleral canal enlargement, cupping and prelaminar neural tissue thickening. Compared to the regional PID Maximums, the lamina cribrosa was posteriorly deformed centrally, inferiorly, inferonasally and superiorly and was thickened centrally. The prelaminar neural tissues were thickened inferiorly, inferonasally and superiorly. Conclusion These data provide the first characterization of PID/PIPD maximums for ONH neural and connective tissue parameters in normal monkeys and serve to further clarify the location and character of early ONH change in experimental glaucoma. However, because of the species differences, the findings in EEG need to be confirmed within EEG rhesus monkey eyes. PMID:18775866

  15. The effect of acute maximal exercise on postexercise hemodynamics and central arterial stiffness in obese and normal-weight individuals.

    PubMed

    Bunsawat, Kanokwan; Ranadive, Sushant M; Lane-Cordova, Abbi D; Yan, Huimin; Kappus, Rebecca M; Fernhall, Bo; Baynard, Tracy

    2017-04-01

    Central arterial stiffness is associated with incident hypertension and negative cardiovascular outcomes. Obese individuals have higher central blood pressure (BP) and central arterial stiffness than their normal-weight counterparts, but it is unclear whether obesity also affects hemodynamics and central arterial stiffness after maximal exercise. We evaluated central hemodynamics and arterial stiffness during recovery from acute maximal aerobic exercise in obese and normal-weight individuals. Forty-six normal-weight and twenty-one obese individuals underwent measurements of central BP and central arterial stiffness at rest and 15 and 30 min following acute maximal exercise. Central BP and normalized augmentation index (AIx@75) were derived from radial artery applanation tonometry, and central arterial stiffness was obtained via carotid-femoral pulse wave velocity (cPWV) and corrected for central mean arterial pressure (cPWV/cMAP). Central arterial stiffness increased in obese individuals but decreased in normal-weight individuals following acute maximal exercise, after adjusting for fitness. Obese individuals also exhibited an overall higher central BP ( P  <   0.05), with no exercise effect. The increase in heart rate was greater in obese versus normal-weight individuals following exercise ( P  <   0.05), but there was no group differences or exercise effect for AIx@75 In conclusion, obese (but not normal-weight) individuals increased central arterial stiffness following acute maximal exercise. An assessment of arterial stiffness response to acute exercise may serve as a useful detection tool for subclinical vascular dysfunction. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  16. Morphology, physiology, genetics, enigmas, and status of an extremely rare tree: Mutant tanoak

    Treesearch

    Philip M. McDonald; Jianwei Zhang; Randy S. Senock; Jessica W. Wright

    2013-01-01

    Important physical characteristics, morphological attributes, physiological functions, and genetic properties of mutant tanoak, Notholithocarpus densiflorus f. attenuato-dentatus (Fagaceae), and normal tanoak, Notholithocarpus densiflorus (Hook. & Arn.) Manos, Cannon & S. H. Oh, were studied on the Challenge...

  17. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium

    NASA Astrophysics Data System (ADS)

    Xu, Lizhi; Gutbrod, Sarah R.; Bonifas, Andrew P.; Su, Yewang; Sulkin, Matthew S.; Lu, Nanshu; Chung, Hyun-Joong; Jang, Kyung-In; Liu, Zhuangjian; Ying, Ming; Lu, Chi; Webb, R. Chad; Kim, Jong-Seon; Laughner, Jacob I.; Cheng, Huanyu; Liu, Yuhao; Ameen, Abid; Jeong, Jae-Woong; Kim, Gwang-Tae; Huang, Yonggang; Efimov, Igor R.; Rogers, John A.

    2014-02-01

    Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable biotic/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy.

  18. The anatomy and physiology of the avian endocrine system.

    PubMed

    Ritchie, Midge; Pilny, Anthony A

    2008-01-01

    The endocrine system of birds is comparable to that of mammals, although there are many unique aspects to consider when studying the anatomy, physiology, and biochemistry. Avian endocrinology is a field of veterinary medicine that is unfamiliar to many practitioners; however, it is important to have a comprehensive understanding when evaluating companion birds in clinical practice. This article covers the anatomy and physiology of the normal avian, and readers are referred to other articles for a more detailed explanation of altered physiology and pathology.

  19. Catheter based mid-infrared reflectance and reflectance generated absorption spectroscopy

    DOEpatents

    Holman, Hoi-Ying N

    2013-10-29

    A method of characterizing conditions in a tissue, by (a) providing a catheter that has a light source that emits light in selected wavenumbers within the range of mid-IR spectrum; (b) directing the light from the catheter to an area of tissue at a location inside a blood vessel of a subject; (c) collecting light reflected from the location and generating a reflectance spectra; and (d) comparing the reflectance spectra to a reference spectra of normal tissue, whereby a location having an increased number of absorbance peaks at said selected wavenumbers indicates a tissue inside the blood vessel containing a physiological marker for atherosclerosis.

  20. Excitatory amino acid neurotoxicity and neurodegenerative disease.

    PubMed

    Meldrum, B; Garthwaite, J

    1990-09-01

    The progress over the last 30 years in defining the role of excitatory amino acids in normal physiological function and in the abnormal neuronal activity of epilepsy has been reviewed in earlier articles in this series. In the last five years it has become clear that excitatory amino acids also play a role in a wide range of neurodegenerative processes. The evidence is clearest where the degenerative process is acute, but is more controversial for slow degenerative processes. In this article Brian Meldrum and John Garthwaite review in vivo and in vitro studies of the cytotoxicity of amino acids and summarize the contribution of such toxicity to acute and chronic neurodegenerative disorders.

  1. Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases

    PubMed Central

    Stevens, Richard G.; Blask, David E.; Brainard, George C.; Hansen, Johnni; Lockley, Steven W.; Provencio, Ignacio; Rea, Mark S.; Reinlib, Leslie

    2007-01-01

    Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light–dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge. PMID:17805428

  2. Eppur Si Muove: The Dynamic Nature of Physiological Control of Renal Blood Flow by the Renal Sympathetic Nerves

    PubMed Central

    Schiller, Alicia M.; Pellegrino, Peter Ricci; Zucker, Irving H.

    2016-01-01

    Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. PMID:27514571

  3. Eppur Si Muove: The dynamic nature of physiological control of renal blood flow by the renal sympathetic nerves.

    PubMed

    Schiller, Alicia M; Pellegrino, Peter Ricci; Zucker, Irving H

    2017-05-01

    Tubuloglomerular feedback and the myogenic response are widely appreciated as important regulators of renal blood flow, but the role of the sympathetic nervous system in physiological renal blood flow control remains controversial. Where classic studies using static measures of renal blood flow failed, dynamic approaches have succeeded in demonstrating sympathetic control of renal blood flow under normal physiological conditions. This review focuses on transfer function analysis of renal pressure-flow, which leverages the physical relationship between blood pressure and flow to assess the underlying vascular control mechanisms. Studies using this approach indicate that the renal nerves are important in the rapid regulation of the renal vasculature. Animals with intact renal innervation show a sympathetic signature in the frequency range associated with sympathetic vasomotion that is eliminated by renal denervation. In conscious rabbits, this sympathetic signature exerts vasoconstrictive, baroreflex control of renal vascular conductance, matching well with the rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and complementing findings from other studies employing dynamic approaches to study renal sympathetic vascular control. In this light, classic studies reporting that nerve stimulation and renal denervation do not affect static measures of renal blood flow provide evidence for the strength of renal autoregulation rather than evidence against physiological renal sympathetic control of renal blood flow. Thus, alongside tubuloglomerular feedback and the myogenic response, renal sympathetic outflow should be considered an important physiological regulator of renal blood flow. Clinically, renal sympathetic vasomotion may be important for solving the problems facing the field of therapeutic renal denervation. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Modelling the heart with the atrioventricular plane as a piston unit.

    PubMed

    Maksuti, Elira; Bjällmark, Anna; Broomé, Michael

    2015-01-01

    Medical imaging and clinical studies have proven that the heart pumps by means of minor outer volume changes and back-and-forth longitudinal movements in the atrioventricular (AV) region. The magnitude of AV-plane displacement has also shown to be a reliable index for diagnosis of heart failure. Despite this, AV-plane displacement is usually omitted from cardiovascular modelling. We present a lumped-parameter cardiac model in which the heart is described as a displacement pump with the AV plane functioning as a piston unit (AV piston). This unit is constructed of different upper and lower areas analogous with the difference in the atrial and ventricular cross-sections. The model output reproduces normal physiology, with a left ventricular pressure in the range of 8-130 mmHg, an atrial pressure of approximatly 9 mmHg, and an arterial pressure change between 75 mmHg and 130 mmHg. In addition, the model reproduces the direction of the main systolic and diastolic movements of the AV piston with realistic velocity magnitude (∼10 cm/s). Moreover, changes in the simulated systolic ventricular-contraction force influence diastolic filling, emphasizing the coupling between cardiac systolic and diastolic functions. The agreement between the simulation and normal physiology highlights the importance of myocardial longitudinal movements and of atrioventricular interactions in cardiac pumping. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Physiological regeneration of skin appendages and implications for regenerative medicine

    PubMed Central

    Chuong, Cheng-Ming; Randall, Valerie A; Widelitz, Randall B.; Wu, Ping; Jiang, Ting-Xin

    2013-01-01

    The concept of regenerative medicine is relatively new, but animals are well known to remake their hair and feathers regularly by normal regenerative physiological processes. Here we focus on 1) how extra-follicular environments can regulate hair and feather stem cell activities and 2) how different configurations of stem cells can shape organ forms in different body regions to fulfil changing physiological needs. PMID:22505663

  6. Insomnia, metabolic rate and sleep restoration.

    PubMed

    Bonnet, M H; Arand, D L

    2003-07-01

    Studies have shown occasional evidence of increased physiological activity in patients with primary insomnia. We hypothesized that metabolic rate, as measured by overall oxygen use (VO2), might be a more general index of increased physiological activity. An initial experiment found elevated VO2 both at night and during the day in patients with primary insomnia as compared with matched normal sleepers. A second experiment found significant but more modest increases in VO2 in patients with Sleep State Misperception Insomnia [who complain of poor sleep but who had normal sleep by electroencephalographic (EEG) criteria]. In a third experiment, normal young adults were given caffeine 400 mg three times per day (TID) for 1 week as a means of increasing VO2 and possibly producing other symptoms of insomnia. Participants developed many symptoms consistent with those seen in patients with primary insomnia (poor sleep, increased latency on the Multiple Sleep Latency Test, increasing fatigue despite physiological activation, and increased anxiety on the Minnesota Multiphasic Personality Inventory (MMPI)). In a final experiment, physiological arousal was again produced by caffeine to determine if sleep with elevated arousal would be less restorative. All subjects (Ss) slept for 3.5 h after being given 400 mg of caffeine. During 41 h of sleep deprivation that followed, there was no significant condition difference for the Multiple Sleep Latency Test or mood measures. The results provided only weak support for the idea that sleep is less restorative after physiological arousal.

  7. Safety analysis of proposed data-driven physiologic alarm parameters for hospitalized children.

    PubMed

    Goel, Veena V; Poole, Sarah F; Longhurst, Christopher A; Platchek, Terry S; Pageler, Natalie M; Sharek, Paul J; Palma, Jonathan P

    2016-12-01

    Modification of alarm limits is one approach to mitigating alarm fatigue. We aimed to create and validate heart rate (HR) and respiratory rate (RR) percentiles for hospitalized children, and analyze the safety of replacing current vital sign reference ranges with proposed data-driven, age-stratified 5th and 95th percentile values. In this retrospective cross-sectional study, nurse-charted HR and RR data from a training set of 7202 hospitalized children were used to develop percentile tables. We compared 5th and 95th percentile values with currently accepted reference ranges in a validation set of 2287 patients. We analyzed 148 rapid response team (RRT) and cardiorespiratory arrest (CRA) events over a 12-month period, using HR and RR values in the 12 hours prior to the event, to determine the proportion of patients with out-of-range vitals based upon reference versus data-driven limits. There were 24,045 (55.6%) fewer out-of-range measurements using data-driven vital sign limits. Overall, 144/148 RRT and CRA patients had out-of-range HR or RR values preceding the event using current limits, and 138/148 were abnormal using data-driven limits. Chart review of RRT and CRA patients with abnormal HR and RR per current limits considered normal by data-driven limits revealed that clinical status change was identified by other vital sign abnormalities or clinical context. A large proportion of vital signs in hospitalized children are outside presently used norms. Safety evaluation of data-driven limits suggests they are as safe as those currently used. Implementation of these parameters in physiologic monitors may mitigate alarm fatigue. Journal of Hospital Medicine 2015;11:817-823. © 2015 Society of Hospital Medicine. © 2016 Society of Hospital Medicine.

  8. Anatomy and Physiology of the Blood-Brain Barrier

    PubMed Central

    Serlin, Yonatan; Shelef, Ilan; Knyazer, Boris; Friedman, Alon

    2015-01-01

    Essential requisite for the preservation of normal brain activity is to maintain a narrow and stable homeostatic control in the neuronal environment of the CNS. Blood flow alterations and altered vessel permeability are considered key determinants in the pathophysiology of brain injuries. We will review the present-day literature on the anatomy, development and physiological mechanisms of the blood-brain barrier, a distinctive and tightly regulated interface between the CNS and the peripheral circulation, playing a crucial role in the maintenance of the strict environment required for normal brain function. PMID:25681530

  9. Characterization of motor units in behaving adult mice shows a wide primary range.

    PubMed

    Ritter, Laura K; Tresch, Matthew C; Heckman, C J; Manuel, Marin; Tysseling, Vicki M

    2014-08-01

    The mouse is essential for genetic studies of motor function in both normal and pathological states. Thus it is important to consider whether the structure of motor output from the mouse is in fact analogous to that recorded in other animals. There is a striking difference in the basic electrical properties of mouse motoneurons compared with those in rats, cats, and humans. The firing evoked by injected currents produces a unique frequency-current (F-I) function that emphasizes recruitment of motor units at their maximum force. These F-I functions, however, were measured in anesthetized preparations that lacked two key components of normal synaptic input: high levels of synaptic noise and neuromodulatory inputs. Recent studies suggest that the alterations in the F-I function due to these two components are essential for recreating firing behavior of motor units in human subjects. In this study we provide the first data on firing patterns of motor units in the awake mouse, focusing on steady output in quiet stance. The resulting firing patterns did not match the predictions from the mouse F-I behaviors but instead revealed rate modulation across a remarkably wide range (10-60 Hz). The low end of the firing range may be due to changes in the F-I relation induced by synaptic noise and neuromodulatory inputs. The high end of the range may indicate that, unlike other species, quiet standing in the mouse involves recruitment of relatively fast-twitch motor units. Copyright © 2014 the American Physiological Society.

  10. Metabolomic strategies to map functions of metabolic pathways

    PubMed Central

    Mulvihill, Melinda M.

    2014-01-01

    Genome sequencing efforts have revealed a strikingly large number of unannotated and uncharacterized genes that fall into metabolic enzymes classes, likely indicating that our current knowledge of biochemical pathways in normal physiology, let alone in disease states, remains largely incomplete. This realization presents a daunting challenge for post-genomic-era scientists in deciphering the biochemical and (patho)physiological roles of these enzymes and their metabolites and metabolic networks. This is further complicated by many recent studies showing a rewiring of normal metabolic networks in disease states to give rise to unique pathophysiological functions of enzymes, metabolites, and metabolic pathways. This review focuses on recent discoveries made using metabolic mapping technologies to uncover novel pathways and metabolite-mediated posttranslational modifications and epigenetic alterations and their impact on physiology and disease. PMID:24918200

  11. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery

    PubMed Central

    Harris, Nancy Lee; Stein, Harald; Isaacson, Peter G.

    2008-01-01

    In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)–cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory. PMID:19029456

  12. Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane.

    PubMed

    Epstein, Tamir; Xu, Liping; Gillies, Robert J; Gatenby, Robert A

    2014-01-01

    Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal oxygen concentrations, also known as the Warburg effect. This metabolism is considered abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood. We examined changes in glucose metabolism following perturbations in membrane activity in different normal and tumor cell lines and found that inhibition or activation of pumps on the cell membrane led to reduction or increase in glycolysis, respectively, while oxidative phosphorylation remained unchanged. Computational simulations demonstrated that these findings are consistent with a new model of normal physiological cellular metabolism in which efficient mitochondrial oxidative phosphorylation supplies chronic energy demand primarily for macromolecule synthesis and glycolysis is necessary to supply rapid energy demands primarily to support membrane pumps. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. The predictions were confirmed experimentally. Our results show that glycolytic metabolism serves a critical physiological function under normoxic conditions by responding to rapid energetic demand, mainly from membrane transport activities, even in the presence of oxygen. This supports a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Cells use efficient but slow-responding aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism, which is inefficient but can rapidly increase adenosine triphosphate (ATP) production, to meet short-timescale energy demands, mainly from membrane transport activities. In this model, the origin of the Warburg effect in cancer cells and aerobic glycolysis in general represents a normal physiological function due to enhanced energy demand for membrane transporters activity required for cell division, growth, and migration.

  13. Lipid-based nutrient supplements containing vitamins and minerals attenuate renal electrolyte loss in HIV/AIDS patients starting antiretroviral therapy: A randomized controlled trial in Zambia.

    PubMed

    Munkombwe, D; Muungo, T L; Michelo, C; Kelly, P; Chirwa, S; Filteau, S

    2016-06-01

    Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. www.pactr.org ID number: PACTR201106000300631. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  14. Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

    NASA Astrophysics Data System (ADS)

    Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

    2004-03-01

    Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

  15. Thermal sensation and climate: a comparison of UTCI and PET thresholds in different climates.

    PubMed

    Pantavou, Katerina; Lykoudis, Spyridon; Nikolopoulou, Marialena; Tsiros, Ioannis X

    2018-06-07

    The influence of physiological acclimatization and psychological adaptation on thermal perception is well documented and has revealed the importance of thermal experience and expectation in the evaluation of environmental stimuli. Seasonal patterns of thermal perception have been studied, and calibrated thermal indices' scales have been proposed to obtain meaningful interpretations of thermal sensation indices in different climate regions. The current work attempts to quantify the contribution of climate to the long-term thermal adaptation by examining the relationship between climate normal annual air temperature (1971-2000) and such climate-calibrated thermal indices' assessment scales. The thermal sensation ranges of two thermal indices, the Universal Thermal Climate Index (UTCI) and the Physiological Equivalent Temperature Index (PET), were calibrated for three warm temperate climate contexts (Cfa, Cfb, Csa), against the subjective evaluation of the thermal environment indicated by interviewees during field surveys conducted at seven European cities: Athens (GR), Thessaloniki (GR), Milan (IT), Fribourg (CH), Kassel (DE), Cambridge (UK), and Sheffield (UK), under the same research protocol. Then, calibrated scales for other climate contexts were added from the literature, and the relationship between the respective scales' thresholds and climate normal annual air temperature was examined. To maintain the maximum possible comparability, three methods were applied for the calibration, namely linear, ordinal, and probit regression. The results indicated that the calibrated UTCI and PET thresholds increase with the climate normal annual air temperature of the survey city. To investigate further climates, we also included in the analysis results of previous studies presenting only thresholds for neutral thermal sensation. The average increase of the respective thresholds in the case of neutral thermal sensation was about 0.6 °C for each 1 °C increase of the normal annual air temperature for both indices, statistically significant only for PET though.

  16. Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

    PubMed

    Musso, Carlos G; Oreopoulos, Dimitrios G

    2011-01-01

    In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

  17. Ecophysiological adaptations to variable salinity environments in the crab Hemigrapsus crenulatus from the Southeastern Pacific coast: Sodium regulation, respiration and excretion.

    PubMed

    Urzúa, Ángel; Urbina, Mauricio A

    2017-08-01

    The estuarine crab Hemigrapsus crenulatus is a key benthic species of estuarine and intertidal ecosystems of the South Pacific, habitats that experience wide fluctuations in salinity. The physiological strategies that allow this crab to thrive under variable salinities, and how they change during the benthic stages of their life cycle, were evaluated under laboratory conditions. Oxygen consumption, ammonia excretion and the regulatory capacity of Na + through the normal range of environmental salinities (i.e. 5, 10, 15, 20, 25, 30) were evaluated in three size classes, ranging from juveniles to adults. In all sizes, the oxygen consumption, ammonia excretion and regulatory capacity of Na + decreased as salinity increased, with the highest values at 5 and the lowest values at 30 salinity. Bigger crabs showed a higher capacity to regulate Na + , as well as higher respiration and excretion rates compared to smaller crabs, suggesting that they are better equipped to exploit areas of the estuary with low salinity. Regardless of its size, H. crenulatus is a strong hyper regulator in diluted media (i.e. 5-20) while a conformer at salinities higher than 20. The regulatory capacity of Na + was positively related with oxygen consumption and ammonia excretion rates. These relationships between sodium regulation, respiration and excretion are interpreted as adaptive physiological mechanisms that allow H. crenulatus to maintain the osmotic and bioenergetic balance over a wide range of environmental salinities. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Creating Simulated Microgravity Patient Models

    NASA Technical Reports Server (NTRS)

    Hurst, Victor; Doerr, Harold K.; Bacal, Kira

    2004-01-01

    The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

  19. Dysphagia in Infants with Single Ventricle Anatomy Following Stage 1 Palliation: Physiologic Correlates and Response to Treatment

    PubMed Central

    McGrattan, Katlyn Elizabeth; McGhee, Heather; DeToma, Allan; Hill, Elizabeth G.; Zyblewski, Sinai C.; Lefton-Greif, Maureen; Halstead, Lucinda; Bradley, Scott M.; Martin-Harris, Bonnie

    2017-01-01

    Background Deficits in swallowing physiology are a leading morbidity for infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliation. Despite the high prevalence of this condition, the underlying deficits that cause this post-operative impairment remain poorly understood. Objective Identify the physiologic correlates of dysphagia in infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliative surgery. Methods Postoperative fiberoptic laryngoscopies and videofluoroscopic swallow studies (VFSS) were conducted sequentially on infants with functional single ventricles following stage 1 palliative surgery. Infants were dichotomized as having normal or impaired laryngeal function based on laryngoscopy findings. VFSS were evaluated frame-by-frame using a scale that quantifies performance within 11 components of swallowing physiology. Physiologic attributes within each component were categorized as high functioning or low functioning based on their ability to support milk ingestion without bolus airway entry. Results Thirty-six infants (25 male) were included in the investigation. Twenty-four underwent the Norwood procedure and twelve underwent the Hybrid procedure. Low function physiologic patterns were observed within multiple swallowing components during the ingestion of thin barium as characterized by ≥ 4 sucks per swallow (36%), initiation of pharyngeal swallow below the level of the valleculae (83%), and incomplete late laryngeal vestibular closure (56%) at the height of the swallow. Swallowing deficits contributed to aspiration in 50% of infants. Although nectar thick liquids reduced the rate of aspiration (p=0.006), aspiration rates remained high (27%). No differences in rates of penetration or aspiration were observed between infants with normal and impaired laryngeal function. Conclusions Deficits in swallowing physiology contribute to penetration and aspiration following stage 1 palliation among infants with normal and impaired laryngeal function. Although thickened liquids may improve airway protection for select infants, they may inhibit their ability to extract the bolus and meet nutritional needs. PMID:28244680

  20. Dysphagia in infants with single ventricle anatomy following stage 1 palliation: Physiologic correlates and response to treatment.

    PubMed

    McGrattan, Katlyn Elizabeth; McGhee, Heather; DeToma, Allan; Hill, Elizabeth G; Zyblewski, Sinai C; Lefton-Greif, Maureen; Halstead, Lucinda; Bradley, Scott M; Martin-Harris, Bonnie

    2017-05-01

    Deficits in swallowing physiology are a leading morbidity for infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliation. Despite the high prevalence of this condition, the underlying deficits that cause this post-operative impairment remain poorly understood. Identify the physiologic correlates of dysphagia in infants with functional single ventricles and systemic outflow tract obstruction following stage 1 palliative surgery. Postoperative fiberoptic laryngoscopies and videofluoroscopic swallow studies (VFSS) were conducted sequentially on infants with functional single ventricles following stage 1 palliative surgery. Infants were dichotomized as having normal or impaired laryngeal function based on laryngoscopy findings. VFSS were evaluated frame-by-frame using a scale that quantifies performance within 11 components of swallowing physiology. Physiologic attributes within each component were categorized as high functioning or low functioning based on their ability to support milk ingestion without bolus airway entry. Thirty-six infants (25 male) were included in the investigation. Twenty-four underwent the Norwood procedure and twelve underwent the Hybrid procedure. Low function physiologic patterns were observed within multiple swallowing components during the ingestion of thin barium as characterized by ≥4 sucks per swallow (36%), initiation of pharyngeal swallow below the level of the valleculae (83%), and incomplete late laryngeal vestibular closure (56%) at the height of the swallow. Swallowing deficits contributed to aspiration in 50% of infants. Although nectar thick liquids reduced the rate of aspiration (P = .006), aspiration rates remained high (27%). No differences in rates of penetration or aspiration were observed between infants with normal and impaired laryngeal function. Deficits in swallowing physiology contribute to penetration and aspiration following stage 1 palliation among infants with normal and impaired laryngeal function. Although thickened liquids may improve airway protection for select infants, they may inhibit their ability to extract the bolus and meet nutritional needs. © 2017 Wiley Periodicals, Inc.

  1. PTEN regulation of local and long-range connections in mouse auditory cortex

    PubMed Central

    Xiong, Qiaojie; Oviedo, Hysell V; Trotman, Lloyd C; Zador, Anthony M

    2012-01-01

    Autism Spectrum Disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN. Through Cre-mediated recombination we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long range connectivity using channelrhodopsin-2 (ChR2) revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser scanning photostimulation (LSPS) showed that local inputs onto PTEN-cko neurons in the auditory cortex were similarly enhanced. The hyperconnectivity caused by PTEN-cko could be blocked by rapamycin, a specific inhibitor of the PTEN downstream molecule mTORC1. Together our results suggest that local and long-range hyperconnectivity may constitute a physiological basis for the effects of mutations in PTEN and possibly other ASD candidate genes. PMID:22302806

  2. Evaluation of type II thyroplasty on phonatory physiology in an excised canine larynx model

    PubMed Central

    Devine, Erin E.; Hoffman, Matthew R.; McCulloch, Timothy M.; Jiang, Jack J.

    2016-01-01

    Objective Type II thyroplasty is an alternative treatment for spasmodic dysphonia, addressing hyperadduction by incising and lateralizing the thyroid cartilage. We quantified the effect of lateralization width on phonatory physiology using excised canine larynges. Methods Normal closure, hyperadduction, and type II thyroplasty (lateralized up to 5mm at 1mm increments with hyperadducted arytenoids) were simulated in excised larynges (N=7). Aerodynamic, acoustic, and videokymographic data were recorded at three subglottal pressures relative to phonation threshold pressure (PTP). One-way repeated measures ANOVA assessed effect of condition on aerodynamic parameters. Random intercepts linear mixed effects models assessed effects of condition and subglottal pressure on acoustic and videokymographic parameters. Results PTP differed across conditions (p<0.001). Condition affected percent shimmer (p<0.005) but not percent jitter. Both pressure (p<0.03) and condition (p<0.001) affected fundamental frequency. Pressure affected vibratory amplitude (p<0.05) and intra-fold phase difference (p<0.05). Condition affected phase difference between the vocal folds (p<0.001). Conclusions Hyperadduction increased PTP and worsened perturbation compared to normal, with near normal physiology restored with 1mm lateralization. Further lateralization deteriorated voice quality and increased PTP. Acoustic and videokymographic results indicate that normal physiologic relationships between subglottal pressure and vibration are preserved at optimal lateralization width, but then degrade with further lateralization. The 1mm optimal width observed here is due to the small canine larynx size. Future human trials would likely demonstrate a greater optimal width, with patient-specific value potentially determined based on larynx size and symptom severity. PMID:27223665

  3. Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

    PubMed

    Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

    2017-11-01

    To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

  4. Quantitative analysis of iris changes after physiologic and pharmacologic mydriasis in a rural Chinese population.

    PubMed

    Zhang, Ye; Li, Si Zhen; Li, Lei; He, Ming Guang; Thomas, Ravi; Wang, Ning Li

    2014-04-24

    To estimate and compare the change in iris cross-sectional area (IA) and iris volume (IV) following physiologic and pharmacologic pupil dilation in primary angle closure suspects (PACS) and normal subjects. Anterior segment-optical coherence tomography (AS-OCT) measurements in light, dark, and following pharmacologic dilation were obtained on 186 PACS and 224 normal subjects examined during the 5-year follow-up of the Handan Eye Study. Iris cross-sectional area, IV, and other biometric parameters calculated using the Zhongshan angle assessment program in the right eyes of all subjects were analyzed. The mean IA and IV decreased in dark compared with light and after pharmacologic dilation in both PACS and normal eyes. This change was statistically significant in normal eyes: light versus pharmacologic dilation for IA (P = 0.038) and for IV, both light versus dark (P = 0.031) and light versus pharmacologic dilation (P = 0.012). A longer axial length (P = 0.028) and a greater change in pupil diameter (PD) (P < 0.001) were associated with a larger decrease of IA for the light to dark comparison. A diagnosis of normal eyes (P = 0.011), larger PD in dark (P = 0.001), and a larger change in PD (P = 0.001) were associated with a larger decrease of IV from light to dark. The differences in iris behavior between PACS and normal rural Chinese subjects following physiologic or pharmacologic pupillary dilation may help provide insights into the pathogenesis of angle closure. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  5. Effects of epidermal growth factor on bone formation and resorption in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marie, P.J.; Hott, M.; Perheentupa, J.

    1990-02-01

    The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in themore » periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse.« less

  6. A comparative study of the characterization of miR-155 in knockout mice

    PubMed Central

    Zhang, Dong; Cui, Yongchun; Li, Bin; Luo, Xiaokang; Li, Bo; Tang, Yue

    2017-01-01

    miR-155 is one of the most important miRNAs and plays a very important role in numerous biological processes. However, few studies have characterized this miRNA in mice under normal physiological conditions. We aimed to characterize miR-155 in vivo by using a comparative analysis. In our study, we compared miR-155 knockout (KO) mice with C57BL/6 wild type (WT) mice in order to characterize miR-155 in mice under normal physiological conditions using many evaluation methods, including a reproductive performance analysis, growth curve, ultrasonic estimation, haematological examination, and histopathological analysis. These analyses showed no significant differences between groups in the main evaluation indices. The growth and development were nearly normal for all mice and did not differ between the control and model groups. Using a comparative analysis and a summary of related studies published in recent years, we found that miR-155 was not essential for normal physiological processes in 8-week-old mice. miR-155 deficiency did not affect the development and growth of naturally ageing mice during the 42 days after birth. Thus, studying the complex biological functions of miR-155 requires the further use of KO mouse models. PMID:28278287

  7. Developmental trajectories of cerebrovascular reactivity in healthy children and young adults assessed with magnetic resonance imaging.

    PubMed

    Leung, Jackie; Kosinski, Przemyslaw D; Croal, Paula L; Kassner, Andrea

    2016-05-15

    Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels. Normal development in children is associated with significant changes in blood pressure, cerebral blood flow (CBF) and cerebral oxygen metabolism. Therefore, it stands to reason that CVR will also undergo changes during this period. The study acquired magnetic resonance imaging measures of CVR and CBF in healthy children and young adults to trace their changes with age. We found that CVR changes in two phases, increasing with age until the mid-teens, followed by a decrease. Baseline CBF declined steadily with age. We conclude that CVR varies with age during childhood, which prompts future CVR studies involving children to take into account the effect of development. Cerebrovascular reactivity (CVR) reflects the vasculature's ability to accommodate changes in blood flow demand thereby serving as a critical imaging tool for mapping vascular reserve. Normal development is associated with extensive physiological changes in blood pressure, cerebral blood flow and cerebral metabolic rate of oxygen, all of which can affect CVR. Moreover, the evolution of these physiological parameters is most prominent during childhood. Therefore, the aim of this study was to use non-invasive magnetic resonance imaging (MRI) to characterize the developmental trajectories of CVR in healthy children and young adults, and relate them to changes in cerebral blood flow (CBF). Thirty-four healthy subjects (17 males, 17 females; age 9-30 years) underwent CVR assessment using blood oxygen level-dependent MRI in combination with a computer controlled CO2 stimulus. In addition, baseline CBF was measured with a pulsed arterial spin labelling sequence. CVR exhibited a gradual increase with age in both grey and white matter up to 14.7 years. After this break point, a negative correlation with age was detected. Baseline CBF maintained a consistent negative linear correlation across the entire age range. The significant age-dependent changes in CVR and CBF demonstrate the evolution of cerebral haemodynamics in children and should be taken into consideration. The shift in developmental trajectory of CVR from increasing to decreasing suggests that physiological factors beyond baseline CBF also influence CVR. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  8. Evaluating the risk of eye injuries: intraocular pressure during high speed projectile impacts.

    PubMed

    Duma, Stefan M; Bisplinghoff, Jill A; Senge, Danielle M; McNally, Craig; Alphonse, Vanessa D

    2012-01-01

    To evaluate the risk of eye injuries by determining intraocular pressure during high speed projectile impacts. A pneumatic cannon was used to impact eyes with a variety of projectiles at multiple velocities. Intraocular pressure was measured with a small pressure sensor inserted through the optic nerve. A total of 36 tests were performed on 12 porcine eyes with a range of velocities between 6.2 m/s and 66.5 m/s. Projectiles selected for the test series included a 6.35  mm diameter metal ball, a 9.25  mm diameter aluminum rod, and an 11.16  mm diameter aluminum rod. Experiments were designed with velocities in the range of projectile consumer products such as toy guns. A range of intraocular pressures ranged between 2017 mmHg to 26,426 mmHg (39 psi-511 psi). Four of the 36 impacts resulted in globe rupture. Intraocular pressures dramatically above normal physiological pressure were observed for high speed projectile impacts. These pressure data provide critical insight to chronic ocular injuries and long-term complications such as glaucoma and cataracts.

  9. Hepatic and renal metallothionein concentrations in Commerson's dolphins (Cephalorhynchus commersonii) from Tierra del Fuego, South Atlantic Ocean.

    PubMed

    Cáceres-Saez, Iris; Polizzi, Paula; Romero, Belén; Dellabianca, Natalia A; Ribeiro Guevara, Sergio; Goodall, R Natalie P; Cappozzo, H Luis; Gerpe, Marcela

    2016-07-15

    The Commerson's dolphin is the most common endemic odontocete of subantarctic waters of Tierra del Fuego, Argentina incidentally caught in fishing nets. The species is classified as "Data Deficient" by the IUCN. Metallothioneins (MTs) are considered as suitable biomarkers for health and environmental monitoring. The aims of the study were to assess MT concentrations in the liver and kidney of bycaught specimens. Moreover, correlations with Zn, Se, Cd, Ag and Hg, and the molar ratios of MT:metals were estimated to evaluate if there is an indication of their respective protective role against metal toxicity in tissues. Hepatic and renal MT concentrations were similar, ranging from 11.6 to 29.1nmol·g(-1) WW, and Kidney/Liver ratios ranging from 0.73 to 1.93 corresponded to normal ranges. Results suggest that MTs are related to physiological ranges for the species. This information constitutes the first MT report on Commerson's dolphins and possibly considered as baseline for species' conservation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Physiological functions of MTA family of proteins.

    PubMed

    Sen, Nirmalya; Gui, Bin; Kumar, Rakesh

    2014-12-01

    Although the functional significance of the metastasic tumor antigen (MTA) family of chromatin remodeling proteins in the pathobiology of cancer is fairly well recognized, the physiological role of MTA proteins continues to be an understudied research area and is just beginning to be recognized. Similar to cancer cells, MTA1 also modulates the expression of target genes in normal cells either by acting as a corepressor or coactivator. In addition, physiological functions of MTA proteins are likely to be influenced by its differential expression, subcellular localization, and regulation by upstream modulators and extracellular signals. This review summarizes our current understanding of the physiological functions of the MTA proteins in model systems. In particular, we highlight recent advances of the role MTA proteins play in the brain, eye, circadian rhythm, mammary gland biology, spermatogenesis, liver, immunomodulation and inflammation, cellular radio-sensitivity, and hematopoiesis and differentiation. Based on the growth of knowledge regarding the exciting new facets of the MTA family of proteins in biology and medicine, we speculate that the next burst of findings in this field may reveal further molecular regulatory insights of non-redundant functions of MTA coregulators in the normal physiology as well as in pathological conditions outside cancer.

  11. Impact of age and sex on normal left heart structure and function.

    PubMed

    Hagström, Linn; Henein, Michael Y; Karp, Kjell; Waldenström, Anders; Lindqvist, Per

    2017-11-01

    Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose. We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions. Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years. Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  12. Physiological impact of patent foramen ovale on pulmonary gas exchange, ventilatory acclimatization, and thermoregulation.

    PubMed

    Lovering, Andrew T; Elliott, Jonathan E; Davis, James T

    2016-08-01

    The foramen ovale, which is part of the normal fetal cardiopulmonary circulation, fails to close after birth in ∼35% of the population and represents a potential source of right-to-left shunt. Despite the prevalence of patent foramen ovale (PFO) in the general population, cardiopulmonary, exercise, thermoregulatory, and altitude physiologists may have underestimated the potential effect of this shunted blood flow on normal physiological processes in otherwise healthy humans. Because this shunted blood bypasses the respiratory system, it would not participate in either gas exchange or respiratory system cooling and may have impacts on other physiological processes that remain undetermined. The consequences of this shunted blood flow in PFO-positive (PFO+) subjects can potentially have a significant, and negative, impact on the alveolar-to-arterial oxygen difference (AaDO2), ventilatory acclimatization to high altitude and respiratory system cooling with PFO+ subjects having a wider AaDO2 at rest, during exercise after acclimatization, blunted ventilatory acclimatization, and a higher core body temperature (∼0.4(°)C) at rest and during exercise. There is also an association of PFO with high-altitude pulmonary edema and acute mountain sickness. These effects on physiological processes are likely dependent on both the presence and size of the PFO, with small PFOs not likely to have significant/measureable effects. The PFO can be an important determinant of normal physiological processes and should be considered a potential confounder to the interpretation of former and future data, particularly in small data sets where a significant number of PFO+ subjects could be present and significantly impact the measured outcomes.

  13. A Physiologically Based Kinetic Model of Rat and Mouse Gestation: Disposition of a Weak Acid

    EPA Science Inventory

    A physiologically based toxicokinetic model of gestation in the rat mouse has been developed. The model is superimposed on the normal growth curve for nonpregnant females. It describes the entire gestation period including organogenesis. The model consists of uterus, mammary tiss...

  14. Predictable root recession coverage.

    PubMed

    Hoexter, David L

    2006-01-01

    Gingival recession, exposure of the tooth's root, is undesirable and, in many situations, contrary to normal physiology. Today's root coverage is predictable. With the use of an acellular dermal matrix membrane (Fasciablast), we can achieve a new blood supply and predictable coverage, with no second surgical procedure. Youth, esthetics and physiology are restored.

  15. Practical otic anatomy and physiology of the dog and cat.

    PubMed

    Njaa, Bradley L; Cole, Lynette K; Tabacca, Natalie

    2012-11-01

    Knowledge of the normal structure and function of the canine and feline ear is critical to be able to diagnose abnormalities that either involve the ear or originate within one or more of the ear compartments. In addition, a veterinarian must be aware of various structures within or associated with the ear so that they are not damaged or destroyed while treating an animal with otic disease. This article provides a brief discussion of the various anatomic features of the ear and normal physiology of portions of the ear. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Analysis of space-time projection of differential and Michelson-type speckle-interferometer output signal for cardiovibration measurement

    NASA Astrophysics Data System (ADS)

    Ulyanov, Sergey S.; Tuchin, Valery V.

    1993-06-01

    The sex differences in cardiovascular system responses to a mild noise stress are established using the physiological and the dynamic systems theory methods. Lower levels of basal systolic arterial pressure and higher rates of its dropping and normalization under influence and after its cessation are typical for women. There are no hypertensive responses to stresses in women in contrast to men. The normalized entropy of the ECG signal, describing the physiological variability, increases in women and decreases in men. The advantages of female cardiovascular system response to mild stresses are discussed.

  17. The energy expenditure of normal and pathologic gait.

    PubMed

    Waters, R L; Mulroy, S

    1999-07-01

    Physiological energy expenditure measurement has proven to be a reliable method of quantitatively assessing the penalties imposed by gait disability. The purpose of this review is to outline the basic principles of exercise physiology relevant to human locomotion; detail the energy expenditure of normal walking; and summarize the results of energy expenditure studies performed in patients with specific neurologic and orthopedic disabilities. The magnitude of the disabilities and the patients' capacity to tolerate the increased energy requirements are compared. This paper also will examine the effectiveness of rehabilitation interventions at mitigating the energetic penalties of disability during ambulation.

  18. Normal venous anatomy and physiology of the lower extremity.

    PubMed

    Notowitz, L B

    1993-06-01

    Venous disease of the lower extremities is common but is often misunderstood. It seems that the focus is on the exciting world of arterial anatomy and pathology, while the topic of venous anatomy and pathology comes in second place. However, venous diseases such as chronic venous insufficiency, leg ulcers, and varicose veins affect much of the population and may lead to disability and death. Nurses are often required to answer complex questions from the patients and his or her family about the patient's disease. Patients depend on nurses to provide accurate information in terms they can understand. Therefore it is important to have an understanding of the normal venous system of the legs before one can understand the complexities of venous diseases and treatments. This presents an overview of normal venous anatomy and physiology.

  19. Neurogenic orthostatic hypotension - management update and role of droxidopa.

    PubMed

    Vijayan, Joy; Sharma, Vijay K

    2015-01-01

    Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy.

  20. Engineering studies of vectorcardiographs in blood pressure measuring systems, appendix 2

    NASA Technical Reports Server (NTRS)

    Mark, R. G.

    1975-01-01

    The development of a cardiovascular monitoring system to noninvasively monitor the blood pressure and heart rate using pulse wave velocity was described. The following topics were covered: (1) pulse wave velocity as a measure of arterial blood pressure, (2) diastolic blood pressure and pulse wave velocity in humans, (3) transducer development for blood pressure measuring device, and (4) cardiovascular monitoring system. It was found, in experiments on dogs, that the pulse wave velocity is linearly related to diastolic blood pressure over a wide range of blood pressure and in the presence of many physiological perturbations. A similar relationship was observed in normal, young human males over a moderate range of pressures. Past methods for monitoring blood pressure and a new method based on pulse wave velocity determination were described. Two systems were tested: a Doppler ultrasonic transducer and a photoelectric plethysmograph. A cardiovascular monitoring system was described, including operating instructions.

  1. Neurogenic orthostatic hypotension – management update and role of droxidopa

    PubMed Central

    Vijayan, Joy; Sharma, Vijay K

    2015-01-01

    Orthostatic hypotension (OH) is defined as a significant decrease in blood pressure (BP) during the first 3 minutes of standing or a head up on a tilt table. Symptoms of OH are highly variable, ranging from mild light-headedness to recurrent syncope. OH occurs due to dysfunction of one or more components of various complex mechanisms that interplay closely to maintain BP in a normal range during various physiological and associated disease states. Various biochemical and electrophysiological studies are often undertaken to assess the severity and etiology of OH. In addition to the lifestyle modifications, various medications that stimulate the adrenergic receptors or increase central blood volume are used in patients with OH. Droxidopa is a newer agent that increases the levels of norepinephrine in postganglionic sympathetic neurons. Management strategies for OH are presented, including the mechanism of action of droxidopa and various studies performed to assess its efficacy. PMID:26089676

  2. Transdisciplinary unifying implications of circadian findings in the 1950s

    PubMed Central

    Halberg, Franz; Cornélissen, Germaine; Katinas, George; Syutkina, Elena V; Sothern, Robert B; Zaslavskaya, Rina; Halberg, Francine; Watanabe, Yoshihiko; Schwartzkopff, Othild; Otsuka, Kuniaki; Tarquini, Roberto; Frederico, Perfetto; Siggelova, Jarmila

    2003-01-01

    A few puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal. PMID:14728726

  3. Real-time in vivo uric acid biosensor system for biophysical monitoring of birds.

    PubMed

    Gumus, A; Lee, S; Karlsson, K; Gabrielson, R; Winkler, D W; Erickson, D

    2014-02-21

    Research on birds has long played an important role in ecological investigations, as birds are relatively easily observed, and their high metabolic rates and diurnal habits make them quite evidently responsive to changes in their environments. A mechanistic understanding of such avian responses requires a better understanding of how variation in physiological state conditions avian behavior and integrates the effects of recent environmental changes. There is a great need for sensor systems that will allow free-flying birds to interact with their environment and make unconstrained decisions about their spatial location at the same time that their physiological state is being monitored in real time. We have developed a miniature needle-based enzymatic sensor system suitable for continuous real-time amperometric monitoring of uric acid levels in unconstrained live birds. The sensor system was constructed with Pt/Ir wire and Ag/AgCl paste. Uricase enzyme was immobilized on a 0.7 mm sensing cavity of Nafion/cellulose inner membrane to minimize the influences of background interferents. The sensor response was linear from 0.05 to 0.6 mM uric acid, which spans the normal physiological range for most avian species. We developed a two-electrode potentiostat system that drives the biosensor, reads the output current, and wirelessly transmits the data. In addition to extensive characterization of the sensor and system, we also demonstrate autonomous operation of the system by collecting in vivo extracellular uric acid measurements on a domestic chicken. The results confirm our needle-type sensor system's potential for real-time monitoring of birds' physiological state. Successful application of the sensor in migratory birds could open up a new era of studying both the physiological preparation for migration and the consequences of sustained avian flight.

  4. Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation.

