Publications by authors named "Douglas A"

In July 2022, a genetically linked and geographically dispersed cluster of 12 cases of Shiga toxin-producing (STEC) O103:H2 was detected by the UK Health Security Agency using whole genome sequencing. Review of food history questionnaires identified cheese (particularly an unpasteurized brie-style cheese) and mixed salad leaves as potential vehicles. A case-control study was conducted to investigate exposure to these products.

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Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

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Physical activity (PA) has a wide range of health benefits. Children with high levels of social support are more likely to achieve adequate levels of PA. The purposes of this pilot study were to examine the impact of an after-school intervention on perceived peer and parental support among adolescent girls and to identify correlates of support to explore in future studies to increase PA.

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Background: Pre-exposure prophylactic rabies vaccination (PrEP) is advised for travellers to countries with high rabies incidence, but rarely available for local residents. Some studies suggest poor cost-effectiveness of PrEP in such settings, but have generally focused upon post-exposure prophylaxis (PEP) cost savings as the main benefit of PrEP, without considering lives saved by PrEP efficacy.

Methods: We compared incremental cost-effectiveness ratios (ICERs) of use of rabies PrEP, against an alternative of using only PEP, by adapting a decision-tree model previously used to inform Gavi's investment in rabies PEP.

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Shiga toxin-producing (STEC) infections are of public health concern as STEC can cause large national foodborne outbreaks of severe gastrointestinal disease, particularly in the young and elderly. In recent years, the implementation of PCR by diagnostic microbiology laboratories has improved the detection of STEC, and there has been an increase in notifications of cases of non-O157 STEC. However, the extent this increase in caseload can be attributed to the improved detection by PCR, or a true increase in non-O157 STEC infections, is unknown.

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Background: Frailty is a recognisable clinical measure of impaired physiological reserve and vulnerability to adverse outcomes that is validated among patients with kidney disease. Practice patterns reveal inconsistent use of objective frailty measures by nephrologists, with clinicians prioritising subjective clinical impressions, possibly risking misclassification and discrimination.

Aims: The aim of this study was to examine correlations between subjective and objective measures of frailty in a cohort of patients attending routine nephrologist review.

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Background And Purpose: Patients with active cancer face an increased risk of ischemic stroke. Also, stroke may be an initial indicator of cancer. In patients with large vessel occlusion (LVO) stroke treated with thrombectomy, analysis of the clot composition may contribute new insights into the pathological connections between these two conditions.

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Shiga toxin-producing (STEC) is a group of bacteria that causes gastrointestinal illness and occasionally causes large foodborne outbreaks. It represents a major public health concern due to its ability to cause severe illness which can sometimes be fatal. This study was undertaken as part of a rapid investigation into a national foodborne outbreak of STEC O145.

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Objective: This systematic review update synthesized recent evidence on the benefits and harms of breast cancer screening in women aged ≥ 40 years and aims to inform the Canadian Task Force on Preventive Health Care's (CTFPHC) guideline update.

Methods: We searched Ovid MEDLINE® ALL, Embase Classic + Embase and Cochrane Central Register of Controlled Trials to update our searches to July 8, 2023. Search results for observational studies were limited to publication dates from 2014 to capture more relevant studies.

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The ongoing effects of climate change have exacerbated two significant challenges to global populations: the transmission of foodborne pathogens and antimicrobial resistance (AMR) through the food chain. Using the latest available scientific information this review explores how climate-related factors such as rainfall, floods, storms, hurricanes, cyclones, dust, temperature and humidity impact the spread of the foodborne pathogens , , , , , and . We explore the complex dynamics between environmental changes and the heightened risk of foodborne diseases, analysing the contribution of wildlife, insects and contaminated environments in the proliferation of AMR and climate change.

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Article Synopsis
  • Motor neuron disease (MND), commonly known as amyotrophic lateral sclerosis (ALS), can be caused by genetic factors in some cases, primarily through autosomal dominant inheritance.
  • The demand for genetic testing and counselling is increasing among individuals affected by MND, but there are currently no established guidelines for predictive genetic testing in this area.
  • The paper discusses the genetic basis of MND, addresses its complex nature, and highlights the need for better understanding and support regarding the psychosocial impacts of genetic testing on patients and families.
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The circadian rhythm of the immune system helps to protect against pathogens; however, the role of circadian rhythms in immune homeostasis is less well understood. Innate T cells are tissue-resident lymphocytes with key roles in tissue homeostasis. Here we use single-cell RNA sequencing, a molecular-clock reporter and genetic manipulations to show that innate IL-17-producing T cells-including γδ T cells, invariant natural killer T cells and mucosal-associated invariant T cells-are enriched for molecular-clock genes compared with their IFNγ-producing counterparts.

