The genetics of Graves' disease.

Graves' disease (GD) is the commonest cause of hyperthyroidism and has a strong female preponderance. Everyday clinical practice suggests strong aggregation within families and twin studies demonstrate that genetic factors account for 60-80% of risk of developing GD. In this review, we collate numerous genetic studies and outline the discoveries over the years, starting with historic candidate gene studies and then exploring more recent genome-wide linkage and association studies, which have involved substantial cohorts of East Asian patients as well as those of European descent.

Expansion of the immature B lymphocyte compartment in Graves' disease.

Objective: The specific mechanisms driving autoimmunity in Graves' disease (GD) remain largely unknown. Kappa-deleting recombination excision circles (KRECs) are circular DNA molecules generated during B cell maturation in the bone marrow which provide a measure of B cell production and proliferation. We aimed to investigate the association between KRECs and B cell subpopulations, with thyroid status and clinical outcome in GD patients.

STEP IN: Supporting Together Exercise and Play and Improving Nutrition; a Feasibility Study of Parent-Led Group Sessions and Fitness Trackers to Improve Family Healthy Lifestyle Behaviors in a Low-Income, Predominantly Black Population.

Background: Pediatric obesity is prevalent and challenging to treat. Although family-centered behavioral management is the gold standard, many families face structural inequities to its access and efficacy. Identifying ways to manage pediatric obesity within primary care is needed.

Graves' disease: moving forwards.

Graves' disease is a rare disorder that continues to present clinicians and families with a series of challenges. There are no new established treatments for children or adolescents, but the outcomes of recent clinical trials and meta-analyses have helped clinicians to prepare families for the road ahead. We have a more refined understanding of how to administer antithyroid drugs, which one to use and how long to treat the young person.

A Technology-Assisted Language Intervention for Children Who Are Deaf or Hard of Hearing: A Randomized Clinical Trial.

Background And Objectives: Children who are deaf or hard of hearing (DHH) often have persistent language delays despite early identification and interventions. The technology-assisted language intervention (TALI), which incorporates augmentative and alternative communication technology into a speech-language therapy model, was designed to support language learning. The study objective was to evaluate the impact of the TALI on spoken language outcomes in DHH children.

A survey of the young person's experience of Graves' disease and its management.

Objective: A suboptimal quality of life (QoL) has been reported in patients with Graves' disease treated in adult life, but long-term QoL in those treated in childhood and adolescence is unclear. We wanted to understand how Graves' disease and its management impact on the physical, psychological and social well-being of young people and their longer-term QoL.

Design, Patients And Measurements: Two questionnaires were used to assess QoL and patient experience of Graves' disease; PedsQL™ Generic Core Scales and a Graves' disease questionnaire devised for this project.

New Therapeutic Horizons for Graves' Hyperthyroidism.

Graves' hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves' hyperthyroidism.

Fifteen-minute consultation: An approach to the child receiving glucocorticoids.

Glucocorticoids (GC) are used in paediatric practice for a broad range of conditions and all paediatricians will prescribe GC, in some form, during their career. A wide variety of GC formulations, doses and administration routes are used for periods of time ranging from days to years. Exposure to exogenous GC can result in hypothalamic-pituitary-adrenal axis suppression-otherwise known as adrenal suppression (AS).

An Intronic HCP5 Variant Is Associated With Age of Onset and Susceptibility to Graves Disease in UK and Polish Cohorts.

Context: The genetic background of young-onset Graves disease (GD) remains largely unknown. An intronic variant in human leukocyte antigen (HLA) complex P5 (HCP5) has previously been associated with GD susceptibility and age of onset in a cohort of Polish patients.

Objective: We aimed to investigate the association of the HCP5 variant rs3094228 with GD susceptibility and age of onset in a UK cohort and conduct a meta-analysis of UK and Polish data.

Graves' disease: developments in first-line antithyroid drugs in the young.

: First-line treatment for most young people with Graves' disease (GD) will include the administration of a thionamide antithyroid medication (ATD); Carbimazole (CBZ), Methimazole (MMZ), or rarely, propylthiouracil (PTU). GD is a challenge for families and clinicians because the likelihood of remission following a course of ATD is lower in young people when compared to adults, yet the risk of adverse events is higher. An overall consensus regarding the optimal ATD treatment regimen is lacking; how ATD are prescribed, for how long and how the associated risk of adverse events is managed varies between clinicians, units and nations.

Puberty: Normal physiology (brief overview).

Puberty is a defining phase of human development where growth ends and the ability to reproduce begins. An understanding of the events leading up to puberty highlights the fact that this is the culmination of a process of skeletal and gonadal activity that has been ongoing since conception. Although there is natural variation in the timing of events in and around puberty the basic underlying processes are common to all healthy human beings.

