Phenotypical Differences at the Physiological and Clinical Level between Two Genetically Closely Related Clavispora lusitaniae Strains Isolated from Patients.

The occurrence of non-albicans species within the genus Candida poses a major challenge in the clinical setting. Clavispora lusitaniae, formerly known as Candida lusitaniae, has gained attention due to its potential multidrug resistance, particularly to amphotericin B (AmB). While intrinsic resistance to AmB is rare, secondary resistance may develop during treatment due to phenotypic rearrangement and the reorganization of the cell wall. Although there is evidence of genetic variability within C. lusitaniae, comprehensive genomic studies are lacking. This study examines the physiological differences within Candida species and focuses on the medical implications of this. Using two case reports, significant physiological and resistance differences between two strains of C. lusitaniae are demonstrated, highlighting the need for further research into genetic variability. While one strain showed higher resistance to antifungal drugs and slower growth compared to Strain 2, both strains showed minimal beta-D-glucan production, suggesting alternative pathogenic mechanisms. The study underlines the importance of understanding microbial adaptation and selection mechanisms, especially in the clinical setting, to effectively combat emerging drug resistance. Furthermore, research is needed to clarify the complex interplay between environmental causes, physiological traits, and the mechanisms of drug resistance in C. lusitaniae.

Design and Development of a Non-invasive Opto-Electronic Sensor for Blood Glucose Monitoring Using a Visible Light Source.

Background The management of diabetes is critically dependent on the continuous monitoring of blood glucose levels. Contemporary approaches primarily utilize invasive methods, which often prove to be uncomfortable and can deter patient adherence. There is a pressing need for the development of novel strategies that improve patient compliance and simplify the process of glucose monitoring. Aim and objectives The primary objective of this research is to develop a non-invasive blood glucose monitoring system (NIBGMS) that offers a convenient alternative to conventional invasive methods. This study aims to demonstrate the feasibility and accuracy of using visible laser light at a wavelength of 650 nm for glucose monitoring and to address physiological and technical challenges associated with in vivo measurements. Methods Our approach involved the design of a device that exploits the quantitative relationship between glucose concentration and the refraction phenomena of laser light. The system was initially calibrated and tested using glucose solutions across a range of concentrations (25-500 mg/dL). To get around the problems that come up when people's skin and bodies are different, we combined an infrared (IR) transmitter (800 nm) and receiver that checks for changes in voltage, which are indicative of glucose levels. Results The prototype device was compared with a commercially available blood glucose monitor (Accu-Chek active machine; Roche Diabetes Care, Inc., Mumbai, India). The results demonstrated an average linearity of 95.7% relative to the Accu-Chek machine, indicating a high level of accuracy in the non-invasive measurement of glucose levels. Conclusions The findings suggest that our NIBGMS holds significant promise for clinical application. It reduces the discomfort associated with blood sampling and provides reliable measurements that are comparable to those of existing invasive methods. The successful development of this device paves the way for further commercial translation and could significantly improve the quality of life for individuals with diabetes, by facilitating easier and more frequent monitoring.

Blood Trace Element Status in Camels: A Review.

Trace minerals play an important role in animal health and productivity. They are involved also in many physiological activities, and their deficiency causes a variety of pathological problems and metabolic defects, reducing consequently the animal productivity. The demand for animal products in semi-arid areas is rapidly increasing, and the supply is still below the required level, partially due to low animal productivity. Camels (Camelus dromedarius and Camelus bactrianus) are considered one of the main sources of healthy, high-quality meat and milk for human consumption within most of the countries in the semi-arid regions. Despite their efficient adaptation to their environment, camels can suffer from the growth retardation of newborns, low feed efficiency, anemia, poor fertility, poor reproduction and many other metabolic disorders. It is well known that trace mineral deficiencies and trace mineral toxicities can influence camels' production and reproductive efficiency, as well as many aspects of their growth and metabolism. Evaluating the trace minerals status of camels and their variability is an obvious step toward improving camels' productivity and health. Thus, the present article reviews the data regarding the status of trace minerals (copper, zinc, iron, selenium, manganese, cobalt, iodine, fluorine, molybdenum, sulfur, bromide and nickel) in camel blood and their physiological variability, with a focus on their deficiency and toxicity effects.

Predicting Failure of Non-Invasive Ventilation With RAM Cannula in Bronchiolitis.

