Predictors of post-thyroidectomy hypocalcaemia: a systematic and narrative review.

OBJECTIVE: Hypocalcaemia is the most common complication after total or completion thyroidectomy. This study assesses recent evidence on predictive factors for post-thyroidectomy hypocalcaemia in order to identify the patients affected and aid prevention. METHOD: Two authors independently assessed articles and extracted data to provide a narrative synthesis. This study was an updated systematic search and narrative review regarding predictors of post-thyroidectomy hypocalcaemia using the Ovid Medline, Embase, Cochrane and Cinahl databases. Results were limited to papers published from January 2012 to August 2019. RESULTS: Sixty-three observational studies with a total of 210 401 patients met the inclusion criteria. The median incidence was 27.5 per cent for transient biochemical hypocalcaemia, 12.5 per cent for symptomatic hypocalcaemia and 2.2 per cent for permanent hypocalcaemia. The most frequent statistically significant predictor of hypocalcaemia was peri-operative parathyroid hormone level. Symptomatic hypocalcaemia and permanent hypocalcaemia were seen more frequently in patients undergoing concomitant neck dissection. CONCLUSION: Many factors have been studied for their link to post-thyroidectomy hypocalcaemia, and this study assesses the recent evidence presented in each case.

The Oxylipin Signaling Pathway Is Required for Increased Aphid Attraction and Retention on Virus-Infected Plants.

Many studies have shown that virus infection alters phytohormone signaling and insect vector contact with hosts. Increased vector contact and movement among plants should increase virus survival and host range. In this study we examine the role of virus-induced changes in phytohormone signaling in plant-aphid interactions, using Pea enation mosaic virus (PEMV), pea aphids (Acyrthosiphon pisum), and pea (Pisum sativum) as a model. We observed that feeding by aphids carrying PEMV increases salicylic acid and jasmonic acid accumulation in pea plants compared to feeding by virus-free aphids. To determine if induction of the oxylipin jasmonic acid is critical for aphid settling, attraction, and retention on PEMV-infected plants, we conducted insect bioassays using virus-induced gene silencing (VIGS), an oxylipin signaling inducer, methyl jasmonate (MeJA), and a chemical inhibitor of oxylipin signaling, phenidone. Surprisingly, there was no impact of phenidone treatment on jasmonic acid or salicylic acid levels in virus-infected plants, though aphid attraction and retention were altered. These results suggest that the observed impacts of phenidone on aphid attraction to and retention on PEMV-infected plants are independent of the jasmonic acid and salicylic acid pathway but may be mediated by another component of the oxylipin signaling pathway. These results shed light on the complexity of viral manipulation of phytohormone signaling and vector-plant interactions.

Bilateral Thyroid Carcinosarcoma in a Cat.

A neutered female domestic shorthaired cat was presented for a rapidly growing left cervical mass and a 6-month history of primary hyperthyroidism. Cytological examination of the mass was consistent with a sarcoma. Due to poor clinical response the cat was humanely destroyed and a post-mortem examination was performed. This revealed a markedly enlarged, irregularly shaped left thyroid gland with signs of infiltration of the trachea. The contralateral (right) thyroid was also moderately enlarged and irregularly shaped. Histopathological examination of the cervical masses indicated bilateral thyroid carcinosarcomas, evidenced by positive immunohistochemical labelling for vimentin, pan-cytokeratin and thyroid transcription factor-1 of the appropriate cell populations. The cat also had a concurrent pulmonary adenocarcinoma (papillary-lepidic type), unrelated to the thyroid neoplasm. Thyroid carcinosarcoma is an uncommonly recorded canine and human neoplasm and this is the first case of this entity to be reported in a cat.

IRC +10 216 in 3-D: morphology of a TP-AGB star envelope.