    PubMed

    Lerant, Anna A; Hester, Robert L; Coleman, Thomas G; Phillips, William J; Orledge, Jeffrey D; Murray, W Bosseau

    2015-01-01

    Insufficient pre-oxygenation before emergency intubation, and hyperventilation after intubation are mistakes that are frequently observed in and outside the operating room, in clinical practice and in simulation exercises. Physiological parameters, as appearing on standard patient monitors, do not alert to the deleterious effects of low oxygen saturation on coronary perfusion, or that of low carbon dioxide concentrations on cerebral perfusion. We suggest the use of HumMod, a computer-based human physiology simulator, to demonstrate beneficial physiological responses to pre-oxygenation and the futility of excessive minute ventilation after intubation. We programmed HumMod, to A.) compare varying times (0-7 minutes) of pre-oxygenation on oxygen saturation (SpO2) during subsequent apnoea; B.) simulate hyperventilation after apnoea. We compared the effect of different minute ventilation rates on SpO2, acid-base status, cerebral perfusion and other haemodynamic parameters. A.) With no pre-oxygenation, starting SpO2 dropped from 98% to 90% in 52 seconds with apnoea. At the other extreme, following full pre-oxygenation with 100% O2 for 3 minutes or more, the SpO2 remained 100% for 7.75 minutes during apnoea, and dropped to 90% after another 75 seconds. B.) Hyperventilation, did not result in more rapid normalization of SpO2, irrespective of the level of minute ventilation. However, hyperventilation did cause significant decreases in cerebral blood flow (CBF). HumMod accurately simulates the physiological responses compared to published human studies of pre-oxygenation and varying post intubation minute ventilations, and it can be used over wider ranges of parameters than available in human studies and therefore available in the literature.

  5. Preventing and Treating Hypoxia: Using a Physiology Simulator to Demonstrate the Value of Pre-Oxygenation and the Futility of Hyperventilation

    PubMed Central

    Lerant, Anna A.; Hester, Robert L.; Coleman, Thomas G.; Phillips, William J.; Orledge, Jeffrey D.; Murray, W. Bosseau

    2015-01-01

    Introduction: Insufficient pre-oxygenation before emergency intubation, and hyperventilation after intubation are mistakes that are frequently observed in and outside the operating room, in clinical practice and in simulation exercises. Physiological parameters, as appearing on standard patient monitors, do not alert to the deleterious effects of low oxygen saturation on coronary perfusion, or that of low carbon dioxide concentrations on cerebral perfusion. We suggest the use of HumMod, a computer-based human physiology simulator, to demonstrate beneficial physiological responses to pre-oxygenation and the futility of excessive minute ventilation after intubation. Methods: We programmed HumMod, to A.) compare varying times (0-7 minutes) of pre-oxygenation on oxygen saturation (SpO2) during subsequent apnoea; B.) simulate hyperventilation after apnoea. We compared the effect of different minute ventilation rates on SpO2, acid-base status, cerebral perfusion and other haemodynamic parameters. Results: A.) With no pre-oxygenation, starting SpO2 dropped from 98% to 90% in 52 seconds with apnoea. At the other extreme, following full pre-oxygenation with 100% O2 for 3 minutes or more, the SpO2 remained 100% for 7.75 minutes during apnoea, and dropped to 90% after another 75 seconds. B.) Hyperventilation, did not result in more rapid normalization of SpO2, irrespective of the level of minute ventilation. However, hyperventilation did cause significant decreases in cerebral blood flow (CBF). Conclusions: HumMod accurately simulates the physiological responses compared to published human studies of pre-oxygenation and varying post intubation minute ventilations, and it can be used over wider ranges of parameters than available in human studies and therefore available in the literature. PMID:26283881

  6. THYROSIM App for Education and Research Predicts Potential Health Risks of Over-the-Counter Thyroid Supplements.

    PubMed

    Han, Simon X; Eisenberg, Marisa; Larsen, P Reed; DiStefano, Joseph

    2016-04-01

    Computer simulation tools for education and research are making increasingly effective use of the Internet and personal devices. To facilitate these activities in endocrinology and metabolism, a mechanistically based simulator of human thyroid hormone and thyrotropin (TSH) regulation dynamics was developed and further validated, and it was implemented as a facile and freely accessible web-based and personal device application: the THYROSIM app. This study elucidates and demonstrates its utility in a research context by exploring key physiological effects of over-the-counter thyroid supplements. THYROSIM has a simple and intuitive user interface for teaching and conducting simulated "what-if" experiments. User-selectable "experimental" test-input dosages (oral, intravenous pulses, intravenous infusions) are represented by animated graphical icons integrated with a cartoon of the hypothalamic-pituitary-thyroid axis. Simulations of familiar triiodothyronine (T3), thyroxine (T4), and TSH temporal dynamic responses to these exogenous stimuli are reported graphically, along with normal ranges on the same single interface page; and multiple sets of simulated experimental results are superimposable to facilitate comparative analyses. This study shows that THYROSIM accurately reproduces a wide range of published clinical study data reporting hormonal kinetic responses to large and small oral hormone challenges. Simulation examples of partial thyroidectomies and malabsorption illustrate typical usage by optionally changing thyroid gland secretion and/or gut absorption rates--expressed as percentages of normal--as well as additions of oral hormone dosing, all directly on the interface, and visualizing the kinetic responses to these challenges. Classroom and patient education usage--with public health implications--is illustrated by predictive simulated responses to nonprescription thyroid health supplements analyzed previously for T3 and T4 content. Notably, it was found that T3 in supplements has potentially more serious pathophysiological effects than does T4--concomitant with low-normal TSH levels. Some preparations contain enough T3 to generate thyrotoxic conditions, with supernormal serum T3-spiking and subnormal serum T4 and TSH levels and, in some cases, with normal or low-normal range TSH levels due to thyroidal axis negative feedback. These results suggest that appropriate regulation of these products is needed.

  7. Could linear MRI measurements of hippocampus differentiate normal brain aging in elderly persons from Alzheimer disease?

    PubMed

    Tarroun, Abdullah; Bonnefoy, Marc; Bouffard-Vercelli, Juliette; Gedeon, Claire; Vallee, Bernard; Cotton, François

    2007-02-01

    Although mild progressive specific structural brain changes are commonly associated with normal human aging, it is unclear whether automatic or manual measurements of these structures can differentiate normal brain aging in elderly persons from patients suffering from cognitive impairment. The objective of this study was primarily to define, with a standard high resolution MRI, the range of normal linear age-specific values for the hippocampal formation (HF), and secondarily to differentiate hippocampal atrophy in normal aging from that occurring in Alzheimer disease (AD). Two MRI-based linear measurements of the hippocampal formation at the level of the head and of the tail, standardized by the cranial dimensions, were obtained from coronal and sagittal T1-weighted MR images in 25 normal elderly subjects, and 26 patients with AD. In this study, dimensions of the HF have been standardized and they revealed normal distributions for each side and each sex: the width of the hippocampal head at the level of the amygdala was 16.42 +/- 1.9 mm, and its height 7.93 +/- 1.4 mm; the width of the tail at the level of the cerebral aqueduct was 8.54 +/- 1.2 mm, and the height 5.74 +/- 0.4 mm. There were no significant differences in standardized dimensions of the HF between sides, sexes, or in comparison to head dimensions in the two groups. In addition, the median inter-observer agreement index was 93%. In contrast, the dimensions of the hippocampal formation decreased gradually with increasing age, owing to physiological atrophy, but this atrophy is more significant in the group of AD.

  8. [The hip joint in neuromuscular disorders].

    PubMed

    Strobl, W M

    2009-07-01

    Physiologic motor and biomechanical parameters are prerequisites for normal hip development and hip function. Disorders of muscle activity and lack of weight bearing due to neuromuscular diseases may cause clinical symptoms such as an unstable hip or reduced range of motion. Disability and handicap because of pain, hip dislocation, osteoarthritis, gait disorders, or problems in seating and positioning are dependent on the severity of the disease, the time of occurrence, and the means of prevention and treatment. Preservation of pain-free and stable hip joints should be gained by balancing muscular forces and by preventing progressive dislocation. Most important is the exact indication of therapeutic options such as movement and standing therapy as well as drugs and surgery.

  9. The functions and clinical applications of tumor-derived exosomes

    PubMed Central

    Shao, Yingkuan; Shen, Yanwei; Chen, Ting; Xu, Fei; Chen, Xuewen; Zheng, Shu

    2016-01-01

    Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm. They can be secreted by all cell types and transfer information in the form of their contents, which include proteins, lipids and nucleic acids, to other cells throughout the body. They have roles in normal physiological processes as well as in disease development. Here, we review recent findings regarding tumor-derived exosomes, including methods for their extraction and preservation. We also describe the actions of exosomes in tumorigenesis. The exosomal antigen-presenting effect during antitumor immune responses and its suppressive function in immune tolerance are discussed. Finally, we describe the potential application of exosomes to cancer therapy and liquid biopsy. PMID:27517627

  10. Probing the Electrophysiology of the Developing Heart

    PubMed Central

    Watanabe, Michiko; Rollins, Andrew M.; Polo-Parada, Luis; Ma, Pei; Gu, Shi; Jenkins, Michael W.

    2016-01-01

    Many diseases that result in dysfunction and dysmorphology of the heart originate in the embryo. However, the embryonic heart presents a challenging subject for study: especially challenging is its electrophysiology. Electrophysiological maturation of the embryonic heart without disturbing its physiological function requires the creation and deployment of novel technologies along with the use of classical techniques on a range of animal models. Each tool has its strengths and limitations and has contributed to making key discoveries to expand our understanding of cardiac development. Further progress in understanding the mechanisms that regulate the normal and abnormal development of the electrophysiology of the heart requires integration of this functional information with the more extensively elucidated structural and molecular changes. PMID:29367561

  11. Physiological changes in largemouth bass exposed to paper mill effluents under laboratory and field conditions

    USGS Publications Warehouse

    Sepulveda, M.S.; Gallagher, E.P.; Gross, T.S.

    2004-01-01

    We report here on studies designed to asses the effects of paper mill effluents on non-reproductive functions of free-ranging and captive Florida largemouth bass (Micropterus salmoides floridanus) This was accomplished by conducting an outdoor tank study, in which fish were exposed to well water or to 10%, 20%, 40%, and 80% full strength effluent for 28 or 56 days, and by sampling largemouth bass from sites within the St. Johns River, Florida, upstream and downstream from a paper mill plant. Blood and plasma samples from fish from the tank study and from fish sampled from the ambient sites were analyzed for over 20 variables. We also determined liver and spleen weights and examined them histologically. The most significant finding from the tank study was an increase in the concentration of albumin and hepatosomatic index for bass exposed to ???20% effluents for 56 days. Spleenosomatic index and number of melanomacrophage centers were decreased in bass from effluent-dominated sites (Palatka and Rice Creek), whereas concentrations of calcium, phosphorous, glucose, and creatinine were elevated in fish from these sites, compared to fish from reference streams. Fish from Rice Creek also had fewer red blood cells, and male bass from Palatka had lower concentrations of cholesterol. Plasma concentrations of albumin and hepatic concentrations of glutathione were elevated in males from Palatka, and both females and males from Rice Creek had higher concentrations of globulin. These results indicate a complex pattern of effects of paper mill effluents on several physiological functions. However, despite the myriad of treatment and site-related effects, most physiological parameters fell within normal ranges when compared to reports on largemouth bass and other freshwater species.

  12. Normal 24-hour ambulatory proximal and distal gastroesophageal reflux parameters in Chinese.

    PubMed

    Hu, W H C; Wong, N Y H; Lai, K C; Hui, W M; Lam, K F; Wong, B C Y; Xia, H H X; Chan, C K; Chan, A O O; Wong, W M; Tsang, K W T; Lam, S K

    2002-06-01

    To quantify normal proximal and distal oesophageal acid parameters in healthy Chinese. Observational study. University teaching hospital, Hong Kong. Twenty healthy adults who were not on medication and were free from gastrointestinal symptoms were recruited by advertisement. Ambulatory oesophageal acid (pH<4) exposure parameters were recorded at distal and proximal sites, 5 and 20 cm, respectively above the lower oesophageal sphincter. The 95th percentile for reflux parameters assessed in the distal/proximal oesophagus were: percent total time pH<4, 4.6/0.7%; percent upright time pH<4, 7.0/1.1%; percent supine time pH<4, 4.5/0.5%; number of reflux episodes, 73/12; number of reflux episodes with pH<4 for >5 minutes, 4/0; and the longest single acid exposure episode, 11.2/3.0 minutes. Physiological gastroesophageal reflux occurs in healthy Chinese. These initial data provide a preliminary reference range that could be utilised by laboratories studying Chinese subjects.

  13. Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity.

    PubMed

    Sorg, Barbara A; Berretta, Sabina; Blacktop, Jordan M; Fawcett, James W; Kitagawa, Hiroshi; Kwok, Jessica C F; Miquel, Marta

    2016-11-09

    Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases. Copyright © 2016 the authors 0270-6474/16/3611459-10$15.00/0.

  14. The physiological determinants of drug-induced lysosomal stress resistance

    PubMed Central

    Woldemichael, Tehetina; Rosania, Gus R.

    2017-01-01

    Many weakly basic, lipophilic drugs accumulate in lysosomes and exert complex, pleiotropic effects on organelle structure and function. Thus, modeling how perturbations of lysosomal physiology affect the maintenance of lysosomal ion homeostasis is necessary to elucidate the key factors which determine the toxicological effects of lysosomotropic agents, in a cell-type dependent manner. Accordingly, a physiologically-based mathematical modeling and simulation approach was used to explore the dynamic, multi-parameter phenomenon of lysosomal stress. With this approach, parameters that are either directly involved in lysosomal ion transportation or lysosomal morphology were transiently altered to investigate their downstream effects on lysosomal physiology reflected by the changes they induce in lysosomal pH, chloride, and membrane potential. In addition, combinations of parameters were simultaneously altered to assess which parameter was most critical for recovery of normal lysosomal physiology. Lastly, to explore the relationship between organelle morphology and induced stress, we investigated the effects of parameters controlling organelle geometry on the restoration of normal lysosomal physiology following a transient perturbation. Collectively, our results indicate a key, interdependent role of V-ATPase number and membrane proton permeability in lysosomal stress tolerance. This suggests that the cell-type dependent regulation of V-ATPase subunit expression and turnover, together with the proton permeability properties of the lysosomal membrane, is critical to understand the differential sensitivity or resistance of different cell types to the toxic effects of lysosomotropic drugs. PMID:29117253

  15. Fractal landscapes in biological systems: long-range correlations in DNA and interbeat heart intervals

    NASA Technical Reports Server (NTRS)

    Stanley, H. E.; Buldyrev, S. V.; Goldberger, A. L.; Hausdorff, J. M.; Havlin, S.; Mietus, J.; Sciortino, F.; Simons, M.

    1992-01-01

    Here we discuss recent advances in applying ideas of fractals and disordered systems to two topics of biological interest, both topics having common the appearance of scale-free phenomena, i.e., correlations that have no characteristic length scale, typically exhibited by physical systems near a critical point and dynamical systems far from equilibrium. (i) DNA nucleotide sequences have traditionally been analyzed using models which incorporate the possibility of short-range nucleotide correlations. We found, instead, a remarkably long-range power law correlation. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences as well as intragenomic DNA, but not in cDNA sequences or intron-less genes. We also found that the myosin heavy chain family gene evolution increases the fractal complexity of the DNA landscapes, consistent with the intron-late hypothesis of gene evolution. (ii) The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis, whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state. We found, however, that under normal conditions, beat-to-beat fluctuations in heart rate display long-range power law correlations.

  16. Understanding auditory distance estimation by humpback whales: a computational approach.

    PubMed

    Mercado, E; Green, S R; Schneider, J N

    2008-02-01

    Ranging, the ability to judge the distance to a sound source, depends on the presence of predictable patterns of attenuation. We measured long-range sound propagation in coastal waters to assess whether humpback whales might use frequency degradation cues to range singing whales. Two types of neural networks, a multi-layer and a single-layer perceptron, were trained to classify recorded sounds by distance traveled based on their frequency content. The multi-layer network successfully classified received sounds, demonstrating that the distorting effects of underwater propagation on frequency content provide sufficient cues to estimate source distance. Normalizing received sounds with respect to ambient noise levels increased the accuracy of distance estimates by single-layer perceptrons, indicating that familiarity with background noise can potentially improve a listening whale's ability to range. To assess whether frequency patterns predictive of source distance were likely to be perceived by whales, recordings were pre-processed using a computational model of the humpback whale's peripheral auditory system. Although signals processed with this model contained less information than the original recordings, neural networks trained with these physiologically based representations estimated source distance more accurately, suggesting that listening whales should be able to range singers using distance-dependent changes in frequency content.

  17. Continuous remote monitoring of COPD patients-justification and explanation of the requirements and a survey of the available technologies.

    PubMed

    Tomasic, Ivan; Tomasic, Nikica; Trobec, Roman; Krpan, Miroslav; Kelava, Tomislav

    2018-04-01

    Remote patient monitoring should reduce mortality rates, improve care, and reduce costs. We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers. Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field. We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain. Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO 2 ) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients. We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise. We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters. The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems. Graphical abstract ᅟ.

  18. Development and Clinical Application of a New Method for the Radioimmunoassay of Arginine Vasopressin in Human Plasma

    PubMed Central

    Robertson, Gary L.; Mahr, Ermelinda A.; Athar, Shahid; Sinha, Tushar

    1973-01-01

    A radioimmunoassay has been developed that permits reliable measurements of plasma arginine vasopressin (AVP) at concentrations as low as 0.5 pg/ml in sample volumes of 1 ml or less. Nonhormonal immunoreactivity associated with the plasma proteins is eliminated by acetone precipitation before assay, leaving unaltered a component that is immunologically and chromatographically indistinguishable from standard AVP. Storage of plasma results in a decline in AVP concentration and, thus, must be carefully regulated. The plasma AVP values obtained by our method approximate the anticipated levels and vary in accordance with physiologic expections. In recumbent normal subjects, plasma AVP ranged from (mean ±SD) 5.4±3.4 pg/ml after fluid deprivation to 1.4±0.8 pg/ml after water loading, and correlated significantly with both plasma osmolality (r=0.52; P<0.001) and urine osmolality (r=0.77; P<0.001). After fluid restriction, plasma AVP was uniformly normal relative to plasma osmolality in patients with nephrogenic diabetes insipidus and primary polydipsia but was distinctly subnormal in all patients with pituitary diabetes insipidus. The infusion of physiologic amounts of posterior pituitary extract caused a dose-related rise in plasma vasopressin that afterwards declined at the expected rate (t½=22.5±4 min). We conclude that, when used appropriately, our radioimmunoassay method provides a useful way of assessing AVP function in man. PMID:4727463

  19. Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi.

    PubMed

    Müller, Marius N; Trull, Thomas W; Hallegraeff, Gustaaf M

    2017-08-01

    Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50 o S, 149 o E) with pH/CO 2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO 2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO 2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO 2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO 2 . Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO 2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies.

  20. Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi

    PubMed Central

    Müller, Marius N; Trull, Thomas W; Hallegraeff, Gustaaf M

    2017-01-01

    Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50oS, 149oE) with pH/CO2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO2. Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies. PMID:28430186

  1. From the Cover: Manganese Stimulates Mitochondrial H2O2 Production in SH-SY5Y Human Neuroblastoma Cells Over Physiologic as well as Toxicologic Range

    PubMed Central

    Fernandes, Jolyn; Hao, Li; Bijli, Kaiser M.; Chandler, Joshua D.; Orr, Michael; Hu, Xin; Jones, Dean P.

    2017-01-01

    Manganese (Mn) is an abundant redox-active metal with well-characterized mitochondrial accumulation and neurotoxicity due to excessive exposures. Mn is also an essential co-factor for the mitochondrial antioxidant protein, superoxide dismutase-2 (SOD2), and the range for adequate intake established by the Institute of Medicine Food and Nutrition Board is 20% of the interim guidance value for toxicity by the Agency for Toxic Substances and Disease Registry, leaving little margin for safety. To study toxic mechanisms over this critical dose range, we treated human neuroblastoma SH-SY5Y cells with a series of MnCl2 concentrations (from 0 to 100 μM) and measured cellular content to compare to human brain Mn content. Concentrations ≤10 μM gave cellular concentrations comparable to literature values for normal human brain, whereas concentrations ≥50 μM resulted in values comparable to brains from individuals with toxic Mn exposures. Cellular oxygen consumption rate increased as a function of Mn up to 10 μM and decreased with Mn dose ≥50 μM. Over this range, Mn had no effect on superoxide production as measured by aconitase activity or MitoSOX but increased H2O2 production as measured by MitoPY1. Consistent with increased production of H2O2, SOD2 activity, and steady-state oxidation of total thiol increased with increasing Mn. These findings have important implications for Mn toxicity by re-directing attention from superoxide anion radical to H2O2-dependent mechanisms and to investigation over the entire physiologic range to toxicologic range. Additionally, the results show that controlled Mn exposure provides a useful cell manipulation for toxicological studies of mitochondrial H2O2 signaling. PMID:27701121

  2. Constitutive Uncoupling of Pathways of Gene Expression That Control Growth and Differentiation in Myeloid Leukemia: A Model for the Origin and Progression of Malignancy

    NASA Astrophysics Data System (ADS)

    Sachs, Leo

    1980-10-01

    Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promoters can regulate a variety of physiological molecules that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expression required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also explain the expression of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors.

  3. Assessment of pubertal development in Egyptian girls.

    PubMed

    Hosny, Laila A; El-Ruby, Mona O; Zaki, Moushira E; Aglan, Mona S; Zaki, Maha S; El Gammal, Mona A; Mazen, Inas M

    2005-06-01

    Puberty is a significant event of human growth and maturation associated with marked physiological and psychological changes. The aim of this study was to assess normal pubertal development in Egyptian girls to define normal, precocious and delayed puberty. The present study included a cross-sectional sample of 1,550 normal Egyptian girls of high and middle socioeconomic class living in Cairo. Their ages ranged from 6.5 to 18.5 years. Pubertal assessment was made according to Tanner staging. The mean menarcheal age (MMA) was estimated using probit analysis. Weight and height were measured and body mass index (BMI) was calculated. The mean age at breast bud stage (B2) was 10.71+/-1.6, pubic hair stage (PH2) was 10.46+/-1.36, while axillary hair stage (A2) was 11.65+/-1.62 and MMA was 12.44 years. The mean age at attainment of puberty was compared with those of other Egyptian studies and other populations. Girls of the present study started pubertal development and achieved menarche earlier than those of previous Egyptian studies confirming a secular trend. Differences between the present study and other worldwide studies can be attributed to various genetic, racial, geographical, nutritional, and secular trend factors.

  4. Normal gene expression in male F344 rat nasal transitional and respiratory epithelium.

    PubMed

    Hester, Susan D; Benavides, Gina B; Sartor, Maureen; Yoon, Lawrence; Wolf, Douglas C; Morgan, Kevin T

    2002-02-20

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Cells lining the rat nasal passages were collected and gene expression analysis was performed using Clontech cDNA Rat Atlas 1.2 arrays (1185 genes). The percentages of genes within specific average expression ranges were 4.2% at 45,000-1000, 14.8% at 1000-200, 25.0% at 200-68, and 56.0% below 68. Nine out of a subset of ten genes were confirmed for relative signal intensity using quantitative real-time RT-PCR. The most highly expressed genes included those involved in phase I (e.g. cytochrome P450s) and phase II (e.g. glutathione S-transferases) xenobiotic metabolism, bioenergetics (e.g. cytochrome oxidase), osmotic balance (e.g. Na(+)/K(+) ATPase) and epithelial ionic homeostasis (e.g. ion channels). Such baseline data will contribute to further understanding the normal physiology of these cells and facilitate the interpretation of responses by the nasal epithelial cells to xenobiotic treatment or disease.

  5. Developing Physiologic Stress Profiles for School-Age Children Who Stutter

    ERIC Educational Resources Information Center

    Ortega, Aishah Y.; Ambrose, Nicoline G.

    2011-01-01

    Purpose: Physiologic reactivity profiles were generated for 9 school-age children with a history of stuttering. Utilizing salivary sampling, stress biomarkers cortisol and alpha-amylase were measured in response to normal daily stressors. Children with a history of stuttering were characterized as high or low autonomic reactors when compared to…

  6. New Ways of Thinking about (and Teaching about) Intestinal Epithelial Function

    ERIC Educational Resources Information Center

    Barrett, Kim E.

    2008-01-01

    This article summarizes a presentation made at the Teaching Refresher Course of the American Physiological Society, which was held at the Experimental Biology meeting in 2007. The intestinal epithelium has important ion transport and barrier functions that contribute pivotally to normal physiological functioning of the intestine and other body…

  7. The Influence of Word Frequency on Word Retrieval: Measuring Covert Behaviors

    ERIC Educational Resources Information Center

    Chih, Yu-Chun; Stierwalt, Julie A. G.; LaPointe, Leonard L.; Chih, Yu-Pin

    2017-01-01

    Physiological activities (heart rate and respiratory rate) during a word retrieval task were measured in normal participants. Word frequency demonstrated a significant effect on naming accuracy and latencies but not on physiological activities. These data will serve as a basis for comparison for individuals with a compromised language system.

  8. Functional metabolite assemblies—a review

    NASA Astrophysics Data System (ADS)

    Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

    2018-05-01

    Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

  9. The Physiology of Adventitious Roots1

    PubMed Central

    Steffens, Bianka; Rasmussen, Amanda

    2016-01-01

    Adventitious roots are plant roots that form from any nonroot tissue and are produced both during normal development (crown roots on cereals and nodal roots on strawberry [Fragaria spp.]) and in response to stress conditions, such as flooding, nutrient deprivation, and wounding. They are important economically (for cuttings and food production), ecologically (environmental stress response), and for human existence (food production). To improve sustainable food production under environmentally extreme conditions, it is important to understand the adventitious root development of crops both in normal and stressed conditions. Therefore, understanding the regulation and physiology of adventitious root formation is critical for breeding programs. Recent work shows that different adventitious root types are regulated differently, and here, we propose clear definitions of these classes. We use three case studies to summarize the physiology of adventitious root development in response to flooding (case study 1), nutrient deficiency (case study 2), and wounding (case study 3). PMID:26697895

  10. Correlation of tissue-plasma partition coefficients between normal tissues and subcutaneous xenografts of human tumor cell lines in mouse as a prediction tool of drug penetration in tumors.

    PubMed

    Poulin, Patrick; Hop, Cornelis Eca; Salphati, Laurent; Liederer, Bianca M

    2013-04-01

    Understanding drug distribution and accumulation in tumors would be informative in the assessment of efficacy in targeted therapy; however, existing methods for predicting tissue drug distribution focus on normal tissues and do not incorporate tumors. The main objective of this study was to describe the relationships between tissue-plasma concentration ratios (Kp ) of normal tissues and those of subcutaneous xenograft tumors under nonsteady-state conditions, and establish regression equations that could potentially be used for the prediction of drug levels in several human tumor xenografts in mouse, based solely on a Kp value determined in a normal tissue (e.g., muscle). A dataset of 17 compounds was collected from the literature and from Genentech. Tissue and plasma concentration data in mouse were obtained following oral gavage or intraperitoneal administration. Linear regression analyses were performed between Kp values in several normal tissues (muscle, lung, liver, or brain) and those in human tumor xenografts (CL6, EBC-1, HT-29, PC3, U-87, MCF-7-neo-Her2, or BT474M1.1). The tissue-plasma ratios in normal tissues reasonably correlated with the tumor-plasma ratios in CL6, EBC-1, HT-29, U-87, BT474M1.1, and MCF-7-neo-Her2 xenografts (r(2) in the range 0.62-1) but not with the PC3 xenograft. In general, muscle and lung exhibited the strongest correlation with tumor xenografts, followed by liver. Regression coefficients from brain were low, except between brain and the glioblastoma U-87 xenograft (r(2) in the range 0.62-0.94). Furthermore, reasonably strong correlations were observed between muscle and lung and between muscle and liver (r(2) in the range 0.67-0.96). The slopes of the regressions differed depending on the class of drug (strong vs. weak base) and type of tissue (brain vs. other tissues and tumors). Overall, this study will contribute to our understanding of tissue-plasma partition coefficients for tumors and facilitate the use of physiologically based pharmacokinetics (PBPK) modeling for chemotherapy in oncology studies. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1355-1369, 2013. Copyright © 2013 Wiley Periodicals, Inc.

  11. Molecular cell biology and physiology of solute transport

    PubMed Central

    Caplan, Michael J.; Seo-Mayer, Patricia; Zhang, Li

    2010-01-01

    Purpose of review An enormous body of research has been focused on exploring the mechanisms through which epithelial cells establish their characteristic polarity. It is clear that under normal circumstances cell–cell contacts mediated by the calcium-dependent adhesion proteins of the intercellular adhesion junctions are required to initiate complete polarization. Furthermore, formation of the tight, or occluding, junctions that limit paracellular permeability has long been thought to help to establish polarity by preventing the diffusion of membrane proteins between the two plasmalemmal domains. This review will discuss several selected kinases and protein complexes and highlight their relevance to transporting epithelial cell polarization. Recent findings Recent work has shed new light on the roles of junctional complexes in establishing and maintaining epithelial cell polarity. In addition, work from several laboratories, suggests that the formation of these junctions is tied to processes that regulate cellular energy metabolism. Summary Junctional complexes and energy sensing kinases constitute a novel class of machinery whose capacity to generate and modulate epithelial cell polarity is likely to have wide ranging and important physiological ramifications. PMID:18695392

  12. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium

    PubMed Central

    Xu, Lizhi; Gutbrod, Sarah R.; Bonifas, Andrew P.; Su, Yewang; Sulkin, Matthew S.; Lu, Nanshu; Chung, Hyun-Joong; Jang, Kyung-In; Liu, Zhuangjian; Ying, Ming; Lu, Chi; Webb, R. Chad; Kim, Jong-Seon; Laughner, Jacob I.; Cheng, Huanyu; Liu, Yuhao; Ameen, Abid; Jeong, Jae-Woong; Kim, Gwang-Tae; Huang, Yonggang; Efimov, Igor R.; Rogers, John A.

    2015-01-01

    Means for high-density multiparametric physiological mapping and stimulation are critically important in both basic and clinical cardiology. Current conformal electronic systems are essentially 2D sheets, which cannot cover the full epicardial surface or maintain reliable contact for chronic use without sutures or adhesives. Here we create 3D elastic membranes shaped precisely to match the epicardium of the heart via the use of 3D printing, as a platform for deformable arrays of multifunctional sensors, electronic and optoelectronic components. Such integumentary devices completely envelop the heart, in a form-fitting manner, and possess inherent elasticity, providing a mechanically stable bioti-/abiotic interface during normal cardiac cycles. Component examples range from actuators for electrical, thermal and optical stimulation, to sensors for pH, temperature and mechanical strain. The semiconductor materials include silicon, gallium arsenide and gallium nitride, co-integrated with metals, metal oxides and polymers, to provide these and other operational capabilities. Ex vivo physiological experiments demonstrate various functions and methodological possibilities for cardiac research and therapy. PMID:24569383

  13. Should modulation of p50 be a therapeutic target in the critically ill?

    PubMed

    Srinivasan, Amudan J; Morkane, Clare; Martin, Daniel S; Welsby, Ian J

    2017-05-01

    A defining feature of human hemoglobin is its oxygen binding affinity, quantified by the partial pressure of oxygen at which hemoglobin is 50% saturated (p50), and the variability of this parameter over a range of physiological and environmental states. Modulation of this property of hemoglobin can directly affect the degree of peripheral oxygen offloading and tissue oxygenation. Areas covered: This review summarizes the role of hemoglobin oxygen affinity in normal and abnormal physiology and discusses the current state of the literature regarding artificial modulation of p50. Hypoxic tumors, sickle cell disease, heart failure, and transfusion medicine are discussed in the context of recent advances in hemoglobin oxygen affinity manipulation. Expert commentary: Of particular clinical interest is the possibility of maintaining adequate end-organ oxygen availability in patients with anemia or compromised cardiac function via an increase in systemic p50. This increase in systemic p50 can be achieved with small molecule drugs or a packed red blood cell unit processing variant called rejuvenation, and human trials are needed to better understand the potential clinical benefits to modulating p50.

  14. Progress and challenges in understanding planar cell polarity signaling.

    PubMed

    Axelrod, Jeffrey D

    2009-10-01

    During development, epithelial cells in some tissues acquire a polarity orthogonal to their apical-basal axis. This polarity, referred to as planar cell polarity (PCP), or tissue polarity, is essential for the normal physiological function of many epithelia. Early studies of PCP focused on insect epithelia (Lawrence, 1966 [1]), and the earliest genetic analyses were carried out in Drosophila (Held et al., 1986; Gubb and Garcia-Bellido, 1982 [2,3]). Indeed, most of our mechanistic understanding of PCP derives from the ongoing use of Drosophila as a model system. However, a range of medically important developmental defects and physiological processes are under the control of PCP mechanisms that appear to be at least partially conserved, driving considerable interest in studying PCP both in Drosophila and in vertebrate model systems. Here, I present a model of the PCP signaling mechanism based on studies in Drosophila. I highlight two areas in which our understanding is deficient, and which lead to current confusion in the literature. Future studies that shed light on these areas will substantially enhance our understanding of the fascinating yet challenging problem of understanding the mechanisms that generate PCP.

  15. Do unliganded thyroid hormone receptors have physiological functions?

    PubMed

    Chassande, O

    2003-08-01

    Thyroid hormone (TH) is required for the development of vertebrates and exerts numerous homeostatic functions in adults. TH acts through nuclear receptors which control the transcription of target genes. Unliganded and liganded thyroid hormone receptors (TRs) have been shown to exert opposite effects on the transcription of target genes in vitro. However, the occurance of an aporeceptor activity in vivo and its potential physiological significance has not been clearly addressed. Several data generated using experimental hypothyroidism and thyrotoxicosis in wild type and TR knockout mice support the notion that apoTRs have an intrinsic activity in several tIssues. ApoTRs, and in particular TRalpha1, are predominant during the early stages of vertebrate development and must be turned into holoTRs for post-natal development to proceed normally. However, the absence of striking alterations of embryonic and fetal development in mice devoid of TRs indicates that apoTRs do not play a fundamental role. During development, as well as in adults, apoTRs rather appears as a system which increases the range of transcriptional responses to moderate variations of T3.

  16. Anthropogenic pollutants: a threat to ecosystem sustainability?

    PubMed

    Rhind, S M

    2009-11-27

    Pollutants, including synthetic organic materials and heavy metals, are known to adversely affect physiological systems in all animal species studied to date. While many individual chemicals can perturb normal functions, the combined actions of multiple pollutants are of particular concern because they can exert effects even when each individual chemical is present at concentrations too low to be individually effective. The biological effects of pollutants differ greatly between species reflecting differences in the pattern of exposure, routes of uptake, metabolism following uptake, rates of accumulation and sensitivity of the target organs. Thus, understanding of the effects of pollutants on wildlife and ecosystems will require detailed study of many different species, representing a wide range of taxa. However, such studies can be informed by knowledge obtained in more controlled conditions which may indicate likely mechanisms of action and suitable endpoint measurements. Responses may be exacerbated by interactions between the effects of pollutants and environmental stressors, such as under-nutrition or osmotic stresses and so changes in such variables associated with climatic changes may exacerbate physiological responses to pollutant burdens.

  17. A Computational Approach to Model Vascular Adaptation During Chronic Hemodialysis: Shape Optimization as a Substitute for Growth Modeling

    NASA Astrophysics Data System (ADS)

    Mahmoudzadeh Akherat, S. M. Javid; Boghosian, Michael; Cassel, Kevin; Hammes, Mary

    2015-11-01

    End-stage-renal disease patients depend on successful long-term hemodialysis via vascular access, commonly facilitated via a Brachiocephalic Fistula (BCF). The primary cause of BCF failure is Cephalic Arch Stenosis (CAS). It is believed that low Wall Shear Stress (WSS) regions, which occur because of the high flow rates through the natural bend in the cephalic vein, create hemodynamic circumstances that trigger the onset and development of Intimal Hyperplasia (IH) and subsequent CAS. IH is hypothesized to be a natural effort to reshape the vessel, aiming to bring the WSS values back to a physiologically acceptable range. We seek to explore the correlation between regions of low WSS and subsequent IH and CAS in patient-specific geometries. By utilizing a shape optimization framework, a method is proposed to predict cardiovascular adaptation that could potentially be an alternative to vascular growth and remodeling. Based on an objective functional that seeks to alter the vessel shape in such a way as to readjust the WSS to be within the normal physiological range, CFD and shape optimization are then coupled to investigate whether the optimal shape evolution is correlated with actual patient-specific geometries thereafter. Supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (R01 DK90769).

  18. Space flight and bone formation.

    PubMed

    Doty, St B

    2004-12-01

    Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

  19. Space flight and bone formation

    NASA Technical Reports Server (NTRS)

    Doty, St B.

    2004-01-01

    Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

  20. MicroRNA-200c: A Novel Way to Attack Breast Cancer Metastases by Restoring the Epithelial Phenotype

    DTIC Science & Technology

    2012-02-01

    complex relationships and reveal the extent to whichmiRNAs are involved with SHRs in normal physiology and the pathobiology of steroid hormoneene regulation...proges- terone counteracts estrogen-mediated proliferation. To determine whethermiRNAs play a physiological role inmodulating hormonal control of gene...effect on uterine physiology to ate is the finding that P4/PGR affects uterine contractility during abor via regulation of ZEB1 and the miR-200 family

  1. Observation of arterial blood pressure of the primate

    NASA Technical Reports Server (NTRS)

    Meehan, J. P.; Henry, J. P.

    1973-01-01

    The developments are reported in physiological instrumentation, surgical procedures, measurement and data analysis techniques, and the definition of flight experiments to determine the effects of prolonged weightlessness on the cardiovascular system of subhuman primates. The development of an implantable telemetric data acquisition system is discussed along with cardiovascular research applications in renal hemodynamics. It is concluded that the implant technique permits a valid interpretation, free of emotional response, for the manipulated variable on physiological functions. It also allows a better definition of normal physiological baseline conditions.

  2. MELATONIN ENHANCES JUNCTIONAL TRANSFER IN NORMAL C3H/1OT1/2 CELLS

    EPA Science Inventory

    There is strong evidence that pineal melatonin is involved in controlling neoplastic processes. e have reported that physiological, but not pharmacological or subphysiological, concentrations of melatonin enhance intercellular communication in normal C3H/1OT1/2 fibroblasts. ap ju...

  3. Effects of environmental enrichment on behaviour, physiology and performance of pigs: A review.

    PubMed

    Mkwanazi, Mbusiseni Vusumuzi; Ncobela, Cyprial Ndumiso; Kanengoni, Arnold Tapera; Chimonyo, Michael

    2017-06-26

    The aim of this paper is to critically analyse and synthesise existing knowledge concerning the use of environmental enrichment and its effect on behaviour, physiology and performance of pigs housed in intensive production systems. The objective is also to provide clarity as to what constitute successful enrichment and recommend on when and how enrichment should be used. Environmental enrichment is usually understood as an attempt to improve animal welfare and to lesser extent, performance. Common enrichment objects used are straw bedding, suspended rope and wood shavings, toys, rubber tubing, coloured plastic keys, table tennis balls, chains and strings. These substrates need to be chewable, deformable, destructible and ingestible. For enrichment to be successful four goals are the prerequisite. Firstly, enrichment should increase the number and range of normal behaviours (2) prevent the phenomenon of anomalous behaviours or reduce their frequency (3) increase positive use of the environment such as space and (4) increase the ability of the animals to deal with behavioural and physiological challenges. The performance, behaviour and physiology of pigs in enriched environments is similar or in some cases slightly better when compared with barren environments. In studies where there was no improvement, it should be born in mind that enriching the environment may not always be practical and yield positive results due to factors such as type of enrichment substrates, duration of provision and type of enrichment used. The review also identifies possible areas which still need further research, especially in understanding the role of enrichment, novelty, breed differences and other enrichment alternatives.

  4. A Physiologically Based Model of Orexinergic Stabilization of Sleep and Wake

    PubMed Central

    Fulcher, Ben D.; Phillips, Andrew J. K.; Postnova, Svetlana; Robinson, Peter A.

    2014-01-01

    The orexinergic neurons of the lateral hypothalamus (Orx) are essential for regulating sleep-wake dynamics, and their loss causes narcolepsy, a disorder characterized by severe instability of sleep and wake states. However, the mechanisms through which Orx stabilize sleep and wake are not well understood. In this work, an explanation of the stabilizing effects of Orx is presented using a quantitative model of important physiological connections between Orx and the sleep-wake switch. In addition to Orx and the sleep-wake switch, which is composed of mutually inhibitory wake-active monoaminergic neurons in brainstem and hypothalamus (MA) and the sleep-active ventrolateral preoptic neurons of the hypothalamus (VLPO), the model also includes the circadian and homeostatic sleep drives. It is shown that Orx stabilizes prolonged waking episodes via its excitatory input to MA and by relaying a circadian input to MA, thus sustaining MA firing activity during the circadian day. During sleep, both Orx and MA are inhibited by the VLPO, and the subsequent reduction in Orx input to the MA indirectly stabilizes sustained sleep episodes. Simulating a loss of Orx, the model produces dynamics resembling narcolepsy, including frequent transitions between states, reduced waking arousal levels, and a normal daily amount of total sleep. The model predicts a change in sleep timing with differences in orexin levels, with higher orexin levels delaying the normal sleep episode, suggesting that individual differences in Orx signaling may contribute to chronotype. Dynamics resembling sleep inertia also emerge from the model as a gradual sleep-to-wake transition on a timescale that varies with that of Orx dynamics. The quantitative, physiologically based model developed in this work thus provides a new explanation of how Orx stabilizes prolonged episodes of sleep and wake, and makes a range of experimentally testable predictions, including a role for Orx in chronotype and sleep inertia. PMID:24651580

  5. Orexins and appetite regulation.

    PubMed

    Rodgers, R J; Ishii, Y; Halford, J C G; Blundell, J E

    2002-10-01

    Initial research on the functional significance of two novel hypothalamic neuropeptides, orexin-A and orexin-B, suggested an important role in appetite regulation. Since then, however, these peptides have also been shown to influence a wide range of other physiological and behavioural processes. In this paper, we review the now quite extensive literature on orexins and appetite control, and consider their additional effects within this context. Although the evidence for orexin (particularly orexin-A and the orexin-1 receptor) involvement in many aspects of ingestive physiology and behaviour is incontrovertible, central administration of orexins is also associated with increased EEG arousal and wakefulness, locomotor activity and grooming, sympathetic and HPA activity, and pain thresholds. Since the orexin system is selectively activated by signals indicating severe nutritional depletion, it would be highly adaptive for a hungry animal not only to seek sustenance but also to remain fully alert to dangers in the environment. Crucial evidence indicates that orexin-A increases food intake by delaying the onset of a behaviourally normal satiety sequence. In contrast, a selective orexin-1 receptor antagonist (SB-334867) suppresses food intake and advances the onset of a normal satiety sequence. These data suggest that orexin-1 receptors mediate the episodic signalling of satiety and appear to bridge the transition from eating to resting in the rats' feeding-sleep cycle. The argument is developed that the diverse physiological and behavioural effects of orexins can best be understood in terms of an integrated set of reactions which function to rectify nutritional status without compromising personal survival. Indeed, many of the non-ingestive effects of orexin administration are identical to the cluster of active defences mediated via the lateral and dorsolateral columns of the midbrain periaqueductal gray matter, i.e., somatomotor activation, vigilance, tachycardia, hypertension and non-opioid analgesia. In our view, therefore, the LH orexin system is very well placed to orchestrate the diverse subsystems involved in foraging under potentially dangerous circumstances, i.e., finding and ingesting food without oneself becoming a meal for someone else.

  6. Physiology undergraduate degree requirements in the U.S.

    PubMed

    VanRyn, Valerie S; Poteracki, James M; Wehrwein, Erica A

    2017-12-01

    Course-level learning objectives and core concepts for undergraduate physiology teaching exist. The next step is to consider how these resources fit into generalizable program-level guidelines for Bachelor of Science (BS) degrees in Physiology. In the absence of program-level guidelines for Physiology degree programs, we compiled a selective internal report to review degree requirements from 18 peer BS programs entitled "Physiology" in the United States (U.S.). There was a range of zero to three required semesters of math, physics, physics laboratory, general biology, biology laboratory, general chemistry, chemistry laboratory, organic chemistry, organic chemistry laboratory, biochemistry, biochemistry laboratory, anatomy, anatomy laboratory, core systems physiology, and physiology laboratory. Required upper division credits ranged from 11 to 31 and included system-specific, exercise and environmental, clinically relevant, pathology/disease-related, and basic science options. We hope that this information will be useful for all programs that consider themselves to be physiology, regardless of name. Reports such as this can serve as a starting point for collaboration among BS programs to improve physiology undergraduate education and best serve our students. Copyright © 2017 the American Physiological Society.

  7. Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Garcia, J.F.; Ebbe, S.N.; Hollander, L.

    1982-05-01

    Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples showmore » a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.« less

  8. THE CONTRIBUTIONS OF NORMAL AND ANOMALOUS OSMOSIS TO THE OSMOTIC EFFECTS ARISING ACROSS CHARGED MEMBRANES WITH SOLUTIONS OF ELECTROLYTES

    PubMed Central

    Grim, Eugene; Sollner, Karl

    1957-01-01

    The osmotic effect arising across a porous membrane separating the solution of an electrolyte from water (or a more dilute solution) is ordinarily due to both normal osmosis, as it occurs also with non-electrolytes, and to "anomalous" osmosis. It is shown that the normal osmotic component cannot be measured quantitatively by the conventional comparison with a non-electrolytic reference solute. Anomalous osmosis does not occur with electroneutral membranes. Accordingly, with membranes which can be charged and discharged reversibly (without changes in geometrical structure), such as many proteinized membranes, the osmotic effects caused by an electrolyte can be measured both when only normal osmosis arises (with the membrane in the electroneutral state) and when normal as well as anomalous osmosis occurs (with the membrane in a charged state). The difference between these two effects is the true anomalous osmosis. Data are presented on the osmotic effects across an oxyhemoglobin membrane in the uncharged state at pH 6.75 and in two charged states, positive at pH 4.0 and negative at pH 10.0, with solutions of a variety of electrolytes using a concentration ratio of 2:1 over a wide range of concentrations. The rates of the movement of liquid across the membrane against an inconsequentially small hydrostatic head are recorded instead of, as conventional, the physiologically less significant pressure rises after a standard time. PMID:13439166

  9. The Influence of Hyperthyroidism and Hypothyroidism on the β-Adrenergic Responsiveness of the Turkey Erythrocyte

    PubMed Central

    Bilezikian, John P.; Loeb, John N.; Gammon, Donald E.

