International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork.

Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.

Phaeochromocytoma and paraganglioma are highly heritable tumours; half of those associated with a germline mutation are caused by mutations in genes for Krebs's cycle enzymes, including succinate dehydrogenase (SDH). Inheritance of SDH alleles is assumed to be Mendelian (probability of 50% from each parent). The departure from transmission of parental alleles in a ratio of 1:1 is termed transmission ratio distortion (TRD).

Iron and Manganese Alginate for Rechargeable Battery Electrodes.

We present a sustainable, inherently safe battery chemistry that is based on widely available and cheap materials, that is, iron and manganese hosted in alginate bio-material known from the food and medical industry. The resulting battery can be recycled to allow circularity. The electrodes were synthesised by the alginate caging the multi-valent metals to form a hydrogel in an aqueous environment.

The immune cell infiltrate in the tumour microenvironment of phaeochromocytomas and paragangliomas.

Emerging evidence suggests the composition of the tumour microenvironment (TME) correlates with clinical outcome and that each tumour type has a unique TME including a variable population of inflammatory cells. We performed immunohistochemistry on 65 phaeochromocytoma and paraganglioma (PPGL) tumour samples with 20 normal adrenal medulla samples for comparison. The immune cells assessed were macrophages, lymphocytes and neutrophils, and we compared the proportion of infiltration of these immune cells with clinical and histopathological factors.

SDHC phaeochromocytoma and paraganglioma: A UK-wide case series.

Objective: Phaeochromocytomas and paragangliomas (PPGL) are rare, but strongly heritable tumours. Variants in succinate dehydrogenase (SDH) subunits are identified in approximately 25% of cases. However, clinical and genetic information of patients with SDHC variants are underreported.

Performance evaluation of scoring systems for predicting post-operative hypertension cure in primary aldosteronism.

Objective: Hypertension cure following adrenalectomy in unilateral primary aldosteronism is not guaranteed. Its likelihood is associated with pre-operative parameters, which have been variably combined in six different predictive scoring systems. The relative performance of these systems is currently unknown.

International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers.

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed.

Discovery of a Novel Antimicrobial Agent by the Virtual Screening of a Library of Small Molecules.

A virtual screening approach based upon a combination of docking and pharmacophore methods was utilized on a library of 1.4 million molecules to identify novel antimicrobial agents, which may potentially act via inhibition of the caseinolytic protease. Using this method, compound 6 was found to be bactericidal against three staphylococcal species (minimum inhibitory concentration (MIC)=4-16 μg/mL).

Pregnancy and phaeochromocytoma/paraganglioma: clinical clues affecting diagnosis and outcome - a systematic review.

Background: Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child.

Objective: To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL.

Search Strategy: Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French.

Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors.

Cholinesterases (ChE) are well-known drug targets for the treatment of Alzheimer's disease (AD). In continuation of work to develop novel cholinesterase inhibitors, we utilized a structure-based scaffold repurposing approach and discovered six novel ChE inhibitors from our recently developed DNA gyrase inhibitor library. Among the identified hits, two compounds (denoted and ) were found to be the most potent inhibitor of acetylcholinesterase (AChE, IC = 6.

Glucocorticoid replacement therapies: past, present and future.

Since the original description of adrenal insufficiency by Thomas Addison in 1855, there has been an exponential growth in the understanding of adrenal gland biology and its role in the hypothalamic-pituitary-adrenal axis. Despite this, the mainstay of therapeutic glucocorticoid replacement for most clinicians has remained unchanged for nearly 50 years. More recently, there has been better recognition of the morbidity and mortality associated with current approaches and the challenges to tackle in reducing this and improving clinical outcomes.

Low-grade Cortisol Cosecretion Has Limited Impact on ACTH-stimulated AVS Parameters in Primary Aldosteronism.

Context: In primary aldosteronism, cosecretion of cortisol may alter cortisol-derived adrenal venous sampling indices.