During their late pulsating phase, AGB stars expel most of their mass in the form of massive dusty envelopes, an event that largely controls the composition of interstellar matter. The envelopes, however, are distant and opaque to visible and NIR radiation: their structure remains poorly known and the mass-loss process poorly understood. Millimeter-wave interferometry, which combines the advantages of longer wavelength, high angular resolution and very high spectral resolution is the optimal investigative tool for this purpose. Mm waves pass through dust with almost no attenuation. Their spectrum is rich in molecular lines and hosts the fundamental lines of the ubiquitous CO molecule, allowing a tomographic reconstruction of the envelope structure. The circumstellar envelope IRC +10 216 and its central star, the C-rich TP-AGB star closest to the Sun, are the best objects for such an investigation. Two years ago, we reported the first detailed study of the CO(2-1) line emission in that envelope, made with the IRAM 30-m telescope. It revealed a series of dense gas shells, expanding at a uniform radial velocity. The limited resolution of the telescope (HPBW 11″) did not allow us to resolve the shell structure. We now report much higher angular resolution observations of CO(2-1), CO(1-0), CN(2-1) and C4H(24-23) made with the SMA, PdB and ALMA interferometers (with synthesized half-power beamwidths of 3″, 1″ and 0.3″, respectively). Although the envelope appears much more intricate at high resolution than with an 11″ beam, its prevailing structure remains a pattern of thin, nearly concentric shells. The average separation between the brightest CO shells is 16″ in the outer envelope, where it appears remarkably constant. Closer to the star (< 40″), the shell pattern is denser and less regular, showing intermediary arcs. Outside the small (r < 0.3″) dust formation zone, the gas appears to expand radially at a constant velocity, 14.5 km s-1, with small turbulent motions. Based on that property, we have reconstructed the 3-D structure of the outer envelope and have derived the gas temperature and density radial profiles in the inner (r < 25″) envelope. The shell-intershell density contrast is found to be typically 3. The over-dense shells have spherical or slightly oblate shapes and typically extend over a few steradians, implying isotropic mass loss. The regular spacing of shells in the outer envelope supports the model of a binary star system with a period of 700 years and a near face-on elliptical orbit. The companion fly-by triggers enhanced episodes of mass loss near periastron. The densification of the shell pattern observed in the central part of the envelope suggests a more complex scenario for the last few thousand years.

The role of Leptospira spp. in horses affected with recurrent uveitis in the UK.

BACKGROUND: Equine recurrent uveitis (ERU) is a common cause of ocular pain and blindness in horses. Leptospira spp. have been commonly implicated in the pathophysiology of ERU in mainland Europe and the USA. No recent studies have been carried out in the UK, but Leptospira is reported not to be a major factor in the aetiology of ERU in the UK. OBJECTIVES: To establish the prevalence of Leptospira-associated ERU in the UK and to identify the serovars involved in these cases; to compare serum vs. aqueous humour antibody levels in cases and controls in order to confirm the diagnosis of Leptospira-associated ERU, and to assess the usefulness of serology alone as a confirmatory test for Leptospira-associated ERU in the UK. STUDY DESIGN: Case-control study. METHODS: Eyes enucleated for clinical reasons in ERU-affected horses were collected. Blood and aqueous humour were obtained to determine antibody levels against a variety of Leptospira serovars and C-values (aqueous humour value/serum value) were calculated. In addition, eyes, blood and aqueous humour were obtained from control cases for comparison. Histopathology was performed in all eyes to confirm uveitis in each case. Differences in seroprevalences between ERU and control cases and between Leptospira- and non-Leptospira-associated ERU cases were calculated. RESULTS: A total of 30 ERU and 43 control eyes were analysed. Of the ERU eyes, only two had a C-value of >4 (prevalence of Leptospira-associated uveitis: 6.7%). Serovars hardjo and javanica were detected. There was no difference in seroprevalence between horses with uveitis and control cases (65.5% and 41.9%, respectively; P = 0.11) or between Leptospira- and non-Leptospira-associated uveitis cases (100% and 63.0%, respectively; P = 0.52). MAIN LIMITATIONS: The study was limited by low case numbers. Eyes were presented at different stages of disease. The only test used to detect Leptospira was the microscopic agglutination test. CONCLUSIONS: Leptospira-associated ERU is uncommon in the UK. Serology alone may not help to definitively diagnose Leptospira-associated uveitis in this country.

