Systemic leukotriene B₄ receptor antagonism lowers arterial blood pressure and improves autonomic function in the spontaneously hypertensive rat

KEY POINTS: Evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B(4) (LTB(4)), a potent chemoattractant involved in the inflammatory response, but its mode of action is poorly understood. In the SHR, we observed an increase in T cells and macrophages in the brainstem; in addition, gene expression profiling data showed that LTB(4) production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. When LTB(4) receptor 1 (BLT1) receptors were blocked with CP‐105,696, arterial pressure was reduced in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in systolic blood pressure (BP) indicators. These data provide new evidence for the role of LTB(4) as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension. ABSTRACT: Accumulating evidence indicates an association between hypertension and chronic systemic inflammation in both human hypertension and experimental animal models. Previous studies in the spontaneously hypertensive rat (SHR) support a role for leukotriene B(4) (LTB(4)), a potent chemoattractant involved in the inflammatory response. However, the mechanism for LTB(4)‐mediated inflammation in hypertension is poorly understood. Here we report in the SHR, increased brainstem infiltration of T cells and macrophages plus gene expression profiling data showing that LTB(4) production, degradation and downstream signalling in the brainstem of the SHR are dynamically regulated during hypertension. Chronic blockade of the LTB(4) receptor 1 (BLT1) receptor with CP‐105,696, reduced arterial pressure in the SHR compared to the normotensive control and this reduction was associated with a significant decrease in low and high frequency spectra of systolic blood pressure, and an increase in spontaneous baroreceptor reflex gain (sBRG). These data provide new evidence for the role of LTB(4) as an important neuro‐immune pathway in the development of hypertension and therefore may serve as a novel therapeutic target for the treatment of neurogenic hypertension

Amplicon-Based Detection and Sequencing of SARS-CoV-2 in Nasopharyngeal Swabs from Patients With COVID-19 and Identification of Deletions in the Viral Genome That Encode Proteins Involved in Interferon Antagonism

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Sequencing the viral genome as the outbreak progresses is important, particularly in the identification of emerging isolates with different pathogenic potential and to identify whether nucleotide changes in the genome will impair clinical diagnostic tools such as real-time PCR assays. Although single nucleotide polymorphisms and point mutations occur during the replication of coronaviruses, one of the biggest drivers in genetic change is recombination. This can manifest itself in insertions and/or deletions in the viral genome. Therefore, sequencing strategies that underpin molecular epidemiology and inform virus biology in patients should take these factors into account. A long amplicon/read length-based RT-PCR sequencing approach focused on the Oxford Nanopore MinION/GridION platforms was developed to identify and sequence the SARS-CoV-2 genome in samples from patients with or suspected of COVID-19. The protocol, termed Rapid Sequencing Long Amplicons (RSLAs) used random primers to generate cDNA from RNA purified from a sample from a patient, followed by single or multiplex PCRs to generate longer amplicons of the viral genome. The base protocol was used to identify SARS-CoV-2 in a variety of clinical samples and proved sensitive in identifying viral RNA in samples from patients that had been declared negative using other nucleic acid-based assays (false negative). Sequencing the amplicons revealed that a number of patients had a proportion of viral genomes with deletions

A comparison, for older people with diabetes, of health and health care utilisation in two different health systems on the island of Ireland

Background: There are social and economic differences between Northern Ireland (NI) and the Republic of Ireland (ROI). There are also differences in the health care systems in the two jurisdictions. The aims of this study are to compare health (prevalence of diabetes and related complications) and health care utilisation (general practitioner, outpatient or accident and emergency utilisation) among older people with diabetes in the NI and ROI. Methods: Large scale comparable surveys of people over 50years of age in Northern Ireland (NICOLA, wave 1) and the Republic of Ireland (TILDA, wave 1) are used to compare people with diabetes (type I and type II) in the two jurisdictions. The combined data set comprises 1536 people with diabetes. A coarsened exact matching approach is used to compare health care utilisation among people with diabetes in NI and ROI with equivalent demographic, lifestyle and illness characteristics (age, gender, education, smoking status and self-related health, number of other chronic diseases and number of diabetic complications). Results: The overall prevalence of diabetes in the 50 to 84years old age group is 3.4 percentage points higher in NI (11.1% in NI, 7.7% ROI, p-value <0.01). The diabetic population in NI appear sicker – with more diabetic complications and more chronic illnesses. Comparing people with diabetes in the two jurisdictions with similar levels of illness we find that there are no statistically significant differences in GP, outpatient or A&E utilisation. Conclusion: Despite the proximity of NI and ROI there are substantial differences in the prevalence of diabetes and its related complications. Despite differences in the health services in the two jurisdictions the differences in health care utilisation for an equivalent cohort are small

Amplicon based MinION sequencing of SARS-CoV-2 and metagenomic characterisation of nasopharyngeal swabs from patients with COVID-19

COVID-19 is a complex disease phenotype where the underlying microbiome could influence morbidity and mortality. Amplicon and metagenomic MinION based sequencing was used to rapidly (within 8 hours) identify SARS-CoV-2 and assess the microbiome in nasopharyngeal swabs obtained from patients with COVID-19 by the ISARIC 4C consortium

Videoscape : An Exhibition of Video Art

Dunn describes the conceptual, performance, synaesthetic and experiential elements of video while Gale highlights the differences between television and video, traditional art forms and video and various centres for video production within Canada. Kennedy defines cybernetic, synaesthetic and synergistic aspects of video. Brief biographical notes on over 60 participating artists. Statements by some of the artists. 77 bibl. ref