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Gastric malignancies will probably never attract the same attention as breast, prostate or lung carcinomas. Yet their prognosis is often bleak. But recent advances raise the prospect of transforming outcomes in this notoriously difficult‐to‐treat malignancy into a cancer manageable by precision medicine. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 outbreak started in March 2020 with more than 120,552,261 cases at present and having caused over 2,667,248 deaths worldwide at the time this paper was written. The clinical signs of SARSCoV-2 infection are especially evident in the respiratory and cardiovascular systems. Patients can be asymptomatic or present mild respiratory symptoms to severe acute lung injury leading to multiorgan failure and death. The study aims to assess the levels of serum 25-hydroxyvitamin D (25-(OH)-D) in 20 hospitalized patients infected with SARS-CoV-2 and 20 deceased people and to analyze the influence of vitamin D status on the severity of their disease. Methods: The present study was conducted on 40 patients who tested positive for SARS-CoV-2 infection. They were divided into two groups: 20 patients admitted to the "Victor Babes" Hospital of Infectious Diseases and 20 postmortem cases autopsied at the Institute of Legal Medicine Timisoara, Romania. During the autopsy, blood and bronchial fluid samples were collected for the laboratory. Automate Viral RNA extraction was performed on the Maxwell 48 RSC Extraction System (Promega, USA) using the Maxwell RSC Viral Total Nucleic Acid Purification kit (Promega, USA). After RNA extraction, the samples were amplified on a 7500 real-time PCR (Applied Biosystems, USA) using the genesig® Real-Time PCR Assay 2G (Primer Design, UK). Results: The living and deceased patients selected for the research presented decreased vitamin D levels, which are associated with increased levels of D-dimers, C reactive protein (CRP), and interleukin-6 (IL-6). These patients had a severe form of the SARS-CoV-2 disease, which led to death. Conclusions: We conclude that deficiency of vitamin D in patients infected with SARS-CoV-2 presents a major risk factor related to the evolution and severity of the disease. [ABSTRACT FROM AUTHOR]

Cetacean morbilliviruses (CeMVs) are significant causes of mortality in many cetacean species in epizootics and smaller outbreaks. Despite the prominence of skin lesions in seals and terrestrial animals, including humans, affected by other morbilliviruses, they have not been reported in CeMV-infected cetaceans. Here we report CeMV-associated skin lesions in a fin whale (Balaenoptera physalus) with subacute, systemic CeMV infection that live-stranded in Scotland, UK. Grossly, the skin was sloughing in large sheets, presumed due to autolysis, but histological examination showed syncytia, below the dermoepidermal junction, that were strongly immunopositive for morbillivirus antigen, as were syncytia in other organs. By polymerase chain reaction (PCR), the relative load of CeMV-specific RNA was largest in the liver and urinary bladder, even in formalin-fixed, paraffin-wax embedded samples. Levels were low in skin and only detectable in frozen samples. Genetic comparison of the CeMV revealed close alignment with isolates from fin whales from the North Atlantic Ocean and Mediterranean Sea, but that it was distinct from the porpoise CeMV clade. These findings show skin samples can be used to diagnose CeMV infection in cetaceans, highlighting the potential of ante-mortem sampling for monitoring disease in current populations and assessment of changes in host and pathogen genetics. [ABSTRACT FROM AUTHOR]

