Decreasing Cerebral Oxygen Consumption During Upright Tilt in Vasovagal Syncope

We measured changes in transcranial Doppler ultrasound (TCD) and near infrared spectroscopy (NIRS) during 70 degrees upright tilt in patients with recurrent vasovagal syncope (VVS, N = 20), postural tachycardia syndrome (POTS, N = 20), and healthy controls (N = 12) aged 15-27 years old. VVS was included if they fainted during testing within 5-15 min of upright tilt. We combined TCD and NIRS to obtain estimates of percent change in the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow velocity (CBFv), and oxygen extraction fraction (OEF). Over the course of 10 min of upright tilt, CBFv decreased from a baseline of 70 +/- 5 to 63 +/- 5 cm/sec in controls and 74 +/- 3 to 64 +/- 3 cm/sec in POTS while decreasing from 74 +/- 4 to 44 +/- 3 cm/sec in VVS CMRO2 was unchanged in POTS and controls during tilt while OEF increased by 19 +/- 3% and 15 +/- 3%, respectively. CMRO2 decreased by 31 +/- 3% in VVS during tilt while OEF only increased by 7 +/- 3%. Oxyhemoglobin decreased by 1.1 +/- 1.3 mumol/kg brain tissue in controls, by 1.1 +/- 1.3 mumol/kg in POTS, and 11.1 +/- 1.3 mumol/kg in VVS CBFv and CMRO2 fell steadily in VVS during upright tilt. The deficit in CMRO2 in VVS results from inadequate OEF in the face of greatly reduced CBF

Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants

BACKGROUND: Postural tachycardia syndrome (POTS) is a heterogeneous condition. We stratified patients previously evaluated for POTS on the basis of supine resting cardiac output (CO) or with the complaint of platypnea or shortness of breath during orthostasis. We hypothesize that postural hyperventilation is one cause of POTS and that hyperventilation-associated POTS occurs when initial reduction in CO is sufficiently large. We also propose that circulatory abnormalities normalize with restoration of CO2. METHODS AND RESULTS: Fifty-eight enrollees with POTS were compared with 16 healthy volunteer controls. Low CO in POTS was defined by a resting supine CO /min. Patients with shortness of breath had hyperventilation with end tidal CO2 photoplethysmography, and CO was measured by ModelFlow. Systemic vascular resistance was defined as mean arterial blood pressure/CO. End tidal CO2 and cerebral blood flow velocity of the middle cerebral artery were only reduced during head-up tilt in the hyperventilation group, whereas blood pressure was increased compared with control. We corrected the reduced end tidal CO2 in hyperventilation by addition of exogenous CO2 into a rebreathing apparatus. With added CO2, heart rate, blood pressure, CO, and systemic vascular resistance in hyperventilation became similar to control. CONCLUSIONS: We conclude that all POTS is related to decreased CO, decreased central blood volume, and increased systemic vascular resistance and that a variant of POTS is consequent to postural hyperventilation

Age and growth of Pomatomus saltatrix in the south-western Pacific Ocean (eastern Australia), with a global comparison

Context: Pomatomus saltatrix is one of few globally distributed pelagic mesopredators that is exploited heavily throughout its range. Despite the implementation of management strategies, the south-western Pacific Ocean (eastern Australian) population has few published estimates of the key life-history parameters including growth. Aims: To estimate the age and growth of P. saltatrix in the south-western Pacific and compare these with the age and growth in other populations. Methods: Age estimates were made using whole otolith readings and an age–length key was used with a length frequency distribution to estimate the age structure of the population. Eight different growth models were compared within a Bayesian framework for both juvenile and overall growth. Key results: The Schnute growth equation provided the best fit for overall growth and yielded parameter values of a = −0.15, b = 2.56, Size-at-age 1 = 24.38-cm fork length (FL) and Size-at-age 4 = 47.36 cm FL. Conclusions: P. saltatrix in the south-western Pacific has a growth rate similar to that in other populations of P. saltatrix. Implications: Despite its geographically and genetically distinct populations, P. saltatrix demonstrates a generally consistent life-history strategy of fast growth and high mortality, except for the north-western Atlantic population, which has lower mortality

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Diagnosis and Management in Young People: A Primer

