The performance of 11 fingertip pulse oximeters during hypoxemia in healthy human participants with varied, quantified skin pigment.

Background: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation.

Methods: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%.

CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease.

Objective: Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.

Identification and Structure-Guided Development of Pyrimidinone Based USP7 Inhibitors.

Ubiquitin specific protease 7 (USP7, HAUSP) has become an attractive target in drug discovery due to the role it plays in modulating Mdm2 levels and consequently p53. Increasing interest in USP7 is emerging due to its potential involvement in oncogenic pathways as well as possible roles in both metabolic and immune disorders in addition to viral infections. Potent, novel, and selective inhibitors of USP7 have been developed using both rational and structure-guided design enabled by high-resolution cocrystallography.

Discovery and characterization of highly potent and selective allosteric USP7 inhibitors.

Given the importance of ubiquitin-specific protease 7 (USP7) in oncogenic pathways, identification of USP7 inhibitors has attracted considerable interest. Despite substantial efforts, however, the development of validated deubiquitinase (DUB) inhibitors that exhibit drug-like properties and a well-defined mechanism of action has proven particularly challenging. In this article, we describe the identification, optimization and detailed characterization of highly potent (IC < 10 nM), selective USP7 inhibitors together with their less active, enantiomeric counterparts.

Extracellular cathepsin S and intracellular caspase 1 activation are surrogate biomarkers of particulate-induced lysosomal disruption in macrophages.

Background: Particulate matter has been shown to stimulate the innate immune system and induce acute inflammation. Therefore, while nanotechnology has the potential to provide therapeutic formulations with improved efficacy, there are concerns such pharmaceutical preparations could induce unwanted inflammatory side effects. Accordingly, we aim to examine the utility of using the proteolytic activity signatures of cysteine proteases, caspase 1 and cathepsin S (CTSS), as biomarkers to assess particulate-induced inflammation.

The application of a novel, cell permeable activity-based probe for the detection of cysteine cathepsins.

Cysteine cathepsins, such as cathepsin S (CTSS), are implicated in the pathology of a wide range of diseases and are of potential utility as diagnostic and prognostic biomarkers. In previous work, we demonstrated the potency and efficiency of a biotinylated diazomethylketone (DMK)-based activity-based probe (ABP), biotin-PEG-LVG-DMK, for disclosure of recombinant CTSS and CTSS in cell lysates. However, the limited cell permeability of both the biotin and spacer groups restricted detection of CTSS to cell lysates.

Strategies for detection and quantification of cysteine cathepsins-evolution from bench to bedside.

The cysteine cathepsins are a family of closely related thiol proteases, normally found in the endosomal and lysosomal compartments of cells. A growing body of evidence has clearly linked the dysregulated activity of these proteases with many diseases and pathological conditions, offering therapeutic, prognostic and diagnostic potential. However, these proteases are synthesised as inactive precursors and once activated, are controlled by factors such as pH and presence of endogenous inhibitors, meaning that overall protein and activity levels do not necessarily correlate.

Impact of counselling on quality of life and sleep in cancer patients.

It has been acknowledged that poor quality of sleep significantly correlates with poor quality of life; evidence suggests that counselling has a positive impact not only on the cancer patient's quality of life, but also on family members and friends. The aim of this service evaluation was to determine if there was an improvement in clients' quality of life and sleep patterns following counselling as offered by a local cancer charity. A total of 60 matched pre- and post-counselling questionnaires were completed and subjected to statistical analysis.

Factors influencing participation in breast cancer screening.

Despite the efficacy of mammography and the widespread promotion of screening programmes, a significant number of eligible women still do not attend for regular breast screening. An integrative review methodology was considered the most appropriate means to critically analyse the available literature pertaining to factors which influence participation in breast cancer screening. From the extensive literature search, 12 selected core research papers met the inclusion criteria and were incorporated in the literature review.

Gastric neuroendocrine cell hyperplasia and type 1 tumours occurring within gastric hyperplastic polyps.

We wish to highlight the unusual occurrence of gastric neuroendocrine cell hyperplasia and type I neuroendocrine tumours within three hyperplastic polyps. In all cases, the neuroendocrine component was present within and between the hyperplastic foveolar glands of the polyps and overall formed the minor part of the polyps. Two of the patients presented with epigastric pain and the other with fatigue from anaemia, and on endoscopy, all three were found to have superficially ulcerated gastric polyps in the body (cases 1 and 2) and fundus (case 3).

Radiologic characteristics and management of screen-detected metastatic carcinoid tumor of the breast: a case report.

Carcinoid tumors are known to metastasize to the breast, but their appearance can mimic a primary breast carcinoma, making biopsy essential in order to give the correct preoperative diagnosis. It has been suggested that core biopsy might precipitate a carcinoid crisis and should be avoided. We describe a case of screen-detected carcinoid tumor metastasis in the breast safely diagnosed by core biopsy and present the imaging findings, including magnetic resonance imaging and elastography.

Low-level TOP2A amplification in prostate cancer is associated with HER2 duplication, androgen resistance, and decreased survival.

HER2 and TOP2A genes, located on 17q, can be coamplified in cancer. Overexpression of both genes has been reported in high-grade, androgen-resistant prostate cancer. Both genes have not been compared in a single prostate cancer study and the frequency of TOP2A amplifications in prostate cancer is unknown.

Parvovirus infects cardiac myocytes in hydrops fetalis.

Parvovirus infection during pregnancy is an important cause of hydrops fetalis. It is attributed to anemia caused by viral-induced destruction of red blood cells. Infection of other organs has been reported including the heart, liver, and lungs.