Severe Foot Lesions in Dairy Goats Associated with Digital Dermatitis Treponemes.

Treponeme-associated foot disease has been described in cattle with digital dermatitis and sheep with contagious ovine digital dermatitis. In this study, severe foot lesions in dairy goats associated with digital dermatitis treponemes (i.e. Treponema medium, Treponema phagedenis and Treponema pedis) were characterized macroscopically, radiographically and histologically. The main macroscopic foot lesion was of extensive solar ulceration with or without exophytic papilliform hyperkeratosis. Radiographically, the distal phalanx and distal sesamoid bones were severely damaged and remodelled. Histologically, the lesion was categorized as a chronic lymphoplasmacytic, suppurative and ulcerative pododermatitis. Immunohistochemistry identified the spirochaetal microorganisms located extracellularly in the superficial horn. Study limitations mean that the treponeme bacteria could not be considered the sole or causal agents in the cases described.

Detection and Isolation of Digital Dermatitis Treponemes from Bovine Pressure Sores.

Pressure sores cause severe pain and discomfort in hospitalized people and in farmed cattle and are often infected with unknown bacteria. Pressure sores occur on the upper legs of 6-10% of recumbent cattle and are generally considered to be caused by constant pressure, commonly on bony areas of the limbs. This study analyzed pressure sores taken from the upper limbs of 14 cattle using isolation in culture and nested polymerase chain reaction (PCR) to detect treponemes associated with digital dermatitis (DD). A 100% association of DD treponemes with the pressure sores was demonstrated, but treponemes were shown not to be part of the normal skin microbiota. Immunohistochemistry showed an association of DD treponemes with lesions and particularly with the hair follicles in lesions, identifying the bacteria deep within wounds, thereby suggesting that they could contribute to lesion pathogenesis. The bacteria isolated from the pressure sore lesions were similar or identical on analysis of the 16S rRNA gene to those found in DD foot lesions in cattle, suggesting the same bacteria can infect multiple lesions. Indeed, the results of this study suggest that these spirochaetal bacteria may be expanding in host range and in their ability to colonize different tissues and contribute to a range of disease manifestations in farm animals.

The association between contact and intellectual disability literacy, causal attributions and stigma.

BACKGROUND: Contact is seen as a key route to tackling stigma and discrimination. Contact theory states that the quality and type of contact, as well as circumstance of the contact experience, influence the effect of contact on prejudice. The majority of research in intellectual disabilities though has focused on contact as present or absent only. METHOD: A total of 1264 adult members of the UK general population completed measures of symptom recognition, social distance (as measure of external stigma) and causal beliefs in response to a diagnostically unlabelled vignette, depicting someone with intellectual disabilities. RESULTS: A nuanced contact variable, including frequency of contact and closeness and nature of the contact relationship, explained more of the variance in social distance, compared to the binary variable (contact as present or absent). Only the closeness of the relationship was individually predictive though, and the models explained only relatively small amounts of the variance. Structural equation modelling of contact, recognition, social distance and causal beliefs demonstrated that the model including the nuanced variable was an adequate fit for the data. CONCLUSIONS: Future research aimed at increasing our understanding of intellectual disability stigma should avoid assessing contact as a binary variable only, but consider other factors, particularly the closeness of contact relationships. Anti-stigma interventions may benefit from focussing on causal attributions as a method of reducing stigma.

Histopathological Characterization of the Lesions of Contagious Ovine Digital Dermatitis and Immunolabelling of Treponema-like Organisms.