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease that affects children and adolescents as well as adults. The etiology has not been established. While many pediatricians and other health-care providers are aware of ME/CFS, they often lack essential knowledge that is necessary for diagnosis and treatment. Many young patients experience symptoms for years before receiving a diagnosis. This primer, written by the International Writing Group for Pediatric ME/CFS, provides information necessary to understand, diagnose, and manage the symptoms of ME/CFS in children and adolescents. ME/CFS is characterized by overwhelming fatigue with a substantial loss of physical and mental stamina. Cardinal features are malaise and a worsening of symptoms following minimal physical or mental exertion. These post-exertional symptoms can persist for hours, days, or weeks and are not relieved by rest or sleep. Other symptoms include cognitive problems, unrefreshing or disturbed sleep, generalized or localized pain, lightheadedness, and additional symptoms in multiple organ systems. While some young patients can attend school, on a full or part-time basis, many others are wheelchair dependent, housebound, or bedbound. Prevalence estimates for pediatric ME/CFS vary from 0.1 to 0.5%. Because there is no diagnostic test for ME/CFS, diagnosis is purely clinical, based on the history and the exclusion of other fatiguing illnesses by physical examination and medical testing. Co-existing medical conditions including orthostatic intolerance (OI) are common. Successful management is based on determining the optimum balance of rest and activity to help prevent post-exertional symptom worsening. Medications are helpful to treat pain, insomnia, OI and other symptoms. The published literature on ME/CFS and specifically that describing the diagnosis and management of pediatric ME/CFS is very limited. Where published studies are lacking, recommendations are based on the clinical observations and practices of the authors

Disorder, inhomogeneity and spin dynamics in f-electron non-Fermi liquid systems

Muon spin rotation and relaxation ($\mu$SR) experiments have yielded evidence that structural disorder is an important factor in many f-electron-based non-Fermi-liquid (NFL) systems. Disorder-driven mechanisms for NFL behaviour are suggested by the observed broad and strongly temperature-dependent $\mu$SR (and NMR) linewidths in several NFL compounds and alloys. Local disorder-driven theories (Kondo disorder, Griffiths-McCoy singularity) are, however, not capable of describing the time-field scaling seen in muon spin relaxation experiments, which suggest cooperative and critical spin fluctuations rather than a distribution of local fluctuation rates. A strong empirical correlation is established between electronic disorder and slow spin fluctuations in NFL materialsComment: 24 pages, 15 figures, submitted to J. Phys.: Condens. Matte

Internal health locus of control as a predictor of pain reduction in multidisciplinary inpatient treatment for chronic pain: a retrospective study.

Purpose Chronic pain is a major health concern and its treatment requires physiological as well as psychological interventions. This study investigates the predictive value of health locus of control (HLOC) in pain intensity in chronic pain patients in an inpatient treatment setting. Patients and methods Data of 225 patients with a chronic pain condition were collected in a psychosomatic university clinic in Switzerland. Self-report assessment tools were used to measure pain intensity pre- and posttreatment and with a questionnaire dimensions of the HLOC were captured. Using hierarchic linear regression analysis, the predictive value of HLOC was investigated. Results A higher internal HLOC at pre-treatment was associated with a greater reduction in pain intensity from pre- to posttreatment (β = -0.151, p<0.05). For social-external and fatalistic-external HLOC no significant effects were observed. Conclusion Internal HLOC showed predictive value regarding the reduction in pain intensity in a multidisciplinary inpatient treatment for chronic pain, whereas social-external and fatalistic-external HLOC did not. Early interventions to strengthen internal beliefs of health control may be a promising component in multidisciplinary inpatient treatment for patients with chronic pain

The Stereotypic Response of the Pulmonary Vasculature to Respiratory Viral Infections: Findings in Mouse Models of SARS-CoV-2, Influenza A and Gammaherpesvirus Infections

The respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19) where acute respiratory distress syndrome is considered the leading cause of death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have been suggested to play a central role in the development of acute lung injury. Similar vascular changes are also observed in animal models of COVID-19. The present study aimed to determine whether the latter are specific for SARS-CoV-2 infection, investigating the vascular response in the lungs of mice infected with SARS-CoV-2 and other respiratory viruses (influenza A and murine gammaherpesvirus) by in situ approaches (histology, immunohistology, morphometry) combined with RNA sequencing and bioinformatic analysis. Non-selective recruitment of monocytes and T and B cells from larger muscular veins and arteries was observed with all viruses, matched by a comparable transcriptional response. There was no evidence of endothelial cell infection in any of the models. Both the morphological investigation and the transcriptomics approach support the interpretation that the lung vasculature in mice mounts a stereotypic response to alveolar and respiratory epithelial damage. This may have implications for the treatment and management of respiratory disease in humans

