The frequency of thyroid gland invasion in advanced laryngeal malignancy: an audit of total laryngectomy histological specimens

This dissertation is submitted as a final copy as the University’s Academic and Clinical supervisorBackground Thyroid gland involvement in advanced laryngeal malignancies is a rare entity, mostly resulting from direct contiguous spread from anterior and inferior tumours. Reported practice is to perform a hemithyroidectomy at the time of laryngectomy. However, this results in pointless excision of functional tissue and the added morbidity of hypothyroidism post operatively. Aim The aim of this study is twofold: firstly, to assess the frequency of thyroid gland involvement in laryngectomy specimens from Chris Hani Baragwanath Hospital, and secondly, to determine any association between the anatomical subsites of tumour and thyroid gland involvement. Methods This is a retrospective clinical audit of histological reports on laryngectomy specimens collected over a 10 year period from January 2005 and December 2014. The study was conducted at Chris Hani Baragwanath Hospital, affiliated to the University of the Witwatersrand, in South Africa. ENT operating registries and the laboratory database were used to access all records of total laryngectomies done over the 10 year period. Seventy-three laryngectomies were done, 9 were excluded as no thyroid tissue was included in the sample and 1 was excluded due to inadequate demographic detail. Thus a total of 63 histological reports were included in the study. Data extracted included age, race, sex, pathological stage of tumour, thyroid gland involvement and anatomical subsites involved by tumour (subglottis, anterior commissure and transglottic tumours). Data was analysed using standard statistical methods including a Fischer-exact test and an ANOVA association test. Statistica software was used. Results Four of the 63 cases had thyroid gland involvement (6.35%). The majority of the patients were black males in the age group 50 to 60 years of age. The tumours were all advanced laryngeal malignancies and only 2 of the 63 cases were found to have a diagnosis of adenosquamous carcinoma and chondrosarcoma. None of the anatomical subsites were found to be statistically significant in association with thyroid gland involvement, however, this result was thought to be skewed due to the small number of tumours involving the thyroid gland. Conclusion In accordance with South African and international studies on the same topic, thyroid gland involvement in laryngeal tumours is a rare occurrence. Due to the complications of performing a thyroidectomy and the hypothyroidism that accompanies it, a thyroidectomy should not always be performed. However, due to the recurrence rates and poor prognosis of patients with stomal recurrence (associated with thyroid gland involvement), thyroidectomy still needs to be considered. Based on known anatomical pathways of extralaryngeal spread of tumours via the anterior commissure, paraglottic spaces and those tumours involving the subglottis, selected patients require thyroidectomy at the time of laryngectomy to achieve adequate oncological margins.MT201

Estimating Lime Requirement for Oregon Soils with Non-Hazardous Soil Test Methods

Various soil tests are routinely used in the United States to predict soil lime requirement. New non-hazardous methods have recently been proposed for adoption in Oregon, however the accuracy of these methods for Oregon soils has not been established. The objectives of this investigation were: (a) to document and describe the development of lime requirement estimate (LRE) soil tests from 1900 to 2020, (b) to evaluate the accuracy of five non-hazardous LRE methods for Oregon soils, and (c) to evaluate how laboratory modifications to the Sikora LRE method affect the accuracy of lime rate recommendations. Four historical periods pertaining to the development of LRE methods were identified. From the 1900s to the 1930s, many wet-chemistry methods were proposed but were not adopted by commercial labs due to lack of method accuracy and to the amount of labor required. From the 1930s to the 1970s, the availability of the pH-sensitive glass electrode led to the development of fast and accurate buffer pH methods that are the foundation for methods that are still used today. From the 2000s to 2020, researchers proposed non-hazardous adaptations of buffer methods as well as the use of other soil test properties. Current research is focused on developing regional calibrations of non-hazardous methods. Twenty-four Oregon soils were incubated with lime (0 – 22.4 Mg ha-1) to determine their incubation lime requirement. Candidate LRE methods were correlated to incubation lime requirement to evaluate their accuracy. The Sikora (r2 = .90 – .92), Modified Mehlich (r2 = .87 – .89), and Sikora-2 (r2 = .81 – .93) buffer methods showed potential as non-hazardous alternatives to SMP (r2 = .90 – .92) based on accuracy and precision. Combining clay concentration, KCl-extractable Al, soil organic matter (SOM), extractable Mg, and pH1:2 also effectively predicted LRE with r2 = .96 – .97. The Moore-Sikora buffer method (r2 = .89 – .93) was similarly accurate but showed precision issues due to high replication variability. The Single Addition of Ca(OH)2 method (r2 = .69 – .77) was not considered to be an accurate predictor of lime requirement for Oregon soils. Five modifications to the Sikora buffer pH method were evaluated for five Oregon soils. Modifications related to mixing method, measurement in supernatant instead of slurry, and soil:water:buffer ratio were found to significantly increase the Sikora buffer pH value by 0.063, 0.065, and 0.058 units respectively in comparison to the control. Mean Sikora buffer pH decreased by 0.02 – 0.05 units when equilibration time was increased from 0 to 180 min. The results of these investigations demonstrate the feasibility of adopting at least one non-hazardous method for predicting lime requirement of Oregon soils. They also demonstrate the importance of accounting for method modifications and inter-laboratory variation for the Sikora LRE method. These results are anticipated to be used to help make accurate lime rate recommendations in Oregon

