Publications by authors named "Sherlock M"

Summary: Adrenocortical carcinoma (ACC) is a rare malignant tumour arising from the adrenal cortex, with an estimated annual incidence of one to two patients per million. Ectopic ACCs are extremely rare. The majority of ACCs are sporadic; however, ACC has been linked with genetic disease processes, including multiple endocrine neoplasia type-1 (MEN-1).

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Context: 11-oxygenated androgens are a group of adrenal-derived steroids that require peripheral activation. In vitro data highlight a putative role for 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) in 11-oxygenated androgen biosynthesis, converting 11β-hydroxyandrostenedione (11OHA4) to 11-ketoandrostenedione (11KA4), the direct precursor of the potent androgen 11-ketotestosterone (11KT). As the kidney is the major site of HSD11B2 expression, we hypothesized that patients with chronic kidney disease (CKD) would have reduced 11-oxygenated androgen biosynthesis due to impaired HSD11B2 activity.

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  • Hypopituitarism is a disorder marked by low levels of one or more anterior pituitary hormones, with notable differences in health outcomes between sexes; women experience higher rates of cardiovascular issues and higher mortality.
  • The dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis leads to hormonal deficiencies (like estrogen and testosterone), and treating these deficiencies with hormone replacement therapy is crucial for health benefits.
  • Despite the positive effects of hormone replacement in reducing mortality risk, the reasons behind the sex disparities in health outcomes for hypopituitarism patients remain unclear, with possibilities including lack of aggressive treatment for women and premature loss of protective estrogen effects.
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Hypogonadism in men is associated with an adverse metabolic phenotype and increased mortality. Reciprocally, obesity and insulin resistance can suppress the hypothalamic-pituitary-gonadal axis in the absence of structural organic disease, further perpetuating a cycle of metabolic dysfunction and low testosterone. The mechanisms underpinning this bidirectional association are complex as hypogonadism is a heterogenous syndrome, and obesity is associated with metabolic perturbations in glucose and lipid metabolism even in the presence of normal testicular function.

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  • * It identified factors influencing healthcare costs, such as age, sex, type of initial treatment, and access to mental health care, highlighting that average costs were about CA$15,168 per child.
  • * The researchers developed a predictive model that could help identify children likely to incur high costs, aiming to find ways to manage expenses while maintaining quality care for these patients.
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We provide analytic expressions for the effective Coulomb logarithm for inverse bremsstrahlung absorption which predict significant corrections to the Langdon effect and overall absorption rate compared to previous estimates. The calculation of the collisional absorption rate of laser energy in a plasma by the inverse bremsstrahlung mechanism usually makes the approximation of a constant Coulomb logarithm. We dispense with this approximation and instead take into account the velocity dependence of the Coulomb logarithm, leading to a more accurate expression for the absorption rate valid in both classical and quantum conditions.

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Unusually for oceanic islands, the granitic Seychelles host multiple lineages of endemic amphibians. This includes an ancient (likely ca. 60 million years) radiation of eight caecilian species, most of which occur on multiple islands.

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Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN.

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Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1.

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  • * This experiment produced 2.05 MJ of laser energy, resulting in 3.1 MJ of total fusion yield, which exceeds the Lawson criterion for ignition, demonstrating a key milestone in fusion research.
  • * The report details the advancements in target design, laser technology, and experimental methods that contributed to this historic achievement, validating over five decades of research in laboratory fusion.
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Iatrogenic adrenal insufficiency (IAI) is the most common form of adrenal insufficiency in adult patients, although its overall exact prevalence remains unclear. IAI is associated with adverse clinical outcomes, including adrenal crisis, impaired quality of life and increased mortality; therefore, it is imperative that clinicians maintain a high index of suspicion in patients at risk of IAI to facilitate timely diagnosis and appropriate management. Herein, we review the major causes, clinical consequences, diagnosis and care of patients with IAI.

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Chronic hypernatraemia is a rare clinical entity. In the younger population, hypernatraemia is often a consequence of failure to generate thirst in response to osmotic stimuli.We report the case of a male patient admitted with severe hypernatraemia (plasma sodium 175 mmol/L) on return from holidays.

