Mismatch repair protein expression defects in endometrioid endometrial adenocarcinoma

Objectives: Endometrioid endometrial carcinoma (EEC) is the sentinel cancer in over half female patients with heritable mismatch repair (MMR) mutations as part of Lynch syndrome. Immunohistochemical testing for tumoural MMR-protein expression is the primary screening test identifying cases potentially harbouring familial cancer syndrome-related mutations and is also a predictive biomarker for immune-checkpoint blockade response.Methods: Following Data Protection and Ethical clearance by the University of Malta, 200 EEC cases were retrospectively identified and categorized into three arms: 151 cases above age 50 at diagnosis, 49 cases at or below age 50 at diagnosis and 30 controls with benign endometrial tissue sampling. H&E case slides were re-examined by an independent pathologist to confirm the diagnosis and identify the block best representing the tumour. Four new slides per case were recut and immunohistochemistry performed for MLH1, PMS2, MSH2, and MSH6 proteins. Protein expression was analysed semiquantitatively using Allred scoring.Results: 31% of the overall EEC cases were deficient for one or more MMR-proteins. Dual loss of the MLH1-PMS2 protein heterodimer was the most common deficiency, occurring in 24.5% of cases. Loss of MSH2-MSH6 protein expression represented 3.2% of MMR-deficient cases. Well differentiated tumours had a 76.5% proficiency rate as opposed to grade 2/3 disease with 53.2% and 52.9% proficiency rate respectively. There was no significant difference in MMR status when age 50 was used as a hypothetical testing threshold. After correcting for tumour grade, MLH1 and PMS2 expression was shown to be negatively correlated with age-at-diagnosis while MSH6 expression was positively correlated.Conclusion: Reflex MMR proficiency testing of all EEC cases is advisable, as using age 50 as a testing threshold would have missed 82.3% of MMR deficient cases. Prospective evidence is required to clarify the role semi-quantitative scoring plays in MMR status interpretation and patient management in the ever-evolving field of targeted therapeutics.peer-reviewe

Biomarkers of pituitary adenoma behaviour

The pathological behaviour of pituitary adenomas (PAs) is complex and difficult to predict. In this study, the proliferation marker, Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analyzed using immunohistochemistry in 74 PA samples (48 non-functional PAs, 26 functional PAs) and correlated with tumour characteristics including size, extension and tumour behaviour patterns. Correlation of protein marker expression with clinical characteristics yielded significant results. A correlation between PTTG expression and age at diagnosis, tumour size, tumour regrowth and Ki-67 was observed. Cyclin D1 and c-MYC also showed significant correlations with gender, tumour size, age at diagnosis and other protein markers. Significant differences in protein expression in the chosen markers were also observed between different tumour types, between patients treated pre-operatively with somatostatin analogues and in tumours with different intensity on MR imaging). Significant correlations were also observed between the markers themselves, with a possible direct link between two of the studied markers which substantiate data from other in vitro studies. Differences in protein localization were also analyzed to identify possible differences in biological behaviour arising in relation to nuclear vs cytoplasmic localization of the studied biomarkers. VEGF and PACAP similarly appeared interesting but exhibited few statistically significant correlations on detailed analysis. In conclusion, interesting and novel observations on the differences in expression of tumour markers studied are reported. Specifically, Ki-67 and PTTG appear to be very strongly correlated to tumour regrowth/recurrence and may be considered useful tools in predicting the proliferative potential of the resected tumours. Further data on the differential role of Cyclin D1 and cMYC in pituitary tumorigenesis and possibly tumour prognosis are presented.Principal author (MG, JV) was funded by the University of Malta Research funds (MEDRP02-05) and the Faculty of Medicine and Surgery (MDSIN08-22).RF is funded by the REACH HIGH Scholars Programme – Post-Doctoral Grant. The Research work disclosed in this publication is partially funded by the REACH HIGH Scholars Programme – Post Doctoral Grants. The grant is part-financed by the European Union, Operational Programme II – Cohesion Policy 2014 – 2020 “Investing in human capital to create more opportunities and promote the wellbeing of society” – European Social Fund.peer-reviewe