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Schizont transcriptome variation among clinical isolates and laboratory-adapted clones of the malaria parasite Plasmodium falciparum

Background: Malaria parasites are genetically polymorphic and phenotypically plastic. In studying transcriptome variation among parasites from different infections, it is challenging to overcome potentially confounding technical and biological variation between samples. We investigate variation in the major human parasite Plasmodium falciparum, generating RNA-seq data on multiple independent replicate sample preparations of merozoite-containing intra-erythrocytic schizonts from a panel of clinical isolates and from long-term laboratory-adapted clones, with a goal of robustly identifying differentially expressed genes. Results: Analysis of biological sample replicates shows that increased numbers improve the true discovery rate of differentially expressed genes, and that six independent replicates of each parasite line allowed identification of most differences that could be detected with larger numbers. For highly expressed genes, focusing on the top quartile at schizont stages, there was more power to detect differences. Comparing cultured clinical isolates and laboratory-adapted clones, genes more highly expressed in the laboratory-adapted clones include those encoding an AP2 transcription factor (PF3D7_0420300), a ubiquitin-binding protein and two putative methyl transferases. In contrast, higher expression in clinical isolates was seen for the merozoite surface protein gene dblmsp2, proposed to be a marker of schizonts forming merozoites committed to sexual differentiation. Variable expression was extremely strongly, but not exclusively, associated with genes known to be targeted by Heterochromatin Protein 1. Clinical isolates show variable expression of several known merozoite invasion ligands, as well as other genes for which new RT-qPCR assays validate the quantitation and allow characterisation in samples with more limited material. Expression levels of these genes vary among schizont preparations of different clinical isolates in the first ex vivo cycle in patient erythrocytes, but mean levels are similar to those in continuously cultured clinical isolates. Conclusions: Analysis of multiple biological sample replicates greatly improves identification of genes variably expressed between different cultured parasite lines. Clinical isolates recently established in culture show differences from long-term adapted clones in transcript levels of particular genes, and are suitable for analyses requiring biological replicates to understand parasite phenotypes and variable expression likely to be relevant in nature

Analysis of SARS-CoV-2 in Nasopharyngeal Samples from Patients with COVID-19 Illustrates Population Variation and Diverse Phenotypes, Placing the Growth Properties of Variants of Concern in Context with Other Lineages

New variants of SARS-CoV-2 are continuing to emerge and dominate the global sequence landscapes. Several variants have been labeled variants of concern (VOCs) because they may have a transmission advantage, increased risk of morbidity and/or mortality, or immune evasion upon a background of prior infection or vaccination. Placing the VOCs in context with the underlying variability of SARS-CoV-2 is essential in understanding virus evolution and selection pressures. Dominant genome sequences and the population genetics of SARS-CoV-2 in nasopharyngeal swabs from hospitalized patients were characterized. Nonsynonymous changes at a minor variant level were identified. These populations were generally preserved when isolates were amplified in cell culture. To place the Alpha, Beta, Delta, and Omicron VOCs in context, their growth was compared to clinical isolates of different lineages from earlier in the pandemic. The data indicated that the growth in cell culture of the Beta variant was more than that of the other variants in Vero E6 cells but not in hACE2-A549 cells. Looking at each time point, Beta grew more than the other VOCs in hACE2-A549 cells at 24 to 48 h postinfection. At 72 h postinfection there was no difference in the growth of any of the variants in either cell line. Overall, this work suggested that exploring the biology of SARS-CoV-2 is complicated by population dynamics and that these need to be considered with new variants. In the context of variation seen in other coronaviruses, the variants currently observed for SARS-CoV-2 are very similar in terms of their clinical spectrum of disease. IMPORTANCE SARS-CoV-2 is the causative agent of COVID-19. The virus has spread across the planet, causing a global pandemic. In common with other coronaviruses, SARS-CoV-2 genomes can become quite diverse as a consequence of replicating inside cells. This has given rise to multiple variants from the original virus that infected humans. These variants may have different properties and in the context of a widespread vaccination program may render vaccines less effective. Our research confirms the degree of genetic diversity of SARS-CoV-2 in patients. By comparing the growth of previous variants to the pattern seen with four variants of concern (VOCs) (Alpha, Beta, Delta, and Omicron), we show that, at least in cells, Beta variant growth exceeds that of Alpha, Delta, and Omicron VOCs at 24 to 48 h in both Vero E6 and hACE2-A549 cells, but by 72 h postinfection, the amount of virus is not different from that of the other VOCs