Contagious ovine digital dermatitis (CODD) is a cause of severe lameness in sheep and the three Treponema phylogroups Treponema medium/Treponema vincentii-like, Treponema phagedenis-like and Treponema pedis have been associated with clinical disease. The aims of this study were: (1) to describe the histopathological changes associated with each previously established grade of clinical lesion, and (2) to investigate immunohistochemically the association of the Treponema-like organisms with the observed histopathological changes. Early lesions were characterized by lymphoplasmacytic infiltration of the distal digital skin, with suppurative coronitis and intracorneal pustules. In more advanced stages of the disease there was complete separation of the dorsal wall of the hoof with a necrotizing and fibrinosuppurative exudate and dermatitis. The later lesions were mostly resolved, but with milder suppurative changes remaining within the cornified layer and periosteal reaction of the dorsal aspect of the distal phalanx. Large numbers of Treponema-like organisms were identified within early grade lesions (as well as later, more advanced grade lesions) and were specifically associated with the observed histopathological changes. The results of this study provide some evidence in support of the hypothesis that the three CODD-associated Treponema phylogroups are involved in the aetiopathogenesis of this disease.

Clinical and radiographic features of contagious ovine digital dermatitis and a novel lesion grading system.

Contagious ovine digital dermatitis (CODD) is an infectious foot disease of sheep causing severe lameness. Diagnosis is currently made using broad anecdotal descriptions. The aim of this study was to systematically and formally describe the clinical presentation of the disease in terms of (1) a lesion grading system; (2) associated radiographic changes and (3) severity of associated lameness. A five-point lesion grading system was developed and applied to 908 sheep affected by CODD from six farms. Sheep with lesions typical of each grade were euthanased and their feet radiographed. Radiographic abnormalities including soft tissue and bony changes were evident in feet with lesions graded 2-5. In order to quantify the welfare impact of CODD, all the 908 sheep were locomotion scored. Five hundred and eighty-five (64.5% (95% CI 61.4% to 67.6%)) were lame. The locomotion score for affected sheep increased with worsening pathological changes. Once healing had begun the locomotion score decreased. In conclusion the five-point grading system may be used to clinically describe stages of CODD lesions. The radiographic changes revealed examples of deeper pathological changes and there was a strong association between the lesion grading system and locomotion score in affected sheep.

Absence of canine papillomavirus sequences in canine mammary tumours.

Human papillomaviruses (PVs) are found in human breast cancer tissue; however, it remains controversial as to whether these viruses play a role in the aetiology of this tumour. There has been minimal study of whether PVs are found in normal or abnormal mammary glands of animals. The present study investigated whether a PV sequence could be found in the mammary glands of 33 female dogs by rolling circle amplification and polymerase chain reaction. No PV DNA was found in normal or neoplastic canine mammary tissues, suggesting that canine PVs are probably not involved in the pathogenesis of canine mammary neoplasia.

Tuning cation-anion interactions in ionic liquids by changing the conformational flexibility of the cation.

Cation-anion interactions can be tuned via the degree of cation constraint. X-ray Photoelectron Spectroscopy (XPS) experiments reveal that anion-cation based interactions may be enhanced by introducing conformational restriction into the substituent chains of quaternary ammonium cations. A larger degree of charge-transfer was observed for the constrained [C8C1Pyrr](+) cation relative to the [N6,6,6,14](+) cation.

Alveolar macrophages are the main target cells in feline calicivirus-associated pneumonia.