    1979-01-01

    The mechanisms responsible for altered adrenergic tone in hyperthyroidism and hypothyroidism are not fully understood. To investigate these mechanisms, the β-adrenergic receptor-cyclic AMP complex of the turkey erythrocyte was studied among groups of normal, hyperthyroid, and hypothyroid turkeys. In erythrocytes obtained from hypothyroid turkeys, there were fewer β-adrenergic receptors than in normal cells as determined by the specific binding of [125I]iodohydroxybenzylpindolol, as well as associated decreases both in catecholamine-responsive adenylate cyclase activity and in cellular cyclic AMP content. In contrast, erythrocytes obtained from hyperthyroid turkeys contained the same number of β-receptors and had the same catecholamine-responsive adenylate cyclase activity as cells from normal birds. Other characteristics of the β-receptors in cells from hyperthyroid birds were indistinguishable from those present in normal erythrocytes. However, within the range of circulating catecholamine concentrations, 5-50 nM, the erythrocytes of the hyperthyroid turkeys generated substantially more cyclic AMP after exposure to isoproterenol than did normal cells. These results suggest that thyroid hormone affects β-receptor-cyclic AMP interrelationships in the turkey erythrocyte by two distinct mechanisms: (a) In hypothyroidism, both β-receptors and catecholamine-dependent cyclic AMP formation are coordinately decreased; (b) in hyperthyroidism, β-receptors are unchanged but there is an amplification of the hormonal signal so that occupation of a given number of receptors at physiological concentrations of catecholamines leads to increased levels of cyclic AMP. PMID:219032

  10. Exploratory factor analysis for differentiating sensory and mechanical variables related to muscle-tendon unit elongation

    PubMed Central

    Chagas, Mauro H.; Magalhães, Fabrício A.; Peixoto, Gustavo H. C.; Pereira, Beatriz M.; Andrade, André G. P.; Menzel, Hans-Joachim K.

    2016-01-01

    ABSTRACT Background Stretching exercises are able to promote adaptations in the muscle-tendon unit (MTU), which can be tested through physiological and biomechanical variables. Identifying the key variables in MTU adaptations is crucial to improvements in training. Objective To perform an exploratory factor analysis (EFA) involving the variables often used to evaluate the response of the MTU to stretching exercises. Method Maximum joint range of motion (ROMMAX), ROM at first sensation of stretching (FSTROM), peak torque (torqueMAX), passive stiffness, normalized stiffness, passive energy, and normalized energy were investigated in 36 participants during passive knee extension on an isokinetic dynamometer. Stiffness and energy values were normalized by the muscle cross-sectional area and their passive mode assured by monitoring the EMG activity. Results EFA revealed two major factors that explained 89.68% of the total variance: 53.13% was explained by the variables torqueMAX, passive stiffness, normalized stiffness, passive energy, and normalized energy, whereas the remaining 36.55% was explained by the variables ROMMAX and FSTROM. Conclusion This result supports the literature wherein two main hypotheses (mechanical and sensory theories) have been suggested to describe the adaptations of the MTU to stretching exercises. Contrary to some studies, in the present investigation torqueMAX was significantly correlated with the variables of the mechanical theory rather than those of the sensory theory. Therefore, a new approach was proposed to explain the behavior of the torqueMAX during stretching exercises. PMID:27437715

  11. A normalization model suggests that attention changes the weighting of inputs between visual areas

    PubMed Central

    Cohen, Marlene R.

    2017-01-01

    Models of divisive normalization can explain the trial-averaged responses of neurons in sensory, association, and motor areas under a wide range of conditions, including how visual attention changes the gains of neurons in visual cortex. Attention, like other modulatory processes, is also associated with changes in the extent to which pairs of neurons share trial-to-trial variability. We showed recently that in addition to decreasing correlations between similarly tuned neurons within the same visual area, attention increases correlations between neurons in primary visual cortex (V1) and the middle temporal area (MT) and that an extension of a classic normalization model can account for this correlation increase. One of the benefits of having a descriptive model that can account for many physiological observations is that it can be used to probe the mechanisms underlying processes such as attention. Here, we use electrical microstimulation in V1 paired with recording in MT to provide causal evidence that the relationship between V1 and MT activity is nonlinear and is well described by divisive normalization. We then use the normalization model and recording and microstimulation experiments to show that the attention dependence of V1–MT correlations is better explained by a mechanism in which attention changes the weights of connections between V1 and MT than by a mechanism that modulates responses in either area. Our study shows that normalization can explain interactions between neurons in different areas and provides a framework for using multiarea recording and stimulation to probe the neural mechanisms underlying neuronal computations. PMID:28461501

  12. A normalization model suggests that attention changes the weighting of inputs between visual areas.

    PubMed

    Ruff, Douglas A; Cohen, Marlene R

    2017-05-16

    Models of divisive normalization can explain the trial-averaged responses of neurons in sensory, association, and motor areas under a wide range of conditions, including how visual attention changes the gains of neurons in visual cortex. Attention, like other modulatory processes, is also associated with changes in the extent to which pairs of neurons share trial-to-trial variability. We showed recently that in addition to decreasing correlations between similarly tuned neurons within the same visual area, attention increases correlations between neurons in primary visual cortex (V1) and the middle temporal area (MT) and that an extension of a classic normalization model can account for this correlation increase. One of the benefits of having a descriptive model that can account for many physiological observations is that it can be used to probe the mechanisms underlying processes such as attention. Here, we use electrical microstimulation in V1 paired with recording in MT to provide causal evidence that the relationship between V1 and MT activity is nonlinear and is well described by divisive normalization. We then use the normalization model and recording and microstimulation experiments to show that the attention dependence of V1-MT correlations is better explained by a mechanism in which attention changes the weights of connections between V1 and MT than by a mechanism that modulates responses in either area. Our study shows that normalization can explain interactions between neurons in different areas and provides a framework for using multiarea recording and stimulation to probe the neural mechanisms underlying neuronal computations.

  13. A computational study of the respiratory airflow characteristics in normal and obstructed human airways.

    PubMed

    Sul, Bora; Wallqvist, Anders; Morris, Michael J; Reifman, Jaques; Rakesh, Vineet

    2014-09-01

    Obstructive lung diseases in the lower airways are a leading health concern worldwide. To improve our understanding of the pathophysiology of lower airways, we studied airflow characteristics in the lung between the 8th and the 14th generations using a three-dimensional computational fluid dynamics model, where we compared normal and obstructed airways for a range of breathing conditions. We employed a novel technique based on computing the Pearson׳s correlation coefficient to quantitatively characterize the differences in airflow patterns between the normal and obstructed airways. We found that the airflow patterns demonstrated clear differences between normal and diseased conditions for high expiratory flow rates (>2300ml/s), but not for inspiratory flow rates. Moreover, airflow patterns subjected to filtering demonstrated higher sensitivity than airway resistance for differentiating normal and diseased conditions. Further, we showed that wall shear stresses were not only dependent on breathing rates, but also on the distribution of the obstructed sites in the lung: for the same degree of obstruction and breathing rate, we observed as much as two-fold differences in shear stresses. In contrast to previous studies that suggest increased wall shear stress due to obstructions as a possible damage mechanism for small airways, our model demonstrated that for flow rates corresponding to heavy activities, the wall shear stress in both normal and obstructed airways was <0.3Pa, which is within the physiological limit needed to promote respiratory defense mechanisms. In summary, our model enables the study of airflow characteristics that may be impractical to assess experimentally. Published by Elsevier Ltd.

  14. Use of Invertebrate Animals to Teach Physiological Principles.

    ERIC Educational Resources Information Center

    Deyrup-Olsen, Ingrith; Linder, Thomas M.

    1991-01-01

    The advantages of using invertebrates in teaching physiological principles are discussed. The ability to illustrate with greater clarity physiological principles, the range and variety of physiological processes available for examination, and the unlimited possibilities for student research are topics of discussion. (KR)

  15. Analysis of dynamic cerebral autoregulation using an ARX model based on arterial blood pressure and middle cerebral artery velocity simulation.

    PubMed

    Liu, Y; Allen, R

    2002-09-01

    The study aimed to model the cerebrovascular system, using a linear ARX model based on data simulated by a comprehensive physiological model, and to assess the range of applicability of linear parametric models. Arterial blood pressure (ABP) and middle cerebral arterial blood flow velocity (MCAV) were measured from 11 subjects non-invasively, following step changes in ABP, using the thigh cuff technique. By optimising parameters associated with autoregulation, using a non-linear optimisation technique, the physiological model showed a good performance (r=0.83+/-0.14) in fitting MCAV. An additional five sets of measured ABP of length 236+/-154 s were acquired from a subject at rest. These were normalised and rescaled to coefficients of variation (CV=SD/mean) of 2% and 10% for model comparisons. Randomly generated Gaussian noise with standard deviation (SD) from 1% to 5% was added to both ABP and physiologically simulated MCAV (SMCAV), with 'normal' and 'impaired' cerebral autoregulation, to simulate the real measurement conditions. ABP and SMCAV were fitted by ARX modelling, and cerebral autoregulation was quantified by a 5 s recovery percentage R5% of the step responses of the ARX models. The study suggests that cerebral autoregulation can be assessed by computing the R5% of the step response of an ARX model of appropriate order, even when measurement noise is considerable.

  16. Sitting-Meditation Interventions Among Youth: A Review of Treatment Efficacy

    PubMed Central

    Black, David S.; Milam, Joel; Sussman, Steve

    2011-01-01

    OBJECTIVE Although the efficacy of meditation interventions has been examined among adult samples, meditation treatment effects among youth are relatively unknown. We systematically reviewed empirical studies for the health-related effects of sitting-meditative practices implemented among youth aged 6 to 18 years in school, clinic, and community settings. METHODS A systematic review of electronic databases (PubMed, Ovid, Web of Science, Cochrane Reviews Database, Google Scholar) was conducted from 1982 to 2008, obtaining a sample of 16 empirical studies related to sitting-meditation interventions among youth. RESULTS Meditation modalities included mindfulness meditation, transcendental meditation, mindfulness-based stress reduction, and mindfulness-based cognitive therapy. Study samples primarily consisted of youth with preexisting conditions such as high-normal blood pressure, attention-deficit/hyperactivity disorder, and learning disabilities. Studies that examined physiologic outcomes were composed almost entirely of African American/black participants. Median effect sizes were slightly smaller than those obtained from adult samples and ranged from 0.16 to 0.29 for physiologic outcomes and 0.27 to 0.70 for psychosocial/behavioral outcomes. CONCLUSIONS Sitting meditation seems to be an effective intervention in the treatment of physiologic, psychosocial, and behavioral conditions among youth. Because of current limitations, carefully constructed research is needed to advance our understanding of sitting meditation and its future use as an effective treatment modality among younger populations. PMID:19706568

  17. Sugar for the brain: the role of glucose in physiological and pathological brain function

    PubMed Central

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

    2013-01-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

  18. Studies on the psychosomatic functioning of ill-health according to Eastern and Western medicine. 1. Visual observation of the sublingual vein for early detection of vital energy stagnation and blood stasis.

    PubMed

    Takeichi, M; Sato, T

    1999-01-01

    Computer-assisted image analyses were performed on the tongue color of 95 medical students without previous history of blood stasis-related condition to clarify the mutual relationship of the color of the tongue proper, the coating, and sublingual vein. The location of the measurement for the tongue proper was the underside of the tongue, and location of the measurement for the tongue coating was the upper surface of the tongue. A linear correlation analysis showed a correlation for each of the different positions for the non-normalized red value and normalized blue value. This analysis also demonstrated a statistically-significant relationship between the tongue proper and the sublingual vein using Red-Green-Blue components and normalized Red-Green-Blue components (r = +0.670 - 0.817, p < 0.0001). The most significant correlation between the tongue proper and the sublingual vein was the normalized red value and the normalized Red-Green-Blue values for minimizing the range of the standard error of the mean (r = +0.745, p < 0.0001), although non-normalized blue had the highest correlation coefficient. Therefore, it seems reasonable to select those normalized red values for the comparison in the tongue color analysis. Correlation of the color between the sublingual vein and the tongue proper strongly suggests that inspection with the naked eye of the sublingual vein is useful for the early detection of vital energy stagnation and blood stasis. Also, because of its close relation to sustained chronic stress, changes in the sublingual vein might be available as one physiological parameter of a stress reaction.

  19. PTEN regulation of local and long-range connections in mouse auditory cortex.

    PubMed

    Xiong, Qiaojie; Oviedo, Hysell V; Trotman, Lloyd C; Zador, Anthony M

    2012-02-01

    Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed that local inputs onto PTEN-cko neurons in the auditory cortex were similarly enhanced. The hyperconnectivity caused by PTEN-cko could be blocked by rapamycin, a specific inhibitor of the PTEN downstream molecule mammalian target of rapamycin complex 1. Together, our results suggest that local and long-range hyperconnectivity may constitute a physiological basis for the effects of mutations in PTEN and possibly other ASD candidate genes.

  20. Hazards of falling debris to people, aircraft, and watercraft

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cole, J.K.; Young, L.W.; Jordan-Culler, T.

    1997-04-01

    This report is a collection of studies performed at Sandia National Laboratories in support of Phase One (inert debris) for the Risk and Lethality Commonality Team. This team was created by the Range Safety Group of the Range Commander`s Council to evaluate the safety issues for debris generated during flight tests and to develop debris safety criteria that can be adopted by the national ranges. Physiological data on the effects of debris impacts on people are presented. Log-normal curves are developed to relate the impact kinetic energy of fragments to the probability of fatality for people exposed in standing, sitting,more » or prone positions. Debris hazards to aircraft resulting from engine ingestion or penetration of a structure or windshield are discussed. The smallest mass fragments of aluminum, steel, and tungsten that may be hazardous to current aircraft are defined. Fragment penetration of the deck of a small ship or a pleasure craft is also considered. The smallest mass fragments of aluminum, steel, or tungsten that can penetrate decks are calculated.« less

  1. Vitamin A Metabolism: An Update

    PubMed Central

    D’Ambrosio, Diana N.; Clugston, Robin D.; Blaner, William S.

    2011-01-01

    Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years. PMID:21350678

  2. Dietary fibers from mushroom Sclerotia: 2. In vitro mineral binding capacity under sequential simulated physiological conditions of the human gastrointestinal tract.

    PubMed

    Wong, Ka-Hing; Cheung, Peter C K

    2005-11-30

    The in vitro mineral binding capacity of three novel dietary fibers (DFs) prepared from mushroom sclerotia, namely, Pleurotus tuber-regium, Polyporous rhinocerus, and Wolfiporia cocos, to Ca, Mg, Cu, Fe, and Zn under sequential simulated physiological conditions of the human stomach, small intestine, and colon was investigated and compared. Apart from releasing most of their endogenous Ca (ranged from 96.9 to 97.9% removal) and Mg (ranged from 95.9 to 96.7% removal), simulated physiological conditions of the stomach also attenuated the possible adverse binding effect of the three sclerotial DFs to the exogenous minerals by lowering their cation-exchange capacity (ranged from 20.8 to 32.3%) and removing a substantial amount of their potential mineral chelators including protein (ranged from 16.2 to 37.8%) and phytate (ranged from 58.5 to 64.2%). The in vitro mineral binding capacity of the three sclerotial DF under simulated physiological conditions of small intestine was found to be low, especially for Ca (ranged from 4.79 to 5.91% binding) and Mg (ranged from 3.16 to 4.18% binding), and was highly correlated (r > 0.97) with their residual protein contents. Under simulated physiological conditions of the colon with slightly acidic pH (5.80), only bound Ca was readily released (ranged from 34.2 to 72.3% releasing) from the three sclerotial DFs, and their potential enhancing effect on passive Ca absorption in the human large intestine was also discussed.

  3. Assessing physiological tipping point of sea urchin larvae exposed to a broad range of pH.

    PubMed

    Dorey, Narimane; Lançon, Pauline; Thorndyke, Mike; Dupont, Sam

    2013-11-01

    Our ability to project the impact of global change on marine ecosystem is limited by our poor understanding on how to predict species sensitivity. For example, the impact of ocean acidification is highly species-specific, even in closely related taxa. The aim of this study was to test the hypothesis that the tolerance range of a given species to decreased pH corresponds to their natural range of exposure. Larvae of the green sea urchin Strongylocentrotus droebachiensis were cultured from fertilization to metamorphic competence (29 days) under a wide range of pH (from pHT  = 8.0/pCO2  ≈ 480 μatm to pHT  = 6.5/pCO2  ≈ 20 000 μatm) covering present (from pHT 8.7 to 7.6), projected near-future variability (from pHT 8.3 to 7.2) and beyond. Decreasing pH impacted all tested parameters (mortality, symmetry, growth, morphometry and respiration). Development of normal, although showing morphological plasticity, swimming larvae was possible as low as pHT  ≥ 7.0. Within that range, decreasing pH increased mortality and asymmetry and decreased body length (BL) growth rate. Larvae raised at lowered pH and with similar BL had shorter arms and a wider body. Relative to a given BL, respiration rates and stomach volume both increased with decreasing pH suggesting changes in energy budget. At the lowest pHs (pHT  ≤ 6.5), all the tested parameters were strongly negatively affected and no larva survived past 13 days post fertilization. In conclusion, sea urchin larvae appeared to be highly plastic when exposed to decreased pH until a physiological tipping point at pHT  = 7.0. However, this plasticity was associated with direct (increased mortality) and indirect (decreased growth) consequences for fitness. © 2013 John Wiley & Sons Ltd.

  4. The effects of host size and temperature on the emergence of Echinoparyphium recurvatum cercariae from Lymnaea peregra under natural light conditions.

    PubMed

    Morley, N J; Adam, M E; Lewis, J W

    2010-09-01

    The production of cercariae from their snail host is a fundamental component of transmission success in trematodes. The emergence of Echinoparyphium recurvatum (Trematoda: Echinostomatidae) cercariae from Lymnaea peregra was studied under natural sunlight conditions, using naturally infected snails of different sizes (10-17 mm) within a temperature range of 10-29 degrees C. There was a single photoperiodic circadian cycle of emergence with one peak, which correlated with the maximum diffuse sunlight irradiation. At 21 degrees C the daily number of emerging cercariae increased with increasing host snail size, but variations in cercarial emergence did occur between both individual snails and different days. There was only limited evidence of cyclic emergence patterns over a 3-week period, probably due to extensive snail mortality, particularly those in the larger size classes. Very few cercariae emerged in all snail size classes at the lowest temperature studied (10 degrees C), but at increasingly higher temperatures elevated numbers of cercariae emerged, reaching an optimum between 17 and 25 degrees C. Above this range emergence was reduced. At all temperatures more cercariae emerged from larger snails. Analysis of emergence using the Q10 value, a measure of physiological processes over temperature ranges, showed that between 10 and 21 degrees C (approximately 15 degrees C) Q10 values exceeded 100 for all snail size classes, indicating a substantially greater emergence than would be expected for normal physiological rates. From 14 to 25 degrees C (approximately 20 degrees C) cercarial emergence in most snail size classes showed little change in Q10, although in the smallest size class emergence was still substantially greater than the typical Q10 increase expected over this temperature range. At the highest range of 21-29 degrees C (approximately 25 degrees C), Q10 was much reduced. The importance of these results for cercarial emergence under global climate change is discussed.

  5. Challenges of ambulatory physiological sensing.

    PubMed

    Healey, Jennifer

    2004-01-01

    Applications for ambulatory monitoring span the spectrum from fitness optimization to cardiac defibrillation. This range of applications is associated with a corresponding range of required detection accuracies and a range of inconvenience and discomfort that wearers are willing to tolerate. This paper describes a selection of physiological sensors and how they might best be worn in the unconstrained ambulatory environment to provide the most robust measurements and the greatest comfort to the wearer. Using wireless mobile computing devices, it will be possible to record, analyze and respond to changes in the wearers' physiological signals in real time using these sensors.

  6. Targeting polyamine metabolism for cancer therapy and prevention

    PubMed Central

    Murray-Stewart, Tracy R.; Woster, Patrick M.; Casero, Robert A.

    2017-01-01

    The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention. PMID:27679855

  7. The role of CCN family genes in haematological malignancies.

    PubMed

    Wells, J E; Howlett, M; Cheung, L C; Kees, Ursula R

    2015-09-01

    Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are treated using similar chemotherapy regimes. In this review we look at the role of the CCN family of matricellular proteins and indicate their role in nine haematological malignancies including both myeloid and lymphoid neoplasms. The potential for further haematological neoplasms with CCN family associations is argued by summarising the demonstrated role of CCN family genes in the differentiation of haematopoietic stem cells (HSC) and mesenchymal stem cells. The expanding field of knowledge encompassing CCN family genes and cancers of the HSC-lineage highlights the importance of extracellular matrix-interactions in both normal physiology and tumorigenesis of the blood, bone marrow and lymph nodes.

  8. Quantifying the roles of random motility and directed motility using advection-diffusion theory for a 3T3 fibroblast cell migration assay stimulated with an electric field.

    PubMed

    Simpson, Matthew J; Lo, Kai-Yin; Sun, Yung-Shin

    2017-03-17

    Directed cell migration can be driven by a range of external stimuli, such as spatial gradients of: chemical signals (chemotaxis); adhesion sites (haptotaxis); or temperature (thermotaxis). Continuum models of cell migration typically include a diffusion term to capture the undirected component of cell motility and an advection term to capture the directed component of cell motility. However, there is no consensus in the literature about the form that the advection term takes. Some theoretical studies suggest that the advection term ought to include receptor saturation effects. However, others adopt a much simpler constant coefficient. One of the limitations of including receptor saturation effects is that it introduces several additional unknown parameters into the model. Therefore, a relevant research question is to investigate whether directed cell migration is best described by a simple constant tactic coefficient or a more complicated model incorporating saturation effects. We study directed cell migration using an experimental device in which the directed component of the cell motility is driven by a spatial gradient of electric potential, which is known as electrotaxis. The electric field (EF) is proportional to the spatial gradient of the electric potential. The spatial variation of electric potential across the experimental device varies in such a way that there are several subregions on the device in which the EF takes on different values that are approximately constant within those subregions. We use cell trajectory data to quantify the motion of 3T3 fibroblast cells at different locations on the device to examine how different values of the EF influences cell motility. The undirected (random) motility of the cells is quantified in terms of the cell diffusivity, D, and the directed motility is quantified in terms of a cell drift velocity, v. Estimates D and v are obtained under a range of four different EF conditions, which correspond to normal physiological conditions. Our results suggest that there is no anisotropy in D, and that D appears to be approximately independent of the EF and the electric potential. The drift velocity increases approximately linearly with the EF, suggesting that the simplest linear advection term, with no additional saturation parameters, provides a good explanation of these physiologically relevant data. We find that the simplest linear advection term in a continuum model of directed cell motility is sufficient to describe a range of different electrotaxis experiments for 3T3 fibroblast cells subject to normal physiological values of the electric field. This is useful information because alternative models that include saturation effects involve additional parameters that need to be estimated before a partial differential equation model can be applied to interpret or predict a cell migration experiment.

  9. Influences of thermal acclimation and acute temperature change on the motility of epithelial wound-healing cells (keratocytes) of tropical, temperate and Antarctic fish.

    PubMed

    Ream, Rachael A; Theriot, Julie A; Somero, George N

    2003-12-01

    The ability to heal superficial wounds is an important element in an organism's repertoire of adaptive responses to environmental stress. In fish, motile cells termed keratocytes are thought to play important roles in the wound-healing process. Keratocyte motility, like other physiological rate processes, is likely to be dependent on temperature and to show adaptive variation among differently thermally adapted species. We have quantified the effects of acute temperature change and thermal acclimation on actin-based keratocyte movement in primary cultures of keratocytes from four species of teleost fish adapted to widely different thermal conditions: two eurythermal species, the longjaw mudsucker Gillichthys mirabilis (environmental temperature range of approximately 10-37 degrees C) and a desert pupfish, Cyprinodon salinus (10-40 degrees C), and two species from stable thermal environments, an Antarctic notothenioid, Trematomus bernacchii (-1.86 degrees C), and a tropical clownfish, Amphiprion percula (26-30 degrees C). For all species, keratocyte speed increased with increasing temperature. G. mirabilis and C. salinus keratocytes reached maximal speeds at 25 degrees C and 35 degrees C, respectively, temperatures within the species' normal thermal ranges. Keratocytes of the stenothermal species continued to increase in speed as temperature increased above the species' normal temperature ranges. The thermal limits of keratocyte motility appear to exceed those of whole-organism thermal tolerance, notably in the case of T. bernacchii. Keratocytes of T. bernacchii survived supercooling to -6 degrees C and retained motility at temperatures as high as 20 degrees C. Mean keratocyte speed was conserved at physiological temperatures for the three temperate and tropical species, which suggests that a certain rate of motility is advantageous for wound healing. However, there was no temperature compensation in speed of movement for keratocytes of the Antarctic fish, which have extremely slow rates of movement at physiological temperatures. Keratocytes from all species moved in a persistent, unidirectional manner at low temperatures but at higher temperatures began to take more circular or less-persistent paths. Thermal acclimation affected the persistence and turning magnitude of keratocytes, with warmer acclimations generally yielding more persistent cells that followed straighter paths. However, acclimation did not alter the effect of experimental temperature on cellular speed. These findings suggest that more than one temperature-sensitive mechanism may govern cell motility: the rate-limiting process(es) responsible for speed is distinct from the mechanism(s) underlying directionality and persistence. Keratocytes represent a useful study system for evaluating the effects of temperature at the cellular level and for studying adaptive variation in actin-based cellular movement and capacity for wound healing.

  10. The role of thermal physiology in recent declines of birds in a biodiversity hotspot.

    PubMed

    Milne, Robyn; Cunningham, Susan J; Lee, Alan T K; Smit, Ben

    2015-01-01

    We investigated whether observed avian range contractions and population declines in the Fynbos biome of South Africa were mechanistically linked to recent climate warming. We aimed to determine whether there were correlations between preferred temperature envelope, or changes in temperature within species' ranges, and recent changes in range and population size, for 12 Fynbos-resident bird species, including six that are endemic to the biome. We then measured the physiological responses of each species at air temperatures ranging from 24 to 42°C to determine whether physiological thermal thresholds could provide a mechanistic explanation for observed population trends. Our data show that Fynbos-endemic species occupying the coolest regions experienced the greatest recent reductions in range and population size (>30% range reduction between 1991 and the present). In addition, species experiencing the largest increases in air temperature within their ranges showed the greatest declines. However, evidence for a physiological mechanistic link between warming and population declines was equivocal, with only the larger species showing low thermal thresholds for their body mass, compared with other birds globally. In addition, some species appear more vulnerable than others to air temperatures in their ranges above physiological thermal thresholds. Of these, the high-altitude specialist Cape rockjumper (Chaetops frenatus) seems most at risk from climate warming. This species showed: (i) the lowest threshold for increasing evaporative water loss at high temperatures; and (ii) population declines specifically in those regions of its range recording significant warming trends. Our findings suggest that caution must be taken when attributing causality explicitly to thermal stress, even when population trends are clearly correlated with rates of warming. Studies explicitly investigating the mechanisms underlying such correlations will be key to appropriate conservation planning.

  11. The role of thermal physiology in recent declines of birds in a biodiversity hotspot

    PubMed Central

    Milne, Robyn; Cunningham, Susan J; Lee, Alan T K

    2015-01-01

    Abstract We investigated whether observed avian range contractions and population declines in the Fynbos biome of South Africa were mechanistically linked to recent climate warming. We aimed to determine whether there were correlations between preferred temperature envelope, or changes in temperature within species' ranges, and recent changes in range and population size, for 12 Fynbos-resident bird species, including six that are endemic to the biome. We then measured the physiological responses of each species at air temperatures ranging from 24 to 42°C to determine whether physiological thermal thresholds could provide a mechanistic explanation for observed population trends. Our data show that Fynbos-endemic species occupying the coolest regions experienced the greatest recent reductions in range and population size (>30% range reduction between 1991 and the present). In addition, species experiencing the largest increases in air temperature within their ranges showed the greatest declines. However, evidence for a physiological mechanistic link between warming and population declines was equivocal, with only the larger species showing low thermal thresholds for their body mass, compared with other birds globally. In addition, some species appear more vulnerable than others to air temperatures in their ranges above physiological thermal thresholds. Of these, the high-altitude specialist Cape rockjumper (Chaetops frenatus) seems most at risk from climate warming. This species showed: (i) the lowest threshold for increasing evaporative water loss at high temperatures; and (ii) population declines specifically in those regions of its range recording significant warming trends. Our findings suggest that caution must be taken when attributing causality explicitly to thermal stress, even when population trends are clearly correlated with rates of warming. Studies explicitly investigating the mechanisms underlying such correlations will be key to appropriate conservation planning. PMID:27293732

  12. An overview of lymphatic vessels and their emerging role in cardiovascular disease

    PubMed Central

    Jones, Dennis; Min, Wang

    2011-01-01

    Over the past decade, molecular details of lymphatic vessels (lymphatics) have been rapidly acquired due to the identification of lymphatic endothelial-specific markers. Separate from the cardiovascular system, the lymphatic system is also an elaborate network of vessels that are important in normal physiology. Lymphatic vessels have the unique task to regulate fluid homeostasis, assist in immune surveillance, and transport dietary lipids. However, dysfunctional lymphatic vessels can cause pathology, while normal lymphatics can exacerbate pathology. This review summarizes the development and growth of lymphatic vessels in addition to highlighting their critical roles in physiology and pathology. Also, we discuss recent work that suggests a connection between lymphatic dysfunction and cardiovascular disease. PMID:22022141

  13. A Pilot Study of Physiological Reactivity in Children and Maternal Figures Who Lost Relatives in a Terrorist Attack

    ERIC Educational Resources Information Center

    Pfefferbaum, Betty; Tucker, Phebe; Jeon-Slaughter, Haekyung; Allen, James R.; Hammond, Donna R.; Whittlesey, Suzanne W.; Vinekar, Shreekumar S.; Feng, Yan

    2013-01-01

    Trauma is thought to interfere with normal grief by superimposing symptoms of posttraumatic stress disorder. This exploratory pilot study examined the association between traumatic grief and objectively measured physiological reactivity to a trauma interview in 13 children who lost relatives in the Oklahoma City bombing as well as a potential link…

  14. JPRS Report Science & Technology USSR: Life Sciences.

    DTIC Science & Technology

    1988-06-10

    V.F. Shilina; GIGIYENA ISANITARIYA No 10, Oct 87] 14 PHYSIOLOGY Changes in Cerebral Electrical Activity of Cats After Intravenous and...from human fibrosarcoma , was studied and compared to expression in normal human leukocytes and slightly transformed cells from human melanoma line...06508 JPRS-ULS-88-009 10 June 1988 PHYSIOLOGY 15 Changes in Cerebral Electrical Activity of Cats After Intravenous and Cerebroventricular

  15. Combined effects of mild-to-moderate obesity and asthma on physiological and sensory responses to exercise.

    PubMed

    Cortés-Télles, Arturo; Torre-Bouscoulet, Luis; Silva-Cerón, Monica; Mejía-Alfaro, Roberto; Syed, Nafeez; Zavorsky, Gerald S; Guenette, Jordan A

    2015-11-01

    Despite the close link between asthma and obesity, there are no studies that have evaluated the sensory and physiological responses to exercise in obese asthmatics. We recently demonstrated that normal weight asthmatics with well controlled disease have preserved cardiorespiratory and sensory responses to exercise relative to non-asthmatic controls. However, these similarities may not hold true in patients with combined obesity and asthma. Accordingly, we sought to determine if combined asthma and obesity was associated with deleterious effects on cardiorespiratory fitness, exercise performance, dyspnoea, and physiological responses to exercise. Fourteen well-controlled obese asthmatics and fourteen age-matched normal weight asthmatics performed routine spirometry and underwent an incremental cardiopulmonary cycle test to assess the ventilatory, pulmonary gas exchange, cardiovascular, and sensory responses to exercise. Groups were well matched for age, height, spirometry, and asthma control. Obese asthmatics had a significantly greater body mass index (33 ± 3 vs. 23 ± 1 kg/m(2), p < 0.001) and lower self-reported activity levels by 47 % relative to normal weight asthmatics (p < 0.05). Obese asthmatics had a significantly lower maximal oxygen uptake (VO(2)) (82 ± 14 vs. 92 ± 10 %predicted) and work rate (75 ± 8 vs. 89 ± 13 %predicted) relative to normal weight asthmatics (p < 0.05). The anaerobic threshold occurred at a lower VO(2) in obese asthmatics vs. normal weight asthmatics (54 ± 15 vs. 66 ± 16 %predicted, p < 0.05). Ventilatory responses were superimposed throughout exercise with no evidence of a ventilatory limitation in either group. Cardiovascular responses were normal in both groups. Dyspnoea responses were similar but the obese asthmatics experienced greater leg fatigue ratings at submaximal work rates. In conclusion, obese individuals with well controlled asthma have reduced cardiorespiratory fitness and greater leg fatigue ratings relative to normal weight asthmatics. The relatively reduced cardiorespiratory fitness and exercise performance in obese compared to normal weight asthmatics is most likely driven by their more sedentary lifestyle and resultant deconditioning rather than due to respiratory factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Physiological pseudomyopia.

    PubMed

    Jones, R

    1990-08-01

    Objective refraction through plus fogging lenses and base-in prisms revealed that normally accommodation is not completely relaxed when the stimulus to accommodation is zero. The myopic shift in the refractive error due to this focus error of accommodation was defined as physiological pseudomyopia. Two previously established features of accommodation are responsible for this behavior: (1) accommodation acts as a proportional control system for steady-state responses; and (2) the rest focus of accommodation is nonzero. It is proposed that the hyperopic shift in refraction observed in cycloplegia is the result of elimination of physiological pseudomyopia.

  17. Growth hormone secretory pattern and response to treatment in children with short stature followed to adult height.

    PubMed

    Radetti, Giorgio; Buzi, Fabio; Cassar, Walburga; Paganini, Claudio; Stacul, Elisabetta; Maghnie, Mohamad

    2003-07-01

    To compare the relative utility of GH stimulation tests and assays of spontaneous GH secretion as predictors of change in height standard deviation score at the end of GH treatment in children with short stature. We retrospectively studied 116 children (67 boys and 49 girls) with subnormal growth rates and short stature, defined as a height of more than 2SD below the mean for age and sex. The patients were classified according to their pattern of findings on baseline pharmacological GH stimulation tests and a 12-h assay of nocturnal spontaneous GH secretion. Twenty-eight patients (24%) had normal hormone levels by both methods (group I); 14 (12%) had normal levels by stimulation tests but subnormal levels by the physiological assay (group II); 48 (41%) had subnormal levels on pharmacological stimulation, with normal physiologic levels (group III); and 26 (22%) had subnormal levels by both methods (group IV). All children in groups II and IV, and 27 in group III, designated IIIb, were treated with recombinant GH at 0.7 U (0.23 mg/kg) of body weight per week. GH secretory patterns were related to final height SD scores and other growth parameters, after the patients had attained their adult stature 6.7 +/- 2.2 years (SD) after GH evaluation. The five groups were similar with respect to mean baseline height SD scores for chronological as well as bone age. Whether assessed as absolute or parentally adjusted (relative) values, mean gains in height SD scores were significantly greater in treated patients with physiological hormone deficiency (groups II and IV) than in those with normal hormone levels (group I, untreated controls). Relative height gains were 1.03 +/- 1.45 cm (6.6 +/- 9.28 cm) and 1.85 +/- 1.21 cm (SDS; 11.8 +/- 7.74 cm) in groups II and IV respectively, compared with only 0.11 +/- 0.42 cm (0.7 +/- 2.68 cm) in group I (P < 0.01 and P < 0.001). GH treatment failed to improve either the absolute or parentally adjusted final height of patients with GH deficiency by stimulation tests but normal levels by physiological assay. Long-term administration of GH to short children with normal spontaneous GH secretion is not associated with an appreciable increase in adult height.

  18. Spatially tuned normalization explains attention modulation variance within neurons.

    PubMed

    Ni, Amy M; Maunsell, John H R

    2017-09-01

    Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One 4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803-813, 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol 116: 1375-1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we show directly that attention modulation and normalization tuning do in fact covary within individual neurons, in addition to across neurons as previously demonstrated. We recorded the activity of isolated neurons in the middle temporal area of two rhesus monkeys as they performed a change-detection task that controlled the focus of spatial attention. Using the same two drifting Gabor stimuli and the same two receptive field locations for each neuron, we found that switching which stimulus was presented at which location affected both attention modulation and normalization in a correlated way within neurons. We present an equal-maximum-suppression spatially tuned normalization model that explains this covariance both across and within neurons: each stimulus generates equally strong suppression of its own excitatory drive, but its suppression of distant stimuli is typically less. This new model specifies how the tuned normalization associated with each stimulus location varies across space both within and across neurons, changing our understanding of the normalization mechanism and how attention modulations depend on this mechanism. NEW & NOTEWORTHY Tuned normalization studies have demonstrated that the variance in attention modulation size seen across neurons from the same cortical area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects. Copyright © 2017 the American Physiological Society.

  19. Imaging of matrix-disorder in normal and pathological human dermis using nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Chen, Jianxin; Xie, Shusen; Zheng, Liqin; Jiang, Xingshan

    2009-11-01

    In dermis, collagen and elastin are important structural proteins of extracellular maxtrix. The matrix-disorder is associated with various physiologic processes, such as localized scleroderma, anetoderma, photoaging. In this work, we demonstrate the capability of nonlinear optical microscopy in imaging structural proteins in normal and pathological human dermis.

  20. Relationship between intracranial pressure and phase contrast cine MRI derived measures of intracranial pulsations in idiopathic normal pressure hydrocephalus.

    PubMed

    Jaeger, Matthias; Khoo, Angela K; Conforti, David A; Cuganesan, Ramesh

    2016-11-01

    Phase contrast cine MRI with determination of pulsatile aqueductal cerebrospinal fluid (CSF) stroke volume and flow velocity has been suggested to assess intracranial pulsations in idiopathic normal pressure hydrocephalus (iNPH). We aimed to compare this non-invasive measure of pulsations to intracranial pressure (ICP) pulse wave amplitude from continuous ICP monitoring. We hypothesised that a significant correlation between these two markers of intracranial pulsations exists. Fifteen patients with suspected iNPH had continuous computerised ICP monitoring with calculation of mean ICP pulse wave amplitude (MWA) from time-domain analysis. MRI measured CSF aqueductal stroke volume and peak flow velocity. Mean MWA was 5.4mmHg (range 2.3-12.4mmHg). Mean CSF stroke volume and peak flow velocity were 65μl (range 3-195μl) and 9.31cm/s (range 1.68-15.0cm/s), respectively. No significant correlation between the invasive and non-invasive measures of pulsations existed (Spearman r=-0.30 and r=-0.27, respectively; p>0.05). We observed marked intra-individual fluctuation of MWA during continuous ICP monitoring of an average of 6.0mmHg (range 2.8-12.2mmHg). The results suggest a complex interplay between measures of pulsations derived from snapshot MRI measurements and continuous computerised ICP measurements, as no significant relationship existed in our data. Further study is needed to better understand the temporal profile of CSF MRI flow studies, as substantial variation in MWA over the course of several hours of ICP monitoring is common, suggesting that these physiologic fluctuations might obscure MRI snapshot measures of intracranial pulsations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Rectal temperatures, respiratory rates, production, and reproduction performances of crossbred Girolando cows under heat stress in northeastern Brazil

    NASA Astrophysics Data System (ADS)

    da Costa, Antônio Nélson Lima; Feitosa, José Valmir; Montezuma, Péricles Afonso; de Souza, Priscila Teixeira; de Araújo, Airton Alencar

    2015-11-01

    This study compared the two breed groups of Girolando (½ Holstein ½ Gyr vs. ¾ Holstein ¼ Gyr) through analysis of the percentages (stressed or non-stressed cows) of rectal temperature (RT), respiratory rate (RR) and pregnancy rate (PR), and means of production and reproduction parameters to determine the group best suited to rearing in semiarid tropical climate. The experiment was conducted at the farm, in the municipality of Umirim, State of Ceará, Brazil. Two hundred and forty cows were used in a 2 × 2 factorial study; 120 of each group were kept under an intensive system during wet and dry seasons. The environmental parameters obtained were relative humidity (RH), air temperature (AT), and the temperature and humidity index (THI). Pregnancy diagnosis (PD) was determined by ultrasonography 30 days after artificial insemination (AI). The milk production of each cow was recorded with automated milkings in the farm. The variables were expressed as mean and standard error, evaluated by ANOVA at 5 % probability using the GLM procedure of SAS. Chi-square test at 5 % probability was applied to data of RT, RR, pregnancy rate (PR), and the number of AIs to obtain pregnancy. The majority of ½ Holstein cows showed mean values of RT and RR within the normal range in both periods and shifts. Most animals of the ¾ Holstein group exhibited the RR means above normal during the afternoon in the rainy and dry periods and RT means above normal during the afternoon in the dry period. After analyses, ½ Holstein crossbred cows are more capable of thermoregulating than ¾ Holstein cows under conditions of thermal stress, and the dry period was more impacting for bovine physiology with significant changes in physiological parameters, even for the first breed group. Knowledge of breed groups adapted to climatic conditions of northeastern Brazil can directly assist cattle farmers in selecting animals best adapted for forming herds.

  2. Rectal temperatures, respiratory rates, production, and reproduction performances of crossbred Girolando cows under heat stress in northeastern Brazil.

    PubMed

    da Costa, Antônio Nélson Lima; Feitosa, José Valmir; Montezuma, Péricles Afonso; de Souza, Priscila Teixeira; de Araújo, Airton Alencar

    2015-11-01

    This study compared the two breed groups of Girolando (½ Holstein ½ Gyr vs. ¾ Holstein ¼ Gyr) through analysis of the percentages (stressed or non-stressed cows) of rectal temperature (RT), respiratory rate (RR) and pregnancy rate (PR), and means of production and reproduction parameters to determine the group best suited to rearing in semiarid tropical climate. The experiment was conducted at the farm, in the municipality of Umirim, State of Ceará, Brazil. Two hundred and forty cows were used in a 2 × 2 factorial study; 120 of each group were kept under an intensive system during wet and dry seasons. The environmental parameters obtained were relative humidity (RH), air temperature (AT), and the temperature and humidity index (THI). Pregnancy diagnosis (PD) was determined by ultrasonography 30 days after artificial insemination (AI). The milk production of each cow was recorded with automated milkings in the farm. The variables were expressed as mean and standard error, evaluated by ANOVA at 5% probability using the GLM procedure of SAS. Chi-square test at 5% probability was applied to data of RT, RR, pregnancy rate (PR), and the number of AIs to obtain pregnancy. The majority of ½ Holstein cows showed mean values of RT and RR within the normal range in both periods and shifts. Most animals of the ¾ Holstein group exhibited the RR means above normal during the afternoon in the rainy and dry periods and RT means above normal during the afternoon in the dry period. After analyses, ½ Holstein crossbred cows are more capable of thermoregulating than ¾ Holstein cows under conditions of thermal stress, and the dry period was more impacting for bovine physiology with significant changes in physiological parameters, even for the first breed group. Knowledge of breed groups adapted to climatic conditions of northeastern Brazil can directly assist cattle farmers in selecting animals best adapted for forming herds.

  3. Determinants and prognostic implications of the negative diastolic pulmonary pressure gradient in patients with pulmonary hypertension due to left heart disease.

    PubMed

    Nagy, Anikó Ilona; Venkateshvaran, Ashwin; Merkely, Béla; Lund, Lars H; Manouras, Aristomenis

    2017-01-01

    The diastolic pulmonary pressure gradient (DPG) has recently been introduced as a specific marker of combined pre-capillary pulmonary hypertension (Cpc-PH) in left heart disease (LHD). However, its diagnostic and prognostic superiority compared with traditional haemodynamic indices has been challenged lately. Current recommendations explicitly denote that in the normal heart, DPG values are greater than zero, with DPG ≥7 mmHg indicating Cpc-PH. However, clinicians are perplexed by the frequent observation of DPG <0 mmHg (DPG NEG ), as its physiological explanation and clinical impact are unclear to date. We hypothesized that large V-waves in the pulmonary artery wedge pressure (PAWP) curve yielding asymmetric pressure transmission might account for DPG NEG and undertook this study to clarify the physiological and prognostic implications of DPG NEG . Right heart catheterization and echocardiography were performed in 316 patients with LHD due to primary myocardial dysfunction or valvular disease. A total of 256 patients had PH-LHD, of whom 48% demonstrated DPG NEG . The V-wave amplitude inversely correlated with DPG (r = -0.45, P < 0.001) in patients with low pulmonary vascular resistance (PVR), but not in those with elevated PVR (P > 0.05). Patients with large V-waves had negative and lower DPG than those without augmented V-waves (P < 0.001) despite similar PVR (P >0.05). Positive, but normal DPG (0-6 mmHg) carried a worse 2-year prognosis for death and/or heart transplantation than DPG NEG (hazard ratio 2.97; P < 0.05). Our results advocate against DPG NEG constituting a measurement error. We propose that DPG NEG can partially be ascribed to large V-waves and carries a better prognosis than DPG within the normal positive range. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  4. Recovery of skeletal muscle after 3 mo of hindlimb immobilization in rats

    NASA Technical Reports Server (NTRS)

    Booth, F. W.; Seider, M. J.

    1979-01-01

    During immobilization, skeletal muscle undergoes decreases in size and strength with concomitant atrophic and degenerative changes in slow-twitch muscle fibers. Currently there are no objective data in slow-twitch muscle demonstrating recovery of biochemical or physiological indices following termination of immobilization. The purpose of this study was to determine whether the soleus, a slow-twitch muscle, could recover normal biochemical or physiological levels following termination of immobilization. Adenosine triphosphate, glycogen, and protein concentration (mg/g wet wt) all significantly decreased following 90 days of hindlimb immobilization, but these three values returned to control levels by the 60th recovery day. Similarly, soleus muscle wet weight and protein content (mg protein/muscle) returned to control levels by the 14th recovery day. In contrast, maximal isometric tension did not return to normal until the 120th day. These results indicate that following muscular atrophy, which was achieved through 90 days of hindlimb immobilization, several biochemical and physiological values in skeletal muscle are recovered at various times after the end of immobilization.