INTRODUCTION: In infants hospitalized for bronchiolitis on non-invasive ventilation (NIV) via the RAM cannula nasal interface, variables predicting subsequent intubation, or NIV non-response, are understudied. We sought to identify predictors of NIV non-response. METHODS: We performed a retrospective cohort study in infants admitted for respiratory failure from bronchiolitis placed on NIV in a quaternary children's hospital. We excluded children with concurrent sepsis, critical congenital heart disease, or with preexisting tracheostomy. The primary outcome was NIV non-response defined as intubation after a trial of NIV. Secondary outcomes were vital sign values before and after NIV initiation, duration of NIV and intubation, and mortality. Primary analyses included Chi-square, Wilcoxon rank-sum, student's t test, paired analyses, and adjusted and unadjusted logistic regression assessing heart rate (HR) and respiratory rate (RR) before and after NIV initiation. RESULTS: Of 138 infants studied, 34% were non-responders. There were no differences in baseline characteristics of responders and non-responders. HR decreased after NIV initiation in responders (156 [143-156] to149 [141-158], p < 0.01) compared to non-responders (158 [149-166] to 158 [145-171], p = 0.73). RR decreased in responders (50 [43-58] vs 47 [41-54]) and non-responders (52 [48-58] vs 51 [40-55], both p < 0.01). Concurrent bacterial pneumonia (OR 6.06, 95% CI: 2.54-14.51) and persistently elevated HR (OR: 1.04, 95% CI: 1.01-1.07) were associated with NIV non-response. CONCLUSION: In children with acute bronchiolitis who fail to respond to NIV and require subsequent intubation, we noted associations with persistently elevated HR after NIV initiation and concurrent bacterial pneumonia.

The sources of electrophysiological variability in the retina of Periplaneta americana.

Variability in the electrophysiological properties of homotypic photoreceptors is widespread and is thought to facilitate functioning under disparate illumination conditions. Compound eyes of insects have three sources of variability: inter-individual, intra-individual, and intra-ommatidial, the latter two overlapping. Here, I explored the causes of variability in Periplaneta americana, a nocturnal insect characterized by highly variable photoreceptor responses. By recording from photoreceptors in dissociated ommatidia, including consecutive recordings from photoreceptors in the same ommatidium (SO), I studied the variability of six properties: whole-cell membrane capacitance (Cm), phototransduction latency, maximal conductance (Gmax) and the slope factor of the sustained Kv current, absolute sensitivity in dim light, and sustained light-induced current (LIC) amplitude in bright light. Coefficient of variation (CV) metrics were used to compare variances in four experimental groups: SO, same animal (SA), all data combined "full sample" (FS), and full sample of all SO recordings (FSSO). For the normally distributed parameters Cm, Gmax, slope factor, and latency, the highest CV values were found in FS and FSSO, intermediate in SA, and the lowest in SO. On average, SO variance accounted for 47% of the full-sample variance in these four parameters. Absolute sensitivity and LIC values were not normally distributed, and the differences in variability between SO and FS/FSSO groups were smaller than for the other four parameters. These results indicate two main sources of variability, intra-ommatidial and inter-individual. Inter-individual variability was investigated by exposing adult cockroaches to constant light or dark for several months. In both groups, the majority of CV measures for the six parameters decreased compared to control, indicating substantial contribution of phenotypic plasticity to inter-individual differences. Analysis of variability of resting potential and elementary voltage responses revealed that resting potential is mainly determined by the sustained Kv conductance, whereas voltage bump amplitude is mainly determined by current bump amplitude and Cm.

Variability in response to salinity stress in natural Tunisian populations of Hordeum marinum subsp. marinum.

Soil salinity is one of the most serious environmental factors affecting crop productivity around the world. In this study, we analysed morpho-physiological variation in responses to salt stress in Tunisian populations of Hordeum marinum subsp. marinum. The plants were grown under two treatments (0 and 200 mm NaCl) until maturity. A total of 19 quantitative traits were measured before and during the harvest. It was observed that most studied traits are influenced by the increasing salinity. High to moderate broad-sense heritability (H2 ) were noted for most of parameters under control and salt treatment, implying that salt tolerance is moderately heritable and environmental variation plays an equally important role. The majority of correlations between measured traits under the two treatments are positive, where the strongest correlations were between spike number (SN) and weight (SW). Based on the salt response index (SRI) values, SN and SW are the most affected by salinity. The 150 studied lines formed three groups according to the SRI values of the 19 quantitative parameters, of which 101 were moderately sensitive, 27 tolerant and 22 highly tolerant. Overall genetic variation of H. marinum in response to salt stress may provide novel insight to identify genes responsible for salt tolerance.