Feline calicivirus (FCV) is a pathogen of felids and one of the most common causative agents of feline upper respiratory disease (URD). Reports of natural FCV pneumonia in the course of respiratory tract infections are sparse. Therefore, knowledge on the pathogenesis of FCV-induced lung lesions comes only from experimental studies. The aim of the present study was to assess the type and extent of pulmonary involvement in natural respiratory FCV infections of domestic cats and to identify the viral target cells in the lung. For this purpose, histology, immunohistochemistry and RNA-in situ hybridisation for FCV and relevant cell markers were performed on diagnostic post-mortem specimens collected after fatal URD, virulent systemic FCV or other conditions. All groups of cats exhibited similar acute pathological changes, dominated by multifocal desquamation of activated alveolar macrophages (AM) and occasional type II pneumocytes with fibrin exudation, consistent with diffuse alveolar damage (DAD). In fatal cases, this was generally seen without evidence of epithelial regeneration. In cats without clinical respiratory signs, type II pneumocyte hyperplasia was present alongside the other changes, consistent with the post-damage proliferative phase of DAD. FCV infected and replicated in AM and, to a lesser extent, type II pneumocytes. This study shows that lung involvement is an infrequent but important feature of FCV-induced URD. AM are the main viral target cell and pulmonary replication site, and their infection is associated with desquamation and activation, as well as death via apoptosis.

Haemolytic anaemia and acute pancreatitis associated with zinc toxicosis in a dog.

We describe a case of zinc toxicity in a 14-month-old, female, neutered, Cavalier King Charles spaniel with a 48-hour history of haematochezia, icterus and collapse. Regenerative anaemia with a packed-cell volume of 7 per cent was seen. Prior to referral, radiography had revealed a gastric, metallic foreign body which was removed at exploratory laparotomy. On presentation, the dog was comatose, hypothermic and bradycardic - resuscitation was performed successfully, but the dog then displayed marked abdominal pain. The dog died 12 hours after presentation. At postmortem examination, the animal showed severe icterus. Both kidneys were diffusely dark red; the pancreas was diffusely pale and nodular. Histopathological examination revealed evidence of intravascular haemolysis with blood vessel lumens containing haemoglobin. The renal tubules also contained large amounts of intraluminal haemoglobin with haemoglobin crystals scattered throughout the cortex and medulla. The pancreas exhibited multifocal coagulative necrosis, surrounded by a neutrophil-dominated inflammatory infiltrate. Zinc levels were markedly increased above the normal reference range in both liver and kidney. This report describes the clinical and pathological findings of a case of acute zinc toxicity in a dog following ingestion of a metallic object which resulted in marked haemolytic anaemia and acute pancreatitis.

Pre-clinical evaluation of three non-viral gene transfer agents for cystic fibrosis after aerosol delivery to the ovine lung.

We use both large and small animal models in our pre-clinical evaluation of gene transfer agents (GTAs) for cystic fibrosis (CF) gene therapy. Here, we report the use of a large animal model to assess three non-viral GTAs: 25 kDa-branched polyethyleneimine (PEI), the cationic liposome (GL67A) and compacted DNA nanoparticle formulated with polyethylene glycol-substituted lysine 30-mer. GTAs complexed with plasmids expressing human cystic fibrosis transmembrane conductance regulator (CFTR) complementary DNA were administered to the sheep lung (n=8 per group) by aerosol. All GTAs gave evidence of gene transfer and expression 1 day after treatment. Vector-derived mRNA was expressed in lung tissues, including epithelial cell-enriched bronchial brushing samples, with median group values reaching 1-10% of endogenous CFTR mRNA levels. GL67A gave the highest levels of expression. Human CFTR protein was detected in small airway epithelial cells in some animals treated with GL67A (two out of eight) and PEI (one out of eight). Bronchoalveolar lavage neutrophilia, lung histology and elevated serum haptoglobin levels indicated that gene delivery was associated with mild local and systemic inflammation. Our conclusion was that GL67A was the best non-viral GTA currently available for aerosol delivery to the sheep lung, led to the selection of GL67A as our lead GTA for clinical trials in CF patients.

Intense star formation within resolved compact regions in a galaxy at z = 2.3.