Objective: To identify whether cortisol cosecretion in primary aldosteronism alters adrenal venous sampling parameters and interpretation.

Design: Retrospective case-control study.

Multiphase matrix of silica, culture medium and air for 3D mammalian cell culture.

The craving for multiphase materials with adjustable properties for mammalian cell encapsulation persists despite intensive research on 3D cell culture and tissue engineering. This interest is incited by the complex interaction between cells and different materials, various manufacturing methods, cell chip applications, and the aspiration to abolish animal experiments. This study aims to show the feasibility of preparing a stable multiphase material for prolonged mammalian cell embedment and 3D cell culture.

First-positive surveillance screening in an asymptomatic SDHA germline mutation carrier.

Summary: At least 40% of phaeochromocytomas and paraganglioma’s (PPGLs) are associated with an underlying genetic mutation. The understanding of the genetic landscape of these tumours has rapidly evolved, with 18 associated genes now identified. Among these, mutations in the subunits of succinate dehydrogenase complex (SDH) are the most common, causing around half of familial PPGL cases.

The draft genome of .

is a devastating pest to many crops worldwide. We present the first genome sequence for this species, produced with PacBio sequencing and assembled with CANU. is a devastating pest to many crops worldwide.

Hypertension due to a deoxycorticosterone-secreting adrenal tumour diagnosed during pregnancy.

Mineralocorticoid hypertension is most often caused by autonomous overproduction of aldosterone, but excess of other mineralocorticoid precursors can lead to a similar presentation. 11-Deoxycorticosterone (DOC) excess, which can occur in 11-β hydroxylase or 17-α hydroxylase deficiencies, in DOC-producing adrenocortical tumours or in patients taking 11-β hydroxylase inhibitors, may cause mineralocorticoid hypertension. We report a 35-year-old woman who in the third trimester of pregnancy was found to have a large adrenal mass on routine obstetric ultrasound.

Impact of thyroiditis on 131I uptake during ablative therapy for differentiated thyroid cancer.

Context: Differentiated thyroid cancer (DTC) is usually treated by thyroidectomy followed by radioiodine ablation and generally has a good prognosis. It may now be possible to limit the amount of treatment without impacting on efficacy. It is not known whether coexistent thyroiditis impacts on radioiodine uptake or on its potential efficacy, but this could provide a rationale for modification to current therapeutic protocols.

Diffusion-weighted imaging (DWI) highlights SDHB-related tumours: A pilot study.

Objective: There is consensus that asymptomatic carriers of SDHB mutations should undergo periodic surveillance imaging. MRI has the advantage of avoiding radiation exposure but its sensitivity and specificity for detecting phaeochromocytoma and paraganglioma (PPGL) are dependent on sequences performed and expertise of reporting radiologists. We aim to highlight the additional value of diffusion-weighted imaging (DWI) for MR based surveillance, demonstrating DWI's ability to identify small PPGLs at all body sites.

An analysis of surveillance screening for SDHB-related disease in childhood and adolescence.

Objective Phaeochromocytomas (PCC) and paragangliomas (PGL) are rare in children. A large proportion of these are now understood to be due to underlying germline mutations. Here we focus on succinate dehydrogenase subunit B (SDHB) gene mutation carriers as these tumours carry a high risk of malignant transformation.

Can subunit-specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?

Objective: With the discovery that familial phaeochromocytoma and paraganglioma syndrome can be caused by mutations in each subunit of the succinate dehydrogenase enzyme (SDH), has come the recognition that mutations in the individual subunits have their own distinct natural histories. Increased genetic screening is leading to the identification of increasing numbers of, mostly asymptomatic, gene mutation carriers and the implementation of screening strategies for these individuals. Yet there is, to date, no international consensus regarding screening strategies for asymptomatic carriers.

A prospective longitudinal study of Pasireotide in Nelson's syndrome.

Purpose: Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome.