Deregulated Long Non-Coding RNAs (lncRNA) as Promising Biomarkers in Hidradenitis Suppurativa.

Background/Objectives: In recent times, epigenetics alterations in Hidradenitis suppurativa (HS) have been explored and exploited translationally to guide investigation of new therapeutic approaches. On the other hand, long noncoding RNAs (LncRNAs), main regulators of the epigenetic status of the human genome, have been scarcely investigated, notwithstanding their potential relevance in broad pathogenesis comprehension. Here, we aim to explore the methylation pattern of lncRNAs in HS. Methods: In this case-control study, 24 HS patients and age-, sex- and BMI-matched controls were analyzed to characterize the methylome of lncRNA genes in peripheral blood cells. Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) network, and MCODE analysis were performed. Results: A set of fifteen lncRNA genes exhibited significantly differential methylation patterns, with ten of them showing hypomethylation and five displaying hypermethylation at specific CpG sites. The hypomethylated lncRNA genes were DLEU2, MESTIT1, CASC2, TUG1, KCNQ1DN, PSORS1C3, PCA3, DSCR8, RFPL1S, and PVT1, while the hypermethylated ones were HAR1A, FAM66B, SNHG9, HCG9, and HCP5. These lncRNA genes have been linked to various important biological processes, including cell proliferation, apoptosis, inflammation, chronic inflammatory skin diseases, and wound healing. Their altered methylation status suggests potential roles in regulating these processes, and may contribute to HS pathogenesis and healing mechanisms. Conclusions: This study revealed an interesting dysregulation pattern of definite lncRNAs in the methylome which is linked to both the development of HS and its comorbidities. Epigenetically altered lncRNAs genes could represent useful biomarkers, and could help in guiding innovative treatment strategies.

Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment.

We implicated the X-chromosome THOC2 gene, which encodes the largest subunit of the highly-conserved TREX (Transcription-Export) complex, in a clinically complex neurodevelopmental disorder with intellectual disability as the core phenotype. To study the molecular pathology of this essential eukaryotic gene, we generated a mouse model based on a hypomorphic Thoc2 exon 37-38 deletion variant of a patient with ID, speech delay, hypotonia, and microcephaly. The Thoc2 exon 37-38 deletion male (Thoc2Δ/Y) mice recapitulate the core phenotypes of THOC2 syndrome including smaller size and weight, and significant deficits in spatial learning, working memory and sensorimotor functions. The Thoc2Δ/Y mouse brain development is significantly impacted by compromised THOC2/TREX function resulting in R-loop accumulation, DNA damage and consequent cell death. Overall, we suggest that perturbed R-loop homeostasis, in stem cells and/or differentiated cells in mice and the patient, and DNA damage-associated functional alterations are at the root of THOC2 syndrome.

Spatial MS multiomics on clinical prostate cancer tissues.

Mass spectrometry (MS) and MS imaging (MSI) are used extensively for both the spatial and bulk characterization of samples in lipidomics and proteomics workflows. These datasets are typically generated independently due to different requirements for sample preparation. However, modern omics technologies now provide higher sample throughput and deeper molecular coverage, which, in combination with more sophisticated bioinformatic and statistical pipelines, make generating multiomics data from a single sample a reality. In this workflow, we use spatial lipidomics data generated by matrix-assisted laser desorption/ionization MSI (MALDI-MSI) on prostate cancer (PCa) radical prostatectomy cores to guide the definition of tumor and benign tissue regions for laser capture microdissection (LCM) and bottom-up proteomics all on the same sample and using the same mass spectrometer. Accurate region of interest (ROI) mapping was facilitated by the SCiLS region mapper software and dissected regions were analyzed using a dia-PASEF workflow. A total of 5525 unique protein groups were identified from all dissected regions. Lysophosphatidylcholine acyltransferase 1 (LPCAT1), a lipid remodelling enzyme, was significantly enriched in the dissected regions of cancerous epithelium (CE) compared to benign epithelium (BE). The increased abundance of this protein was reflected in the lipidomics data with an increased ion intensity ratio for pairs of phosphatidylcholines (PC) and lysophosphatidylcholines (LPC) in CE compared to BE.

