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Biotechnology Journal Jul 2017During the cultivation of E. coli for recombinant protein production, substrate accumulation is often observed in induction phase. Uncontrolled substrate accumulation...
During the cultivation of E. coli for recombinant protein production, substrate accumulation is often observed in induction phase. Uncontrolled substrate accumulation leads to difficulties in transferring or scaling processes and even to failed batches. The phenomenon of metabolite/substrate accumulation occurs as a result of exceeding the physiological capacity to metabolize substrate (q ). In contrast to the common understanding of q as "static" value, we hypothesize that q essentially has a dynamic nature. Following the state of the art approach of physio logical strain characterization, substrate pulse experiments were used to quantify q in induction phase. The q was found to be temperature and time dependent. Subsequently, q was expressed through a linear equation, to serve as boundary for physiologically controlled experiments. Nevertheless, accumulation was observed within a physiologically controlled verification experiment, although the q boundary was not exceeded. A second set of experiments was conducted, by oscillating the q set point between discrete plateaus during physiologically controlled experiments. From the results, we deduced a significant interrelation between the metabolic activity and the timely decline of qScrit. This finding highlights the necessity of a comprehensive but laborious physiological characterization for each strain or alternatively, to use physio logical feedback control to facilitate real time monitoring of q , in order to effectively avoid substrate accumulation.
Topics: Batch Cell Culture Techniques; Escherichia coli; Recombinant Proteins; Temperature; Time Factors
PubMed: 28120503
DOI: 10.1002/biot.201600547 -
Frontiers in Veterinary Science 2021This study aimed to identify the physiological 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in cats using positron emission tomography/computed tomography (PET/CT) and...
This study aimed to identify the physiological 18F-fluoro-2-deoxy-D-glucose (FDG) uptake in cats using positron emission tomography/computed tomography (PET/CT) and determine its characteristics by comparing physiological differences with dogs. Seven healthy cats and six healthy beagle dogs were examined using FDG-PET/CT. Regions of interest (ROIs) were manually drawn over 41 detailed structures of 5 gross structures (brain, head and neck, musculoskeleton, thorax, and abdomen). The mean and maximum standard uptake values (SUVmean and SUVmax) were calculated for each ROI. Physiological variation was classified as having increased radiopharmaceutical activity with no evidence of abnormal clinical or radiological findings. The brain had the highest SUV, which was observed in the cerebellum of both cats (SUVmean: 4.90 ± 1.04, SUVmax: 6.04 ± 1.24) and dogs (SUVmean: 3.15 ± 0.57, SUVmax: 3.90 ± 0.74). Cats had a significantly higher intracranial uptake than dogs did ( < 0.01). In the digestive system, the SUVs of the duodenum and jejunum were significantly higher in dogs than in cats ( < 0.05). FDG uptake of the submandibular tip, tonsils, neck of the gallbladder, and caudal colliculus were physiologically increased in cats. This study demonstrates physiological FDG uptake in normal tissues, and the differences between cats and dogs were interpreted based on species-specificity. This information contributes to improving the accurate diagnosis of cancer in cats and will aid in understanding glucose metabolism in both cats and dogs.
PubMed: 34722693
DOI: 10.3389/fvets.2021.708237 -
Emergency Medicine Clinics of North... Aug 2022Emergency physicians intubate critically ill patients almost daily. Intubation of the critically ill emergency department (ED) patient is a high-risk, high-stress... (Review)
Review
Emergency physicians intubate critically ill patients almost daily. Intubation of the critically ill emergency department (ED) patient is a high-risk, high-stress situation, as many have physiologic derangements such as hypotension, hypoxemia, acidosis, and right ventricular dysfunction that markedly increase the risk of peri-intubation cardiovascular collapse and cardiac arrest. This chapter discusses critical pearls and pitfalls to intubate the critically ill ED patient with physiologic derangements. These pearls and pitfalls include appropriate preoxygenation; circulatory resuscitation; proper patient position and room setup; selection of medications for rapid sequence intubation; and intubation of patients with severe acidosis, traumatic brain injury, and pulmonary hypertension.
Topics: Acidosis; Critical Illness; Humans; Hypotension; Intubation, Intratracheal; Shock
PubMed: 35953220
DOI: 10.1016/j.emc.2022.05.011 -
The Lancet. Haematology Aug 2021Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin...
Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study.
BACKGROUND
Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 μg/L for children and less than 15 μg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES).
METHODS
In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×10/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis.
FINDINGS
5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 μg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 μg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 μg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 μg/L (23·3-24·6; p=0·05).
INTERPRETATION
The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 μg/L for children and 25 μg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency.
FUNDING
None.
Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Biomarkers; Child; Cross-Sectional Studies; Female; Ferritins; Follow-Up Studies; Humans; Male; Middle Aged; Monitoring, Physiologic; Nutrition Surveys; Prognosis; Young Adult
PubMed: 34329578
DOI: 10.1016/S2352-3026(21)00168-X -
Der Anaesthesist Sep 1987Hemoglobin as a vehicle for oxygen carries roughly 65 times the volume of oxygen that would otherwise be transported by simple solution in plasma. Conformational shifts... (Review)
Review
Hemoglobin as a vehicle for oxygen carries roughly 65 times the volume of oxygen that would otherwise be transported by simple solution in plasma. Conformational shifts of the molecule induce a cooperative oxygen-hemoglobin affinity. This property is reflected in the sigmoidal shape of the oxygen-hemoglobin dissociation curve. The affinity of hemoglobin is affected by temperature, hydrogen ions, carbon dioxide, and intraerythrocytic 2,3-DPG, with all these factors mutually influencing each other. Physiologic conditions associated with shifts in hemoglobin-oxygen affinity are oxygen uptake in the lung, oxygen delivery in the capillaries, and particularly oxygen delivery in working muscle, diaplacental oxygen transfer, and the regulation of erythropoesis. Hemoglobin-oxygen affinity attains pathological significance for oxygen supply during respiratory or metabolic alkalosis when the hemodynamic and tissue responses of the individual are limited: the increased affinity can critically lower capillary oxygen tension. Methemoglobin and carbon monoxide shift the oxygen dissociation curve to the left, so that intoxication with both substances reduces both total oxygen capacity and oxygen delivery of the remaining hemoglobin able to bind oxygen. This effect of methemoglobin and carbon monoxide must be considered in intensive care of intoxicated victims. Transfusions of large volumes of stored red cells, whose hemoglobin shows high affinity, can force the capillary oxygen tension down, especially in patients with impaired cardiac performance. The lowered oxygen affinity of patients with chronic renal disease and anemia must be preserved by avoiding an increase in the acidotic plasma pH. In the neonate, hemoglobin possesses a high affinity for oxygen physiologically; the hemodynamic reserve of the neonate is limited. Therefore, the hemoglobin content plays a crucial role in oxygen transport capacity during the initial months of extrauterine life. Consequently, red cell transfusion must be started much earlier in neonatal surgery than in adults. The red cells must be fresh, or at best "rejuvenated". Normally, oxygen affinity is not relevant for oxygen supply, but the position of the oxygen-hemoglobin dissociation curve may be a critical factor in the situations described above, particularly when blood flow is additionally restricted.
Topics: Hemoglobins; Humans; Oxygen Consumption
PubMed: 3318547
DOI: No ID Found -
Journal of the Neurological Sciences Mar 2022The rapid evolution of neuromodulation techniques includes an increasing amount of research into stimulation paradigms that are guided by patients' neurophysiology, to...
The rapid evolution of neuromodulation techniques includes an increasing amount of research into stimulation paradigms that are guided by patients' neurophysiology, to increase efficacy and responder rates. Treatment personalisation and target engagement have shown to be effective in fields such as Parkinson's disease, and closed-loop paradigms have been successfully implemented in cardiac defibrillators. Promising avenues are being explored for physiologically informed neuromodulation in psychiatry. Matching the stimulation frequency to individual brain rhythms has shown some promise in transcranial magnetic stimulation (TMS). Matching the phase of those rhythms may further enhance neuroplasticity, for instance when combining TMS with electroencephalographic (EEG) recordings. Resting-state EEG and event-related potentials may be useful to demonstrate connectivity between stimulation sites and connected areas. These techniques are available today to the psychiatrist to diagnose underlying sleep disorders, epilepsy, or lesions as contributing factors to the cause of depression. These technologies may also be useful in assessing the patient's brain network status prior to deciding on treatment options. Ongoing research using invasive recordings may allow for future identification of mood biomarkers and network structure. A core limitation is that biomarker research may currently be limited by the internal heterogeneity of psychiatric disorders according to the current DSM-based classifications. New approaches are being developed and may soon be validated. Finally, care must be taken when incorporating closed-loop capabilities into neuromodulation systems, by ensuring the safe operation of the system and understanding the physiological dynamics. Neurophysiological tools are rapidly evolving and will likely define the next generation of neuromodulation therapies.
Topics: Brain; Electroencephalography; Epilepsy; Evoked Potentials; Humans; Transcranial Magnetic Stimulation
PubMed: 34998239
DOI: 10.1016/j.jns.2021.120121 -
Journal of Visualized Experiments : JoVE Sep 2014Cardiomyocytes, the workhorse cell of the heart, contain exquisitely organized cytoskeletal and contractile elements that generate the contractile force used to pump...