A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research.

In cardiac electrophysiology, there exist many sources of inter- and intra-personal variability. These include variability in conditions and environment, and genotypic and molecular diversity, including differences in expression and behavior of ion channels and transporters, which lead to phenotypic diversity (e.g., variable integrated responses at the cell, tissue, and organ levels). These variabilities play an important role in progression of heart disease and arrhythmia syndromes and outcomes of therapeutic interventions. Yet, the traditional in silico framework for investigating cardiac arrhythmias is built upon a parameter/property-averaging approach that typically overlooks the physiological diversity. Inspired by work done in genetics and neuroscience, new modeling frameworks of cardiac electrophysiology have been recently developed that take advantage of modern computational capabilities and approaches, and account for the variance in the biological data they are intended to illuminate. In this review, we outline the recent advances in statistical and computational techniques that take into account physiological variability, and move beyond the traditional cardiac model-building scheme that involves averaging over samples from many individuals in the construction of a highly tuned composite model. We discuss how these advanced methods have harnessed the power of big (simulated) data to study the mechanisms of cardiac arrhythmias, with a special emphasis on atrial fibrillation, and improve the assessment of proarrhythmic risk and drug response. The challenges of using in silico approaches with variability are also addressed and future directions are proposed.

Systolic blood pressure variability in patients with early severe sepsis or septic shock: a prospective cohort study.

BACKGROUND: Severe sepsis and septic shock are often lethal syndromes, in which the autonomic nervous system may fail to maintain adequate blood pressure. Heart rate variability has been associated with outcomes in sepsis. Whether systolic blood pressure (SBP) variability is associated with clinical outcomes in septic patients is unknown. The propose of this study is to determine whether variability in SBP correlates with vasopressor independence and mortality among septic patients. METHODS: We prospectively studied patients with severe sepsis or septic shock, admitted to an intensive care unit (ICU) with an arterial catheter. We analyzed SBP variability on the first 5-min window immediately following ICU admission. We performed principal component analysis of multidimensional complexity, and used the first principal component (PC1) as input for Firth logistic regression, controlling for mean systolic pressure (SBP) in the primary analyses, and Acute Physiology and Chronic Health Evaluation (APACHE) II score or NEE dose in the ancillary analyses. Prespecified outcomes were vasopressor independence at 24 h (primary), and 28-day mortality (secondary). RESULTS: We studied 51 patients, 51% of whom achieved vasopressor independence at 24 h. Ten percent died at 28 days. PC1 represented 26% of the variance in complexity measures. PC1 was not associated with vasopressor independence on Firth logistic regression (OR 1.04; 95% CI: 0.93-1.16; p = 0.54), but was associated with 28-day mortality (OR 1.16, 95% CI: 1.01-1.35, p = 0.040). CONCLUSIONS: Early SBP variability appears to be associated with 28-day mortality in patients with severe sepsis and septic shock.

Lack of linear correlation between dynamic and steady-state cerebral autoregulation.