  5. Physiological basis for noninvasive skin cancer diagnosis using diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Yao; Markey, Mia K.; Tunnell, James W.

    2017-02-01

    Diffuse reflectance spectroscopy offers a noninvasive, fast, and low-cost alternative to visual screening and biopsy for skin cancer diagnosis. We have previously acquired reflectance spectra from 137 lesions in 76 patients and determined the capability of spectral diagnosis using principal component analysis (PCA). However, it is not well elucidated why spectral analysis enables tissue classification. To provide the physiological basis, we used the Monte Carlo look-up table (MCLUT) model to extract physiological parameters from those clinical data. The MCLUT model results in the following physiological parameters: oxygen saturation, hemoglobin concentration, melanin concentration, vessel radius, and scattering parameters. Physiological parameters show that cancerous skin tissue has lower scattering and larger vessel radii, compared to normal tissue. These results demonstrate the potential of diffuse reflectance spectroscopy for detection of early precancerous changes in tissue. In the future, a diagnostic algorithm that combines these physiological parameters could be enable non-invasive diagnosis of skin cancer.

  6. Alterations in physiology and anatomy during pregnancy.

    PubMed

    Tan, Eng Kien; Tan, Eng Loy

    2013-12-01

    Pregnant women undergo profound anatomical and physiological changes so that they can cope with the increased physical and metabolic demands of their pregnancies. The cardiovascular, respiratory, haematological, renal, gastrointestinal and endocrine systems all undergo important physiological alterations and adaptations needed to allow development of the fetus and to allow the mother and fetus to survive the demands of childbirth. Such alterations in anatomy and physiology may cause difficulties in interpreting signs, symptoms, and biochemical investigations, making the clinical assessment of a pregnant woman inevitably confusing but challenging. Understanding these changes is important for every practicing obstetrician, as the pathological deviations from the normal physiological alterations may not be clear-cut until an adverse outcome has resulted. Only with a sound knowledge of the physiology and anatomy changes can the care of an obstetric parturient be safely optimized for a better maternal and fetal outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Sugar for the brain: the role of glucose in physiological and pathological brain function.

    PubMed

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

    2013-10-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism

    PubMed Central

    Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Pitteloud, Nelly; Seminara, Stephanie B.; Plummer, Lacey; Pignatelli, Duarte; Crowley, William F.; Welt, Corrine K.

    2013-01-01

    Context: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary. Objectives: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH. Design, Setting, and Subjects: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus). Main Outcome Measures: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced. Results: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative. Conclusions: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect. PMID:23341491

  9. Functionalization of indium-tin-oxide electrodes by laser-nanostructured gold thin films for biosensing applications

    NASA Astrophysics Data System (ADS)

    Grochowska, Katarzyna; Siuzdak, Katarzyna; Karczewski, Jakub; Śliwiński, Gerard

    2015-12-01

    The production and properties of the indium-tin-oxide (ITO) electrodes functionalized by Au nanoparticle (NP) arrays of a relatively large area formed by pulsed laser nanostructuring of thin gold films are reported and discussed. The SEM inspection of modified electrodes reveals the presence of the nearly spherical and disc-shaped particles of dimensions in the range of 40-120 nm. The NP-array geometry can be controlled by selection of the laser processing conditions. It is shown that particle size and packing density of the array are important factors which determine the electrode performance. In the case of NP-modified electrodes the peak current corresponding to the glucose direct oxidation process shows rise with increasing glucose concentration markedly higher comparing to the reference Au disc electrode. The detection limit reaches 12 μM and linear response of the sensor is observed from 0.1 to 47 mM that covers the normal physiological range of the blood sugar detection.

  10. Explaining intermediate filament accumulation in giant axonal neuropathy

    PubMed Central

    Opal, Puneet; Goldman, Robert D.

    2013-01-01

    Giant axonal neuropathy (GAN)1 is a rare autosomal recessive neurological disorder caused by mutations in the GAN gene that encodes gigaxonin, a member of the BTB/Kelch family of E3 ligase adaptor proteins.1 This disease is characterized by the aggregation of Intermediate Filaments (IF)—cytoskeletal elements that play important roles in cell physiology including the regulation of cell shape, motility, mechanics and intra-cellular signaling. Although a range of cell types are affected in GAN, neurons display the most severe pathology, with neuronal intermediate filament accumulation and aggregation; this in turn causes axonal swellings or “giant axons.” A mechanistic understanding of GAN IF pathology has eluded researchers for many years. In a recent study1 we demonstrate that the normal function of gigaxonin is to regulate the degradation of IF proteins via the proteasome. Our findings present the first direct link between GAN mutations and IF pathology; moreover, given the importance of IF aggregations in a wide range of disease conditions, our findings could have wider ramifications. PMID:25003002

  11. The motor cortex: a network tuned to 7-14 Hz

    PubMed Central

    Castro-Alamancos, Manuel A.

    2013-01-01

    The neocortex or six layer cortex consists of at least 52 cytoarchitectonically distinct areas in humans, and similar areas can be distinguished in rodents. Each of these areas has a defining set of extrinsic connections, identifiable functional roles, a distinct laminar arrangement, etc. Thus, neocortex is extensively subdivided into areas of anatomical and functional specialization, but less is known about the specialization of cellular and network physiology across areas. The motor cortex appears to have a distinct propensity to oscillate in the 7–14 Hz frequency range. Augmenting responses, normal mu and beta oscillations, and abnormal oscillations or after discharges caused by enhancing excitation or suppressing inhibition are all expressed around this frequency range. The substrate for this activity may be an excitatory network that is unique to the motor cortex or that is more strongly suppressed in other areas, such as somatosensory cortex. Interestingly, augmenting responses are dependent on behavioral state. They are abolished during behavioral arousal. Here, I briefly review this evidence. PMID:23439785

  12. The impact of obesity on specific airway resistance and conductance among schoolchildren.

    PubMed

    Parraguez Arévalo, Andrea; Rojas Navarro, Francisco; Ruz Céspedes, Macarena; Medina González, Paul; Escobar Cabello, Máximo; Muñoz Cofré, Rodrigo

    2018-04-01

    Child and adolescent obesity is an epidemiological problem in developing countries. Its prevalence among preschoolers and schoolchildren is over 30%. It has been associated with a wide range of health complications, including rapid loss of lung function leading to changes in physiology and ventilatory mechanics. The objective of this study was to analyze the association between obesity and the increase in specific airway resistance (sRaw) in a sample of obese children and adolescents from the district of Talca. In a sample of 36 subjects with an average age of 9.38 ± 1.99 years, divided into 2 groups (normal weight and obese), the tricipital, subscapular, and abdominal skinfolds and lung volumes were measured. For the statistical analysis, data normality was determined and then the Student's t test or the Mann-Whitney U test and Pearson's or Spearman's correlations were used, as applicable. A value of p < 0.05 was considered statistically significant. When comparing normal weight and obese subjects, a significant increase in sRaw and a significant reduction in specific airway conductance (sGaw) were observed in obese subjects. In addition, an adequate and significant correlation was observed between sRaw and fat percentage. Obese subjects showed an increased sRaw and a reduced sGaw. Sociedad Argentina de Pediatría.

  13. Brain-Derived Neurotrophic Factor in the Airways

    PubMed Central

    Prakash, Y.S.; Martin, Richard J.

    2014-01-01

    In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target. PMID:24560686

  14. The transition between the phenotypes of Prader-Willi syndrome during infancy and early childhood.

    PubMed

    Butler, Jill V; Whittington, Joyce E; Holland, Anthony J; McAllister, Catherine J; Goldstone, Anthony P

    2010-06-01

    Prader-Willi syndrome (PWS) is a genetic disorder historically characterized by two phenotypic stages. The early phenotype in infants is associated with hypotonia, poor suck, and failure to thrive. In later childhood, PWS is associated with intellectual disability, hyperphagia, as well as growth and sex hormone deficiency. Little is known about the transition between phenotypes. This study investigates the nature of the change in infancy and childhood PWS. Forty-six children (22 females, 24 males; mean age 2 y 9 mo, SD 18.9 mo; range 7 mo-5 y) with genetically confirmed PWS participated. Information was obtained on childhood height and weight, and eating behaviour from case notes and by parental interview. Weight standard deviation scores (SDS) started to exceed height by the end of the first year. Height SDS appeared to fall from near normal at birth until stabilizing below normal around 2 years. Half of the children whose body mass index (BMI) was higher than normal at interview had food interests greater than that of their peers, and the age at which increased age-appropriate eating was first noted was later than the increase of BMI SDS. Obesity may develop before the increased interest in food, suggesting underlying physiological factors independent of appetite control may be important.

  15. Estimated Tissue and Blood N(2) Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar.

    PubMed

    Kvadsheim, P H; Miller, P J O; Tyack, P L; Sivle, L D; Lam, F P A; Fahlman, A

    2012-01-01

    Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N(2) gas bubbles. Increased tissue and blood N(2) levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N(2) tension [Formula: see text], but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N(2) tension [Formula: see text] from dive data recorded from sperm, killer, long-finned pilot, Blainville's beaked, and Cuvier's beaked whales before and during exposure to Low- (1-2 kHz) and Mid- (2-7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N(2) levels, with deep diving generally resulting in higher end-dive [Formula: see text] as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N(2) levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N(2) tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS.

  16. Contrasting physiological responses to excess heat and irradiance in two tropical savanna sedges

    PubMed Central

    John-Bejai, C.; Farrell, A. D.; Cooper, F. M.; Oatham, M. P.

    2013-01-01

    Tropical hyperseasonal savannas provide a rare example of a tropical climax community dominated by graminoid species. Species living in such savannas are frequently exposed to excess heat and light, in addition to drought and waterlogging, and must possess traits to avoid or tolerate these stress factors. Here we examine the contrasting heat and light stress adaptations of two dominant savanna sedges: Lagenocarpus guianensis, which is restricted to the sheltered forest edge, and Lagenocarpus rigidus, which extends from the forest edge to the open savanna. An ecotone extending from the forest edge to the open savanna was used to assess differences in a range of physiological traits (efficiency of photosystem II, cell membrane thermostability, stomatal conductance, leaf surface reflectance and canopy temperature depression) and a range of leaf functional traits (length : width ratio, specific leaf area and degree of folding). Lagenocarpus guianensis showed significantly less canopy temperature depression than L. rigidus, which may explain why this species was restricted to the forest edge. The range of leaf temperatures measured was within the thermal tolerance of L. guianensis and allowed photosystem II to function normally, at least within the cool forest edge. The ability of L. rigidus to extend into the open savanna was associated with an ability to decouple leaf temperature from ambient temperature combined with enhanced cell membrane thermostability. The high degree of canopy temperature depression seen in L. rigidus was not explained by enhanced stomatal conductance or leaf reflectance, but was consistent with a capacity to increase specific leaf area and reduce leaf length: width ratio in the open savanna. Plasticity in leaf functional traits and in cell membrane thermostability are key factors in the ability of this savanna sedge to survive abiotic stress. PMID:24379971

  17. Lower Urinary Tract Urological Abnormalities and Urodynamic Findings of Physiological Urinary Incontinence Versus Non-mono Symptomatic Nocturnal Enuresis in Children.

    PubMed

    Naseri, Mitra

    2014-03-01

    Although 98% of children attain daytime bladder control by three years of age, urinary incontinence is regarded physiological up to the fifth year of life. This study aimed to assess whether lower urinary tract urological abnormalities and abnormal urodynamic findings are infrequent in children with physiological urinary incontinence in contrast to those with non-monosymptomatic nocturnal enuresis (NMNE). During a three-year period (2007-2009), 66 neurologically normal children including 51 children (34 girls, 17 boys) older than five years of age with NMNE and intermittent daytime incontinence, and 15 children with physiological urinary incontinence (eight girls and seven boys) aged four to five years of age without any known urological abnormalities were enrolled in the study. Patients with neurologic deficits or known urological anomalies were excluded from the study. Kidney-bladder ultrasonography, voiding cystourethrography (VCUG), and urodynamic studies were performed to evaluate the anatomy of urinary tract and bladder function. Urinary tract infection was found in 23 (34.8%) children, 17 (33.3%) and 6 (40%) patients with NMNE and physiological urinary incontinence, respectively. Out of 48 patients who underwent VCUG, vesicoureteral reflux (VUR) was found in seven and eight children younger and older than five years of age, respectively. Abnormal urodynamic findings were reported in 5 (62.5%) of eight children younger than five-year-old, and 14 (63.6%) of 22 patients older than 5-year-old. VUR might be more frequent in children with physiological urinary incontinence than the normal population, and might be as common as NMNE with intermittent daytime incontinence.

  18. Normal male sexual function: emphasis on orgasm and ejaculation

    PubMed Central

    Alwaal, Amjad; Breyer, Benjamin N.; Lue, Tom F.

    2016-01-01

    Orgasm and ejaculation are two separate physiological processes that are sometimes difficult to distinguish. Orgasm is an intense transient peak sensation of intense pleasure creating an altered state of consciousness associated with reported physical changes. Antegrade ejaculation is a complex physiological process that is composed of two phases (emission and expulsion), and is influenced by intricate neurological and hormonal pathways. Despite the many published research projects dealing with the physiology of orgasm and ejaculation, much about this topic is still unknown. Ejaculatory dysfunction is a common disorder, and currently has no definitive cure. Understanding the complex physiology of orgasm and ejaculation allows the development of therapeutic targets for ejaculatory dysfunction. In this article, we summarize the current literature on the physiology of orgasm and ejaculation, starting with a brief description of the anatomy of sex organs and the physiology of erection. Then, we describe the physiology of orgasm and ejaculation detailing the neuronal, neurochemical, and hormonal control of the ejaculation process. PMID:26385403

  19. Reliability of cystometrically obtained intravesical pressures in patients with neurogenic bladders.

    PubMed

    Hess, Marika J; Lim, Lance; Yalla, Subbarao V

    2002-01-01

    Urodynamic studies in patients with neurogenic bladder detect and categorize neurourodynamic states, identify the risk for urologic sequelae, and determine the necessity for interventions. Because urodynamic studies serves as a prognostic indicator and guides patient management, pressure measurements during the study must accurately represent bladder function under physiologic conditions. Because nonphysiologic bladder filling used during conventional urodynamic studies may alter the bladder's accommodative properties, we studied how closely the intravesical pressures obtained before filling cystometry resembled those obtained during the filling phase of the cystometrogram. Twenty-two patients (21 men, 1 woman) with neurogenic bladders underwent standard urodynamic studies. A 16F triple-lumen catheter was inserted into the bladder, and the intravesical pressures were recorded (physiologic volume-specific pressures, PVSP). After emptying the bladder, an equal volume of normal saline solution was reinfused, and the pressures were recorded again (cystometric volume-specific pressure, CVSP). All patients underwent routine fluoroscopically assisted urodynamic testing. The PVSP and the CVSP were compared using the Wilcoxon signed ranks test. P value of .05 was significant. The mean PVSP was 14.5 cmH2O (range, 4-42 cmH2O) and mean CVSP was 20.6 cmH2O (range, 6-70 cmH2O). The CVSP was significantly higher than the PVSP (P = .01). Filling pressures during cystometry (CVSP) were significantly higher than the pressures measured at rest (PVSP). This study also suggests a strong correlation between PVSP and CVSP.

  20. Corneal Equilibrium Flux as a Function of Corneal Surface Oxygen Tension.

    PubMed

    Compañ, Vicente; Aguilella-Arzo, Marcel; Weissman, Barry A

    2017-06-01

    Oxygen is essential for aerobic mammalian cell physiology. Oxygen tension (PO2) should reach a minimum at some position within the corneal stroma, and oxygen flux should be zero, by definition, at this point as well. We found the locations and magnitudes of this "corneal equilibrium flux" (xmin) and explored its physiological implications. We used an application of the Monod kinetic model to calculate xmin for normal human cornea as anterior surface PO2 changes from 155 to 20 mmHg. We find that xmin deepens, broadens, and advances from 1.25 μm above the endothelial-aqueous humor surface toward the epithelium (reaching a position 320 μm above the endothelial-aqueous humor surface) as anterior corneal surface PO2 decreases from 155 to 20 mmHg. Our model supports an anterior corneal oxygen flux of 9 μL O2 · cm · h and an epithelial oxygen consumption of approximately 4 μL O2 · cm · h. Only at the highest anterior corneal PO2 does our model predict that oxygen diffuses all the way through the cornea to perhaps reach the anterior chamber. Of most interest, corneal oxygen consumption should be supported down to a corneal surface PO2 of 60 to 80 mmHg but declines below this range. We conclude that the critical oxygen tension for hypoxia induced corneal swelling is more likely this range rather than a fixed value.

  1. Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

    PubMed

    Verbeke, Kristin A; Boobis, Alan R; Chiodini, Alessandro; Edwards, Christine A; Franck, Anne; Kleerebezem, Michiel; Nauta, Arjen; Raes, Jeroen; van Tol, Eric A F; Tuohy, Kieran M

    2015-06-01

    Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

  2. Possible psycho-physiological consequences of human long-term space missions

    NASA Astrophysics Data System (ADS)

    Belisheva, N. K.; Lammer, H.; Biernat, H. K.; Kachanova, T. L.; Kalashnikova, I. V.

    Experiments carried out on the Earth s surface during different years and under contrast periods of solar activity have shown that the functional state of biosystems including the human organisms are controlled by global and local geocosmical agents Our finding have a close relation to space research because they demonstrate the reactions of biosystems on variations of global and local geocosmical agents and the mechanisms of modulations of biosystems state by geocosmical agents We revealed the role of variations of the geomagnetic field for the stimulation of immune systems functional state of peripheral blood human brain growth of microflora skin covers and pathogenic microorganisms The study of the psycho-physiological state of the human organism has demonstrated that an increase of the neutron intensity near the Earth s surface is associated with anxiety decrease of normal and increase of paradox reactions of examinees The analysis of the human brain functional state in dependent on the geomagnetic variation structure dose under exposure to the variations of geomagnetic field in a certain amplitude-frequency range and also the intensity of the nucleon component of secondary cosmic rays showed that the stable and unstable states of the human brain are determined by geomagnetic field variations and the intensity of the nucleon component The stable state of the brain manifested under the periodic oscillations of the geomagnetic field in a certain amplitude-frequency range The low level of geomagnetic activity associated with an

  3. The G-factor as a tool to learn more about bone structure and function.

    PubMed

    Zerath, E

    1999-07-01

    In normal life on earth, the locomotor system is exposed to two types of stimulation: gravity (passive stimulation) and motion (active stimulation). Both permanently combine, and the interactions between locomotion and gravity induce an overall recruitment which is repeated daily and maintains the bone tissue structure within the range of constraints to which it is adapted. This range is one of the basic hypotheses underlying the mechanical concepts of bone structure control, and it has been considered as logical to assume that weightlessness of spaceflight should produce bone loss since astronauts are outside of the terrestrial gravitational field of forces, no longer relying on muscular work to change positions or move. But, thirty years after the first changes in phospho-calcium metabolism were observed in astronauts after spaceflight, current knowledge does not provide a full understanding of this pathogeny, and prove the G-factor is now considered as an essential component of the experimental tools available to study bone physiology. The study of the physiology of bone tissue usually consists in the investigation of its two fundamental roles, i.e. reservoir of inorganic elements (calcium, phosphorus, magnesium) and mechanical support for soft tissues. Together with the combined action of muscles, tendons, and ligaments, this support permits motion and locomotion. These two functions rely on a sophisticated bone tissue architecture, and on the adaptability of this structure, with modeling and remodeling processes, themselves associated with the coupled activity of specialized bone cell populations.

  4. Psychological and physiological responses following repeated peer death.

    PubMed

    Andersen, Judith Pizarro; Silver, Roxane Cohen; Stewart, Brandon; Koperwas, Billie; Kirschbaum, Clemens

    2013-01-01

    Undergraduates at a university in the United States were exposed - directly and indirectly - to 14 peer deaths during one academic year. We examined how individual and social factors were associated with psychological (e.g., anxiety, depression, somatization) and physiological (i.e., cortisol) distress responses following this unexpected and repeated experience with loss. Two to three months after the final peer death, respondents (N = 122, 61% female, 18-23 years, M = 20.13, SD = 1.14) reported prior adverse experiences, degree of closeness with the deceased, acute responses to the peer deaths, ongoing distress responses, social support, support seeking, and media viewing. A subset (n = 24) returned hair samples for evaluation of cortisol responses during the previous 3 months. Ongoing psychological distress was associated with a) prior interpersonal trauma, b) fewer social supports, and c) media exposure to news of the deaths (p's<.05). Participants who had no prior bereavements showed, on average, high cortisol (>25 p/mg) compared to individuals with one or two prior bereavement experiences (who were, on average, within the normal range, 10 to 25 p/mg) (p<.05). Only 8% of the sample utilized available university psychological or physical health resources and support groups. Limited research has examined the psychological and physiological impact of exposure to chronic, repeated peer loss, despite the fact that there are groups of individuals (e.g., police, military soldiers) that routinely face such exposures. Prior adversity appears to play a role in shaping psychological and physiological responses to repeated loss. This topic warrants further research given the health implications of repeated loss for individuals in high-risk occupations and university settings.

  5. Respiration, and growth-efficiency of coastal prokaryote communities in continuous cultures under different growth rates and temperatures.

    NASA Astrophysics Data System (ADS)

    Maske, H.; Cajal-Medrano, R.; Villegas-Mendoza, J.

    2016-02-01

    Organotrophic prokaryotes in aquatic environments account for about half of community respiration in surface oceans and are key trophic links in the plankton food web connecting dissolved organics and higher trophic levels. The transfer efficiency is partially characterized by the ratio of prokaryote respiration rates (r, day-1) to growth rates (m, day-1) and the resulting growth efficiency (Y). Much literature has been published about the response of these parameters to temperature in monospecific cultures, but little is known about the response of a community of pelagic prokaryotes were the sum of the genotypes and phenotype define the physiological potential. We inoculated 10 turbidostats and 39 chemostats with coastal bacteria and measured CO2 production, carbon biomass and cell abundance, with m ranging from 0.05 to 62 day-1 between 10 and 26oC. Under substrate limited conditions, common in the ocean, r showed no significant trend with temperature and was proportional to m implying constant Y. Under temperature-limited, nutrient replete growth the m of coastal prokaryote communities increased with temperature but r decreased (Q10: 0.4), resulting in an increase of Y with temperature (Q10: 2.5). The carbon demand rate (b, fmol C (cell day)-1) of turbidostat cultures showed a very high Q10 of 8.4. Casting the data in the framework of the metabolic theory of ecology (MTE), the physiological rates normalized to cell carbon showed no significant changes with temperature using either respiration or carbon demand as a proxy for physiological rate. Our results suggest that physiological patterns related to temperature are very different under nutrient limited or replete conditions and under neither condition it followed the pattern expected by MTE.

  6. Fully optimized discrimination of physiological responses to auditory stimuli

    PubMed Central

    Kruglikov, Stepan Y; Chari, Sharmila; Rapp, Paul E; Weinstein, Steven L; Given, Barbara K; Schiff, Steven J

    2008-01-01

    The use of multivariate measurements to characterize brain activity (electrical, magnetic, optical) is widespread. The most common approaches to reduce the complexity of such observations include principal and independent component analyses (PCA and ICA), which are not well suited for discrimination tasks. We addressed two questions: first, how do the neurophysiological responses to elongated phonemes relate to tone and phoneme responses in normal children, and, second, how discriminable are these responses. We employed fully optimized linear discrimination analysis to maximally separate the multi-electrode responses to tones and phonemes, and classified the response to elongated phonemes. We find that discrimination between tones and phonemes is dependent upon responses from associative regions of the brain apparently distinct from the primary sensory cortices typically emphasized by PCA or ICA, and that the neuronal correlates corresponding to elongated phonemes are highly variable in normal children (about half respond with neural correlates of tones and half as phonemes). Our approach is made feasible by the increase in computational power of ordinary personal computers and has significant advantages for a wide range of neuronal imaging modalities. PMID:18430975

  7. Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2014-01-01

    Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Altered erythrocyte sodium-lithium counter-transport and Na+/K(+)-ATPase activity in cystic fibrosis.

    PubMed

    Luczay, A; Vásárhelyi, B; Dobos, M; Holics, K; Ujhelyi, R; Tulassay, T

    1997-03-01

    Patients with cystic fibrosis (CF) exhibit normal concentrations of sodium and chloride in spite of the disturbance of Cl- and Na+ transport in epithelial cells. To characterize compensatory mechanisms in the regulation of sodium homeostasis, erythrocytes of 13 CF patients were analysed for sodium-lithium counter-transport (SLC), Na+/K(+)-ATPase activity and intracellular sodium content. Values were compared to those of healthy controls. Patients with CF had normal serum sodium and chloride concentrations and renal excretions of these ions were within the physiological range. Intracellular sodium concentration was similar in the CF and the control group (6.8 +/- 2.2 vs 5.7 +/- 1.0 mmol/l RBCs). Red blood cells' SLC and Na+/ K(+)-ATPase activity were elevated in CF patients (381 +/- 106 mumol/h/l RBCs vs 281 +/- 64; p < 0.01) and (445 +/- 129 mumol ATP mg prot/h vs 322 +/- 84, p < 0.01). Our study demonstrates that transmembrane cation transport systems are highly activated in CF. The increased sodium transport may be part of a compensatory mechanism of sodium homeostasis in children with CF.

  9. Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

    PubMed Central

    Pinnock, Farena; Parlar, Melissa; Hawco, Colin; Hanford, Lindsay; Hall, Geoffrey B.

    2017-01-01

    This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ± 10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment. PMID:28348889

  10. High-affinity binding of laurate to naturally occurring mutants of human serum albumin and proalbumin.

    PubMed

    Kragh-Hansen, U; Pedersen, A O; Galliano, M; Minchiotti, L; Brennan, S O; Tárnoky, A L; Franco, M H; Salzano, F M

    1996-12-15

    Binding of laurate (n-dodecanoate) to genetic variants of albumin or its proprotein and to normal albumin isolated from the same heterozygous carriers was studied by a kinetic dialysis technique at physiological pH. The first stoichiometric association constant for binding to proalbumin Lille (Arg-2-->His) and albumin (Alb) Roma (Glu321-->Lys) was increased to 126% and 136% respectively compared with that for binding to normal albumin, whereas the constant for Alb Maku (Lys541-->Glu) was decreased to 80%. In contrast, normal laurate-binding properties were found for as many as nine other albumin variants with single amino acid substitutions. Because the net charges of all these mutants were different from that of normal albumin, the results suggest that the examples of modified laurate binding are not caused by long-range electrostatic effects. Rather, the three positions mentioned are located close to different binding sites for the fatty acid anion. The most pronounced effect was observed for the glycosylated Alb Casebrook, the binding constant of which was decreased to 20%. Binding to the glycosylated Alb Redhill was also decreased, but to a smaller extent (68%). These decreases in binding are caused by partial or total blocking of the high-affinity site by the oligosaccharides, by the negative charges of the oligosaccharides, and/or by conformational changes induced by these bulky moieties. Laurate binding to two chain-termination mutants (Alb Catania and Alb Venezia) was normal, indicating that the C-terminus of albumin is not important for binding. By using different preparations of normal albumin as controls in the binding experiments, it was also possible to compare the effect of various methods for isolation and defatting on laurate binding.

  11. Activin B is a novel biomarker for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) diagnosis: a cross sectional study.

    PubMed

    Lidbury, Brett A; Kita, Badia; Lewis, Donald P; Hayward, Susan; Ludlow, Helen; Hedger, Mark P; de Kretser, David M

    2017-03-16

    Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available. A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted. Comparisons with a previously defined activin reference population were also performed. For the total study cohort the age range was 18-65 years with a female: male participant ratio of greater than 3:1. All participants were assessed via a primary care community clinic. Blood samples were collected for pathology testing after physical examination and orthostatic intolerance assessment. Cytokines, activin A, activin B and follistatin were also measured in sera from these samples. All data were compared between the CFS/ME and control cohorts, with the activins and follistatin also compared with previously defined reference intervals. Serum activin B levels for CFS/ME participants were significantly elevated when compared to the study controls, as well as the established reference interval. Serum activin A and follistatin were within their normal ranges. All routine and special pathology markers were within the normal laboratory reference intervals for the total study cohort, with no significant differences detected between CFS/ME and control groups. Also, no significant differences were detected for IL-2, IL-4, IL-6, IL-10, IL-17A, TNF or IFN-gamma. Elevated activin B levels together with normal activin A levels identified patients with the diagnostic symptoms of CFS/ME, thus providing a novel serum based test. The activins have multiple physiological roles and capture the diverse array of symptoms experienced by CFS/ME patients.

  12. Analysis of Adequacy of 25-Hydroxi vitamin D3 Supplementation in Patients on Hemodialysis and Parathormone, Calcium and Phosphorus Level in the Blood of These Patients.

    PubMed

    Prnjavorac, Besim; Irejiz, Nedzada; Kurbasic, Zahid; Krajina, Katarina; Deljkic, Amina; Sinanovic, Albina; Fejzic, Jasmin

    2015-04-01

    Appropriate vitamin D turnover is essential for many physiological function. Knowledge of it's function was improved in last two decades with enlargement of scientific confirmation and understanding of overall importance. In addition to classical (skeletal) roles of vitamin D, many other function (no classical), out of bone and calcium-phosphate metabolism, are well defined today. To analyze vitamin D level in the blood in dialysis and pre dialysis patients and evaluate efficacy of supplementation therapy with vitamin D supplements. Vitamin D3 level in form of 25-hydroxivitamin D3 was measured in dialysis and pre dialysis patients, using combination of enzyme immunoassay competition method with final fluorescent detection (ELFA). Parathormone was measured by ELISA method. Other parameters were measured by colorimetric methods. Statistical analysis was done by nonparametric methods, because of dispersion of results of Vitamin D and parathormone. In group of dialysis patients 38 were analyzed. Among them 35 (92%) presented vitamin D deficiency, whether they took supplementation or not. In only 3 patients vitamin D deficiency was not so severe. Vitamin D form were evaluated in 42 pre dialysis patients. Out of all 19 patients (45 %) have satisfied level, more than 30 ng/ml. Moderate deficiency have 16 patients (38%), 5 of all (12%) have severe deficiency, and two patients (5%) have very severe deficiency, less than 5 ng/ml. Parathormone was within normal range (9.5-75 pg/mL) in 13 patients (34 %), below normal range (2 %) in one subject, and in above normal range in 24 (63 %). Vitamin D3 deficiency was registered in most hemodialysis patients; nevertheless supplemental therapy was given regularly or not. It is to be considered more appropriate supplementation of Vitamin D3 for dialyzed patients as well as for pre dialysis ones. In pre dialysis patient moderate deficiency is shown in half of patients but sever in only two.

  13. Seasonal differences in the physiology of Carcinus maenas (Crustacea: Decapoda) from estuaries with varying levels of anthropogenic contamination

    NASA Astrophysics Data System (ADS)

    Dissanayake, Awantha; Galloway, Tamara S.; Jones, Malcolm B.

    2011-07-01

    This study reports the seasonal variability in aspects of the physiology of the shore crab Carcinus maenas from three estuaries in South-west England, each with varying anthropogenic inputs: Avon Estuary ('relatively low' impact), Yealm Estuary ('intermediate' impact) and Plym Estuary ('relatively high' impact). Crabs collected over 12 months from the Avon had a significantly 'lower' physiological condition in winter and spring compared to summer and autumn; in particular, haemocyte phagocytic capability (a general indicator of immune function) was significantly higher in winter and spring compared to summer and autumn, and total haemolymph antioxidant status (an indicator of oxidative stress) was significantly lower in winter compared to the remainder of the year. Potentially, shore crabs may be more susceptible to the effects of contaminant exposure, such as increased immunotoxicity (thus, reduction of immune function) and/or oxyradicals (or reactive oxygen species) exposure) especially in seasons of increased susceptibility i.e. summer/autumn (lower phagocytic capability) and winter (lowest antioxidant function). As the Avon was taken to represent the 'reference' site, this pattern is considered to reflect the 'normal' seasonal variability in shore crab physiology. Shore crab physiological condition from the 'relatively high' impact estuary (Plym) revealed increased cellular viability and antioxidant status in autumn and winter compared with that of the 'standard' pattern (Avon) However, crabs from the intermediate impact estuary (Yealm) only demonstrated significant physiological differences in summer as shown by a lower cellular viability. All crabs had been exposed to PAHs (confirmed by the presence of PAH metabolites in their urine) which may account for the observed differences in shore crab physiology. In conclusion, to aid understanding of the potential contaminant impacts on biota it is imperative that the 'normal' seasonal variability of physiological condition be established. Biological effects-based monitoring studies should therefore be employed seasonally to potentially highlight 'windows of sensitivity' to contaminant impact.

  14. A near infrared luminescent metal-organic framework for temperature sensing in the physiological range.

    PubMed

    Lian, Xiusheng; Zhao, Dian; Cui, Yuanjing; Yang, Yu; Qian, Guodong

    2015-12-28

    A near infrared pumped luminescent metal-organic framework thermometer Nd(0.577)Yb(0.423)BDC-F4, with near infrared fluorescence and excellent sensitivity in the physiological temperature range (293-313 K), has been first realized, and might be potentially applied for biomedical systems.

  15. Statistical Distance as a Measure of Physiological Dysregulation Is Largely Robust to Variation in Its Biomarker Composition

    PubMed Central

    Cohen, Alan A.; Leroux, Maxime; Faucher, Samuel; Morissette-Thomas, Vincent; Legault, Véronique; Fried, Linda P.; Ferrucci, Luigi

    2015-01-01

    Physiological dysregulation may underlie aging and many chronic diseases, but is challenging to quantify because of the complexity of the underlying systems. Recently, we described a measure of physiological dysregulation, DM, that uses statistical distance to assess the degree to which an individual’s biomarker profile is normal versus aberrant. However, the sensitivity of DM to details of the calculation method has not yet been systematically assessed. In particular, the number and choice of biomarkers and the definition of the reference population (RP, the population used to define a “normal” profile) may be important. Here, we address this question by validating the method on 44 common clinical biomarkers from three longitudinal cohort studies and one cross-sectional survey. DMs calculated on different biomarker subsets show that while the signal of physiological dysregulation increases with the number of biomarkers included, the value of additional markers diminishes as more are added and inclusion of 10-15 is generally sufficient. As long as enough markers are included, individual markers have little effect on the final metric, and even DMs calculated from mutually exclusive groups of markers correlate with each other at r~0.4-0.5. We also used data subsets to generate thousands of combinations of study populations and RPs to address sensitivity to differences in age range, sex, race, data set, sample size, and their interactions. Results were largely consistent (but not identical) regardless of the choice of RP; however, the signal was generally clearer with a younger and healthier RP, and RPs too different from the study population performed poorly. Accordingly, biomarker and RP choice are not particularly important in most cases, but caution should be used across very different populations or for fine-scale analyses. Biologically, the lack of sensitivity to marker choice and better performance of younger, healthier RPs confirm an interpretation of DM physiological dysregulation and as an emergent property of a complex system. PMID:25875923

  16. Relationship between behavioral and physiological spectral-ripple discrimination.

    PubMed

    Won, Jong Ho; Clinard, Christopher G; Kwon, Seeyoun; Dasika, Vasant K; Nie, Kaibao; Drennan, Ward R; Tremblay, Kelly L; Rubinstein, Jay T

    2011-06-01

    Previous studies have found a significant correlation between spectral-ripple discrimination and speech and music perception in cochlear implant (CI) users. This relationship could be of use to clinicians and scientists who are interested in using spectral-ripple stimuli in the assessment and habilitation of CI users. However, previous psychoacoustic tasks used to assess spectral discrimination are not suitable for all populations, and it would be beneficial to develop methods that could be used to test all age ranges, including pediatric implant users. Additionally, it is important to understand how ripple stimuli are processed in the central auditory system and how their neural representation contributes to behavioral performance. For this reason, we developed a single-interval, yes/no paradigm that could potentially be used both behaviorally and electrophysiologically to estimate spectral-ripple threshold. In experiment 1, behavioral thresholds obtained using the single-interval method were compared to thresholds obtained using a previously established three-alternative forced-choice method. A significant correlation was found (r = 0.84, p = 0.0002) in 14 adult CI users. The spectral-ripple threshold obtained using the new method also correlated with speech perception in quiet and noise. In experiment 2, the effect of the number of vocoder-processing channels on the behavioral and physiological threshold in normal-hearing listeners was determined. Behavioral thresholds, using the new single-interval method, as well as cortical P1-N1-P2 responses changed as a function of the number of channels. Better behavioral and physiological performance (i.e., better discrimination ability at higher ripple densities) was observed as more channels added. In experiment 3, the relationship between behavioral and physiological data was examined. Amplitudes of the P1-N1-P2 "change" responses were significantly correlated with d' values from the single-interval behavioral procedure. Results suggest that the single-interval procedure with spectral-ripple phase inversion in ongoing stimuli is a valid approach for measuring behavioral or physiological spectral resolution.

  17. Genomic stability and physiological assessments of live offspring sired by a bull clone, Starbuck II.

    PubMed

    Ortegon, H; Betts, D H; Lin, L; Coppola, G; Perrault, S D; Blondin, P; King, W A

    2007-01-01

    It appears that overt phenotypic abnormalities observed in some domestic animal clones are not transmitted to their progeny. The current study monitored Holstein heifers sired by a bull clone, Starbuck II, from weaning to puberty. Genomic stability was assessed by telomere length status and chromosomal analysis. Growth parameters, blood profiles, physical exams and reproductive parameters were assessed for 12 months (and compared to age-matched control heifers). Progeny sired by the clone bull did not differ (P>0.05) in weight, length and height compared to controls. However, progeny had lower heart rates (HR) (P=0.009), respiratory rates (RR) (P=0.007) and body temperature (P=0.03). Hematological profiles were within normal ranges and did not differ (P>0.05) between both groups. External and internal genitalia were normal and both groups reached puberty at expected ages. Progeny had two or three ovarian follicular waves per estrous cycle and serum progesterone concentrations were similar (P=0.99) to controls. Telomere lengths of sperm and blood cells from Starbuck II were not different (P>0.05) than those of non-cloned cattle; telomere lengths of progeny were not different (P>0.05) from age-matched controls. In addition, progeny had normal karyotypes in peripheral blood leukocytes compared to controls (89.1% versus 86.3% diploid, respectively). In summary, heifers sired by a bull clone had normal chromosomal stability, growth, physical, hematological and reproductive parameters, compared to normal heifers. Furthermore, they had moderate stress responses to routine handling and restraint.

  18. Cardiac mechanics: Physiological, clinical, and mathematical considerations

    NASA Technical Reports Server (NTRS)

    Mirsky, I. (Editor); Ghista, D. N.; Sandler, H.

    1974-01-01

    Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

  19. Circadian rhythms and fractal fluctuations in forearm motion

    NASA Astrophysics Data System (ADS)

    Hu, Kun; Hilton, Michael F.

    2005-03-01

    Recent studies have shown that the circadian pacemaker --- an internal body clock located in the brain which is normally synchronized with the sleep/wake behavioral cycles --- influences key physiologic functions such as the body temperature, hormone secretion and heart rate. Surprisingly, no previous studies have investigated whether the circadian pacemaker impacts human motor activity --- a fundamental physiologic function. We investigate high-frequency actigraph recordings of forearm motion from a group of young and healthy subjects during a forced desynchrony protocol which allows to decouple the sleep/wake cycles from the endogenous circadian cycle while controlling scheduled behaviors. We investigate both static properties (mean value, standard deviation), dynamical characteristics (long-range correlations), and nonlinear features (magnitude and Fourier-phase correlations) in the fluctuations of forearm acceleration across different circadian phases. We demonstrate that while the static properties exhibit significant circadian rhythms with a broad peak in the afternoon, the dynamical and nonlinear characteristics remain invariant with circadian phase. This finding suggests an intrinsic multi-scale dynamic regulation of forearm motion the mechanism of which is not influenced by the circadian pacemaker, thus suggesting that increased cardiac risk in the early morning hours is not related to circadian-mediated influences on motor activity.

  20. A nanocomposite-based electrochemical sensor for non-enzymatic detection of hydrogen peroxide

    PubMed Central

    Du, Xin; Chen, Yuan; Dong, Wenhao; Han, Bingkai; Liu, Min; Chen, Qiang; Zhou, Jun

    2017-01-01

    Hydrogen peroxide (H2O2) plays important signaling roles in normal physiology and disease. However, analyzing the actions of H2O2 is often impeded by the difficulty in detecting this molecule. Herein, we report a novel nanocomposite-based electrochemical sensor for non-enzymatic detection of H2O2. Graphene oxide (GO) was selected as the dopant for the synthesis of polyaniline (PANI), leading to the successful fabrication of a water-soluble and stable GO-PANI composite. GO-PANI was subsequently subject to cyclic voltammetry to generate reduced GO-PANI (rGO-PANI), enhancing the conductivity of the material. Platinum nanoparticles (PtNPs) were then electrodeposited on the surface of the rGO-PANI-modified glassy carbon electrode (GCE) to form an electrochemical H2O2 sensor. Compared to previously reported sensors, the rGO-PANI-PtNP/GCE exhibited an expanded linear range, higher sensitivity, and lower detection limit in the quantification of H2O2. In addition, the sensor displayed outstanding reproducibility and selectivity in real-sample examination. Our study suggests that the rGO-PANI-PtNP/GCE may have broad utility in H2O2 detection under physiological and pathological conditions. PMID:28035076

  1. Human conditions of insulin-like growth factor-I (IGF-I) deficiency

    PubMed Central

    2012-01-01

    Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range. PMID:23148873

  2. Naturally produced citral can significantly inhibit normal physiology and induce cytotoxicity on Magnaporthe grisea.

    PubMed

    Li, Rong-Yu; Wu, Xiao-Mao; Yin, Xian-Hui; Long, You-Hua; Li, Ming

    2015-02-01

    Given the importance of finding alternatives to synthetic fungicides, the antifungal effects of natural product citral on six plant pathogenic fungi (Magnaporthe grisea, Gibberella zeae, Fusarium oxysporum, Valsa mali, Botrytis cinerea, and Rhizoctonia solani) were determined. Mycelial growth rate results showed that citral possessed high antifungal activities on those test fungi with EC50 values ranging from 39.52 to 193.00 µg/mL, which had the highest inhibition rates against M. grisea. Further action mechanism of citral on M. grisea was carried out. Citral treatment was found to alter the morphology of M. grisea hyphae by causing a loss of cytoplasm and distortion of mycelia. Moreover, citral was able to induce an increase in chitinase activity in M. grisea, indicating disruption of the cell wall. These results indicate that citral may act by disrupting cell wall integrity and membrane permeability, thus resulting in physiology changes and causing cytotoxicity. Importantly, the inhibitory effect of citral on M. grisea appears to be associated with its effects on mycelia reducing sugar, soluble protein, chitinase activity, pyruvate content, and malondialdehyde content. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. A Predictive Framework to Elucidate Venous Stenosis: CFD & Shape Optimization.

    PubMed

    Javid Mahmoudzadeh Akherat, S M; Cassel, Kevin; Boghosian, Michael; Hammes, Mary; Coe, Fredric

    2017-07-01

    The surgical creation of vascular accesses for renal failure patients provides an abnormally high flow rate conduit in the patient's upper arm vasculature that facilitates the hemodialysis treatment. These vascular accesses, however, are very often associated with complications that lead to access failure and thrombotic incidents, mainly due to excessive neointimal hyperplasia (NH) and subsequently stenosis. Development of a framework to monitor and predict the evolution of the venous system post access creation can greatly contribute to maintaining access patency. Computational fluid dynamics (CFD) has been exploited to inspect the non-homeostatic wall shear stress (WSS) distribution that is speculated to trigger NH in the patient cohort under investigation. Thereafter, CFD in liaison with a gradient-free shape optimization method has been employed to analyze the deformation modes of the venous system enduring non-physiological hemodynamics. It is observed that the optimally evolved shapes and their corresponding hemodynamics strive to restore the homeostatic state of the venous system to a normal, pre-surgery condition. It is concluded that a CFD-shape optimization coupling that seeks to regulate the WSS back to a well-defined physiological WSS target range can accurately predict the mode of patient-specific access failure.

  4. Overview of the Neurolab Spacelab mission

    NASA Technical Reports Server (NTRS)

    Homick, J. L.; Delaney, P.; Rodda, K.

    1998-01-01

    Neurolab is a NASA Spacelab mission with multinational cooperative participation that is dedicated to research on the nervous system. The nervous systems of all animal species have evolved in a one-g environment and are functionally influenced by the presence of gravity. The absence of gravity presents a unique opportunity to gain new insights into basic neurologic functions as well as an enhanced understanding of physiological and behavioral responses mediated by the nervous system. The primary goal of Neurolab is to expand our understanding of how the nervous system develops, functions in, and adapts to microgravity space flight. Twenty-six peer reviewed investigations using human and nonhuman test subjects were assigned to one of eight science discipline teams. Individual and integrated experiments within these teams have been designed to collect a wide range of physiological and behavior data in flight as well as pre- and postflight. Information from these investigations will be applicable to enhancing the well being and performance of future long duration space travelers, will contribute to our understanding of normal and pathological functioning of the nervous system, and may be applied by the medical community to enhance the health of humans on Earth.

  5. Ligand-displacement-based two-photon fluorogenic probe for visualizing mercapto biomolecules in live cells, Drosophila brains and zebrafish.

