Measurement and data transmission validity of a multi-biosensor system for real-time remote exercise monitoring among cardiac patients

Background: Remote telemonitoring holds great potential to augment management of patients with coronary heart disease (CHD) and atrial fibrillation (AF) by enabling regular physiological monitoring during physical activity. Remote physiological monitoring may improve home and community exercise-based cardiac rehabilitation (exCR) programs and could improve assessment of the impact and management of pharmacological interventions for heart rate control in individuals with AF.Objective: Our aim was to evaluate the measurement validity and data transmission reliability of a remote telemonitoring system comprising a wireless multi-parameter physiological sensor, custom mobile app, and middleware platform, among individuals in sinus rhythm and AF.Methods: Participants in sinus rhythm and with AF undertook simulated daily activities, low, moderate, and/or high intensity exercise. Remote monitoring system heart rate and respiratory rate were compared to reference measures (12-lead ECG and indirect calorimeter). Wireless data transmission loss was calculated between the sensor, mobile app, and remote Internet server.Results: Median heart rate (-0.30 to 1.10 b∙min-1) and respiratory rate (-1.25 to 0.39 br∙min-1) measurement biases were small, yet statistically significant (all P≤.003) due to the large number of observations. Measurement reliability was generally excellent (rho=.87-.97, all P<.001; intraclass correlation coefficient [ICC]=.94-.98, all P<.001; coefficient of variation [CV]=2.24-7.94%), although respiratory rate measurement reliability was poor among AF participants (rho=.43, P<.001; ICC=.55, P<.001; CV=16.61%). Data loss was minimal (<5%) when all system components were active; however, instability of the network hosting the remote data capture server resulted in data loss at the remote Internet server during some trials.Conclusions: System validity was sufficient for remote monitoring of heart and respiratory rates across a range of exercise intensities. Remote exercise monitoring has potential to augment current exCR and heart rate control management approaches by enabling the provision of individually tailored care to individuals outside traditional clinical environments

Promoter optimisation of lentiviral vectors for efficient insulin gene expression in canine mesenchymal stromal cells: potential surrogate beta cells.

BACKGROUND: The lack of an ideal cell type that can be easily acquired, modified to produce insulin, and re-implanted has been a limitation for ex vivo insulin gene therapy. Canine diabetes is currently treated with human insulin and is a good model for human diabetes. Mesenchymal stromal cells (MSCs) are a promising candidate cell type for gene therapy. In the present study, we optimised insulin production using lentiviral transduced canine MSCs (cMSCs), aiming to evaluate their ability for use as surrogate beta cells. METHODS: Canine MSCs were derived from bone marrow and validated by measuring the expression of MSC lineage specific markers. Lentivirus vectors encoding the proinsulin gene (with or without a Kozak sequence) under the control of spleen focus forming virus, cytomegalovirus, elongation factor 1α and simian virus 40 promotors were generated and used to transduce primary cMSCs and a hepatocyte cell line. The insulin-producing capacity of transduced primary cMSCs was assessed by measuring the concentration of C-peptide produced. RESULTS: Primary cMSC could be readily expanded in culture and efficiently transduced using lentiviral vectors encoding proinsulin. Increasing the multiplicity of infection from 3 to 20 led to an increase in C-peptide secretion (from 1700 to 4000 pmol/l). The spleen focus forming virus promoter conferred the strongest transcriptional ability. CONCLUSIONS: The results of the present study suggest that optimised lentiviral transduction of the insulin gene into primary cMSCs renders these cells capable of secreting insulin over both the short- and long-term, in sufficient quantities in vitro to support their potential use in insulin gene therapy.The study was funded by the Lollipop Trust. Work in the laboratory is supported by the Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/jgm.290

Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post‐COVID‐19 condition

Background The post‐COVID‐19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID‐19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC. Objectives Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials. Search methods Laboratory studies review We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms ‘COVID’, ‘amyloid’, ‘fibrin’, ‘fibrinogen’. Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID‐19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. Selection criteria Laboratory studies review Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. Randomized controlled trials review Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC. Data collection and analysis Two review authors applied study inclusion criteria to identify eligible studies and extracted data. Laboratory studies review We assessed the risk of bias of included studies using pre‐developed methods for laboratory studies. We planned to perform synthesis without meta‐analysis (SWiM) as described in our protocol. Randomized controlled trials review We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post‐COVID‐19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind). Main results Laboratory studies review We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. Randomized controlled trials review We identified no trials meeting our inclusion criteria. Authors' conclusions In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well‐conducted randomized controlled trial