KEY POINTS: For correct application and interpretation of cerebral autoregulation (CA) measurements in research and in clinical care, it is essential to understand differences and similarities between dynamic and steady-state CA. The present study found no correlation between dynamic and steady-state CA indices in healthy older adults. There was variability between individuals in all (steady-state and dynamic) autoregulatory indices, ranging from low (almost absent) to highly efficient CA in this healthy population. These findings challenge the assumption that assessment of a single CA parameter or a single set of parameters can be generalized to overall CA functioning. Therefore, depending on specific research purposes, the choice for either steady-state or dynamic measures or both should be weighed carefully. ABSTRACT: The present study aimed to investigate the relationship between dynamic (dCA) and steady-state cerebral autoregulation (sCA). In 28 healthy older adults, sCA was quantified by a linear regression slope of proportionate (%) changes in cerebrovascular resistance (CVR) in response to proportionate (%) changes in mean blood pressure (BP) induced by stepwise sodium nitroprusside (SNP) and phenylephrine (PhE) infusion. Cerebral blood flow (CBF) was measured at the internal carotid artery (ICA) and vertebral artery (VA) and CBF velocity at the middle cerebral artery (MCA). With CVR = BP/CBF, Slope-CVRICA , Slope-CVRVA and Slope-CVRiMCA were derived. dCA was assessed (i) in supine rest, analysed with transfer function analysis (gain and phase) and autoregulatory index (ARI) fit from spontaneous oscillations (ARIBaseline ), and (ii) with transient changes in BP using a bolus injection of SNP (ARISNP ) and PhE (ARIPhE ). Comparison of sCA and dCA parameters (using Pearson's r for continuous and Spearman's ρ for ordinal parameters) demonstrated a lack of linear correlations between sCA and dCA measures. However, comparisons of parameters within dCA and within sCA were correlated. For sCA slope-CVRVA with Slope-CVRiMCA (r = 0.45, P < 0.03); for dCA ARISNP with ARIPhE (ρ = 0.50, P = 0.03), ARIBaseline (ρ = 0.57, P = 0.03) and PhaseLF (ρ = 0.48, P = 0.03); and for GainVLF with GainLF (r = 0.51, P = 0.01). By contrast to the commonly held assumption based on an earlier study, there were no linear correlations between sCA and dCA. As an additional observation, there was strong inter-individual variability, both in dCA and sCA, in this healthy group of elderly, in a range from low to high CA efficiency.

Multi-complexity measures of heart rate variability and the effect of vasopressor titration: a prospective cohort study of patients with septic shock.

BACKGROUND: Septic shock is a common and often devastating syndrome marked by severe cardiovascular dysfunction commonly managed with vasopressors. Whether markers of heart rate complexity before vasopressor up-titration could be used to predict success of the up-titration is not known. METHODS: We studied patients with septic shock requiring vasopressor, newly admitted to the intensive care unit. We measured the complexity of heart rate variability (using the ratio of fractal exponents from detrended fluctuation analysis) in the 5 min before all vasopressor up-titrations in the first 24 h of an intensive care unit (ICU) admission. A successful up-titration was defined as one that did not require further up-titration (or decrease in mean arterial pressure) for 60 min. RESULTS: We studied 95 patients with septic shock, with a median APACHE II of 27 (IQR: 20-37). The median number of up-titrations, normalized to 24 h, was 12.2 (IQR: 8-17) with a maximum of 49. Of the up-titrations, the median proportion of successful interventions was 0.28 (IQR: 0.12-0.42). The median of mean arterial pressure (MAP) at the time of a vasopressor up-titration was 66 mmHg; the average infusion rate of norepinephrine at the time of an up-titration was 0.11 mcg/kg/min. The ratio of fractal exponents was not associated with successful up-titration on univariate or multivariate regression. On exploratory secondary analyses, however, the long-term fractal exponent was associated (p = 0.003) with success of up-titration. Independent of heart rate variability, MAP was associated (p < 0.001) with success of vasopressor up-titration, while neither Sequential Organ Failure Assessment (SOFA) nor Acute Physiology and Chronic Health Evaluation II (APACHE II) score was associated with vasopressor titration. CONCLUSIONS: Only a third of vasopressor up-titrations were successful among patients with septic shock. MAP and the long-term fractal exponent were associated with success of up-titration. These two, complementary variables may be important to the development of rational vasopressor titration protocols.

Variability in cardiac electrophysiology: Using experimentally-calibrated populations of models to move beyond the single virtual physiological human paradigm.

Physiological variability manifests itself via differences in physiological function between individuals of the same species, and has crucial implications in disease progression and treatment. Despite its importance, physiological variability has traditionally been ignored in experimental and computational investigations due to averaging over samples from multiple individuals. Recently, modelling frameworks have been devised for studying mechanisms underlying physiological variability in cardiac electrophysiology and pro-arrhythmic risk under a variety of conditions and for several animal species as well as human. One such methodology exploits populations of cardiac cell models constrained with experimental data, or experimentally-calibrated populations of models. In this review, we outline the considerations behind constructing an experimentally-calibrated population of models and review the studies that have employed this approach to investigate variability in cardiac electrophysiology in physiological and pathological conditions, as well as under drug action. We also describe the methodology and compare it with alternative approaches for studying variability in cardiac electrophysiology, including cell-specific modelling approaches, sensitivity-analysis based methods, and populations-of-models frameworks that do not consider the experimental calibration step. We conclude with an outlook for the future, predicting the potential of new methodologies for patient-specific modelling extending beyond the single virtual physiological human paradigm.