Hypernasality in singing among children with cleft palate: a preliminary study

The aim of this study was to document differences in hypernasality during speaking and singing among children with cleft palate and to compare nasality score ratings of trained and untrained listeners. Twenty subjects with cleft palate aged between 7 and 12 years participated in this study. Audio recordings were made of the children reading a passage and singing a common local song, both in the Malay language. The degree of hypernasality was judged through perceptual assessment. Three trained listeners (a speech therapist, a classical singer, and a linguistic expert – all academicians) and two untrained listeners (a cleft volunteer worker and a national high school teacher) assessed the recordings using a visual analogue scale (VAS). Inter-rater and intra-rater reliability for hypernasality in both speaking and singing were verified using the intra-class correlation coefficient (ICC). A significant reduction in hypernasality was observed during singing as compared to speaking, indicating that hypernasality reduces when a child with cleft palate sings. The act of singing significantly reduces hypernasality. The outcome of this study suggests that children with cleft palate would benefit from singing exercises to ultimately reduce hypernasality. However, future research is needed to objectively measure nasality in singing compared to speaking. © 2019 International Association of Oral and Maxillofacial Surgeon

Membrane Bioreactor: Applications and Limitations in Treating High Strength Industrial Wastewater

This paper reviewed the application of membrane bioreactor in treating high strength industrial wastewater by analysing operational parameters, limitations and mitigations of MBR for industrial wastewater. High strength industrial wastewater is difficult to classify but by its characteristics can be predicted using biodegradability criteria (BOD5/COD). Several factors need to be taken into consideration to find suitable operating parameters such as hydraulic retention time (HRT), solid retention time (SRT), mix liquor suspended solid (MLSS), food to microorganism (F/M), transmembrane pressure (TMP) and Flux (J) to obtain good quality effluent and reduce the fouling effect. Fouling factors by membrane, biomass and MBR operation need to be taken seriously because they are the major problems affecting the performance of the MBR and quality of the effluent. There are specific methods to reduce and clean the clogging membrane depending on the level of severity of the fouling. The mitigation covers physical cleaning such as membrane relaxing, backwashing, a combination of both and chemical cleaning which is used for irreversible fouling. In some cases, modification of MBR is needed to improve the performance and to achieve high quality of effluent

Corrosion characterisation of Al-Cu reinforced in-situ TiB2

Aluminium (Al) based in-situ metal matrix composites (MMCs) have better properties and performance compared to ex-situ MMCs. In this research, aluminium-copper (Al-Cu) alloy was reinforced with 3 and 6wt.% titanium diboride (TiB2). Al-MMCs has been fabricated with salt route reaction process at 800 °C via potassium hexafluorotitanate (K2TiF6) and potassium tetrafluoroborate (KBF4) salts. Hardness vickers tester and Gamry-Electrod Potentiometer were used to characterize the hardness properties and to determine the corrosion rate of Al-Cu alloys. From results obtained, increased TiB2 contents will increase the hardness of Al-Cu alloys. Increased of TiB2 contents also will increase the corrosion rate of Al-Cu alloys. Al-Cu with 3wt.%TiB2 gave the good properties of corrosion when the wear rate recorded the lowest value compare to Al-Cu alloy itself and 6 wt.% TiB2. The corrosion rate of Al-Cu with 3wt.TiB2 was 16.15, while Al-Cu and Al-Cu-6wt%TiB2 were 22.5 and 58.7 mm/y respectively

Demographic characteristics of the <i>Tropidolaemus</i> spp. snake bite patients.

Demographic characteristics of the Tropidolaemus spp. snake bite patients.</p

The frequency of anatomical region involved in bite injury from <i>Tropidolaemus</i> spp.

The frequency of anatomical region involved in bite injury from Tropidolaemus spp.</p

The clinical presentation, management and outcome of <i>Tropidolaemus spp</i>. bite consulted to RECS from 2015–2021.

The clinical presentation, management and outcome of Tropidolaemus spp. bite consulted to RECS from 2015–2021.</p