The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

Hidradenitis suppurativa associated telomere-methylome dysregulations in blood.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic debilitating disease with a significant burden of both organic and psychological comorbidities. It has been shown that certain telomere-related genes (TRGs) affect a wide range of diseases, including HS and its associated comorbidities, but their exact role in HS pathogenesis is still unknown. OBJECTIVES: To determine whether TRG methylomes can be used as biomarkers in HS. METHODS: Using the Illumina HumanMethylation450 BeadChip array, we examined methylation variations associated with TRGs in HS cases and age-, sex- and ethnicity-matched healthy controls. The study utilized integrated bioinformatics statistical methods, such as a false discovery rate (FDR), the area under the receiver operating characteristic curve (AUC) and principal component analysis. RESULTS: There were a total of 585 different differentially methylated CpG sites identified in 585 TRGs associated with HS (474 hypomethylated and 111 hypermethylated) (FDR p-value < 0.05). A number of these CpGs have been identified as being involved in increased pain sensitivity including EPAS1, AHR, CSNK1D, DNMT1, IKBKAP, NOS3, PLCB1 and PRDM16 genes; GABRB3 as a potential alcohol addiction marker; DDB1, NSMCE2 and HNRNPA2B1 associated with cancers. Pathway analysis identified 67 statistically significant pathways, including DNA repair, telomere maintenance, mismatch repair and cell cycle control (p < 0.001). CONCLUSION: The disruption of TRGs leads to the shortening of telomeres, which is associated with HS progression, ageing, cellular senescence and an increased risk of various diseases, including cancer and associated comorbidities, such as metabolic syndrome, cardiovascular disease and inflammatory disorders. Further research is necessary to better understand the underlying mechanisms and establish causal links between TRGs and HS. The present study is the first effort to comprehend potential pathomechanisms of sporadic HS cases concentrating on PBMC methylome since ours.

Importance of online self-assisted assessments for medical students in knowledge acquisition.

BACKGROUND: Assessment is an important aspect of teaching and learning in medical education. Regular early assessments create scope for improvement in students, and this digital era technology should be utilized for ease of administration. E-assessment involves the usage of technology to create, deliver, collect, and provide feedback to the students. The present study aims to understand the importance of online assessment and the preference of students with difficulties faced and the methods of improvement. METHODS AND MATERIALS: This study was a cross-sectional descriptive study conducted among fifty-six undergraduate medical students, where forty-five objective structured practical questions (OSPEs) were administered to the students in anatomy. After the assessment, feedback was collected in the form of a fifteen-item questionnaire. The responses were graded using a five-point Likert scale and represented in the graphs using Microsoft Excel software. RESULTS: The feedback collected has the following responses. The prosected specimen pictures used in the exam, with pointers and markers, were clear and oriented for which 77% agreed, the pointers and markers were clear and easy to identify for which 79% agreed, and 66% preferred the traditional method of assessment over the online mode of assessment and 48% were neutral on the question of whether E-assessment improves knowledge and skills. Most of the students preferred the traditional method of assessment over the online method of assessment. CONCLUSIONS: Traditional methods of teaching or assessment cannot be replaced by online methods, but technology can be utilized as an addition to regular mode to improve the outcome. Regular early formative assessments help teachers to understand areas of deficiency and help students in improvement. E-assessment can be adapted for formative assessment and regular practice because of their ease of administering and providing feedback simultaneously.

Colchicine exerts anti-atherosclerotic and -plaque-stabilizing effects targeting foam cell formation.