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Certain positive-sense single-stranded RNA viruses contain elements at their 3' termini that structurally mimic tRNAs. These tRNA-like structures (TLSs) are classified based on which amino acid is covalently added to the 3' end by host aminoacyl-tRNA synthetase. Recently, a cryoEM reconstruction of a representative tyrosine-accepting tRNA-like structure (TLS) from brome mosaic virus (BMV) revealed a unique mode of recognition of the viral anticodon-mimicking domain by tyrosyl-tRNA synthetase.

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Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging.

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Introduction: Noma is a rapidly spreading infection of the oral cavity which mainly affects young children. Without early treatment, it can have a high mortality rate. Simple gingivitis is a warning sign for noma, and acute necrotizing gingivitis is the first stage of noma.

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  • Strong shocks are critical in high-energy-density environments, like inertial confinement fusion, but spatial measurements of these shocks are limited.
  • This study utilized an imaging spectrometer to examine soft x-ray emissions from shock fronts in helium-neon mixtures and pure neon, finding that the shock width in the helium mixture is approximately double that in pure neon.
  • The research indicates distinct precursor layers in both gases, with higher electron temperatures in the helium mixture, and simulations reveal that thermal conduction and ion kinetics significantly influence precursor formation and shock characteristics.
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Certain viral RNAs encode proteins downstream of the main protein coding region, expressed through "termination-reinitiation" events, dependent on RNA structure. RNA elements located upstream of the first stop codon within these viral mRNAs bind the ribosome, preventing ribosome recycling and inducing reinitiation. We used bioinformatic methods to identify new examples of viral reinitiation-stimulating RNAs and experimentally verified their secondary structure and function.

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  • * Among children treated with ADA, 63% achieved steroid-free clinical remission after one year, compared to 59% for those treated with IFX, indicating no significant difference in effectiveness.
  • * Children on ADA experienced less treatment intensification compared to those on IFX, suggesting that ADA may be associated with a lower need for increased treatment over time.
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Noma is a rapidly progressing infection of the oral cavity, which can cause the disintegration of the cheek, nose and eye, in under a week. One of the most disabling sequelae is trismus, the restriction of mouth opening, which results in difficulties in speech, mastication, social feeding habits and maintenance of oral hygiene. Restriction of mouth opening among noma patients mostly begins during the transition between World Health Organisation (WHO) stage 3 (gangrene) and stage 4 (scarring) of the disease.

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  • - Inflammatory bowel disease (IBD) is a chronic condition that affects the digestive system, leading to issues like growth impairment and fatigue, and physical activity (PA) may help reduce inflammation and offer other health benefits.
  • - A scoping review was done to analyze literature on PA in children with IBD from 1980 to April 2022, identifying 19 relevant studies that looked into descriptive, interventional, and physiological aspects of PA.
  • - Barriers to PA in pediatric IBD patients included low self-esteem and symptoms of the disease, while motivations included personal interest and support from friends and family; further research is needed to understand the short- and medium-term effects of PA on immune health in these patients.
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Yeast-related bloodstream infections (BSIs) in pediatric patients are associated with severe acute malnutrition (SAM), hematological/oncological malignancies and admission to an intensive care unit. These infections are rarely described from low- and middle-income countries. We describe a case series of pediatric patients diagnosed with severe sepsis and yeast isolated from their blood culture in a conflict-affected area of Nigeria from October 2018 to November 2021.

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Hyponatraemia is a common electrolyte abnormality seen in a wide range of oncological and haematological malignancies and confers poor performance status, prolonged hospital admission and reduced overall survival, in patients with cancer. Syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia in malignancy and is characterised by clinical euvolaemia, low plasma osmolality and concentrated urine, with normal renal, adrenal and thyroid function. Causes of SIAD include ectopic production of vasopressin (AVP) from an underlying tumour, cancer treatments, nausea and pain.

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International guidelines designed to minimize the risk of complications that can occur when correcting severe hyponatremia have been widely accepted for a decade. On the basis of the results of a recent large retrospective study of patients hospitalized with hyponatremia, it has been suggested that hyponatremia guidelines have gone too far in limiting the rate of rise of the serum sodium concentration; the need for therapeutic caution and frequent monitoring of the serum sodium concentration has been questioned. These assertions are reminiscent of a controversy that began many years ago.

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