Mycobacterium bovis is the causative agent of bovine tuberculosis (TB), a cattle disease of global importance. M. bovis infects bovine macrophages (Mø) and subverts the host cell response to generate a suitable niche for survival and replication. We investigated the role of the anti-inflammatory cytokine interleukin (IL) 10 during in vitro infection of bovine monocyte-derived Mø (bMDM) with two divergent UK strains of M. bovis, which differentially modulate expression of IL10. The use of IL10-targeting siRNA revealed that IL10 inhibited the production of IL1B, IL6, tumour necrosis factor (TNF) and interferon gamma (IFNG) during infection of bMDM with the M. bovis strain G18. In contrast, IL10 only regulated a subset of these genes; TNF and IFNG, during infection with the M. bovis reference strain AF2122/97. Furthermore, nitric oxide (NO) production was modulated by IL10 during AF2122/97 infection, but not at the nitric oxide synthase 2 (NOS2) mRNA level, as observed during G18 infection. However, IL10 was found to promote survival of both M. bovis strains during early bMDM infection, but this effect disappeared after 24 h. The role of IL10-induced modulation of TNF, IFNG and NO production in M. bovis survival was investigated using siRNA targeting TNF, IFNG receptor 1 (IFNGR1) and NOS2. Knock-down of these genes individually did not promote survival of either M. bovis strain and therefore modulation of these genes does not account for the effect of IL10 on M. bovis survival. However, TNF knock-down was found to be detrimental to the survival of the M. bovis strain G18 during early infection. The results provide further evidence for the importance of IL10 during M. bovis infection of Mø. Furthermore, they highlight M. bovis strain specific differences in the interaction with the infected bMDM, which may influence the course of infection and progression of bovine TB. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome is a hereditary cancer syndrome caused by constitutional pathogenic variants in the DNA mismatch repair (MMR) system, leading to increased risk of colorectal, endometrial and other cancers. The study aimed to identify the incremental costs and consequences of strategies to identify Lynch syndrome in women with endometrial cancer. Methods: A decision-analytic model was developed to evaluate the relative cost-effectiveness of reflex testing strategies for identifying Lynch syndrome in women with endometrial cancer taking the NHS perspective and a lifetime horizon. Model input parameters were sourced from various published sources. Consequences were measured using quality-adjusted life years (QALYs). A cost-effectiveness threshold of £20 000/QALY was used. Results: Reflex testing for Lynch syndrome using MMR immunohistochemistry and MLH1 methylation testing was cost-effective versus no testing, costing £14 200 per QALY gained. There was uncertainty due to parameter imprecision, with an estimated 42% chance this strategy is not cost-effective compared with no testing. Age had a significant impact on cost-effectiveness, with testing not predicted to be cost-effective in patients aged 65 years and over. Conclusions: Testing for Lynch syndrome in younger women with endometrial cancer using MMR immunohistochemistry and MLH1 methylation testing may be cost-effective. Age cut-offs may be controversial and adversely affect implementation. [ABSTRACT FROM AUTHOR]

Background: Some case-control studies reported that mitochondrial haplogroups could be associated with the onset of cardiovascular diseases (CVD), but the literature regarding this topic is limited. We aimed to investigate whether any mitochondrial haplogroup carried a higher or lower risk of CVD in a large cohort of North American people affected by knee osteoarthritis or at high risk for this condition. Materials and methods: A longitudinal cohort study including individuals from the Osteoarthritis Initiative was done. Haplogroups were assigned through a combination of sequencing and PCR-RFLP techniques. All the mitochondrial haplogroups have been named following this nomenclature: HV, JT, UK, IWX, and superHV/others. The strength of the association between mitochondrial haplogroups and incident CVD was evaluated through a Cox’s regression analysis, adjusted for potential confounders, and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). Results: Overall, 3,288 Caucasian participants (56.8% women) with a mean age of 61.3±9.2 years without CVD at baseline were included. During a median follow-up of 8 years, 322 individuals (= 9.8% of baseline population) developed a CVD. After adjusting for 11 potential confounders at baseline and taking those with the HV haplotype as reference (the most frequent), those with JT carried a significant lower risk of CVD (HR = 0.75; 95%CI: 0.54–0.96; p = 0.03). Participants with the J haplogroup had the lowest risk of CVD (HR = 0.71; 95%CI: 0.46–0.95; p = 0.02). Conclusions: The presence of JT haplogroups (particularly J) may be associated with a reduced risk of CVD. However, this result was not based on a high level of statistical significance. Thus, future research with larger sample size is needed to assess whether our results can be corroborated. [ABSTRACT FROM AUTHOR]

This review covers 35 years (1980–2014) representing a period of changing land use and agricultural practices in the United Kingdom (UK), which have also witnessed a marked change in the availability and application of new diagnostic technologies. During this period there have been 53 first records of viruses and viroids, of which 36 were first UK findings and a further 17 previously undescribed viruses. Given the challenges in detection and diagnosis of plant viruses, the field of plant virology has been an early adopter of new diagnostic technologies and these data highlight the transition from a reliance on biological, morphological, and serological based identification to the increased application of nucleic acid based detection methods and latterly the emergence of Next-Generation Sequencing. This review presents a comprehensive record of these findings and an analysis of how the potential drivers of change such as commodity based research, trade, as well as the application of diagnostic technology, could have influenced the frequency and type of findings. [ABSTRACT FROM AUTHOR]