Coefficient of Variation of Coarsely Sampled Heart Rate is Associated With Early Vasopressor Independence in Severe Sepsis and Septic Shock.

PURPOSE: To determine whether variability of coarsely sampled heart rate and blood pressure early in the course of severe sepsis and septic shock predicts successful resuscitation, defined as vasopressor independence at 24 hours after admission. METHODS: In an observational study of patients admitted with severe sepsis or septic shock from 2009 to 2011 to either of 2 intensive care units (ICUs) at a tertiary-care hospital, in whom blood pressure was measured via an arterial catheter, we sampled heart rate and blood pressure every 30 seconds over the first 6 hours of ICU admission and calculated the coefficient of variability of those measurements. Primary outcome was vasopressor independence at 24 hours; and secondary outcome was 28-day mortality. RESULTS: We studied 165 patients, of which 97 (59%) achieved vasopressor independence at 24 hours. Overall, 28-day mortality was 15%. Significant predictors of vasopressor independence at 24 hours included the coefficient of variation of heart rate, age, Acute Physiology and Chronic Health Evaluation II, the number of increases in vasopressor dose, mean vasopressin dose, mean blood pressure, and time-pressure integral of mean blood pressure less than 60 mm Hg. Lower sampling frequencies (up to once every 5 minutes) did not affect the findings. CONCLUSIONS: Increased variability of coarsely sampled heart rate was associated with vasopressor independence at 24 hours after controlling for possible confounders. Sampling frequencies of once in 5 minutes may be similar to once in 30 seconds.

Initial fractal exponent of heart rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study.

INTRODUCTION: Heart rate variability (HRV) reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in HRV upon intensive care unit (ICU) admission would be associated with unsuccessful early resuscitation of sepsis. METHODS: We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of electrocardiogram, sampled at 500 Hz, at ICU admission and calculated heart rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality. RESULTS: We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (P = .04) after controlling for mean heart rate. In the optimal model, Sequential Organ Failure Assessment score and the long-term fractal α parameter were associated with vasopressor independence. CONCLUSIONS: Loss of complexity in HRV is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of HRV could guide treatment in sepsis.

Clinical validation of software for a versatile variability analyzer: Assessment of autonomic function.

Study of physiological variability is an upcoming area of research having manifold clinical applications. Considerable work has been done on heart rate variability and blood pressure variability during the past four decades. Electronics division, Bhabha Atomic Research Centre, has developed an instrument called medical analyzer, which can be used to study several variabilities simultaneously. This instrument has been used to collect data from control subjects and patients with established diagnosis. The data has been analyzed with the help of a software package developed for this purpose and has been found to be consistent with expected manifestations of the disease on the autonomic nervous system. The description of the software package and results of the study are briefly described in this paper.

Pathological Interaction of a Combination of Heterodera schachtii and Meloidogyne hapla on Tomato.

Increased culturing of a tomato population of Heterodera schachtii (UT1C) on tomato for 480 days (eight inoculation periods of 60 days each) significantly increased virulence to 'Stone Improved' tomato. A synergistic relationship existed between Meloidogyne hapla and H. schaehtii on tomato. A combination of H. schachtii (UTIC) and M. hapla significantly reduced tomato root weights by 65, 64, and 61% below root weights of untreated controls, and single inoculations of M. hapla and H. schachtii, respectively. This corresponded to root reductions of 42, 44, and 46% from a combination of H. schachtii (UT1B) and M. hapla. Antagonism existed between H. schachtii and M. hapla with regard to infection courts and feeding sites. The root-knot galling index dropped from 6.0 with a single inoculation of M. hapla to 4.3 and 3.3 with combined inoculations of M. hapla plus UT1B and M. hapla plus UTIC cyst nematode populations. The pathological virulence of H. schachtii to sugarbeet was not lost by extended culturing on tomato; there were no differences in penetration, maturation, and reproduction between sugarbeet populations continually cultured on sugarbeet and the population continually cultured on tomato.