Analysis of BAFF gene polymorphisms in UK Graves' disease patients.

Objective: B lymphocyte activating factor (BAFF), a member of the tumour necrosis factor superfamily, is essential for B cell activation, differentiation and survival. Elevated circulating BAFF levels have been found in patients with several autoimmune conditions, including Graves' disease. In addition, BAFF gene variants have been associated with Graves' disease in a Taiwanese cohort, and with several other autoimmune conditions in non-Taiwanese populations.

Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management.

Background: There is little adult height data in patients with familial male-limited precocious puberty (FMPP) and no management consensus. We assessed the treatment and adult height in local patients with FMPP and those reported in the literature.

Methods: Growth data were obtained on four local patients with FMPP and a search performed to obtain management details and adult height data on cases in the literature.

Assessment for benign paroxysmal positional vertigo in medical patients admitted with falls in a district general hospital.

Having benign paroxysmal positional vertigo (BPPV) puts patients at a significantly higher risk of falling. It is poorly recognised and diagnosis is frequently delayed. BPPV has been studied in outpatient settings, but there have been no studies looking at the prevalence in patients admitted with falls.

Structure and location of the regulatory β subunits in the (αβγδ)4 phosphorylase kinase complex.

Phosphorylase kinase (PhK) is a hexadecameric (αβγδ)(4) complex that regulates glycogenolysis in skeletal muscle. Activity of the catalytic γ subunit is regulated by allosteric activators targeting the regulatory α, β, and δ subunits. Three-dimensional EM reconstructions of PhK show it to be two large (αβγδ)(2) lobes joined with D(2) symmetry through interconnecting bridges.

Mass spectrometry reveals differences in stability and subunit interactions between activated and nonactivated conformers of the (αβγδ)4 phosphorylase kinase complex.

Phosphorylase kinase (PhK), a 1.3 MDa enzyme complex that regulates glycogenolysis, is composed of four copies each of four distinct subunits (α, β, γ, and δ). The catalytic protein kinase subunit within this complex is γ, and its activity is regulated by the three remaining subunits, which are targeted by allosteric activators from neuronal, metabolic, and hormonal signaling pathways.

Canine intravascular lymphoma with overt leukemia.

A 6-year-old spayed Labrador Retriever Mix dog was evaluated for a 2-week history of progressive generalized weakness and reluctance to stand. Physical examination revealed severe weakness with obtunded mentation, head tilt, bilateral nystagmus, and decreased vision. CBC findings included mild nonregenerative anemia, marked thrombocytopenia, and a few atypical mononuclear cells on the blood film.

Disseminated protothecosis diagnosed by evaluation of CSF in a dog.

A 5-year-old female spayed Shetland Sheepdog Mix dog was evaluated for a history of recent seizure activity, progressive hind limb ataxia, polyuria, and polydipsia and no history of gastrointestinal signs. Physical examination findings included conscious proprioceptive deficits, ataxia, and anterior uveitis along with a hypermature cataract in the right eye. Results of a CBC, serum biochemical profile, urinalysis, and computed tomography scan of the brain were unremarkable.

The NFKB1 (g.-24519delATTG) variant is associated with necrotizing enterocolitis (NEC) in premature infants.

Objective: While it is known that gene-environment interactions contribute to necrotizing enterocolitis (NEC) pathogenesis, characterization of genetic risk-factors that can predict NEC in preterm infants remains nascent. We hypothesized that altered intestinal immune responses arising from sequence variation in the toll-like receptor (TLR) pathway genes contribute to NEC susceptibility.

Materials And Methods: Very low birth weight (VLBW) infants were recruited prospectively in a multi-center, cohort study involving collection of blood samples along with collation of clinical information.

Whom are we comforting? An analysis of comfort medications delivered to dying neonates.

Objectives: To clarify the use of end-of-life comfort medications or neuromuscular blockers (NMBs) in culturally different neonatal intensive care units (NICUs).

Study Design: Review of medical files of newborns > 22 weeks gestation who died in the delivery room or the NICU during 12 months in four NICUs (Chicago, Milwaukee, Montreal, and Groningen). We compared use of end-of-life comfort medications and NMBs.

Mass spectrometry reveals stable modules in holo and apo RNA polymerases I and III.

RNA polymerases are essential enzymes which transcribe DNA into RNA. Here, we obtain mass spectra of the cellular forms of apo and holo eukaryotic RNA polymerase I and III, defining their composition under different solution conditions. By recombinant expression of subunits within the initiation heterotrimer of Pol III, we derive an interaction network and couple this data with ion mobility data to define topological restraints.