Cardiomyocytes, the workhorse cell of the heart, contain exquisitely organized cytoskeletal and contractile elements that generate the contractile force used to pump blood. Individual cardiomyocytes were first isolated over 40 years ago in order to better study the physiology and structure of heart muscle. Techniques have rapidly improved to include enzymatic digestion via coronary perfusion. More recently, analyzing the contractility and calcium flux of isolated myocytes has provided a vital tool in the cellular and sub-cellular analysis of heart failure. Echocardiography and EKGs provide information about the heart at an organ level only. Cardiomyocyte cell culture systems exist, but cells lack physiologically essential structures such as organized sarcomeres and t-tubules required for myocyte function within the heart. In the protocol presented here, cardiomyocytes are isolated via Langendorff perfusion. The heart is removed from the mouse, mounted via the aorta to a cannula, perfused with digestion enzymes, and cells are introduced to increasing calcium concentrations. Edge and sarcomere detection software is used to analyze contractility, and a calcium binding fluorescent dye is used to visualize calcium transients of electrically paced cardiomyocytes; increasing understanding of the role cellular changes play in heart dysfunction. Traditionally used to test drug effects on cardiomyocytes, we employ this system to compare myocytes from WT mice and mice with a mutation that causes dilated cardiomyopathy. This protocol is unique in its comparison of live cells from mice with known heart function and known genetics. Many experimental conditions are reliably compared, including genetic or environmental manipulation, infection, drug treatment, and more. Beyond physiologic data, isolated cardiomyocytes are easily fixed and stained for cytoskeletal elements. Isolating cardiomyocytes via perfusion is an extremely versatile method, useful in studying cellular changes that accompany or lead to heart failure in a variety of experimental conditions.
Topics: Animals; Calcium; Mice; Myocardial Contraction; Myocytes, Cardiac
PubMed: 25225886
DOI: 10.3791/51109 -
The Annals of Occupational Hygiene Jun 1991In pharmacokinetic modelling the body is represented as a set of compartments. The characteristics of these compartments are defined either by fitting predetermined...
In pharmacokinetic modelling the body is represented as a set of compartments. The characteristics of these compartments are defined either by fitting predetermined mathematical equations to the data ('data-based compartments') or by defining compartments based on the actual biological structure of the animal ('physiologically based compartments'). Physiological models of chemical disposition are developed using these physiologically based compartments. These models then consist of sets of organs or types of tissue compartments whose characteristics are based as far as possible on the anatomy and physiology of the test species. Individual organs or types of tissue are defined with respect to their blood flow, volume, kinetic constants for metabolism, storage capacity for the compound involved, protein binding and other relevant characteristics. Linking these compartments together in a proper anatomical arrangement yields the physiological model for compound disposition. This paper provides an overview of the basics for constructing physiological models for organic compounds, focusing on the structure of individual compartments in these models and the data required for model development. Some past applications of physiological models are reviewed and speculation offered on future developments in this field.
Topics: Animals; Body Fluid Compartments; Models, Biological; Pharmacokinetics
PubMed: 1888102
DOI: 10.1093/annhyg/35.3.309 -
Medical Engineering & Physics Jan 2006Agitation-sedation cycling in critically ill patients, characterized by oscillations between states of agitation and over-sedation, damages patient health and increases... (Comparative Study)
Comparative Study
Agitation-sedation cycling in critically ill patients, characterized by oscillations between states of agitation and over-sedation, damages patient health and increases length of stay and cost. A model that captures the essential dynamics of the agitation-sedation system and is physiologically representative is developed, and validated using data from 37 critical care patients. It is more physiologically representative than a previously published agitation-sedation model, and captures more realistic and complex dynamics. The median time in the 90% probability band is 90%, and the total drug dose, relative to recorded drug dose data, is a near ideal 101%. These statistical model validation metrics are 5-13% better than a previously validated model. Hence, this research provides a platform to develop and test semi-automated sedation management controllers that offer the significant clinical potential of improved agitation management and reduced length of stay in critical care.
Topics: Conscious Sedation; Critical Care; Critical Illness; Humans; Models, Biological; Models, Statistical; Monitoring, Physiologic; Nonlinear Dynamics; Psychomotor Agitation; Time Factors
PubMed: 15869894
DOI: 10.1016/j.medengphy.2005.03.005 -
Journal of Personality and Social... Jan 1976A study was undertaken to try to ascertain the best model of the relationship between stimuli, physiological responses, and attitudes. Subjects were asked to indicate...
A study was undertaken to try to ascertain the best model of the relationship between stimuli, physiological responses, and attitudes. Subjects were asked to indicate their attitudes toward various nations after having received various bogus information about how they responded physiologically to the stimuli. The results indicate the following: (a) In general, attitudes appear to be physiologically mediated; (b) physiological mediation of attitudes is strongest when prior knowledge about the stimuli is low but is independent of prior attitudes about the stimuli; (c) bogus physiological feedback does not seem to be verbally mediated; and (d) the most fruitful distinction between types of bogus feedback is between any feedback versus no feedback, not between change versus no change or between increase versus decrease in response.
Topics: Attitude; Feedback; Female; Heart Rate; Humans; Male; Psychophysiology
PubMed: 1018226
DOI: 10.1037//0022-3514.33.1.107