The British Association for Sexual Health and HIV (BASHH) revised United Kingdom national guideline for the management of gonorrhoea in adults, 2011, identified five auditable outcome measures, namely, that all patients should receive first-line treatment, be screened or treated for chlamydial infection, have a test of cure (TOC), be offered written information and have partner notification carried out. The UK National Guideline for Gonorrhoea Testing, Clinical Effectiveness Group, BASHH, 2012, recommended in addition that all reactive nucleic acid amplification tests (NAATs) from pharynx and rectum should be confirmed by supplementary testing, using a second NAAT which detects a different nucleic acid target, all those with a positive NAAT for gonorrhoea should have culture and antimicrobial susceptibility testing and that TOC should be done by two weeks. Staff, associate specialist and specialty doctors performed a national audit against these standards. Data from 3233 cases were submitted; 8% of cases of gonorrhoea diagnosed in England, Scotland and Wales over this period. We found that 83% patients received first-line treatment with a reason for not doing so provided for 11%. TOC was documented for 62% and written information was offered to 41%. Results about supplementary testing were inconsistent. The results for the other outcomes were satisfactory. [ABSTRACT FROM AUTHOR]

In everyday settings in the UK the self-determination of identity has been taken for granted. In the decennial census and the bureaucratic practices of modern governance, the ascription of ethnicity is in the hands of the subject who is the final arbiter, even if this sometimes breaks down by default. However, for some minority ethnic groups, notably 'black Africans', a group 'created' by the decennial census, observer-led approaches to determining identity have insinuated themselves into some policy contexts in the UK. The targeting by HIV/AIDS workers of 'black Africans' in mundane public settings based on such signalling devices as appearance and language or accent has been endorsed as a modus operandi in preventative care. For around a decade the UK Border Agency has made use of linguistic analysis and other forensic methods to establish the nationality of Somali-origin asylum seekers as against claims from other East Africans. Its latest Human Provenance Pilot Project - the use of isotope analysis and DNA ancestry testing to establish nationality - again places 'black Africans' on the front line. These external processes of identification raise important ethical challenges, given the potential for harm when assignment is incorrect. [ABSTRACT FROM AUTHOR]

The article discusses a ring-trial involving 7 European testing centers in Great Britain, Sweden and Germany to compare several real-time polymerase chain reaction (PCR) methods in the detection of Coxiella burnetii. Ten nucleic acid samples were received by each testing center. It indicates that real-time PCR assays that target multiple copy genes are more sensitive than those targeting single-copy genes and the additional use of a PCR targeting a single-copy gene can allow accurate quantification of the bacterial load present within a sample.

Background. Diagnostic polymerase chain reaction (PCR) detection of Neisseria meningitidis has enabled accurate quantification of the bacterial load in patients with meningococcal disease. Methods. Quantification of the N. meningitidis DNA level by real time-PCR was conducted on whole-blood samples obtained from patients presenting with meningococcal disease to hospitals throughout England and Wales over a 3-year period. Levels were correlated with clinical outcome, infecting serogroup, and host factors including, interleukin-1 genotype (IL-1). Results. Bacterial loads were available for 1045 patients and were not associated with the age of the patient, delay in sample submission, or administration of antibiotics prior to admission. The median log bacterial load was higher in 95 patients who died (5.29 log10copies/mL; interquartile range, 4.41-6.30 log10copies/mL) than in 950 patients who survived (3.79 log10copies/mL; interquartile range, 2.87-4.71 log10copies/mL). Logistic regression revealed that age (odds ratio, 1.04 per 1-year increase in age) and bacterial load (odds ratio, 2.04 per log10-copies/mL increase) had a statistically significant effect on the risk of death. Infection with N. meningitidis serogroup C was associated with increased risk of death and an increased bacterial load. Also associated with a higher bacterial load were prolonged hospitalization (duration, >10 days); digit, limb, or soft-tissue loss; and requirement of hemodialysis. Carriage of IL-1RN(+2018) was associated with increased mortality (odds ratio, 2.14; P=.07) but not with a higher bacterial load. Conclusions. In meningococcal disease, bacterial load is associated with likelihood of death, development of permanent disease sequelae, and prolonged hospitalization. The bacterial load was relatively higher in patients infected with N. meningitidis serogroup C than in those infected with other serogroups. The effects of age and IL-1 genotype on mortality are independent of a high genomic bacterial load. [ABSTRACT FROM AUTHOR]

