Severe Resistance to Thyroid Hormone Beta in a Patient with Athyreosis.

We report a patient with congenital hypothyroidism due to athyreosis complicated by a heterozygous thyroid hormone receptor beta (THRß) gene mutation (R320L), resulting in a severe resistance to thyroid hormone beta phenotype. The proband inherited the mutant allele from his father, presenting a very mild phenotype. While the precise reason for this discrepancy remains unknown, we postulate the possibility of de novo mutation and mosaicism in the father. Correlating thyrotropin (TSH) with free thyroxine (fT4) allowed us to predict the amount of fT4 required to normalize the proband's TSH, which supported the treatment with high dose of levothyroxine.

Skull base pathology - a diagnostic conundrum.

BACKGROUND: Myoepithelioma is a rare benign neoplasm, most commonly derived from salivary glands, but there are limited cases of extra salivary gland involvement too. There is little knowledge on typical investigative findings and, instead, diagnosis relies on immunohistochemistry analysis. To our knowledge, this paper reports the 13th case of sinonasal myoepithelioma in the English literature. CASE REPORT: This paper presents a 25-year-old man who complained of chronic nasal obstruction. A sinonasal mass was noted on examination that appeared benign on imaging. Biopsy revealed a grade 2 chondrosarcoma that was endoscopically resected; however, excisional margins were positive. On histopathological review at the multidisciplinary team meeting, the lesion was more in keeping with chondromyxoid fibroma, but immunohistochemistry analysis confirmed a myoepithelioma lesion. In light of this revised diagnosis, quorate opinion was for follow up with active monitoring. CONCLUSION: Sinonasal tumours require a thorough history, examination and investigation before a treatment plan can be formulated. If there is diagnostic uncertainty, it is important to keep a wide differential list and seek a second specialist opinion where possible.

Extensive mucocutaneous, oesophageal and otic lichen planus secondary to nivolumab therapy.

We report a 73-year-old female with metastatic renal cell carcinoma who developed a widespread lichenoid reaction following nivolumab treatment. The timeline of the reaction strongly correlated with the nivolumab treatment and subsequent cessation. Our patient had cutaneous, mucosal, otic, ophthalmic and oesophageal involvement, demonstrating the potentially extensive nature of lichenoid reactions to anti-programmed cell death receptor-1 (anti-PD1) therapies. Although lichenoid reactions to anti-PD1 therapies are now well recognized, there have been no previous reports of otic or oesophageal involvement in the literature. Although cutaneous lichenoid reactions do not tend to be severe or treatment limiting, more widespread systemic lichenoid reactions are challenging to manage, particularly in the context of malignancy. This very unusual case highlights the importance of considering involvement beyond the skin in all lichenoid skin reactions.

Sinonasal cancer: an overview of the emerging subtypes.

BACKGROUND: Advances in immunohistochemistry have spearheaded major developments in our understanding and classification of sinonasal tumours. In the last decade, several new distinct histopathological entities of sinonasal cancer have been characterised. OBJECTIVES: This review aims to provide a clinical update of the major emerging subtypes for the ENT surgeon and an overview of the management strategies available for this heterogeneous group of pathologies. CONCLUSION: Although rare, knowledge of sinonasal neoplasm subtypes has implications for prognosis, treatment strategies and the development of novel therapeutic targets.

Sex-related differences in muscle size explained by amplitudes of higher-threshold motor unit action potentials and muscle fibre typing.

AIM: To investigate the relationships between motor unit action potential amplitudes (MUAPAMP ), muscle cross-sectional area (mCSA) and composition (mEI), per cent myosin heavy chain (%MHC) areas and sex in the vastus lateralis (VL). METHODS: Ten males and 10 females performed a submaximal isometric trapezoid muscle action that included a linearly increasing, steady torque at 40% maximal voluntary contraction, and linearly decreasing segments. Surface electromyographic decomposition techniques were utilized to determine MUAPAMPS in relation to recruitment thresholds (RT). Ultrasound images were taken to quantify muscle mCSA and mEI. Muscle biopsies were collected to calculate %MHC areas. Y-intercepts and slopes were calculated for the MUAPAMP vs RT relationships for each subject. Independent-samples t tests and ANOVA models examined sex-related differences in mCSA, mEI, slopes and y-intercepts for the MUAPAMP vs RT relationships and %MHC areas. Correlations were performed among type IIA and total type II %MHC area, mCSA and the slopes and y-intercepts for the MUAPAMP vs RT relationships. RESULTS: Males exhibited greater slopes for the MUAPAMP vs RT relationships (P = .003), mCSA (P < .001) and type IIA %MHC (P = .011), whereas females had greater type I %MHC area (P = .010) and mEI (P = .024). The mCSA, type IIA and total II %MHC area variables were correlated (P < .001-.015, r = .596-.836) with the slopes from the MUAPAMP vs RT relationships. CONCLUSION: Sex-related differences in mCSA and MUAPAMPS of the higher-threshold MUs were likely the result of larger muscle fibres expressing type II characteristics for males.

