Proficiency testing for SARS-CoV-2 in assuring the quality and overall performance in viral RNA detection in clinical and public health laboratories.

Diagnostic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone significant changes over the duration of the pandemic. In early 2020, SARS-CoV-2 specific nucleic acid testing (NAT) protocols were predominantly in-house assays developed based on protocols published in peer reviewed journals. As the pandemic has progressed, there has been an increase in the choice of testing platforms.

Niclosamide-A promising treatment for COVID-19.

Vaccines have reduced the transmission and severity of COVID-19, but there remains a paucity of efficacious treatment for drug-resistant strains and more susceptible individuals, particularly those who mount a suboptimal vaccine response, either due to underlying health conditions or concomitant therapies. Repurposing existing drugs is a timely, safe and scientifically robust method for treating pandemics, such as COVID-19. Here, we review the pharmacology and scientific rationale for repurposing niclosamide, an anti-helminth already in human use as a treatment for COVID-19.

Proficiency testing for bacterial whole genome sequencing in assuring the quality of microbiology diagnostics in clinical and public health laboratories.

The adoption of whole genome sequencing (WGS) data over the past decade for pathogen surveillance, and decision-making for infectious diseases has rapidly transformed the landscape of clinical microbiology and public health. However, for successful transition to routine use of these techniques, it is crucial to ensure the WGS data generated meet defined quality standards for pathogen identification, typing, antimicrobial resistance detection and surveillance. Further, the ongoing development of these standards will ensure that the bioinformatic processes are capable of accurately identifying and characterising organisms of interest, and thereby facilitate the integration of WGS into routine clinical and public health laboratory setting.

Laboratory biosafety measures involving SARS-CoV-2 and the classification as a Risk Group 3 biological agent.

The current public health emergency surrounding the COVID-19 pandemic, that is the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in thousands of cases in Australia since 25 January 2020 when the first case was diagnosed. This emerging virus presents particular hazards to researchers and laboratory staff in a clinical setting, highlighted by rapid and widespread global transmission. Based on the epidemiological and clinical data that have become available in mid-2020, we propose the interim classification of SARS-CoV-2 as a Risk Group 3 organism is reasonable, and discuss establishing Biosafety Level 3 (BSL-3) regulations accordingly.

SARS-CoV-2 seroprevalence and asymptomatic viral carriage in healthcare workers: a cross-sectional study.

Objective: To determine the rates of asymptomatic viral carriage and seroprevalence of SARS-CoV-2 antibodies in healthcare workers.

Design: A cross-sectional study of asymptomatic healthcare workers undertaken on 24/25 April 2020.

Setting: University Hospitals Birmingham NHS Foundation Trust (UHBFT), UK.

Liver homing of clinical grade Tregs after therapeutic infusion in patients with autoimmune hepatitis.

Unlabelled: Autoimmune hepatitis (AIH) is an immune-mediated disease with no curative treatment. Regulatory T cell (Treg) therapy is potentially curative in AIH given the critical role of Tregs in preventing autoimmunity. To work effectively, adoptively transferred Tregs must migrate to and survive within the inflamed liver.

A Randomized Crossover Study to Assess the Usability of Two New Vision Tests in Patients with Low Vision.

Significance: Well-established charts such as Early Treatment Diabetic Retinopathy Study are able to quantify visual acuity (VA) with a low cutoff of 1.6 logMAR. Below this point, nonquantitative measures, such as count fingers, hand movements, and light perception, are used.

Increased central adiposity and decreased subcutaneous adipose tissue 11β-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study.

Objective And Context: Increasing adiposity, ageing and tissue-specific regeneration of cortisol through the activity of 11β-hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance.

Design, Patients, And Measurements: Sixty-five overweight/obese individuals (mean age 50.

Optimisation of dark adaptation time required for mesopic microperimetry.

Background: Macular Integrity Assessment (MAIA) microperimetry is increasingly used in clinical and research settings to assess point retinal sensitivity and fixation stability. Testing occurs under mesopic conditions, commonly after a period of dark adaptation. Our aim was to identify the minimum length of adaptation required to optimise microperimetry performance.

Proficiency testing for the detection of Middle East respiratory syndrome coronavirus demonstrates global capacity to detect Middle East respiratory syndrome coronavirus.

The first reported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was identified in Saudi Arabia in September 2012, since which time there have been over 2000 laboratory-confirmed cases, including 750 deaths in 27 countries. Nucleic acid testing (NAT) is the preferred method for the detection of MERS-CoV. A single round of a Proficiency Testing Program (PTP) was used to assess the capability of laboratories globally to accurately detect the presence of MERS-CoV using NAT.

Slowly progressive retinitis pigmentosa caused by two novel mutations in the MAK gene.

Background: The growing number of clinical trials currently underway for inherited retinal diseases has highlighted the importance of achieving a molecular diagnosis for all new cases presenting to hospital eye services. The male germ cell-associated kinase (MAK) gene encodes a cilium-associated protein selectively expressed in the retina and testis, and has recently been implicated in autosomal recessive retinitis pigmentosa (RP). Whole exome sequencing has previously identified a homozygous Alu insertion in probands with recessive RP and nonsense and missense mutations have also been reported.

Ebola Preparedness: Diagnosis Improvement Using Rapid Approaches for Proficiency Testing.