Abstract: Nucleic acid amplification technique (NAT)-based assays are replacing traditional diagnostic methods in clinical laboratories. However, many of these assays are developed in-house and the lack of standardised reference materials has hindered assay implementation and control. Consequently, in the UK, the Clinical Virology Network (CVN), the National Institute for Biological Standards and Control (NIBSC), and the Health Protection Agency (HPA), are working in collaboration to develop working standards or ‘run controls’ for diagnostic NAT-based assays, particularly real-time PCR. These run controls are intended for use in microbiology laboratories and are designed to be extracted and amplified in the same way as clinical samples and included in each assay run. The aim is to enable clinical laboratories to continuously monitor the performance of their diagnostic NAT assays on a run-by-run basis allowing inter-laboratory comparisons, and ultimately improving the consistency of results. At present, eight candidate run controls representing clinically relevant viral targets have been prepared for evaluation by CVN laboratories. Data have been returned on the performance of each run control in routine diagnostic assays. Preliminary results presented here indicate a high level of variability in intra- and inter-assay detection of these targets, highlighting the need for standardisation of assays within molecular diagnostics. [Copyright &y& Elsevier]

Background: Nucleic acid amplification tests (NAAT) based on PCR provide rapid identification of Mycobacterium tuberculosis and the detection of rifampicin resistance. Indications for their use in clinical samples are now included in British tuberculosis guide- lines. Methods: A retrospective audit of patients with suspected mycobacterial infection in a Liverpool hospital between 2002 and 2006. Documentation of the impact of NAAT usage in acid fast bacillus (AFB) microscopy positive samples on clinical practice and the influence of a multidisciplinary group on their appropriate use, compared with British guidelines. Results: Mycobacteria were seen or isolated from 282 patients and identified as M tuberculosis in 181(64%). NAAT were indicated in 87/1 23 AFB positive samples and performed in 51 (59%). M tuberculosis was confirmed or excluded by this method in 86% of tested samples within 2 weeks, compared with 7% identified using standard methods. The appropriate use of NAAT increased significantly over the study period. The NAAT result had a clinical impact in 20/51 (39%) tested patients. Culture results suggest the potential for a direct clinical impact in 8/36 (22%) patients in which it was indicated but not sent and 5/36 (14%) patients for whom it was not indicated. Patients managed by the multidisciplinary group had a higher rate of HIV testing and appropriate use of NAAT. Conclusions: There were significant clinical benefits from the use of nucleic acid amplification tests in this low prevalence setting. Our data suggest that there would be additional benefit from their use with all AFB smear positive clinical samples. [ABSTRACT FROM AUTHOR]

Since 1920 Simulium reptans (Linnaeus) (Diptera: Simuliidae) has been reported as exhibiting two different larval morphotypes, a typical S. reptans and an atypical S. reptans var. galeratum, which differ in the markings of the larval head capsule. Inconsistent variation in adults and no apparent variation in the pupae have led taxonomists to conclude that these types in Britain are a single species. We investigated populations in Britain where either the typical form or var. galeratum is found, and one population where the two exist sympatrically. A phylogenetic study based upon a region of the mitochondrial cytochrome c oxidase 1 gene (DNA barcoding) produced a tree that delineated the morphotypes into two distinct monophyletic clades. The average Kimura-2-parameter distances within each clade (i.e. within each morphotype) were very low (0.67% and 0.78%), with the distances between morphotypes being 9−10-fold greater (mean 7.06%). This is concordant with differences within and between species in other taxa; based upon the strict correlation between the molecular variation and the morphotypes, we propose the re-instatement of S. galeratum to species status. [ABSTRACT FROM AUTHOR]