    PubMed

    Zhao, Yanfei; Ni, Yun; Wang, Liulin; Xu, Chenchen; Xin, Chenqi; Zhang, Chengwu; Zhang, Gaobin; Xie, Xiaoji; Li, Lin; Huang, Wei

    2018-06-19

    Investigating the change in expression level of mercapto biomolecules (GSH/Cys/Hcy) necessitates a rapid detection method for a series of physiological and pathological processes. Herein, we present a ligand-displacement-based two-photon fluorogenic probe based on an Fe(iii) complex, TPFeS, which is a GSH/Cys/Hcy rapid detection fluorogenic probe for in vitro analysis and live cell/tissue/in vivo imaging. The "in situ" probe is non-fluorescent and was prepared from a 1 : 2 ratio of Fe(iii) and TPS, a novel two-photon (TP) fluorophore with excellent one-photon (OP) and TP properties under physiological conditions, as a fluorescent ligand. This probe shows a rapid and remarkable fluorescence restoration (OFF-ON) property due to the ligand-displacement reaction of mercapto biomolecules in a recyclable manner in vitro. A significant two-photon action cross-section, good selectivity for biothiols, low cytotoxicity, and insensitivity to pH over the biologically relevant pH range allowed the direct visualization of mercapto biomolecules at different levels between normal/drug-treated live cells, as well as in Drosophila brain tissues/zebrafish based on the use of two-photon fluorescence microscopy.

  6. Purification and Properties of Cytidine Deaminase from Normal and Leukemic Granulocytes

    PubMed Central

    Chabner, Bruce A.; Johns, David G.; Coleman, C. Norman; Drake, James C.; Evans, Warren H.

    1974-01-01

    Cytidine deaminase, an enzyme that catalyses the deamination of both cytidine and its nucleoside analogues including the antineoplastic agents cytosine arabinoside (ara-C) and 5-azacytidine (5-azaC), has been partially purified from normal and leukemic human granulocytes. The purification procedure included heat precipitation at 70°C, ammonium sulfate precipitation, calcium phosphate gel ion exchange, and Sephadex G-150 gel filtration. The enzyme has mol wt 51,000, isoelectric pH of 4.8, and maximum activity over a broad pH range of 5-9.5. The enzyme is stabilized by the presence of the sulfhydryl reagent, dithiothreitol. Cytidine deaminase from normal human granulocytes has a greater affinity for its physiologic substrate cytidine (Km = 1.1 × 10−5 M) than for ara-C (8.8 × 10−5 M) or 5-azaC (4.3 × 10−4 M). Halogenated analogues such as 5-fluorocytidine and 5-bromo-2′-deoxycytidine also exhibited substrate activity, with maximum velocities greater than that of the physiologic substrates cytidine and deoxycytidine. No activity was observed with nucleotides or deoxynucleotides. The relative maximum velocity of the enzyme for cytidine and its nucleoside analogues remained constant during purification, indicating that a single enzyme was responsible for deamination of these substrates. Tetrahydrouridine (THU) was found to be a strong competitive inhibitor of partially purified deaminase with a Ki of 5.4 × 10−8 M. The biochemical properties of partially purified preparations of cytidine deaminase from normal and leukemic cells were compared with respect to isoelectric pH, molecular weight, and substrate and inhibitor kinetic parameters, and no differences were observed. However, normal circulating granulocytes contained a significantly greater concentration of cytidine deaminase (3.52±1.86 × 103/mg protein) than chronic myelocytic leukemia (CML) cells (1.40±0.70 × 103 U/mg protein) or acute myelocytic leukemia (AML) cells (0.19±0.17 × 103 U/mg protein). To explain these differences in enzyme levels in leukemic versus normal cells, the changes in cytidine deaminase levels associated with maturation of normal granulocytes were studied in normal human bone marrow. Myeloid precursors obtained from bone marrow aspirates were separated into mature and immature fractions by Ficoll density centrifugation. Deaminase activity in lysates of mature granulocytes was 3.55-14.2 times greater than the activity found in the lysates of immature cells. Decreased enzyme activity was also found in immature myeloid cells from a patient with CML as compared to mature granulocytes from the same patient. These observations support the conclusion that the greater specific activity of cytidine deaminase in normal mature granulocytes as compared to leukemic cells is related to the process of granulocyte maturation rather than a specific enzymatic defect in leukemic cells. PMID:4521417

  7. Defining the physiologically normal coating and pathological deposit: an analysis of sulfur-containing moieties and pellicle thickness on hydrogel contact lenses.

    PubMed

    Hart, D E; Plociniak, M P; Grimes, G W

    1998-04-01

    Historically, biochemical studies of the interaction between tears and hydrogel contact lenses have not been coordinated with the study of the morphological ultrastructure of the phenomena. Moreover, terms that have distinct and different meanings--pellicle, coating, deposit, and biofilm--have been used interchangeably and often incorrectly when applied within the context of the general field of contact lens biotechnology to describe the tear-polymer interaction. We describe our elucidation of morphological and elemental characteristics of the normal pellicle that forms on the lens surface and urge standard use of the word "pellicle" to specify this entity. Fourteen worn hydrogel lenses (8 Group 1 and 6 Group 4 lenses according to the FDA classification) were rinsed, quartered, and fixed or dried, depending on the analysis to be performed. Scanning electron microscopy (SEM) was used to examine the morphology of the pellicle and quantify its thickness. X-ray analysis was used to detect elements associated with the anterior, central, and posterior portions of the lenses and their relative distribution. A distinctive morphological pellicle ranging from 0.1 to 8.6 microns was present on 12 of the 14 lenses. The pellicle was thicker on the Group 4 lenses than on the Group 1 lenses (P < 0.003). However, the pellicle on Group 1 lenses became thicker with increasing lens age (P < 0.02), but not as thick as on Group 4 lenses. Morphologically distinct lipid or jelly bump deposits were observed at the surface of both lenses from a single patient wearing 2 week old Group 4 lenses. Eleven lenses had sulfur-bearing tear components on the anterior zone. Sulfur was deposited within the matrix of nine lenses. The sulfur containing moieties were more prevalent on Group 4 lenses (P < 0.002). More sulfur was assayed on older lenses (P < 0.004). The anterior lens zone had more sulfur-bearing tear components than did the posterior or center zones (P < 0.05). The physiologically normal pellicle is a distinct morphological entity covering the anterior lens surface. Abnormal deposits such as the discrete microgel region, known as jelly bumps, are not part of the physiologically normal pellicle at the anterior lens surface and have the potential to induce pathology. Sulfur-containing moieties within the matrix may represent the breakdown of large proteins and mucoproteins or intact proteins, as well as contaminants such as cosmetics and environmental pollutants. It is also possible that entire small proteins, such as lysozyme, impregnate the matrix. The moieties that become entrapped within the matrix or rigidly adhere to the matrix should be considered true deposits.

  8. Precise measurement of renal filtration and vascular parameters using a two-compartment model for dynamic contrast-enhanced MRI of the kidney gives realistic normal values.

    PubMed

    Tofts, Paul S; Cutajar, Marica; Mendichovszky, Iosif A; Peters, A Michael; Gordon, Isky

    2012-06-01

    To model the uptake phase of T(1)-weighted DCE-MRI data in normal kidneys and to demonstrate that the fitted physiological parameters correlate with published normal values. The model incorporates delay and broadening of the arterial vascular peak as it appears in the capillary bed, two distinct compartments for renal intravascular and extravascular Gd tracer, and uses a small-vessel haematocrit value of 24%. Four physiological parameters can be estimated: regional filtration K ( trans ) (ml min(-1) [ml tissue](-1)), perfusion F (ml min(-1) [100 ml tissue](-1)), blood volume v ( b ) (%) and mean residence time MRT (s). From these are found the filtration fraction (FF; %) and total GFR (ml min(-1)). Fifteen healthy volunteers were imaged twice using oblique coronal slices every 2.5 s to determine the reproducibility. Using parenchymal ROIs, group mean values for renal biomarkers all agreed with published values: K ( trans ): 0.25; F: 219; v ( b ): 34; MRT: 5.5; FF: 15; GFR: 115. Nominally cortical ROIs consistently underestimated total filtration (by ~50%). Reproducibility was 7-18%. Sensitivity analysis showed that these fitted parameters are most vulnerable to errors in the fixed parameters kidney T(1), flip angle, haematocrit and relaxivity. These renal biomarkers can potentially measure renal physiology in diagnosis and treatment. • Dynamic contrast-enhanced magnetic resonance imaging can measure renal function. • Filtration and perfusion values in healthy volunteers agree with published normal values. • Precision measured in healthy volunteers is between 7 and 15%.

  9. Nonlinear dynamics, fractals, cardiac physiology and sudden death

    NASA Technical Reports Server (NTRS)

    Goldberger, Ary L.

    1987-01-01

    The authors propose a diametrically opposite viewpoint to the generally accepted tendency of equating healthy function with order and disease with chaos. With regard to the question of sudden cardiac death and chaos, it is suggested that certain features of dynamical chaos related to fractal structure and fractal dynamics may be important organizing principles in normal physiology and that certain pathologies, including ventricular fibrillation, represent a class of 'pathological periodicities'. Some laboratory work bearing on the relation of nonlinear analysis to physiological and pathophysiological data is briefly reviewed, with tentative theories and models described in reference to the mechanism of ventricular fibrillation.

  10. Assessing and Promoting Functional Resilience in Flight Crews During Exploration Missions

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark

    2015-01-01

    NASA plans to send humans to Mars in about 20 years. The NASA Human Research Program supports research to mitigate the major risks to human health and performance on extended missions. However, there will undoubtedly be unforeseen events on any mission of this nature - thus mitigation of known risks alone is not sufficient to ensure optimal crew health and performance. Research should be directed not only to mitigating known risks, but also to providing crews with the tools to assess and enhance resilience, as a group and individually. We can draw on ideas from complexity theory and network theory to assess crew and individual resilience. The entire crew or the individual crewmember can be viewed as a complex system that is composed of subsystems (individual crewmembers or physiological subsystems), and the interactions between subsystems are of crucial importance for overall health and performance. An understanding of the structure of the interactions can provide important information even in the absence of complete information on the component subsystems. This is critical in human spaceflight, since insufficient flight opportunities exist to elucidate the details of each subsystem. Enabled by recent advances in noninvasive measurement of physiological and behavioral parameters, subsystem monitoring can be implemented within a mission and also during preflight training to establish baseline values and ranges. Coupled with appropriate mathematical modeling, this can provide real-time assessment of health and function, and detect early indications of imminent breakdown. Since the interconnected web of physiological systems (and crewmembers) can be interpreted as a network in mathematical terms, we can draw on recent work that relates the structure of such networks to their resilience (ability to self-organize in the face of perturbation). There are many parameters and interactions to choose from. Normal variability is an established characteristic of a healthy physiological response. Healthy coupling has been investigated less extensively, but there are cases in which too tight or too loose coupling can be problematic. This might be in inter-individual behaviors, such as sleep cycles, coordination of work and meal times, and coupled motions during communication. Less apparent are couplings of physiological systems, nevertheless examples abound of coupled systems which might be monitored: cardio-respiratory rhythms; circadian rhythms, body temperature, and sleep; stress markers and cognition, sleep, and performance; profiles of biochemical markers related to immune function and nutritional status; sensorimotor aspects such as motion sickness, ataxia, reaction time, and manual control. Tools for resilience are then the means to measure and analyze these parameters, incorporate them into appropriate models of normal variability and interconnectedness, and recognize when parameters or their couplings are outside of normal limits. What to do when a problem is identified depends on its nature. Changes can be made to crew procedures, work pacing, interpersonal interactions, sleep cycles, meal timing and content, as guided by the model. Use and continued development of these methods could not only provide tools for resilience, but also meaningful autonomous work for the crew on an extended flight.

  11. Gaussian fitting for carotid and radial artery pressure waveforms: comparison between normal subjects and heart failure patients.

    PubMed

    Liu, Chengyu; Zheng, Dingchang; Zhao, Lina; Liu, Changchun

    2014-01-01

    It has been reported that Gaussian functions could accurately and reliably model both carotid and radial artery pressure waveforms (CAPW and RAPW). However, the physiological relevance of the characteristic features from the modeled Gaussian functions has been little investigated. This study thus aimed to determine characteristic features from the Gaussian functions and to make comparisons of them between normal subjects and heart failure patients. Fifty-six normal subjects and 51 patients with heart failure were studied with the CAPW and RAPW signals recorded simultaneously. The two signals were normalized first and then modeled by three positive Gaussian functions, with their peak amplitude, peak time, and half-width determined. Comparisons of these features were finally made between the two groups. Results indicated that the peak amplitude of the first Gaussian curve was significantly decreased in heart failure patients compared with normal subjects (P<0.001). Significantly increased peak amplitude of the second Gaussian curves (P<0.001) and significantly shortened peak times of the second and third Gaussian curves (both P<0.001) were also presented in heart failure patients. These results were true for both CAPW and RAPW signals, indicating the clinical significance of the Gaussian modeling, which should provide essential tools for further understanding the underlying physiological mechanisms of the artery pressure waveform.

  12. Pulsed 86Sr-labeling and NanoSIMS imaging to study coral biomineralization at ultra-structural length scales

    NASA Astrophysics Data System (ADS)

    Brahmi, C.; Domart-Coulon, I.; Rougée, L.; Pyle, D. G.; Stolarski, J.; Mahoney, J. J.; Richmond, R. H.; Ostrander, G. K.; Meibom, A.

    2012-09-01

    A method to label marine biocarbonates is developed based on a concentration enrichment of a minor stable isotope of a trace element that is a natural component of seawater, resulting in the formation of biocarbonate with corresponding isotopic enrichments. This biocarbonate is subsequently imaged with a NanoSIMS ion microprobe to visualize the locations of the isotopic marker on sub-micrometric length scales, permitting resolution of all ultra-structural details. In this study, a scleractinian coral, Pocillopora damicornis, was labeled 3 times with 86Sr-enhanced seawater for a period of 48 h with 5 days under normal seawater conditions separating each labeling event. Two non-specific cellular stress biomarkers, glutathione-S-transferase activity and porphyrin concentration plus carbonic anhydrase, an enzymatic marker involved in the physiology of carbonate biomineralization, as well as unchanged levels of zooxanthellae photosynthesis efficiency indicate that coral physiological processes are not affected by the 86Sr-enhancement. NanoSIMS images of the 86Sr/44Ca ratio in skeleton formed during the experiment allow for a determination of the average extension rate of the two major ultra-structural components of the coral skeleton: Rapid Accretion Deposits are found to form on average about 4.5 times faster than Thickening Deposits. The method opens up new horizons in the study of biocarbonate formation because it holds the potential to observe growth of calcareous structures such as skeletons, shells, tests, spines formed by a wide range of organisms under essentially unperturbed physiological conditions.

  13. Vital signs in older patients: age-related changes.

    PubMed

    Chester, Jennifer Gonik; Rudolph, James L

    2011-06-01

    Vital signs are objective measures of physiological function that are used to monitor acute and chronic disease and thus serve as a basic communication tool about patient status. The purpose of this analysis was to review age-related changes of traditional vital signs (blood pressure, pulse, respiratory rate, and temperature) with a focus on age-related molecular changes, organ system changes, systemic changes, and altered compensation to stressors. The review found that numerous physiological and pathological changes may occur with age and alter vital signs. These changes tend to reduce the ability of organ systems to adapt to physiological stressors, particularly in frail older patients. Because of the diversity of age-related physiological changes and comorbidities in an individual, single-point measurements of vital signs have less sensitivity in detecting disease processes. However, serial vital sign assessments may have increased sensitivity, especially when viewed in the context of individualized reference ranges. Vital sign change with age may be subtle because of reduced physiological ranges. However, change from an individual reference range may indicate important warning signs and thus may require additional evaluation to understand potential underlying pathological processes. As a result, individualized reference ranges may provide improved sensitivity in frail, older patients. Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

  14. Long-range correlations and fractal dynamics in C. elegans: Changes with aging and stress

    NASA Astrophysics Data System (ADS)

    Alves, Luiz G. A.; Winter, Peter B.; Ferreira, Leonardo N.; Brielmann, Renée M.; Morimoto, Richard I.; Amaral, Luís A. N.

    2017-08-01

    Reduced motor control is one of the most frequent features associated with aging and disease. Nonlinear and fractal analyses have proved to be useful in investigating human physiological alterations with age and disease. Similar findings have not been established for any of the model organisms typically studied by biologists, though. If the physiology of a simpler model organism displays the same characteristics, this fact would open a new research window on the control mechanisms that organisms use to regulate physiological processes during aging and stress. Here, we use a recently introduced animal-tracking technology to simultaneously follow tens of Caenorhabdits elegans for several hours and use tools from fractal physiology to quantitatively evaluate the effects of aging and temperature stress on nematode motility. Similar to human physiological signals, scaling analysis reveals long-range correlations in numerous motility variables, fractal properties in behavioral shifts, and fluctuation dynamics over a wide range of timescales. These properties change as a result of a superposition of age and stress-related adaptive mechanisms that regulate motility.

  15. Architectural analysis and predicted functional capability of the human latissimus dorsi muscle.

    PubMed

    Gerling, Michael E; Brown, Stephen H M

    2013-08-01

    The latissimus dorsi is primarily considered a muscle with actions at the shoulder, despite its widespread attachments at the spine. There is some dispute regarding the potential contribution of this muscle to lumbar spine function. The architectural design of a muscle is one of the most accurate predictors of muscle function; however, detailed architectural data on the latissimus dorsi muscle are limited. Therefore, the aim of this study was to quantify the architectural properties of the latissimus dorsi muscle and model mechanical function in light of these new data. One latissimus dorsi muscle was removed from each of 12 human cadavers, separated into regions, and micro-dissected for quantification of fascicle length, sarcomere length, and physiological cross-sectional area. From these data, sarcomere length operating ranges were modelled to determine the force-length characteristics of latissimus dorsi across the spine and shoulder ranges of motion. The physiological cross-sectional area of latissimus dorsi was 5.6±0.5 cm2 and normalized fascicle length was 26.4±1.0 cm, indicating that this muscle is designed to produce a moderate amount of force over a large range of lengths. Measured sarcomere length in the post-mortem neutral spine posture was nearly optimal at 2.69±0.06 μm. Across spine range of motion, biomechanical modelling predicted latissimus dorsi acts across both the ascending and descending limbs of the force-length curve during lateral bend, and primarily at or near the plateau region (where maximum force generation is possible) during flexion/extension and axial twist. Across shoulder range of motion, latissimus dorsi acts primarily on the plateau region and descending limbs of the force length curve during both flexion/extension and abduction/adduction. These data provide novel insights into the ability of the latissimus dorsi muscle to generate force and change length throughout the spine and shoulder ranges of motion. In addition, these findings provide an improved understanding of the spine and shoulder positions at which the force-generating capacity of this muscle can become jeopardized, and consequently how this may affect its spine-stabilizing ability. © 2013 Anatomical Society.

  16. Architectural analysis and predicted functional capability of the human latissimus dorsi muscle

    PubMed Central

    Gerling, Michael E; Brown, Stephen H M

    2013-01-01

    The latissimus dorsi is primarily considered a muscle with actions at the shoulder, despite its widespread attachments at the spine. There is some dispute regarding the potential contribution of this muscle to lumbar spine function. The architectural design of a muscle is one of the most accurate predictors of muscle function; however, detailed architectural data on the latissimus dorsi muscle are limited. Therefore, the aim of this study was to quantify the architectural properties of the latissimus dorsi muscle and model mechanical function in light of these new data. One latissimus dorsi muscle was removed from each of 12 human cadavers, separated into regions, and micro-dissected for quantification of fascicle length, sarcomere length, and physiological cross-sectional area. From these data, sarcomere length operating ranges were modelled to determine the force–length characteristics of latissimus dorsi across the spine and shoulder ranges of motion. The physiological cross-sectional area of latissimus dorsi was 5.6 ± 0.5 cm2 and normalized fascicle length was 26.4 ± 1.0 cm, indicating that this muscle is designed to produce a moderate amount of force over a large range of lengths. Measured sarcomere length in the post-mortem neutral spine posture was nearly optimal at 2.69 ± 0.06 μm. Across spine range of motion, biomechanical modelling predicted latissimus dorsi acts across both the ascending and descending limbs of the force–length curve during lateral bend, and primarily at or near the plateau region (where maximum force generation is possible) during flexion/extension and axial twist. Across shoulder range of motion, latissimus dorsi acts primarily on the plateau region and descending limbs of the force length curve during both flexion/extension and abduction/adduction. These data provide novel insights into the ability of the latissimus dorsi muscle to generate force and change length throughout the spine and shoulder ranges of motion. In addition, these findings provide an improved understanding of the spine and shoulder positions at which the force-generating capacity of this muscle can become jeopardized, and consequently how this may affect its spine-stabilizing ability. PMID:23758053

  17. The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology.

    PubMed

    Hegyi, Peter; Petersen, Ole H

    2013-01-01

    There are many reviews of pancreatic acinar cell function and also of pancreatic duct function, but there is an almost total absence of synthetic reviews bringing the integrated functions of these two vitally and mutually interdependent cells together. This is what we have attempted to do in this chapter. In the first part, we review the normal integrated function of the acinar-ductal system, with particular emphasis on how regulation of one type of cell also influences the other cell type. In the second part, we review a range of pathological processes, particularly those involved in acute pancreatitis (AP), an often-fatal human disease in which the pancreas digests itself, in order to explore how malfunction of one of the cell types adversely affects the function of the other.

  18. Can complexity decrease in congestive heart failure?

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sayan; Palit, Sanjay Kumar; Banerjee, Santo; Ariffin, M. R. K.; Rondoni, Lamberto; Bhattacharya, D. K.

    2015-12-01

    The complexity of a signal can be measured by the Recurrence period density entropy (RPDE) from the reconstructed phase space. We have chosen a window based RPDE method for the classification of signals, as RPDE is an average entropic measure of the whole phase space. We have observed the changes in the complexity in cardiac signals of normal healthy person (NHP) and congestive heart failure patients (CHFP). The results show that the cardiac dynamics of a healthy subject is more complex and random compare to the same for a heart failure patient, whose dynamics is more deterministic. We have constructed a general threshold to distinguish the border line between a healthy and a congestive heart failure dynamics. The results may be useful for wide range for physiological and biomedical analysis.

  19. Perivascular Spaces, Glymphatic Dysfunction, and Small Vessel Disease

    PubMed Central

    Mestre, Humberto; Kostrikov, Serhii; Mehta, Rupal I.; Nedergaard, Maiken

    2017-01-01

    Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces, cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered. PMID:28798076

  20. Functional importance of blood flow dynamics and partial oxygen pressure in the anterior pituitary.

    PubMed

    Schaeffer, Marie; Hodson, David J; Lafont, Chrystel; Mollard, Patrice

    2010-12-01

    The pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  1. Investigation of patients with polycythaemia.

    PubMed Central

    Pearson, T. C.; Messinezy, M.

    1996-01-01

    Polycythaemia may complicate or be the presenting feature of a wide variety of different pathologies. Early diagnosis and treatment of primary polycythaemia will significantly reduce the morbidity and mortality associated with this condition. Patients with a raised packed cell volume are divided into those with a raised red cell mass (absolute polycythaemia), and those with a red cell mass within their normal range (apparent polycythaemia). A standard investigative approach of an absolute polycythaemia enables patients with primary and secondary polycythaemia to be identified, leaving a group termed idiopathic erythrocytosis. There are a number of physiological situations and pathological events associated with idiopathic erythrocytosis and apparent polycythaemia. Careful follow-up of both groups of these patients is essential to identify possible causative mechanisms. Images Figure 1 Figure 2 Figure 3 PMID:8949586

  2. [Abnormal hepatic function tests in pregnancy: causes and consequences].

    PubMed

    Nemesánszky, Elemér

    2013-07-21

    The well-known normal ranges of laboratory parameters are altered due to the broad spectrum of physiological changes as well as proinflammatory and procoagulant effects of pregnancy. Hepatic disorders of any aetiology can cause potential problems during gravidity. Most frequently toxic-effects, hepatotrop viruses (such as hepatitis B and C), metabolic syndrome and diseases with autoimmune background can be observed. When dealing with "pregnancy-specific hepatic syndromes", it is very important to consider the "timing-factors" of pathologic changes and deterioration of clinical pictures as well. Due to the progress in cholestasis management, early termination of pregnancy can be avoided in many cases. As the overlap is really broad between various hepatic disorders, a multidisciplinary cooperation of different sub-disciplines is emphasized in order to achieve proper diagnosis and curative measures at early phase.

  3. Clinical Applications of Wavefront Refraction

    PubMed Central

    Bruce, Adrian S.; Catania, Louis J.

    2014-01-01

    ABSTRACT Purpose To determine normative reference ranges for higher-order wavefront error (HO-WFE), compare these values with those in common ocular pathologies, and evaluate treatments. Methods A review of 17 major studies on HO-WFE was made, involving data for a total of 31,605 subjects. The upper limit of the 95% confidence interval (CI) for HO-WFE was calculated from the most comprehensive of these studies using normal healthy patients aged 20 to 80 years. There were no studies identified using the natural pupil size for subjects, and for this reason, the HO-WFE was tabulated for pupil diameters of 3 to 7 mm. Effects of keratoconus, pterygium, cataract, and dry eye on HO-WFE were reviewed and treatment efficacy was considered. Results The calculated upper limit of the 95% CI for HO-WFE in a healthy normal 35-year-old patient with a mesopic pupil diameter of 6 mm would be 0.471 μm (471 nm) root-mean-square or less. Although the normal HO-WFE increases with age for a given pupil size, it is not yet completely clear how the concurrent influence of age-related pupillary miosis affects these findings. Abnormal ocular conditions such as keratoconus can induce a large HO-WFE, often in excess of 3.0 μm, particularly attributed to coma. For pterygium or cortical cataract, a combination of coma and trefoil was more commonly induced. Nuclear cataract can induce a negative spherical HO-WFE, usually in excess of 1.0 μm. Conclusions The upper limit of the 95% CI for HO-WFE root-mean-square is about 0.5 μm with normal physiological pupil sizes. With ocular pathologies, HO-WFE can be in excess of 1.0 μm, although many devices and therapeutic and surgical treatments are reported to be highly effective at minimizing HO-WFE. More accurate normative reference ranges for HO-WFE will require future studies using the subjects’ natural pupil size. PMID:25216319

  4. Effects of color temperatures (Kelvin) of LED bulbs on blood physiological variables of broilers grown to heavy weights.

    PubMed

    Olanrewaju, H A; Purswell, J L; Collier, S D; Branton, S L

    2015-08-01

    Light-emitting diode (LED) lighting is being used in the poultry industry to reduce energy usage in broiler production facilities. However, limited data are available comparing efficacy of different spectral distribution of LED bulbs on blood physiological variables of broilers grown to heavy weights (>3 kg). The present study evaluated the effects of color temperature (Kelvin) of LED bulbs on blood physiological variables of heavy broilers in 2 trials with 4 replicates/trial. The study was a randomized complete block design. Four light treatments consisted of 3 LED light bulbs [2,700 K, (Warm-LED); 5,000 K, (Cool-LED-#1); 5,000 K, (Cool-LED-#2)] and incandescent light (ICD, standard) from 1 to 56 d age. A total of 960 1-day-old Ross × Ross 708 chicks (30 males/room 30 females/room) were equally and randomly distributed among 16 environmentally controlled rooms at 50% RH. Each of the 4 treatments was represented by 4 rooms. Feed and water were provided ad libitum. All treatment groups were provided the same diet. Venous blood samples were collected on d 21, 28, 42, and 56 for immediate analysis of selected physiological variables and plasma collection. In comparison with ICD, Cool-LED-#1 had greater (P < 0.05) effects on pH, partial pressure of CO₂(pCO₂), partial pressure of O₂(pO₂), saturated O₂(sO₂), and K⁺. However, all these acid-base changes remained within the normal venous acid-base homeostasis and physiological ranges. In addition, no effect of treatments was observed on HCO(3)(-), hematocrit (Hct), hemoglobin (Hb), Na⁺, Ca²⁺, Cl⁻, mean corpuscular hemoglobin concentration (McHc), osmolality, and anion gap. Moreover, blood glucose concentrations were not affected by treatments. This study shows that the 3 LED light bulbs evaluated in this study may be suitable for replacement of ICD light sources in commercial poultry facilities to reduce energy cost and optimize production efficiency without inducing physiological stress on broilers grown to heavy weights. © 2015 Poultry Science Association Inc.

  5. Pathway profiles based on gene-set enrichment analysis in the honey bee Apis mellifera under brood rearing-suppressed conditions.

    PubMed

    Kim, Kyungmun; Kim, Ju Hyeon; Kim, Young Ho; Hong, Seong-Eui; Lee, Si Hyeock

    2018-01-01

    Perturbation of normal behaviors in honey bee colonies by any external factor can immediately reduce the colony's capacity for brood rearing, which can eventually lead to colony collapse. To investigate the effects of brood-rearing suppression on the biology of honey bee workers, gene-set enrichment analysis of the transcriptomes of worker bees with or without suppressed brood rearing was performed. When brood rearing was suppressed, pathways associated with both protein degradation and synthesis were simultaneously over-represented in both nurses and foragers, and their overall pathway representation profiles resembled those of normal foragers and nurses, respectively. Thus, obstruction of normal labor induced over-representation in pathways related with reshaping of worker bee physiology, suggesting that transition of labor is physiologically reversible. In addition, some genes associated with the regulation of neuronal excitability, cellular and nutritional stress and aggressiveness were over-expressed under brood rearing suppression perhaps to manage in-hive stress under unfavorable conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice

    PubMed Central

    Liu, Xiaojun; Jiang, Shuguang; Fang, Chongyun; Yang, Shiyu; Olalere, Devvora; Pequignot, Edward C.; Cogdill, Alexandria P.; Li, Na; Ramones, Melissa; Granda, Brian; Zhou, Li; Loew, Andreas; Young, Regina M.; June, Carl H.; Zhao, Yangbing

    2015-01-01

    Target-mediated toxicity is a major limitation in the development of chimeric antigen T cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues which express it at physiologic levels. A CAR-expressing T cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach. PMID:26330166

  7. The functional status of the human vestibular analysor following 56 days in an aqueous immersion medium

    NASA Technical Reports Server (NTRS)

    Matsnev, E. I.; Shulzhenko, Y. B.

    1981-01-01

    Two male volunteers were kept hypokinetic in the immersion and physiological parameters were evaluated following the experiment. Prophylactic measures (g-forces, physical exercises, and supplementary salt and water) were applied daily. Caloric and equilibrium tests were utilized to evaluate the physiological responses. The functional changes observed after the 56 day immersion were found to be of a moderate type which normalized quite quickly.

  8. Physiologic changes as patients get older.

    PubMed

    Perlman, P E; Adams, W

    1989-02-01

    As the population ages, primary care physicians are treating increasing numbers of elderly patients. Although certain physiologic changes are known to be age-related, they do not occur uniformly in elderly persons, and it may be difficult to distinguish signs of normal aging from those of disease. Thus, individualized care is important, and with thoughtful diligence, primary care physicians can often improve the quality of life for their elderly patients.

  9. The use of information theory for the evaluation of biomarkers of aging and physiological age.

    PubMed

    Blokh, David; Stambler, Ilia

    2017-04-01

    The present work explores the application of information theoretical measures, such as entropy and normalized mutual information, for research of biomarkers of aging. The use of information theory affords unique methodological advantages for the study of aging processes, as it allows evaluating non-linear relations between biological parameters, providing the precise quantitative strength of those relations, both for individual and multiple parameters, showing cumulative or synergistic effect. Here we illustrate those capabilities utilizing a dataset on heart disease, including diagnostic parameters routinely available to physicians. The use of information-theoretical methods, utilizing normalized mutual information, revealed the exact amount of information that various diagnostic parameters or their combinations contained about the persons' age. Based on those exact informative values for the correlation of measured parameters with age, we constructed a diagnostic rule (a decision tree) to evaluate physiological age, as compared to chronological age. The present data illustrated that younger subjects suffering from heart disease showed characteristics of people of higher age (higher physiological age). Utilizing information-theoretical measures, with additional data, it may be possible to create further clinically applicable information-theory-based markers and models for the evaluation of physiological age, its relation to age-related diseases and its potential modifications by therapeutic interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A mathematics for medicine: The Network Effect

    PubMed Central

    West, Bruce J.

    2014-01-01

    The theory of medicine and its complement systems biology are intended to explain the workings of the large number of mutually interdependent complex physiologic networks in the human body and to apply that understanding to maintaining the functions for which nature designed them. Therefore, when what had originally been made as a simplifying assumption or a working hypothesis becomes foundational to understanding the operation of physiologic networks it is in the best interests of science to replace or at least update that assumption. The replacement process requires, among other things, an evaluation of how the new hypothesis affects modern day understanding of medical science. This paper identifies linear dynamics and Normal statistics as being such arcane assumptions and explores some implications of their retirement. Specifically we explore replacing Normal with fractal statistics and examine how the latter are related to non-linear dynamics and chaos theory. The observed ubiquity of inverse power laws in physiology entails the need for a new calculus, one that describes the dynamics of fractional phenomena and captures the fractal properties of the statistics of physiological time series. We identify these properties as a necessary consequence of the complexity resulting from the network dynamics and refer to them collectively as The Network Effect. PMID:25538622

  11. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    PubMed

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  12. Effect of vitamin D treatments on plasma metabolism and immune parameters of healthy dairy cows.

    PubMed

    Yue, Yuan; Hymøller, Lone; Jensen, Søren Krogh; Lauridsen, Charlotte

    2018-06-01

    The objective of this study was to investigate the possible beneficial effect of vitamin D repletion on certain immune parameters of vitamin D insufficient dairy cows. Twenty dairy cows in late lactation were treated daily with vitamin D in five different ways: sunlight exposure (SUN), D 2 supplementation combined with sunlight exposure (D2SUN), D 2 supplementation (D2), D 3 supplementation (D3), and D 2 and D 3 supplementation combined (D2D3). The cows had very low vitamin D levels at d 0 because of the vitamin D deprivation before the study. After 1 month of vitamin D repletion, all cows had plasma 25(OH)D levels within the normal range. Total 25(OH)D concentration was significantly higher in SUN, D2SUN and D2D3 than D2 or D3 at the end of the study. However, milk yield, as well as protein and fat content of the milk, was not influenced by vitamin D treatments. There was no difference obtained in the measured immune parameters: Leucocyte populations, somatic cell count, immunoglobulin concentrations in plasma and milk, and antigen-stimulated cytokine productions did not change in response to vitamin D repletion or difference in vitamin D sources, and no relations to plasma 25(OH)D levels were identified. Despite the fact that plasma 25(OH)D increased from a very low level to normal range, the present study did not show any effect of vitamin D repletion on the tested immune parameters of healthy dairy cows. Therefore, in this study, it was concluded that repletion to physiologically normal plasma 25-hydroxyvitamin D levels of vitamin D-depleted healthy dairy cows had no influence on immune parameters.

  13. Establishing normal plasma and 24-hour urinary biochemistry ranges in C3H, BALB/c and C57BL/6J mice following acclimatization in metabolic cages.

    PubMed

    Stechman, Michael J; Ahmad, Bushra N; Loh, Nellie Y; Reed, Anita A C; Stewart, Michelle; Wells, Sara; Hough, Tertius; Bentley, Liz; Cox, Roger D; Brown, Steve D M; Thakker, Rajesh V

    2010-07-01

    Physiological studies of mice are facilitated by normal plasma and 24-hour urinary reference ranges, but variability of these parameters may increase due to stress that is induced by housing in metabolic cages. We assessed daily weight, food and water intake, urine volume and final day measurements of the following: plasma sodium, potassium, chloride, urea, creatinine, calcium, phosphate, alkaline phosphatase, albumin, cholesterol and glucose; and urinary sodium, potassium, calcium, phosphate, glucose and protein in 24- to 30-week-old C3H/HeH, BALB/cAnNCrl and C57BL/6J mice. Between 15 and 20 mice of each sex from all three strains were individually housed in metabolic cages with ad libitum feeding for up to seven days. Acclimatization was evaluated using general linear modelling for repeated measures and comparison of biochemical data was by unpaired t-test and analysis of variance (SPSS version 12.0.1). Following an initial 5-10% fall in body weight, daily dietary intake, urinary output and weight in all three strains reached stable values after 3-4 days of confinement. Significant differences in plasma glucose, cholesterol, urea, chloride, calcium and albumin, and urinary glucose, sodium, phosphate, calcium and protein were observed between strains and genders. Thus, these results provide normal reference values for plasma and urinary biochemistry in three strains housed in metabolic cages and demonstrate that 3-4 days are required to reach equilibrium in metabolic cage studies. These variations due to strain and gender have significant implications for selecting the appropriate strain upon which to breed genetically-altered models of metabolic and renal disease.

  14. Brain or strain? Symptoms alone do not distinguish physiologic concussion from cervical/vestibular injury.

    PubMed

    Leddy, John J; Baker, John G; Merchant, Asim; Picano, John; Gaile, Daniel; Matuszak, Jason; Willer, Barry

    2015-05-01

    To compare symptoms in patients with physiologic postconcussion disorder (PCD) versus cervicogenic/vestibular PCD. We hypothesized that most symptoms would not be equivalent. In particular, we hypothesized that cognitive symptoms would be more often associated with physiologic PCD. Retrospective review of symptom reports from patients who completed a 22-item symptom questionnaire. University-based concussion clinic. Convenience sample of 128 patients who had symptoms after head injury for more than 3 weeks and who had provocative treadmill exercise testing. Subjects were classified as either physiologic PCD (abnormal treadmill performance and a normal cervical/vestibular physical examination) or cervicogenic/vestibular PCD (CGV, normal treadmill performance, and an abnormal cervical/vestibular physical examination). Self-reported symptoms. Univariate and multivariate methods, including t tests, tests of equivalence, a logistic regression model, k-nearest neighbor analysis, multidimensional scaling, and principle components analysis were used to see whether symptoms could distinguish PCD from CGV. None of the statistical methods used to analyze self-reported symptoms was able to adequately distinguish patients with PCD from patients with CGV. Symptoms after head injury, including cognitive symptoms, have traditionally been ascribed to brain injury, but they do not reliably discriminate between physiologic PCD and cervicogenic/vestibular PCD. Clinicians should consider specific testing of exercise tolerance and perform a physical examination of the cervical spine and the vestibular/ocular systems to determine the etiology of postconcussion symptoms. Symptoms after head injury, including cognitive symptoms, do not discriminate between concussion and cervical/vestibular injury.

  15. Hot and Bothered: Changes in Microclimate Alter Chlorophyll Fluorescence Measures and Increase Stress Levels in Tropical Epiphytic Orchids

    Treesearch

    Benjamin J. Crain; Raymond L. Tremblay

    2017-01-01

    Premise of research. Tropical epiphytes are susceptible to climatic changes, as evidenced by documented population declines, range contractions, and range shifts; however, physiological changes in individual plants may also be indicative of deteriorating climate conditions. Consequently, physiological analyses of tropical epiphytes whose natural habitats are...

  16. Contractile properties of single permeabilized muscle fibers from congenital cleft palates and normal palates of Spanish goats.

    PubMed

    Hanes, Michael C; Weinzweig, Jeffrey; Kuzon, William M; Panter, Kip E; Buchman, Steven R; Faulkner, John A; Yu, Deborah; Cederna, Paul S; Larkin, Lisa M

    2007-05-01

    Analysis of the composition of muscle fibers constituent to a cleft palate could provide significant insight into the cause of velopharyngeal inadequacy. The authors hypothesized that levator veli palatini muscle dysfunction inherent to cleft palates could affect the timing and outcome of cleft palate repair. Single, permeabilized muscle fibers from levator veli palatini muscles of three normal (n = 19 fibers) and three chemically induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were isolated, and contractile properties were evaluated. The maximum isometric force and rate constants of tension redevelopment (ktr) were measured, and the specific force and normalized power were calculated for each fiber. The ktr measures indicate that cleft fibers are predominantly fast-fatigable; normal fibers are slow fatigue-resistant: after a 10-minute isometric contraction, fibers from cleft palates had a loss of force 16 percent greater than that from normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal palates (2226 +/- 143 microm2). Specific forces did not differ between the two groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82 W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12 W/l). There are clear physiologic differences in single muscle fibers from cleft palates and normal palates: cleft palate fibers are physiologically fast, have greater fatigability, and have greater power production. Detection of functional and/or fiber type differences in muscles of cleft palates may provide preoperative identification of a patient's susceptibility to velopharyngeal inadequacy and permit early surgical intervention to correct this clinical condition.

  17. Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular Interactions

    PubMed Central

    Said, Ahmed S.; Rogers, Stephen C.; Doctor, Allan

    2018-01-01

    Here, we review current data elucidating the role of red blood cell derived microparticles (RMPs) in normal vascular physiology and disease progression. Microparticles (MPs) are submicron-size, membrane-encapsulated vesicles derived from various parent cell types. MPs are produced in response to numerous stimuli that promote a sequence of cytoskeletal and membrane phospholipid changes and resulting MP genesis. MPs were originally considered as potential biomarkers for multiple disease processes and more recently are recognized to have pleiotropic biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in initiating apoptosis. RMPs, specifically, form normally during RBC maturation in response to injury during circulation, and are copiously produced during processing and storage for transfusion. Notably, several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs markedly from that of intact RBCs and the nature/composition of RMP components are affected by the specific circumstances of RMP genesis. Described RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion as well as influence upon vasoregulation via influence upon nitric oxide (NO) bioavailability. Of particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this physiology has been proposed to contribute to the impaired oxygen delivery homeostasis that may be observed following transfusion. In summary, RMPs are submicron particles released from RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in normal and patho-physiology and in transfusion recipients is an area of continued investigation. PMID:29379445

  18. Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular Interactions.

    PubMed

    Said, Ahmed S; Rogers, Stephen C; Doctor, Allan

    2017-01-01

    Here, we review current data elucidating the role of red blood cell derived microparticles (RMPs) in normal vascular physiology and disease progression. Microparticles (MPs) are submicron-size, membrane-encapsulated vesicles derived from various parent cell types. MPs are produced in response to numerous stimuli that promote a sequence of cytoskeletal and membrane phospholipid changes and resulting MP genesis. MPs were originally considered as potential biomarkers for multiple disease processes and more recently are recognized to have pleiotropic biological effects, most notably in: promotion of coagulation, production and handling of reactive oxygen species, immune modulation, angiogenesis, and in initiating apoptosis. RMPs, specifically, form normally during RBC maturation in response to injury during circulation, and are copiously produced during processing and storage for transfusion. Notably, several factors during RBC storage are known to trigger RMP production, including: increased intracellular calcium, increased potassium leakage, and energy failure with ATP depletion. Of note, RMP composition differs markedly from that of intact RBCs and the nature/composition of RMP components are affected by the specific circumstances of RMP genesis. Described RMP bioactivities include: promotion of coagulation, immune modulation, and promotion of endothelial adhesion as well as influence upon vasoregulation via influence upon nitric oxide (NO) bioavailability. Of particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this physiology has been proposed to contribute to the impaired oxygen delivery homeostasis that may be observed following transfusion. In summary, RMPs are submicron particles released from RBCs, with demonstrated vasoactive properties that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs in normal and patho-physiology and in transfusion recipients is an area of continued investigation.

  19. Glycemic extremes in youth with T1DM: the structural and functional integrity of the developing brain.

    PubMed

    Arbelaez, Ana Maria; Semenkovich, Katherine; Hershey, Tamara

    2013-12-01

    The adult brain accounts for a disproportionally large percentage of the body’s total energy consumption (1). However, during brain development,energy demand is even higher, reaching the adult rate by age 2 and increasing to nearly twice the adult rate by age 10, followed by gradual reduction toward adult levels in the next decade (1,2). The dramatic changes in brain metabolism occurring over the first two decades of life coincide with the initial proliferation and then pruning of synapses to adult levels.The brain derives its energy almost exclusively from glucose and is largely driven by neuronal signaling, biosynthesis, and neuroprotection (3–6).Glucose homeostasis in the body is tightly regulated by a series of hormones and physiologic responses. As a result, hypoglycemia and hyperglycemia are rare occurrences in normal individuals, but they occur commonly inpatients with type 1 diabetes mellitus (T1DM) due to a dysfunction of peripheral glucose-insulin-glucagon responses and non-physiologic doses of exogenous insulin, which imperfectly mimic normal physiology. These extremes can occur more frequently in children and adolescents with T1DM due to the inadequacies of insulin replacement therapy, events leading to the diagnosis [prolonged untreated hyperglycemia and diabetic ketoacidosis (DKA)], and to behavioral factors interfering with optimal treatment. When faced with fluctuations in glucose supply the metabolism of the body and brain change dramatically, largely to conserve resources and, at a cost to other organs, to preserve brain function (7). However,if the normal physiological mechanisms that prevent these severe glucose fluctuations and maintain homeostasis are impaired, neuronal function and potentially viability can be affected (8–11).