The unprecedented 2015 Ebolavirus (EBOV) outbreak in West Africa was declared a public health emergency, making diagnosis and quality of testing a global issue. The accuracy of laboratory diagnostic capacity for EBOV was assessed in 2014 to 2016 using a proficiency testing (PT) strategy developed by the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) in Biosecurity. Following a literature search, EBOV-specific gene targets were ranked according to the frequency of their use in published methods.

Single centre outcomes from definitive chemo-radiotherapy and single modality radiotherapy for locally advanced oesophageal cancer.

Background: Definitive chemo-radiotherapy (dCRT) has been advocated as an alternative to surgical resection for the treatment of locally advanced oesophageal cancer (OC). We have retrospectively reviewed 4 years' experience of patients (pts) who underwent contemporary staging and were treated with concurrent chemo-radiotherapy (dCRT) or single modality radical radiotherapy (RT) with curative intent.

Methods: Retrospective analysis permitted identification of consecutive patients who underwent contemporary staging prior to non-surgical treatment for locally advanced oesophageal carcinoma.

Longitudinal changes in glucocorticoid metabolism are associated with later development of adverse metabolic phenotype.

Objective: Dysregulation of enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistance; however, longitudinal changes in glucocorticoid metabolism have not been investigated. This study was performed to evaluate the role of glucocorticoid metabolism in the development of insulin resistance and obesity and to identify biomarkers for future development of metabolic disease.

Design: This was a prospective longitudinal observation study conducted over 5 years.

OPCRIT+: an electronic system for psychiatric diagnosis and data collection in clinical and research settings.

Background: The increasingly large sample size requirements of modern adult mental health research suggests the need for a data collection and diagnostic application that can be used across a broad range of clinical and research populations. Aims To develop a data collection and diagnostic application that can be used across a broad range of clinical and research settings.

Method: We expanded and redeveloped the OPCRIT system into a broadly applicable diagnostic and data-collection package and carried out an interrater reliability study of this new tool.

Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays.

Background: We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations).

Changes in body weight during pharmacological treatment of depression.

The risk of weight gain is an important determinant of the acceptability and tolerability of antidepressant medication. To compare changes in body weight during treatment with different antidepressants, body weight and height were measured at baseline and after 6, 8, 12 and 26 wk treatment with escitalopram or nortriptyline in 630 adults with moderate-to-severe unipolar depression participating in GENDEP, a part-randomized open-label study. Weight increased significantly more during treatment with nortriptyline compared to escitalopram.

The Bipolar Association Case-Control Study (BACCS) and meta-analysis: No association with the 5,10-Methylenetetrahydrofolate reductase gene and bipolar disorder.

Bipolar disorder (BD) is a complex genetic disease for which the underlying pathophysiology has yet to be fully explained. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in folate-mediated one-carbon metabolism and folate deficiency can be associated with psychiatric symptoms. A single base variant in MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme and has recently been implicated in BD.

Genetic predictors of response to antidepressants in the GENDEP project.

The objective of the Genome-based Therapeutic Drugs for Depression study is to investigate the function of variations in genes encoding key proteins in serotonin, norepinephrine, neurotrophic and glucocorticoid signaling in determining the response to serotonin-reuptake-inhibiting and norepinephrine-reuptake-inhibiting antidepressants. A total of 116 single nucleotide polymorphisms in 10 candidate genes were genotyped in 760 adult patients with moderate-to-severe depression, treated with escitalopram (a serotonin reuptake inhibitor) or nortriptyline (a norepinephrine reuptake inhibitor) for 12 weeks in an open-label part-randomized multicenter study. The effect of genetic variants on change in depressive symptoms was evaluated using mixed linear models.

Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder.

It has been suggested that alteration in the muscarinic-cholinergic system is involved in modulation of mood. Three studies have reported linkage on chromosome 7 with major depressive disorder (MDD) in or close to a region containing the muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024-rs2061174-rs324650) has been significantly associated with MDD in a previous study.

Personality and the bipolar spectrum: normative and classification data for the Eysenck Personality Questionnaire-Revised.

Background: Personality traits dispose individuals toward particular affective states and may therefore have an important role in the etiology of affective disorders in particular. Despite being one of the most widely used and well-researched personality instruments, few studies have studied bipolar spectrum disorders using the revised Eysenck Personality Questionnaire (EPQ-R) (Eysenck HJ, Eysenck SBG. The Eysenck Personality Questionnaire-Revised.

Porfimer sodium photodynamic therapy in the treatment of early oesophageal carcinoma.

Background: The gold standard treatment of early oesophageal carcinoma is oesophagectomy but the elderly population affected are often medically unfit for this radical intervention and less invasive curative options are required. We describe our experience of porfimer sodium photodynamic therapy (PDT) as an alternative to surgery in such a patient group.

Methods: From 1999 to 2005 28 oesophageal cancer patients were found to have early stage disease based initially on endoscopy/CT and latterly on CT/endoscopic ultrasound (EUS) criteria.

The current role of photodynamic therapy in oesophageal dysplasia and cancer.

Over the last 15 years photodynamic therapy (PDT) has become a viable treatment for pre-malignant and malignant disease of the oesophagus. Its initial use was in the palliation of oesophageal malignant obstruction bringing improved swallowing hence increasing nutritional intake and improving general quality of life. As the therapeutic boundaries of PDT have stretched, current studies look at the role of PDT in the treatment of pre-malignant dysplastic Barrett's epithelium and early malignancy as a curative mucosal ablative technique.