Phylogenomics and analysis of shared genes suggest a single transition to mutualism in Wolbachia of nematodes

Wolbachia, endosymbiotic bacteria of the order Rickettsiales, are widespread in arthropods but also present in nematodes. In arthropods, A and B supergroup Wolbachia are generally associated with distortion of host reproduction. In filarial nematodes, including some human parasites, multiple lines of experimental evidence indicate that C and D supergroup Wolbachia are essential for the survival of the host, and here the symbiotic relationship is considered mutualistic. The origin of this mutualistic endosymbiosis is of interest for both basic and applied reasons: How does a parasite become a mutualist? Could intervention in the mutualism aid in treatment of human disease? Correct rooting and high-quality resolution of Wolbachia relationships are required to resolve this question. However, because of the large genetic distance between Wolbachia and the nearest outgroups, and the limited number of genomes so far available for large-scale analyses, current phylogenies do not provide robust answers. We therefore sequenced the genome of the D supergroup Wolbachia endosymbiont of Litomosoides sigmodontis, revisited the selection of loci for phylogenomic analyses, and performed a phylogenomic analysis including available complete genomes (from isolates in supergroups A, B, C, and D). Using 90 orthologous genes with reliable phylogenetic signals, we obtained a robust phylogenetic reconstruction, including a highly supported root to the Wolbachia phylogeny between a (A + B) clade and a (C + D) clade. Although we currently lack data from several Wolbachia supergroups, notably F, our analysis supports a model wherein the putatively mutualist endosymbiotic relationship between Wolbachia and nematodes originated from a single transition event

Sialic acid mediated transcriptional modulation of a highly conserved sialometabolism gene cluster in Haemophilus influenzae and its effect on virulence

Background. Sialic acid has been shown to be a major virulence determinant in the pathogenesis of otitis media caused by the bacterium Haemophilus influenzae. This study aimed to characterise the expression of genes required for the metabolism of sialic acid and to investigate the role of these genes in virulence. Results. Using qRT-PCR, we observed decreased transcriptional activity of genes within a cluster that are required for uptake and catabolism of 5-acetyl neuraminic acid (Neu5Ac), when bacteria were cultured in the presence of the sugar. We show that these uptake and catabolic genes, including a sialic acid regulatory gene (siaR), are highly conserved in the H. influenzae natural population. Mutant strains were constructed for seven of the nine genes and their influence upon LPS sialylation and resistance of the bacteria to the killing effect of normal human serum were assessed. Mutations in the Neu5Ac uptake (TRAP transporter) genes decreased virulence in the chinchilla model of otitis media, but the attenuation was strain dependent. In contrast, mutations in catabolism genes and genes regulating sialic acid metabolism (siaR and crp) did not attenuate virulence. Conclusion. The commensal and pathogenic behaviour of H. influenzae involves LPS sialylation that can be influenced by a complex regulatory interplay of sialometabolism genes. © 2010 Jenkins et al; licensee BioMed Central Ltd

Ammonia decomposition catalysis using lithium–calcium imide

Lithium–calcium imide is explored as a catalyst for the decomposition of ammonia. It shows the highest ammonia decomposition activity yet reported for a pure light metal amide or imide, comparable to lithium imide–amide at high temperature, with superior conversion observed at lower temperatures. Importantly, the post-reaction mass recovery of lithium–calcium imide is almost complete, indicating that it may be easier to contain than the other amide–imide catalysts reported to date. The basis of this improved recovery is that the catalyst is, at least partially, solid across the temperature range studied under ammonia flow. However, lithium–calcium imide itself is only stable at low and high temperatures under ammonia, with in situ powder diffraction showing the decomposition of the catalyst to lithium amide–imide and calcium imide at intermediate temperatures of 200–460 °C.</p

Caspase-8 and c-FLIPL associate in lipid rafts with NF-kappaB adaptors during T cell activation.

Humans and mice lacking functional caspase-8 in T cells manifest a profound immunodeficiency syndrome due to defective T cell antigen receptor (TCR)-induced NF-kappaB signaling and proliferation. It is unknown how caspase-8 is activated following T cell stimulation, and what is the caspase-8 substrate(s) that is necessary to initiate T cell cycling. We observe that following TCR ligation, a small portion of total cellular caspase-8 and c-FLIP(L) rapidly migrate to lipid rafts where they associate in an active caspase complex. Activation of caspase-8 in lipid rafts is followed by rapid cleavage of c-FLIP(L) at a known caspase-8 cleavage site. The active caspase.c-FLIP complex forms in the absence of Fas (CD95/APO1) and associates with the NF-kappaB signaling molecules RIP1, TRAF2, and TRAF6, as well as upstream NF-kappaB regulators PKC theta, CARMA1, Bcl-10, and MALT1, which connect to the TCR. The lack of caspase-8 results in the absence of MALT1 and Bcl-10 in the active caspase complex. Consistent with this observation, inhibition of caspase activity attenuates NF-kappaB activation. The current findings define a link among TCR, caspases, and the NF-kappaB pathway that occurs in a sequestered lipid raft environment in T cells