  20. Sensitivity of Physiological Emotional Measures to Odors Depends on the Product and the Pleasantness Ranges Used

    PubMed Central

    Pichon, Aline M.; Coppin, Géraldine; Cayeux, Isabelle; Porcherot, Christelle; Sander, David; Delplanque, Sylvain

    2015-01-01

    Emotions are characterized by synchronized changes in several components of an organism. Among them, physiological variations provide energy support for the expression of approach/avoid action tendencies induced by relevant stimuli, while self-reported subjective pleasantness feelings integrate all other emotional components and are plastic. Consequently, emotional responses evoked by odors should be highly differentiated when they are linked to different functions of olfaction (e.g., avoiding environmental hazards). As this differentiation has been observed for contrasted odors (very pleasant or unpleasant), we questioned whether subjective and physiological emotional response indicators could still disentangle subtle affective variations when no clear functional distinction is made (mildly pleasant or unpleasant fragrances). Here, we compared the sensitivity of behavioral and physiological [respiration, skin conductance, facial electromyography (EMG), and heart rate] indicators in differentiating odor-elicited emotions in two situations: when a wide range of odor families was presented (e.g., fruity, animal), covering different functional meanings; or in response to a restricted range of products in one particular family (fragrances). Results show clear differences in physiological indicators to odors that display a wide range of reported pleasantness, but these differences almost entirely vanish when fragrances are used even though their subjective pleasantness still differed. Taken together, these results provide valuable information concerning the ability of classic verbal and psychophysiological measures to investigate subtle differences in emotional reactions to a restricted range of similar olfactory stimuli. PMID:26648888

  1. The physiological effects of slow breathing in the healthy human

    PubMed Central

    Russo, Marc A.; Santarelli, Danielle M.; O’Rourke, Dean

    2017-01-01

    Slow breathing practices have been adopted in the modern world across the globe due to their claimed health benefits. This has piqued the interest of researchers and clinicians who have initiated investigations into the physiological (and psychological) effects of slow breathing techniques and attempted to uncover the underlying mechanisms. The aim of this article is to provide a comprehensive overview of normal respiratory physiology and the documented physiological effects of slow breathing techniques according to research in healthy humans. The review focuses on the physiological implications to the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems, with particular focus on diaphragm activity, ventilation efficiency, haemodynamics, heart rate variability, cardiorespiratory coupling, respiratory sinus arrhythmia and sympathovagal balance. The review ends with a brief discussion of the potential clinical implications of slow breathing techniques. This is a topic that warrants further research, understanding and discussion. Key points Slow breathing practices have gained popularity in the western world due to their claimed health benefits, yet remain relatively untouched by the medical community. Investigations into the physiological effects of slow breathing have uncovered significant effects on the respiratory, cardiovascular, cardiorespiratory and autonomic nervous systems. Key findings include effects on respiratory muscle activity, ventilation efficiency, chemoreflex and baroreflex sensitivity, heart rate variability, blood flow dynamics, respiratory sinus arrhythmia, cardiorespiratory coupling, and sympathovagal balance. There appears to be potential for use of controlled slow breathing techniques as a means of optimising physiological parameters that appear to be associated with health and longevity, and that may extend to disease states; however, there is a dire need for further research into the area. Educational aims To provide a comprehensive overview of normal human respiratory physiology and the documented effects of slow breathing in healthy humans. To review and discuss the evidence and hypotheses regarding the mechanisms underlying slow breathing physiological effects in humans. To provide a definition of slow breathing and what may constitute “autonomically optimised respiration”. To open discussion on the potential clinical implications of slow breathing techniques and the need for further research. PMID:29209423

  2. In vivo EPR imaging of differential tumor targeting using cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl

    PubMed Central

    Redler, Gage; Barth, Eugene D.; Bauer, Kenneth S.; Kao, Joseph P.Y.; Rosen, Gerald M.; Halpern, Howard J.

    2015-01-01

    Purpose EPR spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as pO2, pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl 3 relative to the corresponding di-acid 4. Methods We obtained images of nitroxide 3 infused intravenously into C3H mice bearing 0.5-cm3 FSa fibrosarcoma on the leg, and compared these with images of similar tumors infused with nitroxide 4. Results The ratio of spectral intensity from within the tumor-bearing region to that of normal tissue was higher in the mice injected with 3 relative to 4. Conclusion This establishes the possibility of tumor imaging with a nitroxide with intracellular distribution and provides the basis for EPR images of animal models to investigate the relationship between crucial aspects of tumor microenvironment and malignancy and its response to therapy. PMID:23776127

  3. Physiological and pathological characterization of capsaicin-induced reversible nerve degeneration and hyperalgesia.

    PubMed

    Chiang, H; Chang, K-C; Kan, H-W; Wu, S-W; Tseng, M-T; Hsueh, H-W; Lin, Y-H; Chao, C-C; Hsieh, S-T

    2018-07-01

    The study aimed to investigate the physiology, psychophysics, pathology and their relationship in reversible nociceptive nerve degeneration, and the physiology of acute hyperalgesia. We enrolled 15 normal subjects to investigate intraepidermal nerve fibre (IENF) density, contact heat-evoked potential (CHEP) and thermal thresholds during the capsaicin-induced skin nerve degeneration-regeneration; and CHEP and thermal thresholds at capsaicin-induced acute hyperalgesia. After 2-week capsaicin treatment, IENF density of skin was markedly reduced with reduced amplitude and prolonged latency of CHEP, and increased warm and heat pain thresholds. The time courses of skin nerve regeneration and reversal of physiology and psychophysics were different: IENF density was still lower at 10 weeks after capsaicin treatment than that at baseline, whereas CHEP amplitude and warm threshold became normalized within 3 weeks after capsaicin treatment. Although CHEP amplitude and IENF density were best correlated in a multiple linear regression model, a one-phase exponential association model showed better fit than a simple linear one, that is in the regeneration phase, the slope of the regression line between CHEP amplitude and IENF density was steeper in the subgroup with lower IENF densities than in the one with higher IENF densities. During capsaicin-induced hyperalgesia, recordable rate of CHEP to 43 °C heat stimulation was higher with enhanced CHEP amplitude and pain perception compared to baseline. There were differential restoration of IENF density, CHEP and thermal thresholds, and changed CHEP-IENF relationships during skin reinnervation. CHEP can be a physiological signature of acute hyperalgesia. These observations suggested the relationship between nociceptive nerve terminals and brain responses to thermal stimuli changed during different degree of skin denervation, and CHEP to low-intensity heat stimulus can reflect the physiology of hyperalgesia. © 2018 European Pain Federation - EFIC®.

  4. International differences in the links between obesity and physiological dysregulation: the United States, England, and Taiwan.

    PubMed

    Vasunilashorn, Sarinnapha; Kim, Jung Ki; Crimmins, Eileen M

    2013-01-01

    Excess weight has generally been associated with adverse health outcomes; however, the link between overweight and health outcomes may vary with socioeconomic, cultural, and epidemiological conditions. We examine associations of weight with indicators of biological risk in three nationally representative populations: the US National Health and Nutrition Examination Survey, the English Longitudinal Study of Ageing, and the Social Environment and Biomarkers of Aging Study in Taiwan. Indicators of biological risk were compared for obese (defined using body mass index (BMI) and waist circumference) and normal weight individuals aged 54+. Generally, obesity in England was associated with elevated risk for more markers examined; obese Americans also had elevated risks except that they did not have elevated blood pressure (BP). Including waist circumference in our consideration of BMI indicated different links between obesity and waist size across countries; we found higher physiological dysregulation among those with high waist but normal BMI compared to those with normal waist and normal BMI. Americans had the highest levels of biological risk in all weight/waist groups. Cross-country variation in biological risk associated with obesity may reflect differences in health behaviors, lifestyle, medication use, and culture.

  5. A comprehensive prediction and evaluation method of pilot workload

    PubMed Central

    Feng, Chuanyan; Wanyan, Xiaoru; Yang, Kun; Zhuang, Damin; Wu, Xu

    2018-01-01

    BACKGROUND: The prediction and evaluation of pilot workload is a key problem in human factor airworthiness of cockpit. OBJECTIVE: A pilot traffic pattern task was designed in a flight simulation environment in order to carry out the pilot workload prediction and improve the evaluation method. METHODS: The prediction of typical flight subtasks and dynamic workloads (cruise, approach, and landing) were built up based on multiple resource theory, and a favorable validity was achieved by the correlation analysis verification between sensitive physiological data and the predicted value. RESULTS: Statistical analysis indicated that eye movement indices (fixation frequency, mean fixation time, saccade frequency, mean saccade time, and mean pupil diameter), Electrocardiogram indices (mean normal-to-normal interval and the ratio between low frequency and sum of low frequency and high frequency), and Electrodermal Activity indices (mean tonic and mean phasic) were all sensitive to typical workloads of subjects. CONCLUSION: A multinominal logistic regression model based on combination of physiological indices (fixation frequency, mean normal-to-normal interval, the ratio between low frequency and sum of low frequency and high frequency, and mean tonic) was constructed, and the discriminate accuracy was comparatively ideal with a rate of 84.85%. PMID:29710742

  6. International Differences in the Links between Obesity and Physiological Dysregulation: The United States, England, and Taiwan

    PubMed Central

    Vasunilashorn, Sarinnapha; Kim, Jung Ki; Crimmins, Eileen M.

    2013-01-01

    Excess weight has generally been associated with adverse health outcomes; however, the link between overweight and health outcomes may vary with socioeconomic, cultural, and epidemiological conditions. We examine associations of weight with indicators of biological risk in three nationally representative populations: the US National Health and Nutrition Examination Survey, the English Longitudinal Study of Ageing, and the Social Environment and Biomarkers of Aging Study in Taiwan. Indicators of biological risk were compared for obese (defined using body mass index (BMI) and waist circumference) and normal weight individuals aged 54+. Generally, obesity in England was associated with elevated risk for more markers examined; obese Americans also had elevated risks except that they did not have elevated blood pressure (BP). Including waist circumference in our consideration of BMI indicated different links between obesity and waist size across countries; we found higher physiological dysregulation among those with high waist but normal BMI compared to those with normal waist and normal BMI. Americans had the highest levels of biological risk in all weight/waist groups. Cross-country variation in biological risk associated with obesity may reflect differences in health behaviors, lifestyle, medication use, and culture. PMID:23781331

  7. A comprehensive prediction and evaluation method of pilot workload.

    PubMed

    Feng, Chuanyan; Wanyan, Xiaoru; Yang, Kun; Zhuang, Damin; Wu, Xu

    2018-01-01

    The prediction and evaluation of pilot workload is a key problem in human factor airworthiness of cockpit. A pilot traffic pattern task was designed in a flight simulation environment in order to carry out the pilot workload prediction and improve the evaluation method. The prediction of typical flight subtasks and dynamic workloads (cruise, approach, and landing) were built up based on multiple resource theory, and a favorable validity was achieved by the correlation analysis verification between sensitive physiological data and the predicted value. Statistical analysis indicated that eye movement indices (fixation frequency, mean fixation time, saccade frequency, mean saccade time, and mean pupil diameter), Electrocardiogram indices (mean normal-to-normal interval and the ratio between low frequency and sum of low frequency and high frequency), and Electrodermal Activity indices (mean tonic and mean phasic) were all sensitive to typical workloads of subjects. A multinominal logistic regression model based on combination of physiological indices (fixation frequency, mean normal-to-normal interval, the ratio between low frequency and sum of low frequency and high frequency, and mean tonic) was constructed, and the discriminate accuracy was comparatively ideal with a rate of 84.85%.

  8. Modelling physiological deterioration in post-operative patient vital-sign data.

    PubMed

    Pimentel, Marco A F; Clifton, David A; Clifton, Lei; Watkinson, Peter J; Tarassenko, Lionel

    2013-08-01

    Patients who undergo upper-gastrointestinal surgery have a high incidence of post-operative complications, often requiring admission to the intensive care unit several days after surgery. A dataset comprising observational vital-sign data from 171 post-operative patients taking part in a two-phase clinical trial at the Oxford Cancer Centre, was used to explore the trajectory of patients' vital-sign changes during their stay in the post-operative ward using both univariate and multivariate analyses. A model of normality based vital-sign data from patients who had a "normal" recovery was constructed using a kernel density estimate, and tested with "abnormal" data from patients who deteriorated sufficiently to be re-admitted to the intensive care unit. The vital-sign distributions from "normal" patients were found to vary over time from admission to the post-operative ward to their discharge home, but no significant changes in their distributions were observed from halfway through their stay on the ward to the time of discharge. The model of normality identified patient deterioration when tested with unseen "abnormal" data, suggesting that such techniques may be used to provide early warning of adverse physiological events.

  9. Frequency response of portable PEF meters.

    PubMed

    Hankinson, J L; Das, M K

    1995-08-01

    Peak expiratory flow (PEF) is a dynamic parameter and therefore requires a measuring device with a high-frequency response. This study evaluated the frequency-response characteristics of eight commercially available PEF meters, using simulated forced-expiratory maneuvers with a computer-controlled mechanical pump. Three different PEF levels were used (200, 400, and 600 L/min) at six levels of harmonic-frequency content similar to those observed in human subjects. For waveforms with higher frequency content (at the high end or above the physiologic range), the Assess, Vitalograph, Pocket Peak, and Spir-O-Flow PEF meters all overread PEF (greater than 15% difference from target values) at all three PEF levels. These results suggest that the frequency response of PEF meters is an important consideration in the selection of such meters and should be included in device requirements. The current practice of using various levels of American Thoracic Society (ATS) waveform 24 with its low-frequency content may not adequately evaluate the frequency characteristics of PEF meters. An upper range (5% of the fundamental frequency) of 12 Hz, within the range observed in normal subjects, appears to be more practical than an upper limit of 20 Hz.

  10. Bmi-1: At the crossroads of physiological and pathological biology

    PubMed Central

    Bhattacharya, Resham; Mustafi, Soumyajit Banerjee; Street, Mark; Dey, Anindya; Dwivedi, Shailendra Kumar Dhar

    2015-01-01

    Bmi-1 is a member of the Polycomb Repressor Complex1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells. Despite three decades of research that have elucidated the transcriptional regulation, post-translational modifications and functions of Bmi-1 in regulating the DNA damage response, cellular bioenergetics, and pathologies, the entire potential of a protein with such varied function remains to be realized. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer. Additionally, since cancer stem cells are emerging as a new paradigm for therapy resistance, the role of Bmi-1 in this perspective is also highlighted. The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy. Nonetheless new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target. PMID:26448339

  11. Effects of scopolamine on autonomic profiles underlying motion sickness susceptibility

    NASA Technical Reports Server (NTRS)

    Uijtdehaage, Sebastian H. J.; Stern, Robert M.; Koch, Kenneth L.

    1993-01-01

    The purpose of this study was to examine the effects of scopolamine on the physiological patterns occurring prior to and during motion sickness stimulation. In addition, the use of physiological profiles in the prediction of motion sickness was evaluated. Sixty subjects ingested either 0.6 mg scopolamine, 2.5 mg methoscopolamine, or a placebo. Heart rate (HR), respiratory sinus arrhythmia (an index of vagal tone), and electrogastrograms were measured prior to and during the exposure to a rotating optokinetic drum. Compared to the other groups, the scopolamine group reported fewer motion sickness symptoms, and displayed lower HR, higher vagal tone, enhanced normal gastric myoelectric activity, and depressed gastric dysrhythmias before and during motion sickness induction. Distinct physiological profiles prior to drum rotation could reliably differentiate individuals who would develop gastric discomfort from those who would not. Symptom-free subjects were characterized by high levels of vagal tone and low HR across conditions, and by maintaining normal (3 cpm) electrogastrographic activity during drum rotation. It was concluded that scopolamine offered motion sickness protection by initiating a pattern of increased vagal tone and gastric myoelectric stability.

  12. Amniotic fluid

    MedlinePlus

    Burton GJ, Sibley CP, Jauniaux ERM. Placental anatomy and physiology. In: Gabbe SG, Niebyl JR, Simpson JL, et al, eds. Obstetrics: Normal and Problem Pregnancies . 7th ed. Philadelphia, PA: Elsevier; 2017:chap 1. ...

  13. Normal male sexual function: emphasis on orgasm and ejaculation.

    PubMed

    Alwaal, Amjad; Breyer, Benjamin N; Lue, Tom F

    2015-11-01

    Orgasm and ejaculation are two separate physiological processes that are sometimes difficult to distinguish. Orgasm is an intense transient peak sensation of intense pleasure creating an altered state of consciousness associated with reported physical changes. Antegrade ejaculation is a complex physiological process that is composed of two phases (emission and expulsion), and is influenced by intricate neurological and hormonal pathways. Despite the many published research projects dealing with the physiology of orgasm and ejaculation, much about this topic is still unknown. Ejaculatory dysfunction is a common disorder, and currently has no definitive cure. Understanding the complex physiology of orgasm and ejaculation allows the development of therapeutic targets for ejaculatory dysfunction. In this article, we summarize the current literature on the physiology of orgasm and ejaculation, starting with a brief description of the anatomy of sex organs and the physiology of erection. Then, we describe the physiology of orgasm and ejaculation detailing the neuronal, neurochemical, and hormonal control of the ejaculation process. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Diagnosis and management of urinary incontinence and functional fecal incontinence (encopresis) in children.

    PubMed

    Nijman, Rien J M

    2008-09-01

    The ability to maintain normal continence for urine and stools is not achievable in all children by a certain age. Gaining control of urinary and fecal continence is a complex process, and not all steps and factors involved are fully understood. While normal development of anatomy and physiology are prerequisites to becoming fully continent, anatomic abnormalities, such as bladder exstrophy, epispadias, ectopic ureters, and neurogenic disturbances that can usually be recognized at birth and cause incontinence, will require specialist treatment, not only to restore continence but also to preserve renal function. Most forms of urinary incontinence are not caused by an anatomic or physiologic abnormality and, hence, are more difficult to diagnose and their management requires a sound knowledge of bladder and bowel function.

  15. Irregular or absent periods--what can an ultrasound scan tell you?

    PubMed

    Khalid, Asma

    2004-02-01

    Transvaginal ultrasonography has increased our appreciation of the physiological changes in the ovary and endometrium that occur during the normal menstrual cycle. It has become a primary investigative tool in women with irregular or absent periods. Its usefulness in cases of primary amenorrhoea to assess anatomy is also undisputed although it may have limitations in terms of its specificity. However, the interpretation of ultrasound images in women with irregular menses or secondary amenorrhoea is not entirely straightforward. This is particularly true in the diagnosis of polycystic ovary syndrome, a condition of uncertain aetiology, which may present with oligoamenorrhoea. This chapter aims to discuss the benefits and limitations of ultrasound while taking into account the broad overlap between normal and abnormal physiology, some of which has still to be elucidated.

  16. Physiology and growth of redwood and Douglas-fir planted after variable density retention outside redwood’s range

    Treesearch

    Lucy Kerhoulas; Nicholas Kerhoulas; Wade Polda; John-Pascal Berrill

    2017-01-01

    Reforestation following timber harvests is an important topic throughout the coast redwood (Sequoia sempervirens (D. Don) Endl.) range. Furthermore, as drought-induced mortality spreads across many of California’s forests, it is important to understand how physiology and stand structure influence reforestation success. Finally, as climate...

  17. EUCLID: an outcome analysis tool for high-dimensional clinical studies

    NASA Astrophysics Data System (ADS)

    Gayou, Olivier; Parda, David S.; Miften, Moyed

    2007-03-01

    Treatment management decisions in three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) are usually made based on the dose distributions in the target and surrounding normal tissue. These decisions may include, for example, the choice of one treatment over another and the level of tumour dose escalation. Furthermore, biological predictors such as tumour control probability (TCP) and normal tissue complication probability (NTCP), whose parameters available in the literature are only population-based estimates, are often used to assess and compare plans. However, a number of other clinical, biological and physiological factors also affect the outcome of radiotherapy treatment and are often not considered in the treatment planning and evaluation process. A statistical outcome analysis tool, EUCLID, for direct use by radiation oncologists and medical physicists was developed. The tool builds a mathematical model to predict an outcome probability based on a large number of clinical, biological, physiological and dosimetric factors. EUCLID can first analyse a large set of patients, such as from a clinical trial, to derive regression correlation coefficients between these factors and a given outcome. It can then apply such a model to an individual patient at the time of treatment to derive the probability of that outcome, allowing the physician to individualize the treatment based on medical evidence that encompasses a wide range of factors. The software's flexibility allows the clinicians to explore several avenues to select the best predictors of a given outcome. Its link to record-and-verify systems and data spreadsheets allows for a rapid and practical data collection and manipulation. A wide range of statistical information about the study population, including demographics and correlations between different factors, is available. A large number of one- and two-dimensional plots, histograms and survival curves allow for an easy visual analysis of the population. Several visual and analytical methods are available to quantify the predictive power of the multivariate regression model. The EUCLID tool can be readily integrated with treatment planning and record-and-verify systems.

  18. EUCLID: an outcome analysis tool for high-dimensional clinical studies.

    PubMed

    Gayou, Olivier; Parda, David S; Miften, Moyed

    2007-03-21

    Treatment management decisions in three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) are usually made based on the dose distributions in the target and surrounding normal tissue. These decisions may include, for example, the choice of one treatment over another and the level of tumour dose escalation. Furthermore, biological predictors such as tumour control probability (TCP) and normal tissue complication probability (NTCP), whose parameters available in the literature are only population-based estimates, are often used to assess and compare plans. However, a number of other clinical, biological and physiological factors also affect the outcome of radiotherapy treatment and are often not considered in the treatment planning and evaluation process. A statistical outcome analysis tool, EUCLID, for direct use by radiation oncologists and medical physicists was developed. The tool builds a mathematical model to predict an outcome probability based on a large number of clinical, biological, physiological and dosimetric factors. EUCLID can first analyse a large set of patients, such as from a clinical trial, to derive regression correlation coefficients between these factors and a given outcome. It can then apply such a model to an individual patient at the time of treatment to derive the probability of that outcome, allowing the physician to individualize the treatment based on medical evidence that encompasses a wide range of factors. The software's flexibility allows the clinicians to explore several avenues to select the best predictors of a given outcome. Its link to record-and-verify systems and data spreadsheets allows for a rapid and practical data collection and manipulation. A wide range of statistical information about the study population, including demographics and correlations between different factors, is available. A large number of one- and two-dimensional plots, histograms and survival curves allow for an easy visual analysis of the population. Several visual and analytical methods are available to quantify the predictive power of the multivariate regression model. The EUCLID tool can be readily integrated with treatment planning and record-and-verify systems.

  19. High frequency oscillations are associated with cognitive processing in human recognition memory.

    PubMed

    Kucewicz, Michal T; Cimbalnik, Jan; Matsumoto, Joseph Y; Brinkmann, Benjamin H; Bower, Mark R; Vasoli, Vincent; Sulc, Vlastimil; Meyer, Fred; Marsh, W R; Stead, S M; Worrell, Gregory A

    2014-08-01

    High frequency oscillations are associated with normal brain function, but also increasingly recognized as potential biomarkers of the epileptogenic brain. Their role in human cognition has been predominantly studied in classical gamma frequencies (30-100 Hz), which reflect neuronal network coordination involved in attention, learning and memory. Invasive brain recordings in animals and humans demonstrate that physiological oscillations extend beyond the gamma frequency range, but their function in human cognitive processing has not been fully elucidated. Here we investigate high frequency oscillations spanning the high gamma (50-125 Hz), ripple (125-250 Hz) and fast ripple (250-500 Hz) frequency bands using intracranial recordings from 12 patients (five males and seven females, age 21-63 years) during memory encoding and recall of a series of affectively charged images. Presentation of the images induced high frequency oscillations in all three studied bands within the primary visual, limbic and higher order cortical regions in a sequence consistent with the visual processing stream. These induced oscillations were detected on individual electrodes localized in the amygdala, hippocampus and specific neocortical areas, revealing discrete oscillations of characteristic frequency, duration and latency from image presentation. Memory encoding and recall significantly modulated the number of induced high gamma, ripple and fast ripple detections in the studied structures, which was greater in the primary sensory areas during the encoding (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images. Furthermore, the induced high gamma, ripple and fast ripple responses discriminated the encoded and the affectively charged images. In summary, our results show that high frequency oscillations, spanning a wide range of frequencies, are associated with memory processing and generated along distributed cortical and limbic brain regions. These findings support an important role for fast network synchronization in human cognition and extend our understanding of normal physiological brain activity during memory processing. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

    PubMed

    Pincelli, A I; Brunani, A; Caumo, A; Scacchi, M; Pasqualinotto, L; Tibaldi, A; Dubini, A; Bonadonna, S; Cavagnini, F

    2001-01-01

    The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

  1. Pregnancy physiology pattern prediction study (4P study): protocol of an observational cohort study collecting vital sign information to inform the development of an accurate centile-based obstetric early warning score.

    PubMed

    Kumar, Fiona; Kemp, Jude; Edwards, Clare; Pullon, Rebecca M; Loerup, Lise; Triantafyllidis, Andreas; Salvi, Dario; Gibson, Oliver; Gerry, Stephen; MacKillop, Lucy H; Tarassenko, Lionel; Watkinson, Peter J

    2017-09-01

    Successive confidential enquiries into maternal deaths in the UK have identified an urgent need to develop a national early warning score (EWS) specifically for pregnant or recently pregnant women to aid more timely recognition, referral and treatment of women who are developing life-threatening complications in pregnancy or the puerperium. Although many local EWS are in use in obstetrics, most have been developed heuristically. No current obstetric EWS has defined the thresholds at which an alert should be triggered using evidence-based normal ranges, nor do they reflect the changing physiology that occurs with gestation during pregnancy. An observational cohort study involving 1000 participants across three UK sites in Oxford, London and Newcastle. Pregnant women will be recruited at approximately 14 weeks' gestation and have their vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation and temperature) measured at 4 to 6-week intervals during pregnancy. Vital signs recorded during labour and delivery will be extracted from hospital records. After delivery, participants will measure and record their own vital signs daily for 2 weeks. During the antenatal and postnatal periods, vital signs will be recorded on an Android tablet computer through a custom software application and transferred via mobile internet connection to a secure database. The data collected will be used to define reference ranges of vital signs across normal pregnancy, labour and the immediate postnatal period. This will inform the design of an evidence-based obstetric EWS. The study has been approved by the NRES committee South East Coast-Brighton and Sussex (14/LO/1312) and is registered with the ISRCTN (10838017). All participants will provide written informed consent and can withdraw from the study at any point. All data collected will be managed anonymously. The findings will be disseminated in international peer-reviewed journals and through research conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. The Use of Fluid Mechanics to Predict Regions of Microscopic Thrombus Formation in Pulsatile VADs.

    PubMed

    Topper, Stephen R; Navitsky, Michael A; Medvitz, Richard B; Paterson, Eric G; Siedlecki, Christopher A; Slattery, Margaret J; Deutsch, Steven; Rosenberg, Gerson; Manning, Keefe B

    2014-03-01

    We compare the velocity and shear obtained from particle image velocimetry (PIV) and computational fluid dynamics (CFD) in a pulsatile ventricular assist device (VAD) to further test our thrombus predictive methodology using microscopy data from an explanted VAD. To mimic physiological conditions in vitro , a mock circulatory loop is used with a blood analog that matched blood's viscoelastic behavior at 40% hematocrit. Under normal physiologic pressures and for a heart rate of 75 bpm, PIV data is acquired and wall shear maps are produced. The resolution of the PIV shear rate calculations are tested using the CFD and found to be in the same range. A bovine study, using a model of the 50 cc Penn State V-2 VAD, for 30 days at a constant beat rate of 75 beats per minute (bpm) provides the microscopic data whereby after the 30 days, the device is explanted and the sac surface analyzed using scanning electron microscopy (SEM) and, after immunofluorescent labeling for platelets and fibrin, confocal microscopy. Areas are examined based on PIV measurements and CFD, with special attention to low shear regions where platelet and fibrin deposition are most likely to occur. Data collected within the outlet port in a direction normal to the front wall of the VAD shows that some regions experience wall shear rates less than 500 s -1 , which increases the likelihood of platelet and fibrin deposition. Despite only one animal study, correlations between PIV, CFD, and in vivo data show promise. Deposition probability is quantified by the thrombus susceptibility potential, a calculation to correlate low shear and time of shear with deposition.

  3. Clinical evaluation of a noninvasive alarm system for nocturnal hypoglycemia.

    PubMed

    Skladnev, Victor N; Ghevondian, Nejhdeh; Tarnavskii, Stanislav; Paramalingam, Nirubasini; Jones, Timothy W

    2010-01-01

    The aim of this study was to evaluate the performance of a prototype noninvasive alarm system (HypoMon) for the detection of nocturnal hypoglycemia. A prospective cohort study evaluated an alarm system that included a sensor belt, a radio frequency transmitter for chest belt signals, and a receiver. The receiver incorporated integrated "real-time" algorithms designed to recognize hypoglycemia "signatures" in the physiological parameters monitored by the sensor belt. Fifty-two children and young adults with type 1 diabetes mellitus (T1DM) participated in this blinded, prospective, in-clinic, overnight study. Participants had a mean age of 16 years (standard deviation 2.1, range 12-20 years) and were asked to follow their normal meal and insulin routines for the day of the study. Participants had physiological parameters monitored overnight by a single HypoMon system. Their BG levels were also monitored overnight at regular intervals via an intravenous cannula and read on two independent Yellow Springs Instruments analyzers. Hypoglycemia was not induced by any manipulations of diabetes management, rather the subjects were monitored overnight for "natural" occurrences of hypoglycemia. Performance analyses included comparing HypoMon system alarm times with allowed time windows associated with each hypoglycemic event. The primary recognition algorithm in the prototype alarm system performed at a level consistent with expectations based on prior user surveys. The HypoMon system correctly recognized 8 out of the 11 naturally occurring overnight hypoglycemic events and falsely alarmed on 13 out of the remaining 41 normal nights [sensitivity 73% (8/11), specificity 68% (28/41), positive predictive value 38%,negative predictive value 90%]. The prototype HypoMon shows potential as an adjunct method for noninvasive overnight monitoring for hypoglycemia events in young people with T1DM. 2010 Diabetes Technology Society.

  4. Products of lipid peroxidation, but not membrane susceptibility to oxidative damage, are conserved in skeletal muscle following temperature acclimation.

    PubMed

    Grim, Jeffrey M; Semones, Molly C; Kuhn, Donald E; Kriska, Tamas; Keszler, Agnes; Crockett, Elizabeth L

    2015-03-01

    Changes in oxidative capacities and phospholipid remodeling accompany temperature acclimation in ectothermic animals. Both responses may alter redox status and membrane susceptibility to lipid peroxidation (LPO). We tested the hypothesis that phospholipid remodeling is sufficient to offset temperature-driven rates of LPO and, thus, membrane susceptibility to LPO is conserved. We also predicted that the content of LPO products is maintained over a range of physiological temperatures. To assess LPO susceptibility, rates of LPO were quantified with the fluorescent probe C11-BODIPY in mitochondria and sarcoplasmic reticulum from oxidative and glycolytic muscle of striped bass (Morone saxatilis) acclimated to 7°C and 25°C. We also measured phospholipid compositions, contents of LPO products [i.e., individual classes of phospholipid hydroperoxides (PLOOH)], and two membrane antioxidants. Despite phospholipid headgroup and acyl chain remodeling, these alterations do not counter the effect of temperature on LPO rates (i.e., LPO rates are generally not different among acclimation groups when normalized to phospholipid content and compared at a common temperature). Although absolute levels of PLOOH are higher in muscles from cold- than warm-acclimated fish, this difference is lost when PLOOH levels are normalized to total phospholipid. Contents of vitamin E and two homologs of ubiquinone are more than four times higher in mitochondria prepared from oxidative muscle of warm- than cold-acclimated fish. Collectively, our data demonstrate that although phospholipid remodeling does not provide a means for offsetting thermal effects on rates of LPO, differences in phospholipid quantity ensure a constant proportion of LPO products with temperature variation. Copyright © 2015 the American Physiological Society.

  5. Public Laws Authorization and Appropriations Acts 1969-2007 for the U.S. Army Chemical Materials Agency

    DTIC Science & Technology

    2006-11-06

    agents, chemical herbicides , smoke and other obscuration materials. (2) The term "lethal chemical agent and munition" means a chemical agent or...military purposes and harmless to human beings under normal circumstances. (k) EFFECTIVE DATE -- The provisions of this section shall take effect on...the ecological and physiological dangers inherent in the use of herbicides , and (B) the 117 ecological and Physiological effects of the defoliation

  6. Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

    PubMed Central

    Schuchardt, Christiane; Kulkarni, Harshad R.; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P.; Beer, Ambros J.

    2016-01-01

    In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25−29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1–3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably. PMID:27611841

  7. Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides.

    PubMed

    Kletting, Peter; Schuchardt, Christiane; Kulkarni, Harshad R; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P; Beer, Ambros J

    2016-01-01

    In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25-29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1-3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably.

  8. Ergonomic implementation and work station design for quilt manufacturing unit.

    PubMed

    Vinay, Deepa; Kwatra, Seema; Sharma, Suneeta; Kaur, Nirmal

    2012-05-01

    Awkward, extreme and repetitive postures have been associated with work related musculoskeletal disorders and injury to the lowerback of workers engaged in quilting manufacturing unit. Basically quilt are made manually by hand stitch and embroidery on the quilts which was done in squatting posture on the floor. Mending, stain removal, washing and packaging were some other associated work performed on wooden table. their work demands to maintain a continuous squatting posture which leads to various injuries related to low back and to calf muscles. The present study was undertaken in Tarai Agroclimatic Zone of Udham Singh Nagar District of Uttarakhand State with the objective to study the physical and physiological parameters as well as the work station layout of the respondent engaged on quilt manufacturing unit. A total of 30 subjects were selected to study the drudgery involved in quilt making enterprise and to make the provision of technology option to reduce the drudgery as well as musculoskeletal disorders, thus enhancing the productivity and comfortability. Findings of the investigation show that majority of workers (93.33 per cent) were female and very few (6.66 per cent) were the male with the mean age of 24.53±6.43. The body mass index and aerobic capacity (lit/min) values were found as 21.40±4.13 and 26.02±6.44 respectively. Forty per cent of the respondents were having the physical fitness index of high average whereas 33.33 per cent of the respondents had low average physical fitness. All the assessed activities involved to make the quilt included a number of the steps which were executed using two types of work station i.e squatting posture on floor and standing posture using wooden table. A comparative study of physiological parameters was also done in the existing conditions as well as in improved conditions by introducing low height chair and wooden spreader to hold the load of quilt while working, to improve the work posture of the worker. The average working heart rate values were found to reduced by performing the activity using improved technology followed by energy expenditure (6.99 kj/min), total cardiac cost of work (1037.95 beats), physiological cost of work (103.79 beats) and rate of perceived rate of exertion to the score of 2.6 Results of postural analysis that is change in motion at cervical region reveal that range of motion in case of extension was found beyond the normal range in existing setup where as it reduced to normal range in improved work station. The finding of the study concludes that to ensure safety and to reduce occupational health hazards while performing the activity, an ergonomically designed work station by introduction of improved technology option will be a right choice which also enhances the productivity.

  9. Frequency modulation of follicle-stimulating hormone (FSH) during the luteal-follicular transition: evidence for FSH control of inhibin B in normal women.

    PubMed

    Welt, C K; Martin, K A; Taylor, A E; Lambert-Messerlian, G M; Crowley, W F; Smith, J A; Schoenfeld, D A; Hall, J E

    1997-08-01

    To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the effect of differing levels of FSH on inhibin B secretion during the luteal-follicular transition, exogenous GnRH was administered to GnRH-deficient women using one of two regimens, and the results were compared to those in normal women. In the GnRH-deficient women, the GnRH pulse frequency was increased from every 4 h in the late luteal phase to every 90 min on the day of menses to mimic normal cycling women (physiological frequency transition; n = 8 studies) or the GnRH pulse frequency was kept constant at a late luteal phase frequency of every 4 h through the first 6 days of the subsequent early follicular phase of cycle 2 (slow frequency transition; n = 6 studies). The differential rise in FSH secretion induced in these studies allowed us to examine the subsequent contribution of varying levels of FSH to inhibin B secretion. A physiological regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH and inhibin B levels that did not differ from that in normal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnRH for 6 days into the subsequent early follicular phase produced FSH levels significantly lower than those in the physiological transition (P < 0.05), with the greatest difference seen on the day after menses (9.1 +/- 1.0 vs. 16.4 +/- 1.4 IU/L for the slow and physiological transition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associated with significantly lower inhibin B levels (43.3 +/- 21.5 vs. 140.0 +/- 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later doubling of estradiol from baseline (day 9.6 +/- 0.9 vs. day 5.6 +/- 0.1; P < 0.02), and a longer follicular phase length (16.0 +/- 1.4 vs. 11.6 +/- 0.9 days; P < 0.05) compared with those in the physiological transition group. In conclusion, during the luteal-follicular transition, the GnRH pulse frequency contributes to but is not solely responsible for the FSH rise that initiates folliculogenesis. Alteration of FSH dynamics induced by changes in GnRH pulse frequency in GnRH-deficient women provides evidence that FSH stimulates inhibin B production in the human. Timely follicular development indicated by both estradiol and inhibin B secretion appears to be dependent on the pattern of increase in FSH during the luteal-follicular transition.

  10. Enlarged prostate gland

    MedlinePlus Videos and Cool Tools

    ... have symptoms of the disease, or their symptoms are minor and do not restrict their life style. ... normal physiological process of aging and treatment options are available. The choice of the appropriate treatment is ...

  11. EMG normalization to study muscle activation in cycling.

    PubMed

    Rouffet, David M; Hautier, Christophe A

    2008-10-01

    The value of electromyography (EMG) is sensitive to many physiological and non-physiological factors. The purpose of the present study was to determine if the torque-velocity test (T-V) can be used to normalize EMG signals into a framework of biological significance. Peak EMG amplitude of gluteus maximus (GMAX), vastus lateralis (VL), rectus femoris (RF), biceps femoris long head (BF), gastrocnemius medialis (GAS) and soleus (SOL) was calculated for nine subjects during isometric maximal voluntary contractions (IMVC) and torque-velocity bicycling tests (T-V). Then, the reference EMG signals obtained from IMVC and T-V bicycling tests were used to normalize the amplitude of the EMG signals collected for 15 different submaximal pedaling conditions. The results of this study showed that the repeatability of the measurements between IMVC (from 10% to 23%) and T-V (from 8% to 20%) was comparable. The amplitude of the peak EMG of VL was 99+/-43% higher (p<0.001) when measured during T-V. Moreover, the inter-individual variability of the EMG patterns calculated for submaximal cycling exercises differed significantly when using T-V bicycling normalization method (GMAX: 0.33+/-0.16 vs. 1.09+/-0.04, VL: 0.07+/-0.02 vs. 0.64+/-0.14, SOL: 0.07+/-0.03 vs. 1.00+/-0.07, RF: 1.21+/-0.20 vs. 0.92+/-0.13, BF: 1.47+/-0.47 vs. 0.84+/-0.11). It was concluded that T-V bicycling test offers the advantage to be less time and energy-consuming and to be as repeatable as IMVC tests to measure peak EMG amplitude. Furthermore, this normalization method avoids the impact of non-physiological factors on the amplitude of the EMG signals so that it allows quantifying better the activation level of lower limb muscles and the variability of the EMG patterns during submaximal bicycling exercises.

  12. Comparison of stroke work between repaired tetralogy of Fallot and normal right ventricular physiologies.

    PubMed

    Lee, Namheon; Das, Ashish; Banerjee, Rupak K; Gottliebson, William M

    2013-01-01

    Adult patients who underwent tetralogy of Fallot repair surgery (rTOF) confront life-threatening ailments due to right ventricular (RV) myocardial dysfunction. Pulmonary valve replacement (PVR) needs to be performed to restore the deteriorating RV function. Determination of correct timing to perform PVR in an rTOF patient remains subjective, due to the unavailability of quantifiable clinical diagnostic parameters. The objective of this study is to evaluate the possibility of using RV body surface area (BSA)-indexed stroke work (SW(I)) to quantify RV inefficiency in TOF patients. We hypothesized that RV SW(I) required to push blood to the lungs in rTOF patients is significantly higher than that of normal subjects. Seven patients with rTOF pathophysiology and eight controls with normal RV physiology were registered for this study. Right ventricular volume and pressure were measured using cardiac magnetic resonance imaging and catheterization, respectively. Statistical analysis was performed to quantify the difference in SW(I) between the RV of the rTOF and control groups. Right ventricular SW(I) in rTOF patients (0.176 ± 0.055 J/m(2)) was significantly higher by 93.4% (P = 0.0026) than that of controls (0.091 ± 0.030 J/m(2)). Further, rTOF patients were found to have significantly higher (P < 0.05) BSA normalized RV end-systolic volume, end-systolic pressure, and regurgitation fraction than control subjects. Ejection fraction and peak ejection rate of rTOF patients were significantly lower (P < 0.05) than those of controls. Patients with rTOF pathophysiology had significantly higher RV SW(I) compared with subjects with normal RV physiology. Therefore, RV SW(I) may be useful to quantify RV inefficiency in rTOF patients along with currently used clinical end points such as RV volume, pressure, regurgitation fraction, and ejection fraction.

  13. Centrifuges in gravitational physiology research

    NASA Technical Reports Server (NTRS)

    Ballard, Rodney W.; Davies, Phil; Fuller, Charles A.

    1993-01-01

    Data from space flight and ground based experiments have clearly demonstrated the importance of Earth gravity for normal physiological function in man and animals. Gravitational Physiology is concerned with the role and influence of gravity on physiological systems. Research in this field examines how we perceive and respond to gravity and the mechanisms underlying these responses. Inherent in our search for answers to these questions is the ability to alter gravity, which is not physically possible without leaving Earth. However, useful experimental paradigms have been to modify the perceived force of gravity by changing either the orientation of subjects to the gravity vector (i.e., postural changes) or by applying inertial forces to augment the magnitude of the gravity vector. The later technique has commonly been used by applying centripetal force via centrifugation.

  14. Sex Differences in Pitch Range and Speech Fundamental Frequency After Arytenoid Adduction and Thyroplasty.

    PubMed

    Konomi, Ujimoto; Watanabe, Yusuke; Komazawa, Daigo

    2016-05-01

    The purpose of this study was to clarify the sex differences in pitch range (PR) and speech fundamental frequency (SFF) after arytenoid adduction (AA) combined with type 1 thyroplasty (TP1) in patients with unilateral vocal fold paralysis (UVFP) and to assess the cause of these differences. This is a retrospective review of clinical records. The records of 50 patients with UVFP for whom PR, SFF, and maximum phonation time (MPT) had been evaluated before and 1 year after AA combined with TP1 were analyzed. Patients consisted of 36 men and 14 women. In particular, in the 37 patients (24 men and 13 women) who had ≥2 semitones (STs) in preoperative PR (pre-PR), the differences and correlations between the pre-PR and the postoperative PR (post-PR), SFF, and MPT were compared between the sexes. We also discussed cases of post-PR deterioration and abnormal SFF. The characteristics of PR in men are narrow pre-PR (14.7 ± 11.5 STs) and significant extension of post-PR (22.6 ± 6.3 STs). MPT extended from 4.6 ± 2.5 seconds to 14.8 ± 7.2 seconds. In contrast, women had a wide pre-PR (18.1 ± 7.2 STs) and showed no significant post-PR extension (21.7 ± 7.8 STs). MPT extended from 5.1 ± 1.9 seconds to 16.8 ± 7.2 seconds. Although there were no significant changes in average SFF, as well as the highest and lowest pitch after the operation, the variance of the pre-SFF tended to converge into the physiological range in the post-SFF (P = 0.08). Compared with the SFF data of normal adult controls, post-SFF in the normal range was 46.0% (23/50). In patients who showed a >20% improvement in PR, normal post-SFF appeared in 68.8% of the patients (11/16). Particularly in those women, 83.3% (5/6) showed a normal post-SFF. Men showed greater difficulty in recovery of normal PR, SFF, and MPT; however, there were fewer patients (4.2%; 1/24) with a PR deterioration of >20%. Regarding women, although some patients showed a parallel recovery in PR and SFF to the normal range, there was a high rate of patients showing PR deterioration (30.8%; 4/13). AA combined with TP1 resulted in the recovery of not only MPT but also PR and SFF. In addition, sex differences in operative effects were suggested. In men, although MPT is difficult to be fully recovered, PR deterioration was mild. In women, although MPT was more easily extended, PR deterioration occurred more readily because of operative effects such as hypermedialization of their smaller larynx. The post-PR variation appeared to be associated with SFF. Our results indicate the necessity to assess patients' PR and SFF even if their MPTs recover, particularly in patients with postoperative voice insufficiency. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  15. The Applicability of Nonlinear Systems Dynamics Chaos Measures to Cardiovascular Physiology Variables

    NASA Technical Reports Server (NTRS)

    Hooker, John C.

    1991-01-01

    Three measures of nonlinear chaos (fractal dimension, Approximate Entropy (ApEn), and Lyapunov exponents) were studied as potential measures of cardiovascular condition. It is suggested that these measures have potential in the assessment of cardiovascular condition in environments of normal cardiovascular stress (normal gravity on the Earth surface), cardiovascular deconditioning (microgravity of space), and increased cardiovascular stress (lower body negative pressure (LBNP) treatments).

  16. Influence of zinc deficiency on AKT-MDM2-P53 signaling axes in normal and malignant human prostate cells

    USDA-ARS?s Scientific Manuscript database

    With prostate being the highest zinc-accumulating tissue before the onset of cancer, the effects of physiologic levels of zinc on Akt-Mdm2-p53 and Akt-p21 signaling axes in human normal prostate epithelial cells (PrEC) and malignant prostate LNCaP cells were examined. Cells were cultured for 6 d in...

  17. Population dynamics can be more important than physiological limits for determining range shifts under climate change.

    PubMed

    Fordham, Damien A; Mellin, Camille; Russell, Bayden D; Akçakaya, Reşit H; Bradshaw, Corey J A; Aiello-Lammens, Matthew E; Caley, Julian M; Connell, Sean D; Mayfield, Stephen; Shepherd, Scoresby A; Brook, Barry W

    2013-10-01

    Evidence is accumulating that species' responses to climate changes are best predicted by modelling the interaction of physiological limits, biotic processes and the effects of dispersal-limitation. Using commercially harvested blacklip (Haliotis rubra) and greenlip abalone (Haliotis laevigata) as case studies, we determine the relative importance of accounting for interactions among physiology, metapopulation dynamics and exploitation in predictions of range (geographical occupancy) and abundance (spatially explicit density) under various climate change scenarios. Traditional correlative ecological niche models (ENM) predict that climate change will benefit the commercial exploitation of abalone by promoting increased abundances without any reduction in range size. However, models that account simultaneously for demographic processes and physiological responses to climate-related factors result in future (and present) estimates of area of occupancy (AOO) and abundance that differ from those generated by ENMs alone. Range expansion and population growth are unlikely for blacklip abalone because of important interactions between climate-dependent mortality and metapopulation processes; in contrast, greenlip abalone should increase in abundance despite a contraction in AOO. The strongly non-linear relationship between abalone population size and AOO has important ramifications for the use of ENM predictions that rely on metrics describing change in habitat area as proxies for extinction risk. These results show that predicting species' responses to climate change often require physiological information to understand climatic range determinants, and a metapopulation model that can make full use of this data to more realistically account for processes such as local extirpation, demographic rescue, source-sink dynamics and dispersal-limitation. © 2013 John Wiley & Sons Ltd.