Results from the third Scottish National Prevalence Survey: is a population health approach now needed to prevent healthcare-associated infections?

BACKGROUND: Healthcare-associated infections (HCAIs) are a major public health concern and a significant cause of morbidity and mortality. A robust and current evidence base that is specific to local, national and Europe-wide settings is necessary to inform the development of strategies to reduce HCAI and contain antimicrobial resistance. AIM: To measure the prevalence of HCAI and antimicrobial prescribing and identify key priority areas for interventions to reduce the burden of infection. METHODS: A national rolling point-prevalence survey (PPS) in National Health Service (NHS) acute, NHS non-acute, NHS paediatric, and independent hospitals was carried out between September and November 2016 using the European Centre for Disease Prevention and Control protocol designed for the European PPS. FINDINGS: The prevalence of HCAI was 4.6%, 2.7%, and 3.2% in acute adults, paediatric and non-acute patient groups, respectively. The most frequent HCAI types reported in adult patients were urinary tract infection and pneumonia. The prevalence of antimicrobial prescribing was 35.7%, 29.3%, and 13.8% in acute adults, paediatric, and non-acute patient groups, respectively. Respiratory, skin and soft tissue, gastrointestinal, and urinary tract infections were the most common infections being treated at the time of survey. CONCLUSION: HCAI continues to be a public health concern in Scotland. Urinary tract infection and pneumonia continue to place a significant burden on patients and on healthcare delivery, including those that develop in the community and require hospital admission. A broader population health approach which focuses on reducing the risk of infection upstream would reduce these infections in both community and hospital settings.

Characterizing ammonia emissions from horses fed different crude protein concentrations.

Evaluating impact of animal agriculture on air quality has been the focus of recent research. Ammonia (NH) volatilization occurs when undigested protein in feces and urea in urine is broken down by bacteria and enzymes. Information regarding NH emission from equine facilities is limited, and effects of CP intake on NH emissions have not been investigated. Nine mature geldings were used in a 3 × 3 replicated Latin square design study to determine effects of dietary CP on potential NH losses from feces and urine. We hypothesized feeding horses above the CP requirement would result in an increase in NH emissions from urine and feces and different bedding materials would affect NH emissions from urine. Diets were formulated using different ratios of bahiagrass () and Tifton-85 bermudagrass () hays, and a commercial vitamin mineral supplement to provide 3 different CP concentrations and labeled in relation to each other: LOW-CP, MED-CP, and HIGH-CP (10.6%, 11.5%, and 12%, respectively). Each study period consisted of an 11-d diet adaptation phase, followed by a 3-d total collection of urine and feces. To determine total nitrogen (TN) and urea-N concentrations, samples were pooled by period ( = 9). For in vitro determination of NH concentrations, urine and fecal samples were pooled within period by diet ( = 3) and mixed with either wheat straw or wood shavings. Ammonia emission of these samples was measured using a vessel system with an airflow rate (2.5 L/min) at 20°C over a 7-d period. Concentration of NH in each vessel was measured using a photoacoustic multigas analyzer. Temperature, airflow rate, and NH concentration in each vessel were used to calculate NH emission rate (ER). Data were analyzed using a mixed model ANOVA with repeated measures. Urinary TN and urea-N excretion increased as CP intake increased ( < 0.0001). Vessel urinary NH concentrations were not different across diets ( = 0.1225), ranging from 55.48 ppm (LOW-CP) to 101.14 ppm (HIGH-CP); however, they differed between bedding types ( < 0.0001), with straw higher than shavings (97 vs. 73.5 ppm, respectively). Cumulative urinary NH ER tended to be different across diets ( = 0.0550) ranging from 5.87 g/m to 9.97 g/m and bedding types ( = 0.0129), with straw being higher than shavings (11.1 vs. 6.9 g/m, respectively). Overfeeding CP to horses can lead to increased urinary TN and urea-N excretion, which could lead to greater of NH in the atmosphere.

Blood lactate accumulation decreases during the slow component of oxygen uptake without a decrease in muscular efficiency.

Pulmonary oxygen uptake ([Formula: see text]) slowly increases during exercise above the anaerobic threshold, and this increase is called the slow component of [Formula: see text]. The mechanism of the increase in [Formula: see text] is assumed to be due to increasing energy cost associated with increasingly inefficient muscle contraction. We hypothesized that the increase in [Formula: see text] would be accompanied by a constant or increasing rate of accumulation of blood lactate, indicating sustained anaerobic metabolism while [Formula: see text] increased. Ten male subjects performed cycle ergometry for 3, 6, and 9 min at a power output representing 60% of the difference between lactate threshold and maximal [Formula: see text] while [Formula: see text] and blood lactate accumulation were measured. Blood lactate accumulation decreased over time, providing the energy equivalent of (mean ± SD) 1586 ± 265, 855 ± 287, and 431 ± 392 ml of [Formula: see text] during 0-3, 3-6, and 6-9 min of exercise, respectively. As duration progressed, [Formula: see text] supplied 86.3 ± 2.0, 93.6 ± 1.9, and 96.8 ± 2.9% of total energy from 0 to 3, 3 to 6, and 6 to 9 min, respectively, while anaerobic contribution decreased. There was no change in total energy cost after 3 min, except that required by ventilatory muscles for the progressive increase in ventilation. The slow component of [Formula: see text] is accompanied by decreasing anaerobic energy contribution beyond 3 min during heavy exercise.