Liver test abnormalities in patients with HIV mono-infection: assessment with simple noninvasive fibrosis markers

Abstract Background Patients with HIV mono-infection may develop chronic liver disease due to a number of factors including hepatic steatosis. We estimated the prevalence and predictors of hepatic steatosis and fibrosis in a cohort of HIV-mono-infected patients with persistently deranged liver function tests

Autochthonous Human Babesia divergens Infection, England

We describe a case of autochthonous human Babesia divergens infection in an immunocompetent woman in England. The patient had fever, hemolysis, multiorgan failure, and 18% parasitemia. We confirmed B. divergens by 18S rDNA PCR and sequencing. Clinicians should consider babesiosis as a differential diagnosis in patients with unexplained hemolysis

Illegal activity in the UK halal (sheep) supply chain: towards greater understanding

Food Supply chain theory and practice assumes that the processes involved are legal and value adding. In this paper, using examples from the UK halal (sheep) meat supply chain, we outline a value extracting value chain through a mixed methods qualitative approach consisting of face-to-face-interviews and a documentary research strategy underpinned by Narrative Inquiry. Building on previous theoretical work on Illegal Rural Enterprise, we present a narrative of an individual rogue-farmer, and explore his involvement in the illegal halal (‘smokies’) trade over a fifteen-year period. The paper provides a compelling story that will enable investigators to better understand illegal enterprise from a supply chain perspective and more adequately address the concerns stated in the UK Fraud Act 2006. The paper will be useful to food standards agencies in that furthers our understanding of entrepreneurial practice and morality in the food industry. The results demonstrate that illegal rural enterprise is a multi-faceted concept that requires an understanding of business practices and processes alongside a multi-agency approach to enterprise orientated crime. Our approach suggests that supply chains can be ‘flipped’ in order to understand illegal processes in addition to conventional legal processes

Predictors of aetiology and outcomes of acute gastrointestinal illness in returning travellers: a retrospective cohort analysis.

BACKGROUND: Gastrointestinal illness is a major cause of morbidity in travellers and is a common reason for presentation to healthcare services on return. Whilst the aetiology of imported gastrointestinal disease is predominantly infectious, outcomes are variable due to a range of phenomena such as post-infectious irritable bowel syndrome, drug resistance and occult pathology (both infectious and non-infectious). Previous studies have focussed on predictors of aetiology of gastrointestinal disease in travellers; we present a retrospective study combining both aetiological and early outcome data in a large cohort of returned travellers. METHOD: We identified 1450 patients who attended our post-travel walk-in clinic with gastrointestinal symptoms between 2010 and 2016. Demographic, travel, clinical and laboratory data was collected through case note review. Logistic regression analysis to examine correlates of aetiology and outcome were performed in R (CRAN Project 2017). RESULTS: Of 1450 patients in our cohort 153 reported bloody diarrhoea and 1081 (74.6%) reported non-bloody diarrhoea. A definitive microbiological diagnosis was made in 310 (20.8%) of which 137 (9.4%) had a parasite identified and 111 (7.7%) had a bacterial cause identified. Factors associated with a parasitological diagnosis included history of travel to South Asia (aOR = 2.55; 95%CI 1.75-3.70, p 5iu/dL (aOR = 4.68; 95%CI 2.91-7.72, p < 0.0001). The majority (1235/1450, 82.6%) reported full symptomatic resolution by the first follow up visit; factors associated with lack of symptomatic resolution included female gender (aOR = 1.45 95%CI 1.06-1.99, p < 0.05), dysenteric diarrhoea (aOR = 2.14 (95%CI 1.38-3.25, p < 0.0005) and elevated peripheral leukocyte count (aOR = 1.58 95%CI 1.02-2.40, p < 0.05). CONCLUSIONS: In a cohort of returned travellers, we were able to identify multiple factors that are correlated with both aetiology and outcome of imported gastrointestinal syndromes. We predict these data will be valuable in the development of diagnostic and therapeutic pathways for patients with imported gastrointestinal infections