  18. Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

    PubMed

    Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

    2013-06-01

    Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

  19. Compression Stiffening of Brain and its Effect on Mechanosensing by Glioma Cells

    NASA Astrophysics Data System (ADS)

    Pogoda, Katarzyna

    The stiffness of tissues, often characterized by their time-dependent elastic properties, is tightly controlled under normal condition and central nervous system tissue is among the softest tissues. Changes in tissue and organ stiffness occur in some physiological conditions and are frequently symptoms of diseases such as fibrosis, cardiovascular disease and many forms of cancer. Primary cells isolated from various tissues often respond to changes in the mechanical properties of their substrates, and the range of stiffness over which these responses occur appear to be limited to the tissue elastic modulus from which they are derived. Our goal was to test the hypotheses that the stiffness of tumors derived from CNS tissue differs from that of normal brain, and that transformed cells derived from such tumors exhibit mechanical responses that differ from those of normal glial cells. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, our data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression. However, both normal brain and glioma samples stiffen with compression, but not in elongation and increased shear strains. On the other hand, different classes of immortalized cells derived from human glioblastoma show substantially different responses to the stiffness of substrates in vitrowhen grown on soft polyacrylamide and hyaluronic acid gels. This outcome supports the hypothesis that compression stiffening, which might occur with increased vascularization and interstitial pressure gradients that are characteristic of tumors, effectively stiffens the environment of glioma cells, and that in situ, the elastic resistance these cells sense might be sufficient to trigger the same responses that are activated in vitro by increased substrate stiffness.

  20. Microgravity Analogues of Herpes Virus Pathogenicity: Human Cytomegalovirus (hCMV) and Varicella Zoster (VZV) Infectivity in Human Tissue Like Assemblies (TLAs)

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Albrecht, T.; Cohrs, R.

    2009-01-01

    The old adage we are our own worst enemies may perhaps be the most profound statement ever made when applied to man s desire for extraterrestrial exploration and habitation of Space. Consider the immune system protects the integrity of the entire human physiology and is comprised of two basic elements the adaptive or circulating and the innate immune system. Failure of the components of the adaptive system leads to venerability of the innate system from opportunistic microbes; viral, bacteria, and fungal, which surround us, are transported on our skin, and commonly inhabit the human physiology as normal and imunosuppressed parasites. The fine balance which is maintained for the preponderance of our normal lives, save immune disorders and disease, is deregulated in microgravity. Thus analogue systems to study these potential Risks are essential for our progress in conquering Space exploration and habitation. In this study we employed two known physiological target tissues in which the reactivation of hCMV and VZV occurs, human neural and lung systems created for the study and interaction of these herpes viruses independently and simultaneously on the innate immune system. Normal human neural and lung tissue analogues called tissue like assemblies (TLAs) were infected with low MOIs of approximately 2 x 10(exp -5) pfu hCMV or VZV and established active but prolonged low grade infections which spanned .7-1.5 months in length. These infections were characterized by the ability to continuously produce each of the viruses without expiration of the host cultures. Verification and quantification of viral replication was confirmed via RT_PCR, IHC, and confocal spectral analyses of the respective essential viral genomes. All host TLAs maintained the ability to actively proliferate throughout the entire duration of the experiments as is analogous to normal in vivo physiological conditions. These data represent a significant advance in the ability to study the triggering mechanisms which surround Herpes vial reactivation and proliferation. Additionally, prolonged replication of these viruses will allow the tracking of viral genomic shift.

  1. Effect of eggshell temperature and oxygen concentration during incubation on the developmental and physiological status of broiler hatchlings in the perinatal period.

    PubMed

    Molenaar, R; van den Anker, I; Meijerhof, R; Kemp, B; van den Brand, H

    2011-06-01

    This study evaluated the influence of incubation conditions on the developmental and physiological status of birds in the perinatal period, which spans the end of incubation until the early posthatch period. Embryos were incubated at a normal (37.8°C) or high (38.9°C) eggshell temperature (EST) and a low (17%), normal (21%), or high (25%) O(2) concentration from d 7 until 19 of incubation. After d 19 of incubation, EST was maintained, but O(2) concentrations were 21% for all embryos. Body and organ weights, and hepatic glycogen levels were measured at d 18 of incubation and at 12 and 48 h after emergence from the eggshell. In addition, blood metabolites were measured at 12 and 48 h after emergence from the eggshell. Embryos incubated at a high EST and low O(2) concentration had the highest mortality in the last week of incubation, which may be related to their low yolk-free body mass (YFBM) or a reduced nutrient availability for hatching (i.e., hepatic glycogen). High EST, compared with normal EST, decreased YFBM. This may be due to the shorter incubation duration of 8 h, the lower weight of supply organs (i.e., heart and lung), or a lack of glucose precursors. Because of this lack of glucose precursors, embryos incubated at high EST may have used proteins for energy production instead of for body development at the end of incubation. The YFBM at d 18 of incubation increased with an increase in O(2) concentration. However, differences between the normal and high O(2) concentration disappeared at 12 and 48 h after emergence, possibly because the high O(2) concentration had difficulties adapting to lower O(2) concentrations in the perinatal period. Blood metabolites and hepatic glycogen were comparable among O(2) concentrations, indicating that the physiological status at hatch may be related to the environment that the embryo experienced during the hatching process. In conclusion, EST and O(2) concentration differentially influence the developmental and physiological status of broilers during the perinatal period.

  2. Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells.

    PubMed

    Sanguri, Sweta; Gupta, Damodar

    2018-06-27

    Low LET Ionizing radiation is known to alter intracellular redox balance by inducing free radical generation, which may cause oxidative modification of various cellular biomolecules. The extent of biomolecule-modifications/ damages and changes in vital processes (viz. cellular homeostasis, inter-/intra-cellular signaling, mitochondrial physiology/dynamics antioxidant defence systems) are crucial which in turn determine fate of cells. In the present study, we expended TLR expressing (normal/ transformed) and TLR null cells; and we have shown that mannan pretreatment in TLR expressing normal cells offers survival advantage against lethal doses of ionizing radiation. On the contrary, mannan pretreatment does not offer any protection against radiation to TLR null cells, NKE ρ° cells and transformed cells. In normal cells, abrupt decrease in mitochondrial membrane potential and endogenous ROS levels occurs following treatment with mannan. We intend to irradiate mannan-pretreated cells at a specific stage of perturbed mitochondrial functioning and ROS levels to comprehend if mannan pretreatment offers any survival advantage against radiation exposure to cells. Interestingly, pre-irradiation treatment of cells with mannan activates NFκB, p38 and JNK, alters mitochondrial physiology, increases expression of Cu/ZnSOD and MnSOD, minimizes oxidation of mitochondrial phospholipids and offers survival advantage in comparison to irradiated group, in TLR expressing normal cells. The study demonstrates that TLR and mitochondrial ETC functions are inevitable in radio-protective efficacy exhibited by mannan.

  3. Exercise detraining: Applicability to microgravity

    NASA Technical Reports Server (NTRS)

    Coyle, Edward F.

    1994-01-01

    Physical training exposes the various systems of the body to potent physiologic stimuli. These stimuli induce specific adaptations that enhance an individual's tolerance for the type of exercise encountered in training. The level of adaptation and the magnitude of improvement in exercise tolerance is proportional to the potency of the physical training stimuli. Likewise, our bodies are stimulated by gravity, which promotes adaptations of both the cardiovascular and skeletal muscles. Exposure to microgravity removes normal stimuli to these systems, and the body adapts to these reduced demands. In many respects the cessation of physical training in athletes and the transition from normal gravity to microgravity represent similar paradigms. Inherent to these situations is the concept of the reversibility of the adaptations induced by training or by exposure to normal gravity. The reversibility concept holds that when physical training is stopped (i.e., detraining) or reduced, or a person goes from normal gravity to microgravity, the bodily systems readjust in accordance with the diminished physiologic stimuli. The focus of this chapter is on the time course of loss of the adaptations to endurance training as well as on the possibility that certain adaptations persist, to some extent, when training is stopped. Because endurance exercise training generally improves cardiovascular function and promotes metabolic adaptations within the exercising skeletal musculature, the reversibility of these specific adaptations is considered. These observations have some applicability to the transition from normal to microgravity.

  4. Maternal thyroid hormones enhance hatching success but decrease nestling body mass in the rock pigeon (Columba livia).

    PubMed

    Hsu, Bin-Yan; Dijkstra, Cor; Darras, Veerle M; de Vries, Bonnie; Groothuis, Ton G G

    2017-01-01

    Thyroid hormones (THs) - triiodothyronine (T3) and thyroxine (T4) - are essential for embryonic development in vertebrates. All vertebrate embryos are exposed to THs from maternal origin. As maternal TH levels are known to be essential to embryonic development, the natural variation of maternal THs probably represents a pathway of maternal effects that can modify offspring phenotype. However, potential fitness consequences of variation of maternal TH exposure within the normal physiological range and without confounding effects of the mother have never been experimentally investigated. We experimentally manipulated the levels of yolk T3 and T4 within the physiological range in a species in which the embryo develops outside the mother's body, the Rock Pigeon (Columba livia) eggs. Making use of the natural difference of yolk testosterone between the two eggs of pigeon clutches, we were also able to investigate the potential interaction between THs and testosterone. Elevated yolk TH levels enhanced embryonic development and hatching success, and reduced body mass but not tarsus length between day 14 and fledging. The yolk hormones increased plasma T4 concentrations in females but reduced it in males, in line with the effect on metabolic rate at hatching. Plasma concentrations of T3 and testosterone were not significantly affected. The effects of treatment did not differ between eggs with high or low testosterone levels. Our data indicate that natural variation in maternal yolk TH levels affects offspring phenotype and embryonic survival, potentially influencing maternal and chick fitness. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Variation in lung volumes and capacities among young males in relation to height.

    PubMed

    Bhatti, Urooj; Rani, Keenjher; Memon, Muhammad Qasim

    2014-01-01

    Vital Capacity (VC) is defined as a change in volume of lung after maximal inspiration followed by maximal expiration is called Vital Capacity of lungs. It is the sum of tidal volume, inspiratory reserve volume .and expiratory reserve volume. Vital capacity of normal adults ranges between 3 to 5 litres. A number of physiological factors like age, gender, height and ethnicity effect lung volumes. The reference values of lung volume and capacities were calculated previously and those studies played pivotal role in establishing the fact that air volume capacities measured in an individual fall within a wide range among healthy persons of same age, gender and height buit with different ethnicity. The objective of this study was to evaluate the changes in vital capacity in with height and gender. This cross-sectional study included 74 male students in the Department of Physiology, Liaquat University of Medical and Health Sciences, Jamshoro during January-March, 2014. The volunteers were divided into 2 groups of height ≤ 167.4 cm and > 167.4 cm. The volunteers' height was measured in cm. Vital capacity of the subjects was measured using standard protocol. Mean ± SD of age, height and vital capacity were calculated. Mean vital capacity in students with height > 167.4 cm was higher than average vital capacity of students with height ≤ 167.4 cm. It might be due to the increased surface area of the lungs in relation with increasing height. There are variations in vital capacity of individuals in relation to their heights, within the same ethnic and age groups.

  6. Obturator internus muscle autotransfer: a new concept for the treatment of anismus. Clinical experience.

    PubMed

    Farag, A

    1997-01-01

    In this study 20 patients suffering from chronic constipation due to spastic anal sphincters were operated upon using a new surgical technique. The technique aimed at constructing an active anal dilator mechanism using the obturator internus muscles mobilized from both sides and sutured to the side wall of the anal canal in order to overcome the spastic anal sphincters during defaecation. This series included 3 failures (15%), 16 successful cases (80%), and 1 dissatisfied patient despite normal postoperative investigations (5%). Eleven patients (55%) showed immediate postoperative normalization of their defaecation. Five patients (25%) showed normalization of their defaecation after 10 sessions of electric stimulation of the transposed muscles given 1 month postoperatively for 10 successive days. All the successful cases (16 patients) maintained their good results during the period of follow-up which ranged from 16 to 45 months (average = 30.31 months). For the successful cases, follow-up was from 16 to 42 months (average = 26.72 months). Immediate postoperative complications included 3 cases of wound infection and 2 cases of transient incontinence to gases which responded completely to postoperative Faradic stimulation. No cases of persistent incontinence of any degree were detected among the 20 patients studied. The 3 failures were mainly due to avoidable technical problems. The technique was safe, easy, and physiological, using a strictly perineal approach.

  7. Physiological and behavioural assessment of pain in ruminants: principles and caveats.

    PubMed

    Mellor, David J; Stafford, Kevin J

    2004-06-01

    Pain elicits a range of physiological and behavioural responses. These are commonly used to assess the impact of pain-inducing stimuli on animals, to determine whether or not significant pain is experienced and to devise strategies for alleviating pain. This paper outlines a range of principles and caveats to guide the evaluation of physiological and behavioural responses to painful stimuli, so that they can be better used to minimise pain in the experimental context. Although this advice is based on studies of farm animals responding to painful husbandry practices, it is more generally applicable.

  8. Sex-specific ecophysiological responses to environmental fluctuations of free-ranging Hermann's tortoises: implication for conservation.

    PubMed

    Sibeaux, Adélaïde; Michel, Catherine Louise; Bonnet, Xavier; Caron, Sébastien; Fournière, Kévin; Gagno, Stephane; Ballouard, Jean-Marie

    2016-01-01

    Physiological parameters provide indicators to evaluate how organisms respond to conservation actions. For example, individuals translocated during reinforcement programmes may not adapt to their novel host environment and may exhibit elevated chronic levels of stress hormones and/or decreasing body condition. Conversely, successful conservation actions should be associated with a lack of detrimental physiological perturbation. However, physiological references fluctuate over time and are influenced by various factors (e.g. sex, age, reproductive status). It is therefore necessary to determine the range of natural variations of the selected physiological metrics to establish useful baselines. This study focuses on endangered free-ranging Hermann's tortoises ( Testudo hermanni hermanni ), where conservation actions have been preconized to prevent extinction of French mainland populations. The influence of sex and of environmental factors (site, year and season) on eight physiological parameters (e.g. body condition, corticosterone concentrations) was assessed in 82 individuals from two populations living in different habitats. Daily displacements were monitored by radio-tracking. Most parameters varied between years and seasons and exhibited contrasting sex patterns but with no or limited effect of site. By combining behavioural and physiological traits, this study provides sex-specific seasonal baselines that can be used to monitor the health status of Hermann's tortoises facing environmental threats (e.g. habitat changes) or during conservation actions (e.g. translocation). These results might also assist in selection of the appropriate season for translocation.

  9. A Multi-Scale Sampling Strategy for Detecting Physiologically Significant Signals in AVIRIS Imagery

    NASA Technical Reports Server (NTRS)

    Gamon, John A.; Lee, Lai-Fun; Qiu, Hong-Lie; Davis, Stephen; Roberts, Dar A.; Ustin, Susan L.

    1998-01-01

    Models of photosynthetic production at ecosystem and global scales require multiple input parameters specifying physical and physiological surface features. While certain physical parameters (e.g., absorbed photosynthetically active radiation) can be derived from current satellite sensors, other physiologically relevant measures (e.g., vegetation type, water status, carboxylation capacity, or photosynthetic light-use efficiency), are not generally directly available from current satellite sensors at the appropriate geographic scale. Consequently, many model parameters must be assumed or derived from independent sources, often at an inappropriate scale. An abundance of ecophysiological studies at the leaf and canopy scales suggests strong physiological control of vegetation-atmosphere CO2 and water vapor fluxes, particularly in evergreen vegetation subjected to diurnal or seasonal stresses. For example hot, dry conditions can lead to stomatal closure, and associated "downregulation" of photosynthetic biochemical processes, a phenomenon often manifested as a "midday photosynthetic depression". A recent study with the revised simple biosphere (SiB2) model demonstrated that photosynthetic downregulation can significantly impact global climate. However, at the global scale, the exact significance of downregulation remains unclear, largely because appropriate physiological measures are generally unavailable at this scale. Clearly, there is a need to develop reliable ways of extracting physiologically relevant information from remote sensing. Narrow-band spectrometers offer many opportunities for deriving physiological parameters needed for ecosystem and global scale photosynthetic models. Experimental studies on the ground at the leaf- to stand-scale have indicated that several narrow-band features can be used to detect plant physiological status. One physiological signal is caused by xanthophyll cycle pigment activity, and is often expressed as the Photochemical Reflectance Index (PRI). Because the xanthophyll cycle pigments are photoregulatory pigments closely linked to photosynthetic function, this index can be used to derive relative photosynthetic rates. An additional signal with physiological significance is the 970 nm water absorption band, which provides a measure of liquid water content. This feature has been quantified both using a simple 2-band ratio (900/970 nm, here referred to as the "Water Band Index" or WBI;), and using the "continuum removal" method. Current atmospheric correction methods for AVIRIS imagery also obtain quantitative expressions of surface liquid water absorption based on the 970 nm water band and may be comparable to ground-based estimates of water content using this feature. However, physiological interpretations of both the PRI and the WBI are best understood at the leaf and canopy scales, where complications of atmospheric interference and complex stand and landscape features can be minimized, and where experimental manipulations can be readily applied. Currently it is not known whether these physiological indices can be used to derive meaningful physiological information from AVIRIS imagery. In addition to the problem of atmospheric interference, another challenge is that any simple physiological index can be confounded by multiple factors unrelated to physiology, and this problem can become more severe at progressively larger spatial scales. For example, previous work has suggested that both the PRI and the WBI, are strongly correlated with other optical measures of canopy structure (e.g., the Normalized Difference Vegetation Index or green vegetation fraction), indicating a confounding effect of structure on physiological signals at the larger, landscape scale. Furthermore, the normal operating mode of most imaging spectrometers does not allow simultaneous, ground truthing at a level of detail needed for physiological sampling. Additionally, manipulative experiments of physiology are difficult to apply at a geographic scale suitable for comparison with remote imagery, which often works at spatial scales that are several orders of magnitude larger than those typically used for physiological studies. These limitations require the consideration of alternative approaches to validating physiological information derived from AVIRIS data. In this report, we present a multi-scale sampling approach to detecting physiologically significant signals in narrow-band spectra. This approach explores the multi-dimensional data space provided by narrow-band spectrometry, and combines AVIRIS imagery at a large scale, with ground spectral sampling at an intermediate scale, and detailed ecophysiological measurements at a fine scale, to examine seasonally and spatially changing relationships between multiple structural and physiological variables. Examples of this approach are provided by simultaneous sampling of the Normalized Difference Vegetation Index (NDVI), an index of fractional PAR interception and green vegetation cover, the Water Band Index (WBI, an index of liquid water absorption, and the Photochemical Reflectance Index (PRI, an index of xanthophyll cycle pigment activity and photosynthetic light-use efficiency. By directly linking changing optical properties sampled on the ground with measurable physiological states, we hope to develop a basis for interpreting similar signals in AVIRIS imagery.

  10. Insomnia with physiological hyperarousal is associated with hypertension.

    PubMed

    Li, Yun; Vgontzas, Alexandros N; Fernandez-Mendoza, Julio; Bixler, Edward O; Sun, Yuanfeng; Zhou, Junying; Ren, Rong; Li, Tao; Tang, Xiangdong

    2015-03-01

    Previous studies have suggested that insomnia with objective short sleep duration is associated with a higher risk of hypertension, and it has been speculated that the underlying mechanism is physiological hyperarousal. In this study, we tested whether insomnia with physiological hyperarousal measured by Multiple Sleep Latency Test (MSLT), a standard test of sleepiness/alertness, is associated with increased risk of hypertension. Two hundred nineteen chronic insomniacs and 96 normal sleepers were included in this study. Chronic insomnia was defined based on standard diagnostic criteria with symptoms lasting ≥6 months. All subjects underwent 1 night in laboratory polysomnography followed by a standard MSLT. We used the median mean MSLT value (ie, >14 minutes) and the 75th percentile of mean MSLT value (ie, >17 minutes) to define hyperarousal. Hypertension was defined based either on blood pressure measures or on diagnosis treatment by a physician. After controlling for age, sex, body mass index, apnea-hypopnea index, diabetes mellitus, smoking, alcohol, and caffeine use, insomnia combined with MSLT >14 minutes increased the odds of hypertension by 300% (odds ratio=3.27; 95% confidence interval=1.20-8.96), whereas insomnia combined with MSLT >17 minutes increased even further the odds of hypertension by 400% (odds ratio=4.33; 95% confidence interval=1.48-12.68) compared with normal sleepers with MSLT ≤14 minutes. Insomnia associated with physiological hyperarousal is associated with a significant risk of hypertension. Long MSLT values may be a reliable index of the physiological hyperarousal and biological severity of chronic insomnia. © 2015 American Heart Association, Inc.

  11. Real-time physiological monitoring with distributed networks of sensors and object-oriented programming techniques

    NASA Astrophysics Data System (ADS)

    Wiesmann, William P.; Pranger, L. Alex; Bogucki, Mary S.

    1998-05-01

    Remote monitoring of physiologic data from individual high- risk workers distributed over time and space is a considerable challenge. This is often due to an inadequate capability to accurately integrate large amounts of data into usable information in real time. In this report, we have used the vertical and horizontal organization of the 'fireground' as a framework to design a distributed network of sensors. In this system, sensor output is linked through a hierarchical object oriented programing process to accurately interpret physiological data, incorporate these data into a synchronous model and relay processed data, trends and predictions to members of the fire incident command structure. There are several unique aspects to this approach. The first includes a process to account for variability in vital parameter values for each individual's normal physiologic response by including an adaptive network in each data process. This information is used by the model in an iterative process to baseline a 'normal' physiologic response to a given stress for each individual and to detect deviations that indicate dysfunction or a significant insult. The second unique capability of the system orders the information for each user including the subject, local company officers, medical personnel and the incident commanders. Information can be retrieved and used for training exercises and after action analysis. Finally this system can easily be adapted to existing communication and processing links along with incorporating the best parts of current models through the use of object oriented programming techniques. These modern software techniques are well suited to handling multiple data processes independently over time in a distributed network.

  12. A Futile Redox Cycle Involving Neuroglobin Observed at Physiological Temperature.

    PubMed

    Liu, Anyang; Brittain, Thomas

    2015-08-24

    Previous studies identifying the potential anti-apoptotic role of neuroglobin raise the question as to how cells might employ neuroglobin to avoid the apoptotic impact of acute hypoxia whilst also avoiding chronic enhancement of tumour formation. We show that under likely physiological conditions neuroglobin can take part in a futile redox cycle. Determination of the rate constants for each of the steps in the cycle allows us to mathematically model the steady state concentration of the active anti-apoptotic ferrous form of neuroglobin under various conditions. Under likely normal physiological conditions neuroglobin is shown to be present in the ferrous state at approximately 30% of its total cellular concentration. Under hypoxic conditions this rapidly rises to approximately 80%. Temporal analysis of this model indicates that the transition from low concentrations to high concentration of ferrous neuroglobin occurs on the seconds time scale. These findings indicate a potential control model for the anti-apoptotic activity of neuroglobin, under likely physiological conditions, whereby, in normoxic conditions, the anti-apoptotic activity of neuroglobin is maintained at a low level, whilst immediately a transition occurs to a hypoxic situation, as might arise during stroke, the anti-apoptotic activity is drastically increased. In this way the cell avoids unwanted increased oncogenic potential under normal conditions, but the rapid activation of neuroglobin provides anti-apoptotic protection in times of acute hypoxia.

  13. Investigation on maternal physiological and psychological factors of cheilopalatognathus.

    PubMed

    Ma, J; Zhao, W; Ma, R M; Li, X J; Wen, Z H; Liu, X F; Hu, W D; Zhang, C B

    2013-01-01

    Case-control study on mothers of cheilopalatognathus children was conducted, to investigate the maternal physiological and psychological factors for occurrence of cheilopalatognathus. One hundred ten mothers of cheilopalatognathus children who were scheduled for one-stage surgery were selected as a research group, and 110 mothers of normal children served as a normal control group at the same time. Trait Anxiety Inventory (T-AI), Life Events Scale (LES), Trait Coping Style Questionnaire (TCSQ), Type C Behavior Scale (CBS), adult Eysenck Personality Questionnaire (EPQ), and homemade general questionnaire survey were employed for the investigation. Compared with the control group, the scores for negative event tension value, anxiety, and depressive factors were higher in the study group (p < 0.05); while the scores for positive event tension value, intellect, optimism, and social support factors were lower (p < 0.05). Regression analysis found that physiological factors included were five: education, changes in body weight during pregnancy, the intake amount of milk and beans, and intake of healthcare products, and supplementary folic acid taken or not, while the psychological factors included were four: positive event stimulation, negative event stimulation, the amount of social support, as well as introvert and extrovert personalities. The study results suggest that pregnant women's physiological and psychological factors can cause changes in cheilopalatognathus incidence, which is expected to be guidance for healthcare during pregnancy, to prevent the occurrence of cheilopalatognathus.

  14. CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

    PubMed Central

    Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

    2017-01-01

    The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500–2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2. PMID:28054631

  15. Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference

    PubMed Central

    Santi, C. M.; Yuan, A.; Fawcett, G.; Wang, Z.-W.; Butler, A.; Nonet, M. L.; Wei, A.; Rojas, P.; Salkoff, L.

    2003-01-01

    GFP-promoter experiments have previously shown that at least nine genes encoding potassium channel subunits are expressed in Caenorhabditis elegans muscle. By using genetic, RNA interference, and physiological techniques we revealed the molecular identity of the major components of the outward K+ currents in body wall muscle cells in culture. We found that under physiological conditions, outward current is dominated by the products of only two genes, Shaker (Kv1) and Shal (Kv4), both expressing voltage-dependent potassium channels. Other channels may be held in reserve to respond to particular circumstances. Because GFP-promoter experiments indicated that slo-2 expression is prominent, we created a deletion mutant to identify the SLO-2 current in vivo. In both whole-cell and single-channel modes, in vivo SLO-2 channels were active only when intracellular Ca2+ and Cl- were raised above normal physiological conditions, as occurs during hypoxia. Under such conditions, SLO-2 is the largest outward current, contributing up to 87% of the total current. Other channels are present in muscle, but our results suggest that they are unlikely to contribute a large outward component under physiological conditions. However, they, too, may contribute currents conditional on other factors. Hence, the picture that emerges is of a complex membrane with a small number of household conductances functioning under normal circumstances, but with additional conductances that are activated during unusual circumstances. PMID:14612577

  16. The reduction potential of nitric oxide (NO) and its importance to NO biochemistry

    PubMed Central

    Bartberger, Michael D.; Liu, Wei; Ford, Eleonora; Miranda, Katrina M.; Switzer, Christopher; Fukuto, Jon M.; Farmer, Patrick J.; Wink, David A.; Houk, Kendall N.

    2002-01-01

    A potential of about −0.8 (±0.2) V (at 1 M versus normal hydrogen electrode) for the reduction of nitric oxide (NO) to its one-electron reduced species, nitroxyl anion (3NO−) has been determined by a combination of quantum mechanical calculations, cyclic voltammetry measurements, and chemical reduction experiments. This value is in accord with some, but not the most commonly accepted, previous electrochemical measurements involving NO. Reduction of NO to 1NO− is highly unfavorable, with a predicted reduction potential of about −1.7 (±0.2) V at 1 M versus normal hydrogen electrode. These results represent a substantial revision of the derived and widely cited values of +0.39 V and −0.35 V for the NO/3NO− and NO/1NO− couples, respectively, and provide support for previous measurements obtained by electrochemical and photoelectrochemical means. With such highly negative reduction potentials, NO is inert to reduction compared with physiological events that reduce molecular oxygen to superoxide. From these reduction potentials, the pKa of 3NO− has been reevaluated as 11.6 (±3.4). Thus, nitroxyl exists almost exclusively in its protonated form, HNO, under physiological conditions. The singlet state of nitroxyl anion, 1NO−, is physiologically inaccessible. The significance of these potentials to physiological and pathophysiological processes involving NO and O2 under reductive conditions is discussed. PMID:12177417

  17. CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

    NASA Astrophysics Data System (ADS)

    Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

    2017-01-01

    The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500-2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2.

  18. Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders

    PubMed Central

    Iriki, Atsushi; Isoda, Masaki

    2015-01-01

    Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles. PMID:26180116

  19. Pollen mitosis and pollen tube growth inhibition by SO/sub 2/ in cultured pollen tubes of Tradescantia

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, T.H.; Khan, S.H.

    Mature pollen of Tradescantia paludosa Anders, Sax clone-3 was collected from greenhouse grown plants and desiccated in the dark for 4--5 hours. The pollen was sown on microslides coated with lactose agar medium (supplemented with 0.02 percent colchicine). Five minutes after sowing, pollen cultures were treated with various concentrations (0.075--2000 ppM) of SO/sub 2/ obtained from the chemical reaction between K/sub 2/S/sub 2/O/sub 5/ and HCl. Treatments were carried out in an airtight Plexiglas chamber throughout the full incubation period of 19 hours. Treated and control pollen cultures were fixed and stained in aceto-carmine or Feulgen reaction to determine themore » tube lengths and mitotic indices. Results of repeated experiments indicated that the values of mitotic indices dropped from the normal 38.7 percent in the control to the range of 24.3--3.8 percent when treated with 0.075--50.00 ppM of SO/sub 2/. Pollen tube growth was inhibited from the normal length of 1.5 mm in the control to the range of 800--100 ..mu..m when treated with 10--2000 ppM of SO/sub 2/. The inhibitory effect of SO/sub 2/ presumably resulted from physiological disturbance of the cell and severe damage to chromosomes of both generative and tube nuclei of the pollen tubes.« less

  20. Perivascular spaces, glymphatic dysfunction, and small vessel disease.

    PubMed

    Mestre, Humberto; Kostrikov, Serhii; Mehta, Rupal I; Nedergaard, Maiken

    2017-09-01

    Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces (EPVS) and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces (PVSs), cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Management of ejaculatory disorders in infertile men

    PubMed Central

    Barazani, Yagil; Stahl, Peter J; Nagler, Harris M; Stember, Doron S

    2012-01-01

    Ejaculatory dysfunction is a highly prevalent clinical condition that may be classified along a continuum that ranges from premature ejaculation (PE), through retarded or delayed ejaculation (DE), to complete anejaculation (AE). Retrograde ejaculation (RE) represents a distinct entity in which ejaculate is expelled either partially or completely into the bladder. While DE and PE are significant sources of sexual dissatisfaction among men and their partners, patients with these disorders retain normal fertility in most cases. Conversely, men with AE and RE are unable to deliver sperm into the female genital tract and are therefore rendered subfertile. Therefore, in reviewing ejaculatory disorders as they relate to fertility, this paper will primarily focus on the diagnosis and management of AE and RE. Physiology, diagnostic strategies, pharmacological treatments, and procedural interventions relevant to AE and RE are discussed. PMID:22580636

  2. New Insight into the Role of Reactive Oxygen Species (ROS) in Cellular Signal-Transduction Processes.

    PubMed

    Russell, Eileen G; Cotter, Thomas G

    2015-01-01

    Reactive oxygen species (ROS) were once considered to be deleterious agents, contributing to a vast range of pathologies. But, now their protective effects are being appreciated. Both their damaging and beneficial effects are initiated when they target distinct molecules and consequently begin functioning as part of complex signal-transduction pathways. The recognition of ROS as signaling mediators has driven a wealth of research into their roles in both normal and pathophysiological states. The present review assesses the relevant recent literature to outline the current perspectives on redox-signaling mechanisms, physiological implications, and therapeutic strategies. This study highlights that a more fundamental knowledge about many aspects of redox signaling will allow better targeting of ROS, which would in turn improve prophylactic and pharmacotherapy for redox-associated diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Environmental stressors alter relationships between physiology and behaviour.

    PubMed

    Killen, Shaun S; Marras, Stefano; Metcalfe, Neil B; McKenzie, David J; Domenici, Paolo

    2013-11-01

    Although correlations have frequently been observed between specific physiological and behavioural traits across a range of animal taxa, the nature of these associations has been shown to vary. Here we argue that a major source of this inconsistency is the influence of environmental stressors, which seem capable of revealing, masking, or modulating covariation in physiological and behavioural traits. These effects appear to be mediated by changes in the observed variation of traits and differential sensitivity to stressors among phenotypes. Considering that wild animals routinely face a range of biotic and abiotic stressors, increased knowledge of these effects is imperative for understanding the causal mechanisms of a range of ecological phenomena and evolutionary responses to stressors associated with environmental change. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  4. Power spectral density analysis of physiological, rest and action tremor in Parkinson’s disease patients treated with deep brain stimulation

    PubMed Central

    2013-01-01

    Background Observation of the signals recorded from the extremities of Parkinson’s disease patients showing rest and/or action tremor reveal a distinct high power resonance peak in the frequency band corresponding to tremor. The aim of the study was to investigate, using quantitative measures, how clinically effective and less effective deep brain stimulation protocols redistribute movement power over the frequency bands associated with movement, pathological and physiological tremor, and whether normal physiological tremor may reappear during those periods that tremor is absent. Methods The power spectral density patterns of rest and action tremor were studied in 7 Parkinson’s disease patients treated with (bilateral) deep brain stimulation of the subthalamic nucleus. Two tests were carried out: 1) the patient was sitting at rest; 2) the patient performed a hand or foot tapping movement. Each test was repeated four times for each extremity with different stimulation settings applied during each repetition. Tremor intermittency was taken into account by classifying each 3-second window of the recorded angular velocity signals as a tremor or non-tremor window. Results The distribution of power over the low frequency band (<3.5 Hz – voluntary movement), tremor band (3.5-7.5 Hz) and high frequency band (>7.5 Hz – normal physiological tremor) revealed that rest and action tremor show a similar power-frequency shift related to tremor absence and presence: when tremor is present most power is contained in the tremor frequency band; when tremor is absent lower frequencies dominate. Even under resting conditions a relatively large low frequency component became prominent, which seemed to compensate for tremor. Tremor absence did not result in the reappearance of normal physiological tremor. Conclusion Parkinson’s disease patients continuously balance between tremor and tremor suppression or compensation expressed by power shifts between the low frequency band and the tremor frequency band during rest and voluntary motor actions. This balance shows that the pathological tremor is either on or off, with the latter state not resembling that of a healthy subject. Deep brain stimulation can reverse the balance thereby either switching tremor on or off. PMID:23834737

  5. Quantitative analysis of the Ca2+ -dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes.

    PubMed

    Bartos, Daniel C; Morotti, Stefano; Ginsburg, Kenneth S; Grandi, Eleonora; Bers, Donald M

    2017-04-01

    [Ca 2+ ] i enhanced rabbit ventricular slowly activating delayed rectifier K + current (I Ks ) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K + current (I Kr ) amplitude and voltage dependence were unaffected by high [Ca 2+ ] i . When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca 2+ transient or when [Ca 2+ ] i was buffered to 500 nm. The slowly activating delayed rectifier K + current (I Ks ) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca 2+ ([Ca 2+ ] i ) and β-adrenergic receptor (β-AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca 2+ ] i dependence of I Ks in steady-state conditions and with dynamically changing membrane potential and [Ca 2+ ] i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca 2+ ] i , we found that raising [Ca 2+ ] i from 100 to 600 nm produced similar increases in I Ks as did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca 2+ ] i increased maximally activated tail I Ks , negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, I Ks recorded during a normal physiological Ca 2+ transient was similar to I Ks measured with [Ca 2+ ] i clamped at 500-600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca 2+ ] i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca 2+ ] i , in the submembrane or junctional cleft space, is not required to maximize [Ca 2+ ] i -dependent I Ks activation during normal Ca 2+ transients. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

  6. Using pupil size and heart rate to infer affective states during behavioral neurophysiology and neuropsychology experiments

    PubMed Central

    Mitz, Andrew R.; Chacko, Ravi V.; Putnam, Philip T.; Rudebeck, Peter H.; Murray, Elisabeth A.

    2017-01-01

    Background Nonhuman primates (NHPs) are a valuable research model because of their behavioral, physiological and neuroanatomical similarities to humans. In the absence of language, autonomic activity can provide crucial information about cognitive and affective states during single-unit recording, inactivation and lesion studies. Methods standardized for use in humans are not easily adapted to NHPs and detailed guidance has been lacking. New Method We provide guidance for monitoring heart rate and pupil size in the behavioral neurophysiology setting by addressing the methodological issues, pitfalls and solutions for NHP studies. The methods are based on comparative physiology to establish a rationale for each solution. We include examples from both electrophysiological and lesion studies. Results Single-unit recording, pupil responses and heart rate changes represent a range of decreasing temporal resolution, a characteristic that impacts experimental design and analysis. We demonstrate the unexpected result that autonomic measures acquired before and after amygdala lesions are comparable despite disruption of normal autonomic function. Comparison with Existing Methods Species and study design differences can render standard techniques used in human studies inappropriate for NHP studies. We show how to manage data from small groups typical of NHP studies, data from the short behavioral trials typical of neurophysiological studies, issues associated with longitudinal studies, and differences in anatomy and physiology. Conclusions Autonomic measurement to infer cognitive and affective states in NHP is neither off-the-shelf nor onerous. Familiarity with the issues and solutions will broaden the use of autonomic signals in NHP single unit and lesion studies. PMID:28089759

  7. A role for the thermal environment in defining co-stimulation requirements for CD4+ T cell activation

    PubMed Central

    Zynda, Evan R; Grimm, Melissa J; Yuan, Min; Zhong, Lingwen; Mace, Thomas A; Capitano, Maegan; Ostberg, Julie R; Lee, Kelvin P; Pralle, Arnd; Repasky, Elizabeth A

    2015-01-01

    Maintenance of normal core body temperature is vigorously defended by long conserved, neurovascular homeostatic mechanisms that assist in heat dissipation during prolonged, heat generating exercise or exposure to warm environments. Moreover, during febrile episodes, body temperature can be significantly elevated for at least several hours at a time. Thus, as blood cells circulate throughout the body, physiologically relevant variations in surrounding tissue temperature can occur; moreover, shifts in core temperature occur during daily circadian cycles. This study has addressed the fundamental question of whether the threshold of stimulation needed to activate lymphocytes is influenced by temperature increases associated with physiologically relevant increases in temperature. We report that the need for co-stimulation of CD4+ T cells via CD28 ligation for the production of IL-2 is significantly reduced when cells are exposed to fever-range temperature. Moreover, even in the presence of sufficient CD28 ligation, provision of extra heat further increases IL-2 production. Additional in vivo and in vitro data (using both thermal and chemical modulation of membrane fluidity) support the hypothesis that the mechanism by which temperature modulates co-stimulation is linked to increases in membrane fluidity and membrane macromolecular clustering in the plasma membrane. Thermally-regulated changes in plasma membrane organization in response to physiological increases in temperature may assist in the geographical control of lymphocyte activation, i.e., stimulating activation in lymph nodes rather than in cooler surface regions, and further, may temporarily and reversibly enable CD4+ T cells to become more quickly and easily activated during times of infection during fever. PMID:26131730

  8. Physiological and behavioral risk factors of type 2 diabetes mellitus in rural India.

    PubMed

    Barik, Anamitra; Mazumdar, Sumit; Chowdhury, Abhijit; Rai, Rajesh Kumar

    2016-01-01

    The dynamics of physiological and behavioral risk factors of diabetes in rural India is poorly understood. Using data from a health and demographic surveillance site of Birbhum district in West Bengal, India, this study aims to assess the risk factors associated with type 2 diabetes mellitus. A total of 7674 individuals aged ≥18 years participated in a cross-sectional study. Venous plasma glucose method was used for measuring and reporting glucose concentrations in blood, categorized as individuals with diabetes, pre-diabetes or impaired, and normoglycemic. Aside from a set of physiological and behavioral risk factors, a range of socioeconomic confounders of diabetes was computed. Bivariate analysis with χ(2) test, and multivariate ordered logit regression methods were deployed to attain the study's objective. Overall 2.95% and 3.34% of study participants were diagnosed as individuals with diabetes and pre-diabetes or impaired, respectively. Compared to the poorest, the richest have higher probability (β: 0.730; 95% CI 0.378 to 1.083) of being diagnosed with diabetes. As compared to people with normal body mass index, overweight/obese people are more prone to being diagnosed with diabetes (β: 0.388; 95% CI 0.147 to 0.628). With a decreasing level of physical activity, people are more likely to be diagnosed with diabetes. To curb the level of diabetes, this study recommends a culturally sensitive, focused intervention for the adoption of physical activity with more traditional dietary practices, to control the level of overweight/obesity. Attention should be paid to relatively older patients with diabetes or adults with pre-diabetes.

  9. Preliminary results from digestive adaptation: a new surgical proposal for treating obesity, based on physiology and evolution.

    PubMed

    Santoro, Sérgio; Velhote, Manoel Carlos Prieto; Malzoni, Carlos Eduardo; Milleo, Fábio Quirino; Klajner, Sidney; Campos, Fábio Guilherme

    2006-07-06

    Most bariatric surgical techniques include essentially non-physiological features like narrowing anastomoses or bands, or digestive segment exclusion, especially the duodenum. This potentially causes symptoms or complications. The aim here was to report on the preliminary results from a new surgical technique for treating morbid obesity that takes a physiological and evolutionary approach. Case series description, in Hospital Israelita Albert Einstein and Hospital da Polícia Militar, São Paulo, and Hospital Vicentino, Ponta Grossa, Paraná. The technique included vertical (sleeve) gastrectomy, omentectomy and enterectomy that retained three meters of small bowel (initial jejunum and most of the ileum), i.e. the lower limit for normal adults. The operations on 100 patients are described. The mean follow-up was nine months (range: one to 29 months). The mean reductions in body mass index were 4.3, 6.1, 8.1, 10.1 and 10.7 kg/m2, respectively at 1, 2, 4, 6 and 12 months. All patients reported early satiety. There was major improvement in comorbidities, especially diabetes. Operative complications occurred in 7% of patients, all of them resolved without sequelae. There was no mortality. This procedure creates a proportionally reduced gastrointestinal tract, leaving its basic functions unharmed and producing adaptation of the gastric chamber size to hypercaloric diet. It removes the sources of ghrelin, plasminogen activator inhibitor-1 (PAI-1) and resistin production and leads more nutrients to the distal bowel, with desirable metabolic consequences. Patients do not need nutritional support or drug medication. The procedure is straightforward and safe.

  10. Review of the gastrointestinal tract: from macro to micro.

    PubMed

    Reed, Kathleen K; Wickham, Rita

    2009-02-01

    To review the normal anatomy and physiology of the gastrointestinal (GI) tract, the malignant transformations in GI cancers, and the rationale for targeted therapy for these cancers. Published articles, book chapters and web sources. Oncology nurses require an understanding of normal GI anatomy and physiology, along with an understanding of malignant transformations at the cellular and molecular level, to effectively educate and care for the patient with a diagnosis of a GI cancer. Challenges for the oncology nurse include continuing education related to GI cancer, the development of effective patient education skills, ensuring safe administration of oral agents and remaining current regarding GI clinical trial opportunities. Education of nursing colleagues, development of an area of expertise through specialization, and development of leadership skills are opportunities associated with practicing in the dynamic environment of oncology nursing.

  11. Role of Corticosteroids in Bone Loss During Space Flight

    NASA Technical Reports Server (NTRS)

    Wronski, Thomas J.; Halloran, Bernard P.; Miller, Scott C.

    1998-01-01

    The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

  12. Animal Enclosure Module (AEM)

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The primary objective of this research project is to test the hypothesis that corticosteroids contribute to the adverse skeletal effects of space flight. To achieve this objective, serum corticosteroids, which are known to increase during space flight, must be maintained at normal physiologic levels in flight rats by a combination of adrenalectomy and corticosteroid supplementation via implanted hormone pellets. Bone analyses in these animals will then be compared to those of intact flight rats that, based on past experience, will undergo corticosteroid excess and bone loss during space flight. The results will reveal whether maintaining serum corticosteroids at physiologic levels in flight rats affects the skeletal abnormalities that normally develop during space flight. A positive response to this question would indicate that the bone loss and decreased bone formation associated with space flight are mediated, at least in part, by corticosteroid excess.

  13. Murine Electrophysiological Models of Cardiac Arrhythmogenesis

    PubMed Central

    2016-01-01

    Cardiac arrhythmias can follow disruption of the normal cellular electrophysiological processes underlying excitable activity and their tissue propagation as coherent wavefronts from the primary sinoatrial node pacemaker, through the atria, conducting structures and ventricular myocardium. These physiological events are driven by interacting, voltage-dependent, processes of activation, inactivation, and recovery in the ion channels present in cardiomyocyte membranes. Generation and conduction of these events are further modulated by intracellular Ca2+ homeostasis, and metabolic and structural change. This review describes experimental studies on murine models for known clinical arrhythmic conditions in which these mechanisms were modified by genetic, physiological, or pharmacological manipulation. These exemplars yielded molecular, physiological, and structural phenotypes often directly translatable to their corresponding clinical conditions, which could be investigated at the molecular, cellular, tissue, organ, and whole animal levels. Arrhythmogenesis could be explored during normal pacing activity, regular stimulation, following imposed extra-stimuli, or during progressively incremented steady pacing frequencies. Arrhythmic substrate was identified with temporal and spatial functional heterogeneities predisposing to reentrant excitation phenomena. These could arise from abnormalities in cardiac pacing function, tissue electrical connectivity, and cellular excitation and recovery. Triggering events during or following recovery from action potential excitation could thereby lead to sustained arrhythmia. These surface membrane processes were modified by alterations in cellular Ca2+ homeostasis and energetics, as well as cellular and tissue structural change. Study of murine systems thus offers major insights into both our understanding of normal cardiac activity and its propagation, and their relationship to mechanisms generating clinical arrhythmias. PMID:27974512

  14. Neonatal hygroscopic condenser humidifier.

    PubMed

    Gedeon, A; Mebius, C; Palmer, K

    1987-01-01

    A hygroscopic condenser humidifier was developed for neonates on mechanical ventilation and was evaluated by laboratory tests and clinically. Humidification provided by the unit was measured in the 10- to 50-ml tidal-volume range at ambient temperatures of 24 degrees C and 38 degrees C. The effect of a leaking patient connection on device performance was investigated. Leakage rates were measured routinely in a neonatal ICU and surgery to determine the clinical significance. In the entire tidal volume and temperature range, the unit provided an inspiratory water content in excess of 30 g/m3 when the leak fraction (volume leaked/volume delivered at Y-piece) was less than 15%. This was found in three out of four cases. In about one out of ten cases, the leak exceeded 30%, which invariably led to corrective action, such as repositioning or changing the endotracheal tube. However, even at a 30% leak, a water content of about 26 g/m3 was still available for humidifying the inspired gas, which corresponds to normal physiologic conditions found in the trachea for nasal breathing of room air.

