Verylow frequency variability in arterial blood pressure and blood volume pulse

Several parameters of the cardiovascular system fluctuate spontaenously owing to the activity of the autonomic nervous system. In the study, the simultaneous very low frequency (VLF) fluctuations of the arterial blood pressure, the tissue blood content and the tissue blood volume pulse are investigated. The latter two parameters are derived from the baseline BL and the amplitude AM of the photoplethysmographic (PPG) signal, measured on the fingertips of 20 healthy male subjects: the changes in the PPG parameters AM and BV, defined by BV=const.-BL, are related to the change in the tissue blood volume pulse and the total tissue blood volume, respectively. The VLF fluctuations in BV and AM are directly correlated, those of AM preceding those of BV by 4–13 heart-beats. The VLF fluctuations in the systolic (SBP) and the diastolic (DBP) blood pressure are inversely correlated to those of AM and BV, those of AM preceding those of SBP and lagging behing those of DBP by about one heart-beat. For most subjects, the period P of the PPG pulse, which is equal to the cardiac cycle period, directly correlates with AM and BV and inversely correlates with DBP and SBP. On average, the fluctuations fluctuations in tissue blood volume, systolic blood volume pulse, diastolic and systolic blood pressure, and heart period, together with their interrelationship, can provide a better understanding of the autonomic nervous control of the peripheral circulation and a potential tool for the evaluation of its function.     

Drug adverse events in hospitals in the State of Rio de Janeiro, Brazil

OBJECTIVE: The occurrence of drug adverse events in hospital settings is high and generates cost excess. The purpose of the study was to identify drug-related events during hospital admissions and to estimate their prevalence. METHODS: A retrospective study was carried out in the State of Rio de Janeiro, Southeastern Brazil. Hospitalizations from the Brazilian Health System's national hospital database during the period between 1999 and 2002 were assessed. Admitted cases including suspected drug adverse event cases with ICD-10 (2000) coding in the main diagnosis and/or secondary diagnosis fields were included in the study. Means and standard deviations of continuous variables as well as the statistical significance of differences were estimated using variance analysis (ANOVA with a 95% confidence interval). RESULTS: There were identified 3,421 drug-related adverse events, and a prevalence of 1.8 cases per 1,000 hospitalizations was estimated. Most cases occurred in males (64.5%) admitted in contracted (34.9%) and local public hospitals (23.1%) in the departments of psychiatry (51.4%) and internal medicine (45.2%), of them, 84.1% were discharged. Most of them were adverse drug reactions or drug poisoning, and there were significant difference (p<0.000) regarding age and length of stay between these categories. Patients having adverse events were younger (35.8 vs 40.5 years old) and stayed longer in hospital (26.5 vs 5.0 days). CONCLUSIONS: The frequency of drug adverse events, although lower than those findings of international studies, is significant. National hospital admission database was considered useful in the study of drug-related events.     

Out-of-pocket drug expenditures by retirees and pensioners 60 years and older in Belo Horizonte, Minas Gerais, Brazil

The aim of this study was to analyze the structure of private drug expenditures by individuals 60 years and older in Belo Horizonte, Minas Gerais, Brazil. The study population consisted of a representative sample of retirees under the National Social Security Institute (INSS) in the city of Belo Horizonte, interviewed through a household survey. Monthly out-of-pocket drug expenditures were calculated, and a drug cost structure analysis was performed according to drug characteristics. 667 elders answered the survey. Mean drug expenditures per month were US$ 38.91. The therapeutic groups representing the majority of drug expenditures were: cardiovascular system (26%), nervous system (24%), and digestive/metabolic system (15%). Considering drug registration categories, brand-name drugs accounted for the majority of expenditures (54%). The results of this study can support policies to improve both access to medicines and overall health conditions for the Brazilian elderly population.     

Correlation of blood temperature fluctuations with blood pressure waves

Summary Constant blood temperature in the pulmonary artery is assumed when the thermal dilution method is used for cardiac output determination. In some cases, however, slow temperature fluctuations (2–6 cycles per min.) occur in arterial and venous blood and interfere in the measurement. Those thermal fluctuations were investigated in the pulmonary artery and venae cavae of dogs. The temperature variations were found to be correlated with blood pressure waves: an increase of blood pressure was accompanied by an increase in the blood temperature in the pulmonary artery and a decrease in the blood temperature in the venae cavae. Therefore, measurement of the temperature of the pulmonary artery relative to that of the venae cavae does not rule out those fluctuations, and will not improve the thermal dilution method.