ILEEM-survey on the Heart Team approach and team training for lead extraction procedures

Background: The Heart Team approach has become an integral part of modern cardiovascular medicine. To evaluate current opinions and real-world practice among lead extraction practitioners, an online survey was created and distributed among a pool of lead extraction specialists participating in the International Lead Extraction Expert Meeting (ILEEM) 2018. Methods: The online survey consisted of 10 questions and was performed using an online survey tool (www.surveymonkey.com). The collector link was sent to 48 lead extraction experts via email. Results: A total of 43 answers were collected (89% return rate) from lead extraction experts in 16 different countries. A great majority (83.7%) of the respondents performed more than 30 lead extraction procedures per year. The most common procedural environment in this survey was the hybrid operating room (67.4%). Most procedures were performed by electrophysiologists and cardiologists (80.9%). Important additional members of the current lead extraction teams were cardiac surgeons (79.1%), anesthesiologists (95.3%) and operating room scrub nurses (76.7%). An extended Heart Team is regarded beneficial for patient care by 86.0%, with potential further members being infectious diseases specialists, intensivists and radiologists. Team training activities are performed in 48.8% of participating centers. Conclusions: This survey supports the importance of establishing lead extraction Heart Teams in specialized lead extraction centers to potentially improve patient outcomes. The concept of a core and an extended heart team approach in lead extraction procedures is introduced

Efficacy and safety of an intravenous monoclonal anti-HBs in chronic hepatitis B patients

Background Aims: In this study the safety and efficacy of a monoclonal anti-HBs, Tuvirumab (Mab), were investigated. Tuvirumab is a human monoclonal antibody recognizing the stable 'a'-determinant of the HBsAg. Methods: We included ten chronic hepatitis B patients: four received monotherapy, and six combination therapy with interferon alpha 2b. Results: Because the development of insoluble [HBsAg-HBsAb] complexes led to adverse events, the Mab dose had to be reduced in seven patients. In nine patients treatment was stopped prematurely because of lack of efficacy, i.e. neutralization of HBsAg in serum. However, temporary HBsAg levels were reduced by at least 50% in all patients; in three patients receiving combination therapy, background levels of HBsAg in serum were reached. A loss of serum HBV-DNA was seen in three patients in the combination group, followed by HBeAg seroconversion in two patients. Conclusions: We conclude that Mab was not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg. Whether a combination of Mab with an antiviral agent that reduces the HBsAg load - and therefore minimizes the risk of adverse events - may result in clinical efficacy should be investigated

A historical reflection on the discovery of human retroviruses

The discovery of HIV-1 as the cause of AIDS was one of the major scientific achievements during the last century. Here the events leading to this discovery are reviewed with particular attention to priority and actual contributions by those involved. Since I would argue that discovering HIV was dependent on the previous discovery of the first human retrovirus HTLV-I, the history of this discovery is also re-examined. The first human retroviruses (HTLV-I) was first reported by Robert C. Gallo and coworkers in 1980 and reconfirmed by Yorio Hinuma and coworkers in 1981. These discoveries were in turn dependent on the previous discovery by Gallo and coworkers in 1976 of interleukin 2 or T-cell growth factor as it was called then. HTLV-II was described by Gallo's group in 1982. A human retrovirus distinct from HTLV-I and HTLV-II in that it was shown to have the morphology of a lentivirus was in my mind described for the first time by Luc Montagnier in an oral presentation at Cold Spring Harbor in September of 1983. This virus was isolated from a patient with lymphadenopathy using the protocol previously described for HTLV by Gallo. The first peer reviewed paper by Montagnier's group of such a retrovirus, isolated from two siblings of whom one with AIDS, appeared in Lancet in April of 1984. However, the proof that a new human retrovirus (HIV-1) was the cause of AIDS was first established in four publications by Gallo's group in the May 4th issue of Science in 1984