Colchicine is a broad-acting anti-inflammatory agent that has attracted interest for repurposing in atherosclerotic cardiovascular disease. Here, we studied its ability at a human equivalent dose of 0.5 mg/day to modify plaque formation and composition in murine atherosclerosis and investigated its actions on macrophage responses to atherogenic stimuli in vitro. In atherosclerosis induced by high-cholesterol diet, Apoe-/- mice treated with colchicine had 50% reduction in aortic oil Red O+ plaque area compared to saline control (p = .001) and lower oil Red O+ staining of aortic sinus lesions (p = .03). In vitro, addition of 10 nM colchicine inhibited foam cell formation from murine and human macrophages after treatment with oxidized LDL (ox-LDL). Mechanistically, colchicine downregulated glycosylation and surface expression of the ox-LDL uptake receptor, CD36, and reduced CD36+ staining in aortic sinus plaques. It also decreased macrophage uptake of cholesterol crystals, resulting in lower intracellular lysosomal activity, inhibition of the NLRP3 inflammasome, and reduced secretion of IL-1ß and IL-18. Colchicine's anti-atherosclerotic actions were accentuated in a mouse model of unstable plaque induced by carotid artery tandem stenosis surgery, where it decreased lesion size by 48% (p = .01), reduced lipid (p = .006) and necrotic core area (p = .007), increased collagen content and cap-to-necrotic core ratio (p = .05), and attenuated plaque neutrophil extracellular traps (p < .001). At low dose, colchicine's effects were not accompanied by the evidence of microtubule depolymerization. Together, these results show that colchicine exerts anti-atherosclerotic and plaque-stabilizing effects at low dose by inhibiting foam cell formation and cholesterol crystal-induced inflammation. This provides a new framework to support its repurposing for atherosclerotic cardiovascular disease.

Crosstalk between Immune Checkpoint Modulators, Metabolic Reprogramming and Cellular Plasticity in Triple-Negative Breast Cancer.

Breast cancer is one of the major causes of mortality in women worldwide. Accounting for 15-20% of all breast cancer diagnoses, the triple-negative breast cancer (TNBC) subtype presents with an aggressive clinical course, heightened metastatic potential and the poorest short-term prognosis. TNBC does not respond to hormonal therapy, only partially responds to radio- and chemotherapy, and has limited targeted therapy options, thus underlining the critical need for better therapeutic treatments. Although immunotherapy based on immune checkpoint inhibition is emerging as a promising treatment option for TNBC patients, activation of cellular plasticity programs such as metabolic reprogramming (MR) and epithelial-to-mesenchymal transition (EMT) causes immunotherapy to fail. In this report, we review the role of MR and EMT in immune checkpoint dysregulation in TNBCs and specifically shed light on development of novel combination treatment modalities for this challenging disease. We highlight the clinical relevance of crosstalk between MR, EMT, and immune checkpoints in TNBCs.

In vitro Evaluation of Laser vs. Handpiece for Tooth Preparation.

Background: The erbium-doped yttrium aluminium garnet (Er:YAG) laser has been revealed to effectively ablate dental hard tissues, and its utilisation to caries eradication and cavity preparation is envisaged. Nevertheless, only a limited research has been performed on the Er:YAG laser's capacity to treat caries. Aim and Objectives: The efficiency of caries elimination with an Er:YAG laser in vitro was equated to that of traditional mechanical therapy in this study. Methodology: The investigation made use of teeth that had suffered from root caries. The Er:YAG laser was used to treat half of each tooth, while the other half was either removed with a conventional bur or left untouched as a control. Each therapy was evaluated in terms of how long it took to remove cavities, histological examinations of decalcified serial sections, scanning electron microscopy (SEM) analyses and the density of the dentin. Result: A longer treatment time was required for the Er:YAG laser to completely eradicate carious dentin because of its precise irradiation strategy. However, the Er:YAG laser was effective in removing diseased and softening carious dentin with little heat injury to neighbouring intact dentin, much as the bur treatment. It was also shown that the Er:YAG laser treatment had a lower amount of vibration than other methods. The SEM study of the lased dentin surface revealed characteristic micro-irregularities. Conclusion: The Er:YAG laser system appears to be a potential novel technical option for caries therapy, based on our findings.

An In Vitro study to Compare Dental Laser with other Treatment Modalities on Biofilm Ablation from Implant and Tooth Surfaces.