A closer look at the physical and optical properties of gold nanostars: an experimental and computational study.

A combined experimental and computational study was carried out to design a semi-empirical method to determine the volume, surface area, and extinction coefficients of gold nanostars. The values obtained were confirmed by reconstructing the nanostar 3D topography through high-tilt TEM tomography and introducing the finite elements in COMSOL Multiphysics through which we have also calculated the morphology-dependent extinction coefficient. Doing so, we have, for the first time, modeled the heat losses of a real, experimentally synthesized nanostar, and found the plasmon resonances to be in excellent agreement with those obtained experimentally. We believe that our approach could substantially improve the applicability of this remarkable nanomaterial.

Pathways of Acetyl-CoA Metabolism Involved in the Reversal of Palmitate-Induced Glucose Production by Metformin and Salicylate.

The pathways through which fatty acids induce insulin resistance have been the subject of much research. We hypothesise that by focussing on the reversal of insulin resistance, novel insights can be made regarding the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered during the prevention of palmitate-induced glucose production in hepatocytes using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075 mM, 48 h) with or without metformin (0.25 mM) and sodium salicylate (2 mM) in the final 24 h of palmitate treatment, and effects on glucose production were determined. RNA microarray measurements followed by gene set enrichment analysis were performed to investigate pathway regulation. Lipidomic analysis and measurement of secreted bile acids and cholesterol were also performed. Reversal of palmitate-induced glucose production by metformin and sodium salicylate was characterised by co-ordinated down-regulated expression of pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. All 20 enzymes that regulate the conversion of acetyl-CoA to cholesterol were reduced following metformin and sodium salicylate. Selected findings were confirmed using primary mouse hepatocytes. Although total intracellular levels of diacylglycerol, triacylglycerol and cholesterol esters increased with palmitate, these were not, however, further altered by metformin and sodium salicylate. 6 individual diacylglycerol, triacylglycerol and cholesterol ester species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. These results implicate acetyl-CoA metabolism and C18 lipid species as modulators of hepatic glucose production that could be targeted to improve glucose homeostasis.

Electromyographic Responses from the Vastus Medialis during Isometric Muscle Actions.

This study examined the electromyographic (EMG) responses from the vastus medialis (VM) for electrodes placed over and away from the innervation zone (IZ) during a maximal voluntary isometric contraction (MVIC) and sustained, submaximal isometric muscle action. A linear electrode array was placed on the VM to identify the IZ and muscle fiber pennation angle during an MVIC and sustained isometric muscle action at 50% MVIC. EMG amplitude and frequency parameters were determined from 7 bipolar channels of the electrode array, including over the IZ, as well as 10 mm, 20 mm and 30 mm proximal and distal to the IZ. There were no differences between the channels for the patterns of responses for EMG amplitude or mean power frequency during the sustained, submaximal isometric muscle action; however, there were differences between channels during the MVIC. The results of the present study supported the need to standardize the placement of electrodes on the VM for the assessment of EMG amplitude and mean power frequency. Based on the current findings, it is recommended that electrode placements be distal to the IZ and aligned with the muscle fiber pennation angle during MVICs, as well as sustained, submaximal isometric muscle actions.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women.

AIMS: The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. METHODS: Subcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, lipid and gene profiling were performed. RESULTS: In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, phosphatidylethanolamine methyl transferase (PEMT), decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. INTERPRETATION: The relevance of these findings to insulin resistance in humans is supported by published mouse studies, in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action and PEMT was required for adipocyte lipid storage. Thus in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.

Isolated herpes simplex in the adult larynx as a rare complication of methotrexate-induced immunosuppression.

OBJECTIVE: This report describes the clinical presentation and management of a rare case of herpes simplex virus infection in the larynx of a patient treated with methotrexate. CASE REPORT: We report a case of a clinically suspicious laryngeal lesion in an 82-year-old woman who started methotrexate treatment for rheumatoid arthritis. Shortly afterwards she developed dysphonia, which worsened over four months. On microlaryngoscopy, there was bilateral erythema and ulceration of the vocal folds. No other mucocutaneous lesions or systemic features were present. Biopsies revealed herpes simplex virus infection of the vocal folds; there was complete resolution with oral aciclovir. A brief literature review for this rare entity is presented and the diagnostic challenges arising from under-recognition of atypical presentations are discussed. CONCLUSION: To our knowledge, this is the first report of a rare complication of herpes simplex virus infection in the context of methotrexate-induced immunosuppression. It may present therapeutic challenges for conditions which rely on immunosuppressive treatments.

LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.