  15. Gene transcription in sea otters (Enhydra lutris); development of a diagnostic tool for sea otter and ecosystem health

    USGS Publications Warehouse

    Bowen, Lizabeth; Miles, A. Keith; Murray, Michael; Haulena, Martin; Tuttle, Judy; van Bonn, William; Adams, Lance; Bodkin, James L.; Ballachey, Brenda E.; Estes, James A.; Tinker, M. Tim; Keister, Robin; Stott, Jeffrey L.

    2012-01-01

    Gene transcription analysis for diagnosing or monitoring wildlife health requires the ability to distinguish pathophysiological change from natural variation. Herein, we describe methodology for the development of quantitative real-time polymerase chain reaction (qPCR) assays to measure differential transcript levels of multiple immune function genes in the sea otter (Enhydra lutris); sea otter-specific qPCR primer sequences for the genes of interest are defined. We establish a ‘reference’ range of transcripts for each gene in a group of clinically healthy captive and free-ranging sea otters. The 10 genes of interest represent multiple physiological systems that play a role in immuno-modulation, inflammation, cell protection, tumour suppression, cellular stress response, xenobiotic metabolizing enzymes, antioxidant enzymes and cell–cell adhesion. The cycle threshold (CT) measures for most genes were normally distributed; the complement cytolysis inhibitor was the exception. The relative enumeration of multiple gene transcripts in simple peripheral blood samples expands the diagnostic capability currently available to assess the health of sea otters in situ and provides a better understanding of the state of their environment.

  16. Quinine reduces the dynamic range of the human auditory system.

    PubMed

    Berninger, E; Karlsson, K K; Alván, G

    1998-01-01

    The aim of the study was to evaluate and quantify quinine-induced changes in the human auditory dynamic range, as a model for cochlear hearing loss. Six otologically normal volunteers (21-40 years old) received quinine hydrochloride (15 mg/kg body weight) in two identical oral doses and one intravenous infusion. Refined hearing tests were performed monaurally at threshold, at moderate hearing levels and at high hearing levels. Quinine induced a maximal pure-tone threshold shift of 23 dB (1000-2000 Hz). The increase in the psychoacoustical click threshold agreed with an increase in the detection threshold of click-evoked otoacoustic emissions. The change in the stimulus-response relationship of the emissions reflected recruitment. The self-attained most comfortable speech level and the acoustic stapedius reflex thresholds were not affected by quinine administration. Quinine is a useful model substance for reversibly inducing complete loudness recruitment in humans as it acts specifically on some parts of the hearing function. Its mechanism of action on the molecular level is likely to reveal further information on the physiology of hearing.

  17. A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells.

    PubMed

    Saha, Sonali; Prakash, Ved; Halder, Saheli; Chakraborty, Kasturi; Krishnan, Yamuna

    2015-07-01

    The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5-130 mM), and is tightly regulated by intracellular chloride channels or transporters. Chloride-sensitive protein reporters have been used to study the role of these chloride regulators, but they are limited to a small range of chloride concentrations and are pH-sensitive. Here, we show that a DNA nanodevice can precisely measure the activity and location of subcellular chloride channels and transporters in living cells in a pH-independent manner. The DNA nanodevice, called Clensor, is composed of sensing, normalizing and targeting modules, and is designed to localize within organelles along the endolysosomal pathway. It allows fluorescent, ratiometric sensing of chloride ions across the entire physiological regime. We used Clensor to quantitate the resting chloride concentration in the lumen of acidic organelles in Drosophila melanogaster. We showed that lumenal lysosomal chloride, which is implicated in various lysosomal storage diseases, is regulated by the intracellular chloride transporter DmClC-b.

  18. Cyclical secretion of prorenin during the menstrual cycle: synchronization with luteinizing hormone and progesterone.

    PubMed Central

    Sealey, J E; Atlas, S A; Glorioso, N; Manapat, H; Laragh, J H

    1985-01-01

    Plasma prorenin, a high molecular weight precursor form of renin, (renin, EC 3.4.23.15; old number, EC 3.4.99.19), was measured three times weekly in normal young women during the menstrual cycle and was related to changes in luteinizing hormone, estradiol, and progesterone. In all subjects a stable baseline level of prorenin occurred during the follicular phase. Then, simultaneously or soon after the luteinizing hormone peak, plasma prorenin consistently increased about 2-fold. Baseline prorenin ranged from 18 to 40 ng per ml per hr, and peak prorenin ranged from 35 to 65 ng per ml per hr. The maximum increase in prorenin averaged 80%. Prorenin remained elevated during the mid-luteal phase of the menstrual cycle and returned to baseline during the late-luteal phase in coordination with the decrease in progesterone. The changes in prorenin were not synchronized with changes in active renin which was significantly increased only during the mid-luteal phase. These findings suggest that prorenin may be involved in reproductive physiology. PMID:3909151

  19. A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells

    NASA Astrophysics Data System (ADS)

    Saha, Sonali; Prakash, Ved; Halder, Saheli; Chakraborty, Kasturi; Krishnan, Yamuna

    2015-07-01

    The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5-130 mM), and is tightly regulated by intracellular chloride channels or transporters. Chloride-sensitive protein reporters have been used to study the role of these chloride regulators, but they are limited to a small range of chloride concentrations and are pH-sensitive. Here, we show that a DNA nanodevice can precisely measure the activity and location of subcellular chloride channels and transporters in living cells in a pH-independent manner. The DNA nanodevice, called Clensor, is composed of sensing, normalizing and targeting modules, and is designed to localize within organelles along the endolysosomal pathway. It allows fluorescent, ratiometric sensing of chloride ions across the entire physiological regime. We used Clensor to quantitate the resting chloride concentration in the lumen of acidic organelles in Drosophila melanogaster. We showed that lumenal lysosomal chloride, which is implicated in various lysosomal storage diseases, is regulated by the intracellular chloride transporter DmClC-b.

  20. Evidence for suppression of immunity as a driver for genomic introgressions and host range expansion in races of Albugo candida, a generalist parasite

    PubMed Central

    McMullan, Mark; Gardiner, Anastasia; Bailey, Kate; Kemen, Eric; Ward, Ben J; Cevik, Volkan; Robert-Seilaniantz, Alexandre; Schultz-Larsen, Torsten; Balmuth, Alexi; Holub, Eric; van Oosterhout, Cock; Jones, Jonathan DG

    2015-01-01

    How generalist parasites with wide host ranges can evolve is a central question in parasite evolution. Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species. By analyzing genome sequence assemblies of five isolates, we show they represent three races that are genetically diverged by ∼1%. Despite this divergence, their genomes are mosaic-like, with ∼25% being introgressed from other races. Sequential infection experiments show that infection by adapted races enables subsequent infection of hosts by normally non-infecting races. This facilitates introgression and the exchange of effector repertoires, and may enable the evolution of novel races that can undergo clonal population expansion on new hosts. We discuss recent studies on hybridization in other eukaryotes such as yeast, Heliconius butterflies, Darwin's finches, sunflowers and cichlid fishes, and the implications of introgression for pathogen evolution in an agro-ecological environment. DOI: http://dx.doi.org/10.7554/eLife.04550.001 PMID:25723966

  1. Monomeric insulins obtained by protein engineering and their medical implications.

    PubMed

    Brange, J; Ribel, U; Hansen, J F; Dodson, G; Hansen, M T; Havelund, S; Melberg, S G; Norris, F; Norris, K; Snel, L

    1988-06-16

    The use of insulin as an injected therapeutic agent for the treatment of diabetes has been one of the outstanding successes of modern medicine. The therapy has, however, had its associated problems, not least because injection of insulin does not lead to normal diurnal concentrations of insulin in the blood. This is especially true at meal times when absorption from subcutaneous tissue is too slow to mimic the normal rapid increments of insulin in the blood. In the neutral solutions used for therapy, insulin is mostly assembled as zinc-containing hexamers and this self-association, which under normal physiological circumstances functions to facilitate proinsulin transport, conversion and intracellular storage, may limit the rate of absorption. We now report that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations (0.6 mM) and which have largely preserved their biological activity. These monomeric insulins are absorbed two to three times faster after subcutaneous injection than the present rapid-acting insulins. They are therefore capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.

  2. Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

    PubMed

    Barisione, Giovanni; Brusasco, Claudia; Garlaschi, Alessandro; Baroffio, Michele; Brusasco, Vito

    2016-05-01

    Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO. Copyright © 2016 the American Physiological Society.

  3. Emerging ciliopathies: are respiratory cilia compromised in Usher syndrome?

    PubMed

    Piatti, G; De Santi, M M; Brogi, M; Castorina, P; Ambrosetti, U

    2014-01-01

    Usher syndrome is a ciliopathy involving photoreceptors and cochlear hair cells (sensory cilia): since sensory and motor ciliopathies can overlap, we analysed the respiratory cilia (motile) in 17 patients affected by Usher syndrome and 18 healthy control subject. We studied the mucociliary transport time with the saccharine test, ciliary motility and ultrastructure of respiratory cilia obtained by nasal brushing; we also recorded the classical respiratory function values by spirometry. All enrolled subjects showed normal respiratory function values. The mean mucociliary transport time with saccharine was 22.33 ± 17.96 min, which is in the range of normal values. The mean ciliary beat frequency of all subjects was 8.81 ± 2.18 Hz, which is a value approaching the lower physiological limit. None of the classical ciliary alterations characterizing the "ciliary primary dyskinesia" was detected, although two patients showed alterations in number and arrangement of peripheral microtubules and one patient had abnormal ciliary roots. Respiratory cilia in Usher patients don't seem to have evident ultrastructural alterations, as expected, but the fact that the ciliary motility appeared slightly reduced could emphasize that a rigid distinction between sensory and motor ciliopathies may not reflect what really occurs. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Do women with female ejaculation have detrusor overactivity?

    PubMed

    Cartwright, Rufus; Elvy, Susannah; Cardozo, Linda

    2007-11-01

    Questionnaire surveys suggest that 40-54% of women have experienced an expulsion of fluid at orgasm. Some of these women have coital incontinence, whereas others identify the fluid passed as female ejaculate. To assess whether women who have experienced female ejaculation have detrusor overactivity or the bothersome lower urinary tract symptoms associated with coital incontinence. We recruited six women who self-identified as having experienced female ejaculation and six controls who had not. Each woman completed a 3-day bladder diary and two validated bladder questionnaires: the Urgency Perception Scale (UPS) and the Incontinence Impact Questionnaire (IIQ). Each woman underwent short provocative ambulatory urodynamics, a modified form of urodynamics, with a high sensitivity for detrusor overactivity. Prevalence of detrusor overactivity, 24-hour urinary frequency, IIQ and UPS scores. No woman in either group had detrusor overactivity. The bladder diaries and questionnaire results were within the normal range for all women. Women who experience female ejaculation may have normal voiding patterns, no bothersome incontinence symptoms, and no demonstrable detrusor overactivity. Women who report female ejaculation, in the absence of other lower urinary tract symptoms, do not require further investigation, and may be reassured that it is an uncommon, but physiological, phenomenon.

  5. Prolactin--a novel neuroendocrine regulator of human keratin expression in situ.

    PubMed

    Ramot, Yuval; Bíró, Tamás; Tiede, Stephan; Tóth, Balázs I; Langan, Ewan A; Sugawara, Koji; Foitzik, Kerstin; Ingber, Arieh; Goffin, Vincent; Langbein, Lutz; Paus, Ralf

    2010-06-01

    The controls of human keratin expression in situ remain to be fully elucidated. Here, we have investigated the effects of the neurohormone prolactin (PRL) on keratin expression in a physiologically and clinically relevant test system: organ-cultured normal human hair follicles (HFs). Not only do HFs express a wide range of keratins, but they are also a source and target of PRL. Microarray analysis revealed that PRL differentially regulated a defined subset of keratins and keratin-associated proteins. Quantitative immunohistomorphometry and quantitative PCR confirmed that PRL up-regulated expression of keratins K5 and K14 and the epithelial stem cell-associated keratins K15 and K19 in organ-cultured HFs and/or isolated HF keratinocytes. PRL also up-regulated K15 promoter activity and K15 protein expression in situ, whereas it inhibited K6 and K31 expression. These regulatory effects were reversed by a pure competitive PRL receptor antagonist. Antagonist alone also modulated keratin expression, suggesting that "tonic stimulation" by endogenous PRL is required for normal expression levels of selected keratins. Therefore, our study identifies PRL as a major, clinically relevant, novel neuroendocrine regulator of both human keratin expression and human epithelial stem cell biology in situ.

  6. Dynamic release and clearance of circulating microparticles during cardiac stress.

    PubMed

    Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

    2014-01-03

    Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

  7. A stroke patient with impairment of auditory sensory (echoic) memory.

    PubMed

    Kojima, T; Karino, S; Yumoto, M; Funayama, M

    2014-04-01

    A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.

  8. Endoplasmic Reticulum Stress in the Diabetic Kidney, the Good, the Bad and the Ugly.

    PubMed

    Cunard, Robyn

    2015-04-20

    Diabetic kidney disease is the leading worldwide cause of end stage kidney disease and a growing public health challenge. The diabetic kidney is exposed to many environmental stressors and each cell type has developed intricate signaling systems designed to restore optimal cellular function. The unfolded protein response (UPR) is a homeostatic pathway that regulates endoplasmic reticulum (ER) membrane structure and secretory function. Studies suggest that the UPR is activated in the diabetic kidney to restore normal ER function and viability. However, when the cell is continuously stressed in an environment that lies outside of its normal physiological range, then the UPR is known as the ER stress response. The UPR reduces protein synthesis, augments the ER folding capacity and downregulates mRNA expression of genes by multiple pathways. Aberrant activation of ER stress can also induce inflammation and cellular apoptosis, and modify signaling of protective processes such as autophagy and mTORC activation. The following review will discuss our current understanding of ER stress in the diabetic kidney and explore novel means of modulating ER stress and its interacting signaling cascades with the overall goal of identifying therapeutic strategies that will improve outcomes in diabetic nephropathy.

  9. VOLTAGE-GATED POTASSIUM CHANNELS AT THE CROSSROADS OF NEURONAL FUNCTION, ISCHEMIC TOLERANCE, AND NEURODEGENERATION

    PubMed Central

    Shah, Niyathi Hegde; Aizenman, Elias

    2013-01-01

    Voltage-gated potassium (Kv) channels are widely expressed in the central and peripheral nervous system, and are crucial mediators of neuronal excitability. Importantly, these channels also actively participate in cellular and molecular signaling pathways that regulate the life and death of neurons. Injury-mediated increased K+ efflux through Kv2.1 channels promotes neuronal apoptosis, contributing to widespread neuronal loss in neurodegenerative disorders such as Alzheimer’s disease and stroke. In contrast, some forms of neuronal activity can dramatically alter Kv2.1 channel phosphorylation levels and influence their localization. These changes are normally accompanied by modifications in channel voltage-dependence, which may be neuroprotective within the context of ischemic injury. Kv1 and Kv7 channel dysfunction leads to neuronal hyperexcitability that critically contributes to the pathophysiology of human clinical disorders such as episodic ataxia and epilepsy. This review summarizes the neurotoxic, neuroprotective, and neuroregulatory roles of Kv channels, and highlights the consequences of Kv channel dysfunction on neuronal physiology. The studies described in this review thus underscore the importance of normal Kv channel function in neurons, and emphasize the therapeutic potential of targeting Kv channels in the treatment of a wide range of neurological diseases. PMID:24323720

  10. Estimated Tissue and Blood N2 Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar

    PubMed Central

    Kvadsheim, P. H.; Miller, P. J. O.; Tyack, P. L.; Sivle, L. D.; Lam, F. P. A.; Fahlman, A.

    2012-01-01

    Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N2 gas bubbles. Increased tissue and blood N2 levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N2 tension PN2, but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N2 tension PN2 from dive data recorded from sperm, killer, long-finned pilot, Blainville’s beaked, and Cuvier’s beaked whales before and during exposure to Low- (1–2 kHz) and Mid- (2–7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N2 levels, with deep diving generally resulting in higher end-dive PN2 as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N2 levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N2 tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS. PMID:22590458

  11. Human physiology in space

    NASA Technical Reports Server (NTRS)

    Vernikos, J.

    1996-01-01

    The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

  12. Physiological work performance in chronic low back disability: effects of a progressive activity program.

    PubMed

    Thomas, L K; Hislop, H J; Waters, R L

    1980-04-01

    Fifteen patients were tested before and after treatment in a multifaceted inpatient program for chronic low back pain to determine if a gradually progressive activity program affected gait performance and physiological capacity. Before treatment, all patients demonstrated decreased physiological conditioning by higher-than-expected values for oxygen consumption and heart rate and by lower-than-normal gait velocity, stride length, and cadence. After treatment, an increase in mean walking velocity of 19 meters/minute reflected parallel gains in cadence and stride length. Improved mechanical performance resulted in improved "energetics." Energy spent per unit of distance walked decreased by 18 percent after treatment, providing a useful measure of increased physiological efficiency. Results indicated that patients with chronic low back disability can derive significant conditioning effects from an exercise program based on general function.

  13. Towards a molecular taxonomy for protists: benefits, risks, and applications in plankton ecology.

    PubMed

    Caron, David A

    2013-01-01

    The increasing use of genetic information for the development of methods to study the diversity, distributions, and activities of protists in nature has spawned a new generation of powerful tools. For ecologists, one lure of these approaches lies in the potential for DNA sequences to provide the only immediately obvious means of normalizing the diverse criteria that presently exist for identifying and counting protists. A single, molecular taxonomy would allow studies of diversity across a broad range of species, as well as the detection and quantification of particular species of interest within complex, natural assemblages; goals that are not feasible using traditional methods. However, these advantages are not without their potential pitfalls and problems. Conflicts involving the species concept, disagreements over the true (physiological/ecological) meaning of genetic diversity, and a perceived threat by some that sequence information will displace knowledge regarding the morphologies, functions and physiologies of protistan taxa, have created debate and doubt regarding the efficacy and appropriateness of some genetic approaches. These concerns need continued discussion and eventual resolution as we move toward the irresistible attraction, and potentially enormous benefits, of the application of genetic approaches to protistan ecology. © 2013 The Author(s) Journal of Eukaryotic Microbiology © 2013 International Society of Protistologists.

  14. Cellular and molecular mechanisms in the hypoxic tissue: role of HIF-1 and ROS.

    PubMed

    Zepeda, Andrea B; Pessoa, Adalberto; Castillo, Rodrigo L; Figueroa, Carolina A; Pulgar, Victor M; Farías, Jorge G

    2013-08-01

    Reactive oxygen species such as superoxide anion radicals (O2 (-) ) and hydrogen peroxide (H2 O2 ) have for long time been recognized as undesirable by-products of the oxidative mitochondrial generation of adenosine triphosphate (ATP). Recently, these highly reactive species have been associated to important signaling pathways in diverse physiological conditions such as those activated in hypoxic microenvironments. The molecular response to hypoxia requires fast-acting mechanisms acting within a wide range of partial pressures of oxygen (O2 ). Intracellular O2 sensing is an evolutionary preserved feature, and the best characterized molecular responses to hypoxia are mediated through transcriptional activation. The transcription factor, hypoxia-inducible factor 1 (HIF-1), is a critical mediator of these adaptive responses, and its activation by hypoxia involves O2 -dependent posttranslational modifications and nuclear translocation. Through the induction of the expression of its target genes, HIF-1 coordinately regulates tissue O2 supply and energetic metabolism. Other transcription factors such as nuclear factor κB are also redox sensitive and are activated in pro-oxidant and hypoxic conditions. The purpose of this review is to summarize new developments in HIF-mediated O2 sensing mechanisms and their interactions with reactive oxygen species-generating pathways in normal and abnormal physiology. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Review: Zinc’s functional significance in the vertebrate retina

    PubMed Central

    Chappell, Richard L.

    2014-01-01

    This review covers a broad range of topics related to the actions of zinc on the cells of the vertebrate retina. Much of this review relies on studies in which zinc was applied exogenously, and therefore the results, albeit highly suggestive, lack physiologic significance. This view stems from the fact that the concentrations of zinc used in these studies may not be encountered under the normal circumstances of life. This caveat is due to the lack of a zinc-specific probe with which to measure the concentrations of Zn2+ that may be released from neurons or act upon them. However, a great deal of relevant information has been garnered from studies in which Zn2+ was chelated, and the effects of its removal compared with findings obtained in its presence. For a more complete discussion of the consequences of depletion or excess in the body’s trace elements, the reader is referred to a recent review by Ugarte et al. in which they provide a detailed account of the interactions, toxicity, and metabolic activity of the essential trace elements iron, zinc, and copper in retinal physiology and disease. In addition, Smart et al. have published a splendid review on the modulation by zinc of inhibitory and excitatory amino acid receptor ion channels. PMID:25324679

  16. Acute exposure to 2G phase shifts the rat circadian timing system

    NASA Technical Reports Server (NTRS)

    Hoban-Higgins, T. M.; Murakami, D. M.; Tandon, T.; Fuller, C. A.

    1995-01-01

    The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

  17. Engineering of functional, perfusable 3D microvascular networks on a chip.

    PubMed

    Kim, Sudong; Lee, Hyunjae; Chung, Minhwan; Jeon, Noo Li

    2013-04-21

    Generating perfusable 3D microvessels in vitro is an important goal for tissue engineering, as well as for reliable modelling of blood vessel function. To date, in vitro blood vessel models have not been able to accurately reproduce the dynamics and responses of endothelial cells to grow perfusable and functional 3D vascular networks. Here we describe a microfluidic-based platform whereby we model natural cellular programs found during normal development and angiogenesis to form perfusable networks of intact 3D microvessels as well as tumor vasculatures based on the spatially controlled co-culture of endothelial cells with stromal fibroblasts, pericytes or cancer cells. The microvessels possess the characteristic morphological and biochemical markers of in vivo blood vessels, and exhibit strong barrier function and long-term stability. An open, unobstructed microvasculature allows the delivery of nutrients, chemical compounds, biomolecules and cell suspensions, as well as flow-induced mechanical stimuli into the luminal space of the endothelium, and exhibits faithful responses to physiological shear stress as demonstrated by cytoskeleton rearrangement and increased nitric oxide synthesis. This simple and versatile platform provides a wide range of applications in vascular physiology studies as well as in developing vascularized organ-on-a-chip and human disease models for pharmaceutical screening.

  18. The normalization heuristic: an untested hypothesis that may misguide medical decisions.

    PubMed

    Aberegg, Scott K; O'Brien, James M

    2009-06-01

    Medical practice is increasingly informed by the evidence from randomized controlled trials. When such evidence is not available, clinical hypotheses based on pathophysiological reasoning and common sense guide clinical decision making. One commonly utilized general clinical hypothesis is the assumption that normalizing abnormal laboratory values and physiological parameters will lead to improved patient outcomes. We refer to the general use of this clinical hypothesis to guide medical therapeutics as the "normalization heuristic". In this paper, we operationally define this heuristic and discuss its limitations as a rule of thumb for clinical decision making. We review historical and contemporaneous examples of normalization practices as empirical evidence for the normalization heuristic and to highlight its frailty as a guide for clinical decision making.

  19. A three-dimensional virtual environment for modeling mechanical cardiopulmonary interactions.

    PubMed

    Kaye, J M; Primiano, F P; Metaxas, D N

    1998-06-01

    We have developed a real-time computer system for modeling mechanical physiological behavior in an interactive, 3-D virtual environment. Such an environment can be used to facilitate exploration of cardiopulmonary physiology, particularly in situations that are difficult to reproduce clinically. We integrate 3-D deformable body dynamics with new, formal models of (scalar) cardiorespiratory physiology, associating the scalar physiological variables and parameters with the corresponding 3-D anatomy. Our framework enables us to drive a high-dimensional system (the 3-D anatomical models) from one with fewer parameters (the scalar physiological models) because of the nature of the domain and our intended application. Our approach is amenable to modeling patient-specific circumstances in two ways. First, using CT scan data, we apply semi-automatic methods for extracting and reconstructing the anatomy to use in our simulations. Second, our scalar physiological models are defined in terms of clinically measurable, patient-specific parameters. This paper describes our approach, problems we have encountered and a sample of results showing normal breathing and acute effects of pneumothoraces.

  20. A pilot study of physiological reactivity in children and maternal figures who lost relatives in a terrorist attack.

    PubMed

    Pfefferbaum, Betty; Tucker, Phebe; Jeon-Slaughter, Haekyung; Allen, James R; Hammond, Donna R; Whittlesey, Suzanne W; Vinekar, Shreekumar S; Feng, Yan

    2013-01-01

    Trauma is thought to interfere with normal grief by superimposing symptoms of posttraumatic stress disorder. This exploratory pilot study examined the association between traumatic grief and objectively measured physiological reactivity to a trauma interview in 73 children who lost relatives in the Oklahoma City bombing as well as a potential link between children and their maternal figures in physiological reactivity. Although the authors found no association between posttraumatic stress and objectively measured physiological reactivity among children, they found significant differences in objectively measured reactivity associated with loss and grief. Children who lost "close" relatives evidenced greater objectively measured reactivity than those who lost "distant" relatives. For the most part, children with higher levels of grief evidenced greater objectively measured reactivity than those with lower levels of grief. The most interesting of the findings was the parallel pattern in objectively measured physiological reactivity between children and their maternal figures along with a positive association between children's objectively measured physiological reactivity and maternal figures' self-reported physiological reactivity. Research using larger representative samples studied early and over time is indicated to determine the potential significance of these findings.

  1. Physiology of aging of older adults: systemic and oral health considerations.

    PubMed

    Abrams, Alan P; Thompson, Lisa A

    2014-10-01

    This article reviews the concepts of physiologic reserve, the principles of the normative aging process as exemplified by the cardiovascular, neurologic, and musculoskeletal systems. How these principles apply to oral health, and age-related changes in the oral cavity itself, is reviewed and suggests how they may affect disease management by oral health care providers. It does not focus on diseases related to aging, but rather aims to explore the normal physiologic changes associated with aging dentition and systemic changes related to age, thus enabling clinicians to obtain a better understanding of the presentation of older adults and how it may change their approach to diagnosis and treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Method for Dissecting the Auditory Epithelium (Basilar Papilla) in Developing Chick Embryos.

    PubMed

    Levic, Snezana; Yamoah, Ebenezer N

    2016-01-01

    Chickens are an invaluable model for exploring auditory physiology. Similar to humans, the chicken inner ear is morphologically and functionally close to maturity at the time of hatching. In contrast, chicks can regenerate hearing, an ability lost in all mammals, including humans. The extensive morphological, physiological, behavioral, and pharmacological data available, regarding normal development in the chicken auditory system, has driven the progress of the field. The basilar papilla is an attractive model system to study the developmental mechanisms of hearing. Here, we describe the dissection technique for isolating the basilar papilla in developing chick inner ear. We also provide detailed examples of physiological (patch clamping) experiments using this preparation.

  3. Role of growth differentiation factor 11 in development, physiology and disease

    PubMed Central

    Zhang, Yonghui; Wei, Yong; Liu, Dan; Liu, Feng; Li, Xiaoshan; Pan, Lianhong; Pang, Yi; Chen, Dilong

    2017-01-01

    Growth differentiation factor (GDF11) is a member of TGF-β/BMP superfamily that activates Smad and non-Smad signaling pathways and regulates expression of its target nuclear genes. Since its discovery in 1999, studies have shown the involvement of GDF11 in normal physiological processes, such as embryonic development and erythropoiesis, as well as in the pathophysiology of aging, cardiovascular disease, diabetes mellitus, and cancer. In addition, there are contradictory reports regarding the role of GDF11 in aging, cardiovascular disease, diabetes mellitus, osteogenesis, skeletal muscle development, and neurogenesis. In this review, we describe the GDF11 signaling pathway and its potential role in development, physiology and disease. PMID:29113418

  4. Reciprocal interactions between circadian clocks and aging.

    PubMed

    Banks, Gareth; Nolan, Patrick M; Peirson, Stuart N

    2016-08-01

    Virtually, all biological processes in the body are modulated by an internal circadian clock which optimizes physiological and behavioral performance according to the changing demands of the external 24-h world. This circadian clock undergoes a number of age-related changes, at both the physiological and molecular levels. While these changes have been considered to be part of the normal aging process, there is increasing evidence that disruptions to the circadian system can substantially impact upon aging and these impacts will have clear health implications. Here we review the current data of how both the physiological and core molecular clocks change with age and how feedback from external cues may modulate the aging of the circadian system.

  5. Ecological and physiological thermal niches to understand distribution of Chagas disease vectors in Latin America.

    PubMed

    DE LA Vega, G J; Schilman, P E

    2018-03-01

    In order to assess how triatomines (Hemiptera, Reduviidae), Chagas disease vectors, are distributed through Latin America, we analysed the relationship between the ecological niche and the limits of the physiological thermal niche in seven species of triatomines. We combined two methodological approaches: species distribution models, and physiological tolerances. First, we modelled the ecological niche and identified the most important abiotic factor for their distribution. Then, thermal tolerance limits were analysed by measuring maximum and minimum critical temperatures, upper lethal temperature, and 'chill-coma recovery time'. Finally, we used phylogenetic independent contrasts to analyse the link between limiting factors and the thermal tolerance range for the assessment of ecological hypotheses that provide a different outlook for the geo-epidemiology of Chagas disease. In triatomines, thermo-tolerance range increases with increasing latitude mainly due to better cold tolerances, suggesting an effect of thermal selection. In turn, physiological analyses show that species reaching southernmost areas have a higher thermo-tolerance than those with tropical distributions, denoting that thermo-tolerance is limiting the southern distribution. Understanding the latitudinal range along its physiological limits of disease vectors may prove useful to test ecological hypotheses and improve strategies and efficiency of vector control at the local and regional levels. © 2017 The Royal Entomological Society.

  6. [Autonomic regulation at emotional stress under hypoxic conditions in the elderly with physiological and accelerated aging: effect of hypoxic training].

    PubMed

    Os'mak, E D; Asanov, É O

    2014-01-01

    The effect of hypoxic training on autonomic regulation in psycho-emotional stress conditions in hypoxic conditions in older people with physiological (25 people) and accelerated (28 people) aging respiratory system. It is shown that hypoxic training leads to an increase in vagal activity indicators (HF) and reduced simpatovagal index (LF/HF), have a normalizing effect on the autonomic balance during stress loads in older people with different types of aging respiratory system.

  7. Space colonization - Some physiological perspectives

    NASA Technical Reports Server (NTRS)

    Winkler, L. H.

    1978-01-01

    Physiological criteria determining the design of the habitat for a space colony with 10,000 people are discussed. Centrifugally generated earth-normal gravity, maximum ionizing radiation dose standards less than or equal to 0.5 rem/year (obtained with passive shielding), and an atmosphere with reduced nitrogen partial pressures were established as design requirements for the habitat. However, further research is needed to determine whether humans experience complete adaptation to weightlessness and whether there are long-term effects of breathing various atmospheric mixtures and pressures.

  8. Modification of cytogenetic and physiological effects of space flight factors by biologically active compounds

    NASA Technical Reports Server (NTRS)

    Aliyev, A. A.; Mekhti-Zade, E. R.; Mashinskiy, A. L.; Alekperov, U. K.

    1986-01-01

    Physiological and cytogenetic changes in the Welsh onion plants induced by a short (82 days) and long term (522 days) space flight are expressed in decrease of seed germination, inhibition of stem growth, depression of cell division in root meristem, and increase in the number of structural chromosome rearrangements. The treatment of such plants with solutions of a-tocopherol, auxin, and kinetin decreased the level of chromosome aberrations to the control one and normalized cell divisions and growth partly or completely.

  9. Shallow Habitat Air Dive Series (SHAD I and II): The Effects on Visual Performance and Physiology

    DTIC Science & Technology

    1974-10-02

    APPLICATION Since the tests employed cover all the major, known visual symptoms of oxygen toxicity , the data indicate that man can live under...included a number of measures of visual physiology and visual performance, since many of the symptoms of oxygen toxicity involve the visual system. The...oxygen toxic - ity. Nitrogen narcosis, which normally occurs at 200 to 300 ft, is the lesser of the two problems for shaUow habitat divers, since

  10. When pain and hunger collide; psychological influences on differences in brain activity during physiological and non-physiological gastric distension.

    PubMed

    Coen, S J

    2011-06-01

    Functional neuroimaging has been used extensively in conjunction with gastric balloon distension in an attempt to unravel the relationship between the brain, regulation of hunger, satiety, and food intake tolerance. A number of researchers have also adopted a more physiological approach using intra-gastric administration of a liquid meal which has revealed different brain responses to gastric balloon distension. These differences are important as they question the utility and relevance of non-physiological models such as gastric balloon distension, especially when investigating mechanisms of feeding behavior such as satiety. However, an assessment of the relevance of physiological versus non-physiological gastric distension has been problematic due to differences in distension volumes between studies. In this issue of Neurogastroenterology and Motility, Geeraerts et al. compare brain activity during volume matched nutrient gastric distension and balloon distension in healthy volunteers. Gastric balloon distension activated the 'visceral pain neuromatrix'. This network of brain regions was deactivated during nutrient infusion, supporting the notion that brain activity during physiological versus non-physiological distension is indeed different. The authors suggest deactivation of the pain neuromatrix during nutrient infusion serves as a prerequisite for tolerance of normal meal volumes in health. © 2011 Blackwell Publishing Ltd.

  11. The Interaction of Motor Performance and Psycho-Physiological Effects During Acceleration to Hypergravity

    NASA Astrophysics Data System (ADS)

    Guardiera, Simon; Schneider, Stefan

    2008-06-01

    Several studies reported that human motor performance is impaired during acceleration to hypergravity. While physiological explanations (e.g. vestibular activity) are widely discussed, psycho-physiological reasons (e.g. stress) are less considered. The present study therefore evaluates the interaction between psycho-physiological effects and motor performance in hypergravity. Eleven subjects performed a manual tracking task. Additionally, stress hormone concentration, EEG and subjective mood were evaluated. All measurements were performed in normal (+1Gz), and in (or directly after) three times gravitational acceleration (+3Gz). Motor performance decreased, while all determined stress hormone concentrations increased in +3Gz. EEG analysis revealed an increase of brain cortical activity in right frontal lobe in +3Gz. Subjective mood decreased due to +3Gz. Our data confirm, that motor performance is decreased in hypergravity, whereas an increase in psychophysiological stress markers could be obtained. We conclude that psycho-physiological changes have to be regarded as a possible explanation for deficits in motor performance in hypergravity.

  12. The Core Principles ("Big Ideas") of Physiology: Results of Faculty Surveys

    ERIC Educational Resources Information Center

    Michael, Joel; McFarland, Jenny

    2011-01-01

    Physiology faculty members at a wide range of institutions (2-yr colleges to medical schools) were surveyed to determine what core principles of physiology they want their students to understand. From the results of the first survey, 15 core principles were described. In a second survey, respondents were asked to rank order these 15 core…

  13. The dark side of light at night: physiological, epidemiological, and ecological consequences.

    PubMed

    Navara, Kristen J; Nelson, Randy J

    2007-10-01

    Organisms must adapt to the temporal characteristics of their surroundings to successfully survive and reproduce. Variation in the daily light cycle, for example, acts through endocrine and neurobiological mechanisms to control several downstream physiological and behavioral processes. Interruptions in normal circadian light cycles and the resulting disruption of normal melatonin rhythms cause widespread disruptive effects involving multiple body systems, the results of which can have serious medical consequences for individuals, as well as large-scale ecological implications for populations. With the invention of electrical lights about a century ago, the temporal organization of the environment has been drastically altered for many species, including humans. In addition to the incidental exposure to light at night through light pollution, humans also engage in increasing amounts of shift-work, resulting in repeated and often long-term circadian disruption. The increasing prevalence of exposure to light at night has significant social, ecological, behavioral, and health consequences that are only now becoming apparent. This review addresses the complicated web of potential behavioral and physiological consequences resulting from exposure to light at night, as well as the large-scale medical and ecological implications that may result.

  14. Physiological, ecological, and behavioural correlates of the size of the geographic ranges of sea kraits (Laticauda; Elapidae, Serpentes): A critique

    NASA Astrophysics Data System (ADS)

    Heatwole, Harold; Lillywhite, Harvey; Grech, Alana

    2016-09-01

    Recent, more accurate delineation of the distributions of sea kraits and prior dubious use of proxy temperatures and mean values in correlative studies requires re-assessment of the relationships of temperature and salinity as determinants of the size of the geographic ranges of sea kraits. Correcting the sizes of geographic ranges resolved the paradox of lack of correspondence of size of range with degree of terrestrialism, but did not form a definitive test of the theory. Recent ecological, physiological, and behavioural studies provide an example of the kind of approach likely to either validate or refute present theory.

  15. A Preliminary Videofluoroscopic Investigation of Swallowing Physiology and Function in Individuals with Oculopharyngeal Muscular Dystrophy (OPMD).

    PubMed

    Waito, Ashley A; Steele, Catriona M; Peladeau-Pigeon, Melanie; Genge, Angela; Argov, Zohar

    2018-05-03

    Dysphagia is one of the primary symptoms experienced by individuals with Oculopharyngeal Muscular Dystrophy (OPMD). However, we lack understanding of the discrete changes in swallowing physiology that are seen in OPMD, and the resulting relationship to impairments of swallowing safety and efficiency. This study sought to describe the pathophysiology of dysphagia in a small sample of patients with OPMD using a videofluoroscopy examination (VFSS) involving 3 × 5 mL boluses of thin liquid barium (22% w/v). The aim of this study is to extend what is known about the pathophysiology of dysphagia in OPMD, by quantifying changes in swallow timing, kinematics, safety, and efficiency, measured from VFSS. This study is a secondary analysis of baseline VFSS collected from 11 adults (4 male), aged 48-62 (mean 57) enrolled in an industry-sponsored phase 2 therapeutic drug trial. Blinded raters scored the VFSS recordings for safety [Penetration-Aspiration Scale (PAS)], efficiency [Normalized Residue Ratio Scale (NRRS)], timing [Pharyngeal Transit Time (PTT), Swallow Reaction Time (SRT), Laryngeal Vestibule Closure Reaction Time (LVCrt), Upper Esophageal Sphincter Opening Duration (UESD)], and kinematics (hyoid movement, pharyngeal constriction, UES opening width). Impairment thresholds from existing literature were defined to characterize swallowing physiology and function. Further, Fisher's Exact tests and Pearson's correlations were used to conduct a preliminary exploration of associations between swallowing physiology (e.g., kinematics, timing) and function (i.e., safety, efficiency). Compared to published norms, we identified significant differences in the degree of maximum pharyngeal constriction, hyoid movement distance and speed, as well as degree and timeliness of airway closure. Unsafe swallowing (PAS ≥ 3) was seen in only 3/11 patients. By contrast, clinically significant residue (i.e., NRRS scores ≥ 0.09 vallecular; ≥ 0.2 pyriform) was seen in 7/11 patients. Fisher's Exact tests revealed associations between prolonged SRT, PTT, and unsafe swallowing. Weak associations were also identified between post-swallow residue and poor pharyngeal constriction during the swallow. Detailed analysis of swallowing physiology in this series of adults with OPMD aligns with impaired muscular function (e.g., reduced pharyngeal constriction, incomplete laryngeal vestibule closure) associated with the disease, and primary functional challenges with swallow efficiency. Further work is needed to explore a greater range of food and liquid textures, and to identify additional physiological mechanisms underlying swallowing impairment in OPMD.

  16. GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

    PubMed

    Jetten, Anton M

    2018-05-19

    Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

  17. Evidence of Physiological Decoupling from Grassland Ecosystem Drivers by an Encroaching Woody Shrub

    PubMed Central

    Nippert, Jesse B.; Ocheltree, Troy W.; Orozco, Graciela L.; Ratajczak, Zak; Ling, Bohua; Skibbe, Adam M.

    2013-01-01

    Shrub encroachment of grasslands is a transformative ecological process by which native woody species increase in cover and frequency and replace the herbaceous community. Mechanisms of encroachment are typically assessed using temporal data or experimental manipulations, with few large spatial assessments of shrub physiology. In a mesic grassland in North America, we measured inter- and intra-annual variability in leaf δ13C in Cornus drummondii across a grassland landscape with varying fire frequency, presence of large grazers and topographic variability. This assessment of changes in individual shrub physiology is the largest spatial and temporal assessment recorded to date. Despite a doubling of annual rainfall (in 2008 versus 2011), leaf δ13C was statistically similar among and within years from 2008-11 (range of −28 to −27‰). A topography*grazing interaction was present, with higher leaf δ13C in locations that typically have more bare soil and higher sensible heat in the growing season (upland topographic positions and grazed grasslands). Leaf δ13C from slopes varied among grazing contrasts, with upland and slope leaf δ13C more similar in ungrazed locations, while slopes and lowlands were more similar in grazed locations. In 2011, canopy greenness (normalized difference vegetation index – NDVI) was assessed at the centroid of individual shrubs using high-resolution hyperspectral imagery. Canopy greenness was highest mid-summer, likely reflecting temporal periods when C assimilation rates were highest. Similar to patterns seen in leaf δ13C, NDVI was highest in locations that typically experience lowest sensible heat (lowlands and ungrazed). The ability of Cornus drummondii to decouple leaf physiological responses from climate variability and fire frequency is a likely contributor to the increase in cover and frequency of this shrub species in mesic grassland and may be generalizable to other grasslands undergoing woody encroachment. PMID:24339950

  18. Development of a rate model to investigate contributions of anatomic and physiologic determinants of in vivo skin permeation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fleischer, N.M.

    The skin is a heterogeneous, bi-directional impediment to chemical flux, in which the stratum corneum is a major, though not the sole, rate-limiting barrier layer to permeation. Systemic toxicity following dermal exposure to environmental chemicals and use of skin as a portal for systemic administration of drugs have led to extensive investigations of the inward flux of xenobiotics applied to the outer surface of skin. Those investigations mainly utilized in vitro experimental systems that were limited by the absence of normal physiologic functions. The objective of the present research was to investigate an in vivo skin permeation model system thatmore » was sensitive to perturbations of skin capillary physiology and stratum corneum. A [open quotes]fuzzy[close quotes] rat model system was devised that employed outward cutaneous migration of a systemically administered permeation probe, isoflurane. Specially devised, transdermal vapor collection devices were used to capture the outward flux of isoflurane through the skin. Isoflurane flux measurements, coupled with blood isoflurane concentrations, were used to calculate cutaneous permeability coefficients (K[sub p]) of isolflurane, as an index of permeation, under various conditions of normal or perturbed cutaneous physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil-mediated vasodilation, phenylephrine-mediated vasoconstriction, and leukotriene D[sub 4]-mediated increased capillary permeability on the outward flux of isoflurane. Tape stripping and topical ether-ethanol application produced either physical removal or chemical disruption of the stratum corneum, respectively. Minoxidil, leukotriene D[sub 4], tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to 193%) in the K[sub p's], while phenylephrine had no significant effect on isoflurane permeation.« less

  19. A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways.

    PubMed

    Dallmann, André; Ince, Ibrahim; Coboeken, Katrin; Eissing, Thomas; Hempel, Georg

    2017-09-18

    Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women. The objective of this study was to extend and verify a previously developed physiologically based pharmacokinetic model for pregnant women for the prediction of pharmacokinetics of drugs metabolized via several cytochrome P450 enzymes. Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted. The tested drugs were caffeine, midazolam, nifedipine, metoprolol, ondansetron, granisetron, diazepam, and metronidazole. Pharmacokinetic predictions were evaluated by comparison with in-vivo pharmacokinetic data obtained from the literature. The pregnancy physiologically based pharmacokinetic model successfully predicted the pharmacokinetics of all tested drugs. The observed pregnancy-induced pharmacokinetic changes were qualitatively and quantitatively reasonably well predicted for all drugs. Ninety-seven percent of the mean plasma concentrations predicted in pregnant women fell within a twofold error range and 63% within a 1.25-fold error range. For all drugs, the predicted area under the concentration-time curve was within a 1.25-fold error range. The presented pregnancy physiologically based pharmacokinetic model can quantitatively predict the pharmacokinetics of drugs that are metabolized via one or multiple cytochrome P450 enzymes by integrating prior knowledge of the pregnancy-related effect on these enzymes. This pregnancy physiologically based pharmacokinetic model may thus be used to identify potential exposure changes in pregnant women a priori and to eventually support informed decision making when clinical trials are designed in this special population.

  20. Effects of an Elastic Hamstring Assistance Device During Downhill Running

    PubMed Central

    Aldret, Randy L; Trahan, Brittany A; Davis, Greggory; Campbell, Brian; Bellar, David M

    2017-01-01

    Abstract The purpose of this study was to determine the appropriateness of using an elastic hamstring assistance device to reduce perceived levels of soreness, increase isometric strength, increase passive range of motion, and decrease biomarkers of muscle damage after eccentric exercise, specifically, downhill running This study was conducted in a university exercise physiology laboratory placing sixteen apparently healthy males (X = 21.6 ± 2.5 years) into two groups using a pre-test/post-test design. Pre-intervention measures taken included participants’ body height, body mass, body fat, capillary blood samples, VO2max, isometric hamstring strength at 45 and 90 degrees of flexion and passive hamstring range of motion. Post-intervention measures included blood biomarkers, passive range of motion, the perceived level of soreness and isometric strength. An analysis of normality of data was initially conducted followed by multivariate analysis of variance (MANOVA) of hamstring strength at 45 and 90 degrees of flexion, blood myoglobin and passive range of motion of the hamstrings. Statistically significant changes were noted in subject-perceived muscle soreness and isometric strength at 90 degrees at the 24-hour post-exercise trial measure between the two groups. Results would suggest the findings could be explained by the decrease in muscle soreness from utilizing the device during the exercise trial. Further research should be conducted to address sample size issues and to determine if the results are comparable on different surfaces. PMID:28713460

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