Background: Periodontal and peri-implant disorders are etiologically linked to bacterial biofilms. The researchers wanted to see how well the erbium-doped yttrium aluminum garnet (Er:YAG) laser removed bacterial biofilms along with attached epithelial cells (EC), gingival fibroblasts (GF), in addition to osteoblast-like cells (OC) dentin along with titanium surfaces compared to previous therapy methods. Methodology: 3.5 days were spent growing bacterial biofilms on standardized dentin and also titanium samplings using a sand-blasted along with the acid-etched surface. Following that, the specimens were positioned into pockets that had been formed artificially. The following approaches were used to remove biofilm: (1) Er:YAG, (2) photodynamic therapy (PDT), and (3) curette (CUR) along with supplementary PDT (CUR/PDT). The remaining biofilms' colony forming units (CFUs) were determined, as well as the attachment of EC, GF, in addition to OC. Analysis of variance with a posthoc least significant difference was utilized in the statistical analysis. Results: When compared to untreated dentin and titanium surfaces, all therapy strategies reduced total CFUs in statistically significant biofilms (p = 0.001). On the dentin, Er:YAG was as effective as CUR and PDT, but not as effective as CUR/PDT (p = 0.005). The application of Er:YAG on titanium surfaces leads to statistically significantly improved biofilm eradication equated to the supplementary three therapies (all p = 0.001). On untouched infested dentin and titanium surfaces, the counts of attached EC, GF, and OC were the lowermost. Atop the dentin, increased EC counts were detected after CUR/PDT (p = 0.006). On titanium, all cleaning procedures increased the counts of attached EC by a statistically significant amount (p = 0.001), with no variations between groups. After Er:YAG decontamination, there were statistically substantially elevated amounts of GF (p = 0.024) and OC (p = 0.001) than on untreated surfaces. Conclusion: The usage of Er:YAG laser to ablate subgingival biofilms and, specifically, to decontaminate titanium implant surfaces appears to be a promising strategy that needs further research.

Morphologic Variation of Liver Associated With Hourglass Stomach: Case Report and Literature Review.

Ectopic liver tissue is a rare developmental abnormality, and its association with hourglass constriction of the stomach is undocumented to date. This case report describes the discovery of morphologic variations in the liver of an adult female cadaver during routine dissection. The variations include a small, pedunculated, club-shaped accessory lobe covered by a glistening fibrous capsule connecting it to the gallbladder wall, with vessels radiating into the lobe. Two additional lobes were present, one attached to the right upper margin of the caudate lobe, overlapping the inferior vena cava, and another near the quadrate lobe. The right lobe had an abnormal shape with multiple incomplete fissures and furrows. The left lobe was hypoplastic with an elongated end, resembling a lingular process. Further dissection revealed a prominent fibrous band on the posterior surface of the stomach, which continued anteriorly, giving it an hourglass appearance. Knowledge of such variations helps surgeons and radiologists rule out related abnormalities.

FAST-IT: Find A Simple Test - In TIA (transient ischaemic attack): a prospective cohort study to develop a multivariable prediction model for diagnosis of TIA through proteomic discovery and candidate lipid mass spectrometry, neuroimaging and machine learning-study protocol.

INTRODUCTION: Transient ischaemic attack (TIA) may be a warning sign of stroke and difficult to differentiate from minor stroke and TIA-mimics. Urgent evaluation and diagnosis is important as treating TIA early can prevent subsequent strokes. Recent improvements in mass spectrometer technology allow quantification of hundreds of plasma proteins and lipids, yielding large datasets that would benefit from different approaches including machine learning. Using plasma protein, lipid and radiological biomarkers, our study will develop predictive algorithms to distinguish TIA from minor stroke (positive control) and TIA-mimics (negative control). Analysis including machine learning employs more sophisticated modelling, allowing non-linear interactions, adapting to datasets and enabling development of multiple specialised test-panels for identification and differentiation. METHODS AND ANALYSIS: Patients attending the Emergency Department, Stroke Ward or TIA Clinic at the Royal Adelaide Hospital with TIA, minor stroke or TIA-like symptoms will be recruited consecutively by staff-alert for this prospective cohort study. Advanced neuroimaging will be performed for each participant, with images assessed independently by up to three expert neurologists. Venous blood samples will be collected within 48 hours of symptom onset. Plasma proteomic and lipid analysis will use advanced mass spectrometry (MS) techniques. Principal component analysis and hierarchical cluster analysis will be performed using MS software. Output files will be analysed for relative biomarker quantitative differences between the three groups. Differences will be assessed by linear regression, one-way analysis of variance, Kruskal-Wallis H-test, χ2 test or Fisher's exact test. Machine learning methods will also be applied including deep learning using neural networks. ETHICS AND DISSEMINATION: Patients will provide written informed consent to participate in this grant-funded study. The Central Adelaide Local Health Network Human Research Ethics Committee approved this study (HREC/18/CALHN/384; R20180618). Findings will be disseminated through peer-reviewed publication and conferences; data will be managed according to our Data Management Plan (DMP2020-00062).