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Article Synopsis
  • - This study investigates the prevalence and characteristics of frailty among outpatients with chronic kidney disease (CKD) and those on haemodialysis (HD), noting its significant impact on survival rates.
  • - In a cohort of 256 adult participants, 36.3% were frail, and 46.5% were prefrail, with frailty being a stronger predictor of mortality than age or comorbidities, showing a hazard ratio of 2.83.
  • - The findings suggest that frailty is common among CKD and HD patients, and while many showed stable frailty status, some exhibited improvement, highlighting that targeted interventions may enhance patient outcomes.
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Campylobacter species, predominantly Campylobacter jejuni, remains a significant zoonotic pathogen worldwide, with the poultry sector being the primary vector for human transmission. In recent years. there has been a notable rise in the incidence of human campylobacteriosis, necessitating a deeper understanding of the pathogen's survival mechanisms and transmission dynamics.

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We report an increase in GII.17 norovirus outbreaks and sporadic infections of acute gastroenteritis in Austria, Germany, France, Ireland, the Netherlands, England and the United States during the 2023/24 season. A decrease in GII.

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Glioblastoma (GBM) is driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drive tumor progression and therapeutic resistance. Here, we show that the extracellular matrix-cell adhesion protein integrin-linked kinase (ILK) stimulates phenotypic plasticity and mesenchymal-like, invasive behavior in a murine GBM stem cell model. ILK is required for the interconversion of GBM stem cells between malignancy-associated glial-like states, and its loss produces cells that are unresponsive to multiple cell state transition cues.

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Background: hexanucleotide repeat expansions are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in European populations. Variable disease penetrance between families presents a challenge for genetic counselling of at-risk relatives and reduces the predictive utility of testing asymptomatic relatives. We have developed a novel model for estimating penetrance in individual families affected by using available family history information, allowing the calculation of personalised risk estimates.

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Introduction: Interhospital transfer is an important mechanism for improving access to specialized neurologic care but there are large gaps in our understanding of interhospital transfer for the management of non-stroke-related neurologic disease.

Methods: This observational study included consecutive patients admitted to an adult academic general neurology service via interhospital transfer from July 1, 2015 to July 1, 2017. Characteristics of the referring hospital and transferred patients were obtained through the American Hospital Association Directory, a hospital transfer database maintained by the accepting hospital, and the electronic medical record.

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Background: Understanding the patient perspective of frailty is critical to offering holistic patient-centred care. Rehabilitation strategies for patients with advanced chronic kidney disease (CKD) and frailty are limited in their ability to overcome patient-perceived barriers to participation, resulting in high rates of drop-out and non-adherence. The aim of this study was to explore patient perspectives and preferences regarding experiences with rehabilitation to inform a CKD/Frailty rehabilitation model.

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HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with nuclear speckles (NSs). Although CPSF6 displays liquid-liquid phase separation (LLPS) activity in vitro, the contributions of its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) with capsid binding FG motif and C-terminal mixed-charge domain (MCD), to LLPS activity and to HIV-1 infection remain unclear. Herein, we determined that the PrLD and MCD both contribute to CPSF6 LLPS activity in vitro.

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Background: Many patients with hematological malignancy develop fever after chemotherapy/conditioning but before chemotherapy-induced neutropenia (preneutropenic fever [PNF]). The proportion of PNF with an infectious etiology is not well established.

Methods: We conducted a single-center, prospective observational substudy of PNF (neutrophils >0.

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Article Synopsis
  • RNA sequencing (RNA-seq) is being used to enhance diagnostics in cases where DNA testing doesn't provide clear answers, particularly for detecting abnormal gene expression and splicing patterns.
  • The study analyzed blood samples from 86 patients with suspected genetic disorders, focusing on identifying splicing abnormalities and gene expression outliers in VUSs and undiagnosed cases.
  • The results showed that RNA-seq helped diagnose four new cases by revealing novel splicing events and provided insights into the utility of RNA analysis for improving diagnostic outcomes in genetic disorders.
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