Massive galaxies in the early Universe have been shown to be forming stars at surprisingly high rates. Prominent examples are dust-obscured galaxies which are luminous when observed at sub-millimetre wavelengths and which may be forming stars at a rate of 1,000 solar masses (M(middle dot in circle)) per year. These intense bursts of star formation are believed to be driven by mergers between gas-rich galaxies. Probing the properties of individual star-forming regions within these galaxies, however, is beyond the spatial resolution and sensitivity of even the largest telescopes at present. Here we report observations of the sub-millimetre galaxy SMMJ2135-0102 at redshift z = 2.3259, which has been gravitationally magnified by a factor of 32 by a massive foreground galaxy cluster lens. This magnification, when combined with high-resolution sub-millimetre imaging, resolves the star-forming regions at a linear scale of only 100 parsecs. We find that the luminosity densities of these star-forming regions are comparable to the dense cores of giant molecular clouds in the local Universe, but they are about a hundred times larger and 10(7) times more luminous. Although vigorously star-forming, the underlying physics of the star-formation processes at z approximately 2 appears to be similar to that seen in local galaxies, although the energetics are unlike anything found in the present-day Universe.

Atrial myocarditis as a cause of sinus arrest in a dog.

A 10-year-old male cairn terrier cross was presented with a history of myxomatous mitral valve disease diagnosed six months previously and with a four-week history of intermittent collapse. On 24 hour electrocardiograph (Holter) analysis, periods of no discernable electrical cardiac activity, which coincided with three collapsing episodes, were identified. Unfortunately, on re-presentation for removal of the Holter monitor, the dog collapsed and died. A post-mortem examination was conducted, and histology of the right and left atrium showed evidence of myocarditis. This is the first reported case, to our knowledge, of collapse because of electrical asystole in a dog with atrial myocarditis.

Emphysema: the challenge of the remodelled lung.

Emphysema is recognized as the component of chronic obstructive airways disease that is responsible for airways obstruction. Different patterns of emphysema are, however, recognized, suggesting possible different pathogenetic processes within the lung. This, coupled with the associated idea of susceptibility factors to the development of emphysema, has led to studies of genes that may be involved in the defence of the lung from proteolytic and oxidative damage. These studies have been driven by the goal of finding a treatment for emphysema, but appear to have lost sight of the fundamental remodelling of the lung that has occurred in patients with emphysema and the fact that it is not a single morphological entity.

Identifying demand for health resources using waiting times information.

In this paper the differences in average waiting times are utilized to identify the determinants of demand for health services. The equilibrium waiting time framework is used, but the full equilibrium assumption is relaxed by selecting areas with low waiting times and by estimating a (semi-)parametric selection model. Determinants of supply are used as instruments for the endogeneity of waiting times. A model for the demand for acute services at the ward level in the UK is estimated. The model estimates, and their implications for health service allocations in the UK, are contrasted against more standard allocation models. The present results show that it is critically important to account for rationing by waiting times when identifying needs from care utilization data.

Characterisation of lectin binding patterns of mouse bronchiolar and rat alveolar epithelial cells in culture.

Lung epithelial cell differentiation pathways remain unclear. This is due in part to the plasticity of these cells and the lack of markers which accurately reflect their differentiation status. The aim of this study was to determine if lectin binding properties are useful determinants of functional differentiation status in vitro. Mouse Clara cells were cultured for 5 days. During this time, no alteration in differentiation was evident by electron microscopy. No significant alteration in binding reactivity of Bauhinia purpurea (BPA), Maclura pomifera (MPA), Concanavalin A, Wheat germ or Helix pomatia lectins occurred in cultures compared with Clara cells in mouse lung tissue. In contrast, nitrotetrazolium blue reductase activity and CC10 expression declined in culture. Rat type II cells were cultured for 8 days. Between days 0 and 4, the number of type II cells identified by electron microscopy was constant at 70-80%, decreasing to 8% by day 6. In contrast, by day 4, only 42% cells retained alkaline phosphatase activity. BPA and MPA reactivity was altered at day 0 and day 4 respectively, compared with cells in situ. Therefore, the reactivity of lectins analysed here does not reflect functional differentiation status of cultured mouse Clara cells. However, BPA and MPA reactivity may be a sensitive indicator of alterations in rat type II cell differentiation in vitro.