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Zusammenfassung Bei Bestimmung des Herzminutenvolumens nach der Kälteverdünnungsmethode wird eine konstante Bluttemperatur in der Pulmonalarterie unterstellt. Jedoch treten in einigen Fällen langsame Temperaturfluktuationen (2–6 Zykl. pro Minute) im arteriellen und venösen Blut auf, die mit der Messung interferieren. Diese Temperaturfluktuationen wurden in der Pulmonalarterie und V. cava des Hundes untersucht. Es zeigte sich, daß die Änderung der Temperatur mit den Blutdruckwellen korreliert sind: Ein Anstieg des Blutdrucks war von einem Anstieg der Bluttemperatur in der Pulmonalarterie und einem Rückgang der Temperatur in der V. cava begleitet. Die Meßprozedur läßt sich nicht dadurch verbessern, daß die Temperatur in der Pulmonalarterie auf die der Hohlvenen bezogen wird.

     

Revealing lineage-related signals in single-cell gene expression using random matrix theory

Gene expression profiles of a cellular population, generated by single-cell RNA sequencing, contains rich information about biological state, including cell type, cell cycle phase, gene regulatory patterns, and location within the tissue of origin. A major challenge is to disentangle information about these different biological states from each other, including distinguishing from cell lineage, since the correlation of cellular expression patterns is necessarily contaminated by ancestry. Here, we use a recent advance in random matrix theory, discovered in the context of protein phylogeny, to identify differentiation or ancestry-related processes in single-cell data. Qin and Colwell [C. Qin, L. J. Colwell, Proc. Natl. Acad. Sci. U.S.A. 115, 690–695 (2018)] showed that ancestral relationships in protein sequences create a power-law signature in the covariance eigenvalue distribution. We demonstrate the existence of such signatures in scRNA-seq data and that the genes driving them are indeed related to differentiation and developmental pathways. We predict the existence of similar power-law signatures for cells along linear trajectories and demonstrate this for linearly differentiating systems. Furthermore, we generalize to show that the same signatures can arise for cells along tissue-specific spatial trajectories. We illustrate these principles in diverse tissues and organisms, including the mammalian epidermis and lung, Drosophila whole-embryo, adult Hydra, dendritic cells, the intestinal epithelium, and cells undergoing induced pluripotent stem cells (iPSC) reprogramming. We show how these results can be used to interpret the gradual dynamics of lineage structure along iPSC reprogramming. Together, we provide a framework that can be used to identify signatures of specific biological processes in single-cell data without prior knowledge and identify candidate genes associated with these processes.