We previously reported evidence of West Nile virus (WNV) circulation in UK birds, probably introduced by migratory birds from overseas. We now demonstrate WNV-specific seroconversion in sentinel chickens raised on an English farm. Maternal neutralizing antibodies to WNV in hatchlings declined within three weeks. During the following months, healthy chickens developed WNV neutralizing antibodies that were confirmed by immunoblotting and indirect immunofluorescence tests using WNV antigens. The proportion of seropositive chickens was higher for WNV than for Usutu virus or Sindbis virus. Attempts to isolate infectious virus or to detect viral RNA in the sera, failed. [ABSTRACT FROM AUTHOR]

Random amplified polymorphic DNA (RAPD) has been used to investigate the interrelationships of 20 populations of Globodera pallida collected originally from field soils around the UK. RAPD analysis revealed a high level of relative genomic diversity within British G. pallida but there was no general correlation of genomic similarity with geographic distribution. Two populations of pathotype Pa1 were clearly divergent from the bulk of G. pallida and might represent a distinct introduction. Two other populations, from Scotland and Wales, were also dissimilar from each other and from the rest of the G. pallida populations. [ABSTRACT FROM AUTHOR]

The article reports on DNA regulation in Great Britain. In this locality, the concern of genetic manipulation is the responsibility of three different working groups in the government. First, the Ashby Working Party is set up to gauge the potential benefits and potential hazards of DNA research. Second, the Williams Working Party creates codes of procedures and practice for the conduct of the research. Lastly, the Genetic Manipulation Advisory Group (GMAG) provides an essential guide in designating legal responsibility for the consequences of accidents.

• 32% of enteroviral samples referred to a national reference laboratory failed typing. • Regular re-evaluation of RT-PCR primers is required in enteroviral diagnostics. • Recommended WHO primers remain optimal for contemporary genomes, including EV-D68. • 23 of 24 (96%) viable but 'untypable' samples were typed by this alternative assay. • Simple and effective in-house enteroviral typing could support national surveillance. Human enteroviruses (EV) are the leading cause of viral meningitis. EV genotyping is predominantly performed through amplification and sequencing of viral capsid protein-1 (VP1), frequently by national reference laboratories (NRLs). To determine the frequency of genotyping failure in our NRL-submitted samples and apply a superior alternative assay to resolve untyped specimens. We initially audited genotyping data received for a cohort of patients in the East Midlands, UK by the NRL between 2013 and 2017, then identified an alternative RT-PCR typing method by literature review and evaluated primers from both assays in silico against comprehensive publicly available genomic data. The alternative assay was further optimised and applied to archived nucleic acids from previously untypable samples. Genotyping data showed a significant increase in untypable EV strains through the study period (p = 0.0073). Typing failure appeared unrelated to sample type or viral load. In silico analyses of 2,201 EV genomes showed high levels of mismatch between reference assay primers and clinically significant EV-species, in contrast to a selected alternative semi-nested RT-PCR VP1-typing assay. This alternative assay, with minor modifications, successfully genotyped 23 of 24 previously untypable yet viable archived specimens (EV-A, n = 4; EV-B, n = 19). Phylogenetic analyses identified no predominant strain within NRL untypable isolates, suggesting sub-optimal reference assay sensitivity across EV species, in agreement with in silico analyses. This modified highly sensitive RT-PCR assay presents a suitable alternative to the current English national reference VP1-typing assay and is recommended in other settings experiencing typing failure. [ABSTRACT FROM AUTHOR]

The objective of this study was to detect and characterise the biovar of equine herpesvirus type 1 (EHV-1) from submandibular lymph nodes (SMLNs) and trigeminal ganglia from 153 equids undergoing routine postmortem examination for various medical and surgical reasons. A combination of nucleic acid precipitation and preamplification steps was used to increase the analytical sensitivity of the analysis. The presence of latent EHV-1 was determined when tissue samples were PCR-positive for the glycoprotein B (gB) gene and the DNA polymerase (ORF 30) gene of EHV-1 in the absence of detectable late structural protein gene (gB gene) mRNA. The SMLNs of five of the study animals (3.3 per cent) were PCR- positive for the gB gene of EHV-1. Two SMLNs carried a latent neurotropic strain of the virus, whereas three SMLNs were PCR-positive for both neurotropic and non-neurotropic EHV-1. A total of 30 trigeminal ganglia collected from 19 horses were PCR-positive for the gB gene of EHV-1. Nine trigeminal ganglia harboured either latent non-neurotropic or neurotropic EHV-1 strains. Twelve trigeminal ganglia contained both latent neurotropic and non-neurotropic EHV-1. The prevalence and distribution of EHV-1 biovars among the study horses appeared to be influenced by their breed and the type of tissue tested. [ABSTRACT FROM AUTHOR]