Surgical treatment of a primary malignant pericardial mesothelioma: case report.

Pericardial malignant mesothelioma (MM) is a rare tumour which accounts for about 1% of all mesotheliomas, 4% of the primary heart and pericardial tumours. It carries an extremely poor prognosis, with a reported overall survival of less than 6 months. Clinical symptoms and signs are frequently nonspecific, and the diagnosis is usually made after surgery or at autopsy. We report a case of a 72 years old woman with primary pericardial malignant mesothelioma involving the right atrium. Nine months following surgery, the patient is alive with good performance status.

Prevalence of menopausal symptoms among women in Vadodara, Central Gujarat: The urban-rural divide.

Aim: The aim of this article is to estimate prevalence of menopausal symptoms among women in the menopausal age group and study the urban-rural differences. Methods and Design: Analytical cross-sectional study conducted in rural and urban field practice areas of a tertiary care center affiliated to Medical College, where 290 women (145 each from urban and rural areas) were interviewed to measure prevalence of menopausal symptoms. Forty-one symptoms were divided into 'Psycho-somatic' (17 symptoms), 'genito-urinary (9 symptoms)' and musculo-skeletal (5 symptoms) domains. The prevalence of each of these symptoms is reported as proportion and the differences in the median scores in the two groups were tested using Mann-Whitney U test. Results: From among 145 women each, in urban and rural settings, most common psychosomatic symptoms were physical exhaustion-fatigue (73.1%), difficulty climbing stairs (59.3%), sleep problems (45.2%), body ache (43.4%), and hot flushes (41.4%). Among the urban participants, most common was physical exhaustion (42.1%), difficulty climbing stairs (62.1%), anger (46.9%), sleep problems (45.5%), and irritability (42.1%), while among the rural participants they were physical exhaustion (66.2%), difficulty climbing stairs (56.6%), insomnia (54.5%), and body ache (46.2%). Most common genito-urinary symptoms overall and in rural areas were urinary urgency (35.9% and 38.6%), increased frequency of urine (31.7% and 37.2%) and incontinence (30% and 35.2% respectively). Among the urban women, common symptoms were urinary urgency (33.1%) followed by itching of private parts (30.3%) and increased frequency of urination (26.2%). Among musculo-skeletal symptoms, joint pain (74.1%, 74.5%, 73.8%) was the most common symptom followed by joint and muscular discomfort (71.7%, 73.8%, 69.7%) among the overall, urban and rural participants. There was a significant difference in the median psychosomatic score as per the symptoms experienced by the urban and rural participants (U = 36, Z statistic = 2.31, and P = 0.02). However, there was no significant difference in the scores for genito-urinary and musculo-skeletal symptoms; thereby, median scores under both these domains were almost similar in both urban and rural groups. Conclusion: There was significant difference in the median psychosomatic score as per the symptoms experienced by the urban and rural participants however; there was no significant difference in genito-urinary and musculo-skeletal symptom scores.

Elongation factor eEF2 kinase and autophagy jointly promote survival of cancer cells.