Advances in single-cell RNA sequencing (scRNA-seq) have led to the identification of diverse and heterogeneous cellular populations (1–3). Sampling a large number of nonsynchronized single cells also enables reconstruction of tissue structure (4–6), the cell cycle (7), and differentiation pathways (reviewed in refs. 8 and 9). Trajectory inference in particular, including inferring developmental trajectories or lineage relationships between cells, is a fast-moving research field and includes dozens of methods that have been proposed to approach this challenge [e.g., in refs. 10–17 and recent benchmarking analysis (9)]. In general, these inference approaches rely on the assumption that single-cell expression profiles span a low dimensional manifold in high dimensional expression space, which represents an underlying biological process and the progression, or “phase,” of single cells along that process. Therefore, in principle, it is possible to both reconstruct the process and recover the locations of single cells along it. Using rich single-cell data, it has also been possible to infer regulatory interaction networks within single cells and infer their variation across different perturbations and conditions [e.g., refs. 11 and 18 and recent benchmarking study (19)]. However, the biological picture is more complicated: The expression profile of each cell contains multiple signatures, simultaneously encoding information about its location within a tissue and its microenvironment, multiple temporal processes, and differentiation pathways as well as internal patterns of regulatory interactions, along with technical or experimentally driven signals (2). Despite recent advances (e.g., refs. 20–25), disentangling these different biological processes from each other and from signals attributed to the experimental procedure in single-cell expression data is still a major challenge.The key insight of this paper is that different biological processes may exhibit different geometric, or topological, structures in gene expression space, which induce distinct patterns in the covariance spectrum of single-cell data (which can relate both different cells and different genes to each other). While biological processes such as differentiation, the cell cycle, and spatial relationships induce correlations between different cells, regulatory interactions induce correlations between different genes. This is directly analogous to protein sequence data that exhibit both phylogeny-driven correlations between different sequences as well as correlation between different amino acids in individual sequences arising from physical structural interactions. Qin and Colwell (26) demonstrated that phylogenetic correlations between sequences lead to a characteristic signature in the eigenvalue distribution of the sequence covariance matrix, specifically a power-law tail of large eigenvalues, in which the exponent of the power law is determined by the underlying branching process.Here, we demonstrate that this same phenomenon occurs in scRNA-seq data, in which lineage or developmental signals give rise to unique covariance structures, reflecting either cell-to-cell or gene-to-gene correlations between the vectors representing the gene expression profiles for each cell or between the vectors representing the expression of each gene across all cells, respectively. Specifically, we find power-law tails of large eigenvalues in the spectra of the gene–gene covariance matrix of the data. We demonstrate this phenomenon for various types of single-cell data, including mammalian lung and epidermis, fly whole embryo, whole Hydra, and cells undergoing induced pluripotent stem cells (iPSCs) reprogramming. We show that single yeast cells do not exhibit such signature for lineage. We show that power-law tails of large eigenvalues are also expected to arise for populations of cells along linear trajectories in differentiating systems and demonstrate such signal for subpopulations of dendritic cells (DCs). Furthermore, we generalize these findings to populations of cells whose expression correlations are induced by their spatial organization within a tissue, which may be a result, for example, of external gradients of oxygen, morphogenes or nutrients, patterns of cellular movement, or cell–cell communication. Specifically, we exemplify our findings in the case of enterocytes along the crypt-to-villus axis in the intestinal epithelium. We support these findings by showing that the genes driving the power-law covariance patterns are indeed related to lineage and developmental processes. Finally, we show that we can predict the dynamically changing spectral signatures of differentiating cells sequenced at multiple time points, such as in iPSC reprogramming.     

Fructose-1,6-diphosphatase deficiency: a rare cause of prolonged prothrombin time

A 20-year-old woman presented with severe life-threatening metabolic acidosis and hypoglycemia. In addition, her blood tests revealed elevated hepatic enzymes and a prolonged prothrombin time, with a reduction in factor VII activity. After treatment with a glucose and bicarbonate-containing intravenous infusion, there was a dramatic clinical improvement and normalization of the prothrombin time within 2 days. The patient was found to have fructose-1,6-diphosphatase deficiency, a rare metabolic disorder which has not been described previously as causing coagulation defects.     

Distribution of hantavirus foci in Belgium

During 1999 and 2000, we performed rodent captures on 15 sites all over Belgium to evaluate the presence of hantaviruses in local rodent populations. Viral antibody and RNA detection was performed by ELISA/focus reduction neutralisation test and RT-PCR, respectively. We found hantavirus-positive rodents on 13 out of 15 trapping sites and 3 rodent species were found positive for hantavirus infection. Apart from Puumala virus that was carried by Clethrionomys glareolus, 2 additional rodent species, Microtus arvalis and Apodemus sylvaticus, were found antibody- and/or RNA-positive.     

Unilateral pulmonary edema: a rare presentation of congestive heart failure

The authors present a case of an 85-year-old woman known to suffer from severe congestive heart failure who presented with dyspnea and a unilateral infiltrate in the right lung on chest x-ray. Following clinical judgment, she was diagnosed with unilateral pulmonary edema and was treated accordingly, with rapid improvement of symptoms and disappearance of the infiltrate within 12 hours. The patient had been hospitalized many times during the previous years with pulmonary edema affecting both lung fields. Unilateral pulmonary edema is an unusual clinical condition that has been reported as a manifestation of left heart failure, mostly affecting the right lung. The authors emphasize the possible presentation of unilateral pulmonary edema in a patient with heart failure and recurrent bilateral pulmonary edema.