Influence of Genetics on Disease Susceptibility and Progression

For many chronic diseases, the influence of genetics is complex and phenotypes do not conform to simpl

Delivering multi-disease screening to migrants for latent TB and blood-borne viruses in an emergency department setting: A feasibility study.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) in migrants is important for elimination of tuberculosis in low-incidence countries, alongside the need to detect blood-borne infections to align with new guidelines on migrant screening for multiple infections in European countries. However, feasibility needs to be better understood. METHODS: We did a feasibility study to test an innovative screening model offering combined testing for LTBI (QuantiFERON), HIV, hepatitis B/C in a UK emergency department, with two year follow-up. RESULTS: 96 economic migrants, asylum seekers and refugees from 43 countries were screened (46 [47.9%] women; mean age 35.2 years [SD 11.7; range 18-73]; mean time in the UK 4.8 years [SD 3.2; range 0-10]). 14 migrants (14.6%) tested positive for LTBI alongside HIV [1], hepatitis B [2], and hepatitis C [1] Of migrants with LTBI, 5 (35.7%) were successfully engaged in treatment. 74 (77.1%) migrants reported no previous screening since migrating to the UK. CONCLUSION: Multi-disease screening in this setting is feasible and merits being further tested in larger-scale studies. However, greater emphasis must be placed on ensuring successful treatment outcomes. We identified major gaps in current screening provision; most migrants had been offered no prior screening despite several years since migration, which holds relevance to policy and practice in the UK and other European countries

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Effects of β blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke

Summary Background Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that β blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk

Mitochondrial DNA depletion induces innate immune dysfunction rescued by interferon-γ

Monocytes from sepsis patients have mitochondrial DNA (mtDNA) depletion and immune deactivation. Here we find that THP-1 cell immune responses are impaired by experimentally depleting mtDNA, through dysregulated immune signalling, and rescued by interferon-γ treatment

Histopathological Observation of Immunized Rhesus Macaques with Plague Vaccines after Subcutaneous Infection of Yersinia pestis

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×106 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague

Motion -Helicobacter pylori causes or worsens GERD: Arguments against the motion

Data from large epidemiological studies show that Helicobacter pylori is less prevalent in patients with gastroesophageal reflux disease (GERD) than in control subjects. The more virulent cagA-positive strains of the organism are also less commonly seen in patients with erosive esophagitis and in those with Barrett's esophagus than in those with less severe forms of GERD. Although the relationship between H pylori and gastric physiology is complex, the organism has little effect on acid secretion in most North American or Western European subjects, and has a net suppressive effect, especially in elderly subjects, in other parts of the world. Thus, the organism has a potential protective effect against GERD, which is exacerbated by gastric acidity. H pylori has no proven effect on other gastric factors that might provoke reflux, including delayed gastric emptying or inappropriate relaxation of the gastric fundus. Two well-designed interventional studies have found that eradication of H pylori either provoked GERD or had no effect. A third smaller study, which seemed to demonstrate that persistent infection was associated with GERD, was flawed, in that the two treatment groups were not comparable. The evidence thus does not support the idea that H pylori infection provokes or aggravates GERD. Key Words: Gastroesophageal reflux disease; Helicobacter pylori Proposition -Helicobacter pylori cause ou aggrave le reflux gastro-oesophagien : arguments contre la proposition RÉSUMÉ : Selon des données provenant d'importantes études épidémi-ologiques, la prévalence d'Helicobacter pylori serait moins forte chez les patients souffrant de reflux gastro-oesophagien (RGO) que chez les témoins. Les souches positives à l'égard du gène cagA les plus virulentes se rencontrent également moins souvent chez les patients présentant une oesophagite érosive ou un oesophage de Barrett que chez ceux qui sont atteints de formes moins graves de RGO. Même si les liens entre H. pylori et la physiologie de l'estomac sont complexes, le micro-organisme n'a que très peu d'effet sur la sécrétion d'acide chez la plupart des sujets en Amérique du Nord et en Europe occidentale et a un effet suppressif marqué, surtout chez les sujets âgés, dans d'autres parties du monde. La bactérie a donc un effet potentiellement protecteur contre le RGO, amplifié par l'acidité gastrique. Par ailleurs, H. pylori n'a aucun effet avéré sur d'autres facteurs de nature gastrique, susceptibles de provoquer le reflux, comme le retard de vidange de l'estomac ou la relaxation inappropriée de la grosse tubérosité gastrique. Deux études interventionnelles bien conçues ont montré que l'éradication d'H. pylori provoquait le RGO ou n'avait aucun effet. Une troisième étude, plus petite, semblant montrer une association entre une infection persistante et le RGO comportait un vice de forme en ce sens que les deux groupes expérimentaux n'étaient pas comparables. Aussi l'hypothèse selon laquelle une infection à H. pylori provoque ou aggrave le RGO est-elle dénuée de fondement

The Challenges of Brain Disease

Faculty Profile Presentation: 1:31:3

SIR MICHAEL GEORGE PARKE STOKER - Publications from SIR MICHAEL GEORGE PARKE STOKER. 4 July 1918 — 13 August 2013

Michael Stoker was a renowned virologist and cell biologist. He gained his interest in research while serving as a medical officer during the Second World War in India, studying infectious diseases such as typhus. He began to study viruses in the Department of Pathology in Cambridge and in 1958 was appointed to the first established UK chair of virology and as head of the Medical Research Council Virus Unit at the University of Glasgow. He pioneered studies of cancer-causing viruses using polyomavirus of mice, and developed the baby hamster kidney cell lines still used today for vaccine production. In 1968 he moved to London as director of research at the Imperial Cancer Research Fund (ICRF) Laboratories, now part of the Cancer Research UK funded laboratories at the Francis Crick Institute. He brought many virologists to ICRF, while he himself turned to cell biology, first of mesenchymal cells and then of normal and malignant epithelial cells, particularly breast epithelium. Returning to Cambridge in 1978, he discovered scatter factor (also known as hepatocyte growth factor), a paracrine cytokine that stimulates motility and proliferation of epithelial cells. Michael had broad-ranging interests and there are few virologists in the UK who have not been influenced either by him directly or by his protégés. Among the many activities beyond the institutions where he worked, he served from 1976 to 1981 as Foreign Secretary and Vice-President of the Royal Society