The article focuses on the molecular evidence which shows that two skuas which were discovered in Great Britain were sister of taxa of a group comprising the Brown Skua Stecorarius antarctica and Chilean Skua Stecorarius chilensis group. The feather characteristics excluded Chilean Skua, which suggested that they were Brown Skuas. Such finding would have been the first North Atlantic records of this species. A study of the deoxyribonucleic acid (DNA) of the species were conducted. Researchers concluded that with the addition of new mtDNA sequence data from South Polar Skuas, they can no longer identify between Brown, Chilean and South Polar Skua and that the two British skuas are not Great Skuas.

The article presents information on the setback for gene proteins in Great Britain and related issues. The recently concluded litigation on Kirin-Amgen's erythro-protein patent in Great Britain courts has added a further chapter to the intriguing saga of recombinant DNA patents and their enforcement. Whenever a new process is invented for the preparation of a previously known substance, the new process can in principle be patented. But in European Patent Office practice, a claim to the product when prepared by the new process is not allowed unless the product is in some way different from the previously known substance. This practice stems from Technical Board of Appeal decisions and is apparently here to stay.

The article discusses the cost-effectivity of nucleic acid amplification point-of-care (POC) testing for chlamydia and gonorrhea. As of March 2014, chlamydia and gonorrhea is considered as the most treatable bacterial infections in Great Britain and still remain a considerable public health concern. The ability of POC nucleic acid amplification test (NAAT) testing to reduce the delay in receiving test results to a matter of hours than days is mentioned.

The article presents a study on the one-step nucleic acid amplification (OSNA) automated molecular diagnostic system of sentinel lymph node (SLN) analysis. For the study, researchers intraoperatively examined SLNs of 204 patients diagnosed with breast cancer in Great Britain. They found that the overall concordance rate of OSNA compared to histopathology was 96.0 per cent. They concluded that OSNA allows accurate automated intraoperative diagnosis.

Summary: The UK''s human DNA database may look very different by the end of the year. Nigel Williams reports. [Copyright &y& Elsevier]

The article focuses on research studies related to DNA sequence analysis. A high degree of organismal diversity in analyzing DNA sequences has been documented, and extending this approach to terrestrial systems has uncovered previously unsuspected and intermingled communities of bacteria, archaea, and fungi. Some scientists have begun to took at the exchange of goods in one such market-place by exposing pieces of turf from Great Britain grassland or from French peatland to 13CO2 and following the transfer of the isotope into ribosomal RNA of microbes associated with the plant roots.

The article reports on the readiness of the British government to accept cybrids, a technology made by inserting human DNA into enucleated animal oocytes. Caroline Flint, Minister for Public Health, responded by saying that such experiments will bring insights into Alzheimer's disease and motor neuron disease. Major sponsors for such research include the Wellcome Trust, the Medical Research Council and the Human Genetics Commission Research Council.

This article informs that a new game promises to be a big hit in the world's genomics laboratories. Inspired by the haplotype mapping project that is cataloging human genetic variation, the game calls for players to collect and sequence the DNA necessary to finish building the HapMap as they travel around the board. At $400,000, the Wellcome Trust, which supports large-scale sequencing in Great Britain, is a prime location as rent there is $50,000 a visit poor data, dead laptop batteries, and contaminated experiments dictated by "Chance" cards lead to lost turns and fines.

The dove from Mexico's Socorro Island, new extinct in the wild, is to be among the first beneficiaries of a "Frozen Ark" established this week in Great Britain. Billed as "the world's first DNA and tissue bank dedicated to all the world's endangered animals," it's a project of London's Natural History Museum, the Zoological Society of London, and the Institute of Genetics at the University of Nottingham. The ark will be both a real and a virtual resource, explains Philip Rainbow, keeper of biology at the museum. Ark headquarters will be at Nottingham, and specimens will be kept in zoo and museum freezers.