Cells within solid tumours can become deprived of nutrients; in order to survive, they need to invoke mechanisms to conserve these resources. Using cancer cells in culture in the absence of key nutrients, we have explored the roles of two potential survival mechanisms, autophagy and elongation factor 2 kinase (eEF2K), which, when activated, inhibits the resource-intensive elongation stage of protein synthesis. Both processes are regulated through the nutrient-sensitive AMP-activated protein kinase and mechanistic target of rapamycin complex 1 signalling pathways. We find that disabling both autophagy and eEF2K strongly compromises the survival of nutrient-deprived lung and breast cancer cells, whereas, for example, knocking out eEF2K alone has little effect. Contrary to some earlier reports, we find no evidence that eEF2K regulates autophagy. Unexpectedly, eEF2K does not facilitate survival of prostate cancer PC3 cells. Thus, eEF2K and autophagy enable survival of certain cell-types in a mutually complementary manner. To explore this further, we generated, by selection, cells which were able to survive nutrient starvation even when autophagy and eEF2K were disabled. Proteome profiling using mass spectrometry revealed that these 'resistant' cells showed lower levels of diverse proteins which are required for energy-consuming processes such as protein and fatty acid synthesis, although different clones of 'resistant cells' appear to adapt in dissimilar ways. Our data provide further information of the ways that human cells cope with nutrient limitation and to understanding of the utility of eEF2K as a potential target in oncology.

A study to assess communication hindrances by the means of work authorization for fixed dental prosthesis: A survey.

AIM: The aim of the study was to assess the hindrances in communication between the prosthodontic office and the laboratory technicians through work authorization. SETTING AND DESIGN: A questionnaire-based survey was carried out to assess communication gap between dentist and lab technicians through work authorization for FDPs. MATERIALS AND METHODS: A total of 114 dental laboratory technicians were provided with a questionnaire regarding work authorization form via Google doc files. The survey focused questions pertaining to fulfilling the following areas of work authorization: patient's information, name of the prescribing dentist, material for the prosthesis, pontic design of the prosthesis, shade description, and date of completion of work. STATISTICAL ANALYSIS USED: The number of responses received was statistically evaluated using Fisher's t-test and nonparametric Spearman's correlation coefficient (P ≤ 0.05). RESULTS: Eighty-five (74.5%) out of 114 laboratory technicians surveyed responded to the questionnaire. The patient's general information was satisfactorily filled in 75%-100% of the forms. Information regarding the pontic design, staining diagram, and preferred margin were on the lower side of the scale ranging between 25% and 50%. CONCLUSIONS: The survey concluded that areas of work authorization with respect to fixed dental prosthesis require attention and need to be adequately filled by the dentist. In addition, the study suggests that the foundation of communication skill training programs in work authorization should be laid from the undergraduate curriculum. The concerned authorized bodies/specialty organizations should formulate a standardized work authorization format which can bridge the wide gap between the crown and bridge office and laboratory.

Cadaver as a first teacher: A module to learn the ethics and values of cadaveric dissection.

OBJECTIVES: The undergraduate medical students must be made aware of the ethical and humanistic values of cadaveric dissection. This study therefore designed, implemented, and evaluated the impact of the module 'Cadaver as a Teacher' (CrAFT) that examines the ethical values of cadaveric dissection. METHODS: This prospective, multimethod study involved 447 first-year undergraduate medical students who had participated in all three sessions of the CrAFT module. Activities included interactive lectures, individual assignments, and a poster-making competition. Students offered a silent tribute and wrote words of gratitude down on a tribute wall. They also expressed their thoughts in the form of essays, poems, and collages. These reflections were qualitatively analysed to generate themes. At the end of the module, an online quiz was conducted to assess the knowledge gained by the students. Their scores were correspondingly recorded and calculated. RESULTS: The major themes identified were: cadaver as a teacher, acknowledgement and thanksgiving, bonding, and empathy. Out of all the test takers, 316 students (94.32%) scored more than a five out of ten. The students strongly felt that the module effectively sensitised them towards the ethical and humanitarian aspects of handling cadavers. CONCLUSIONS: The implementation of an educational module about cadavers is a novel approach towards sensitising medical students. The students believed that sensitising them early on would have helped them establish a practice grounded in professionalism, human values, and empathy.

Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception. METHODS AND ANALYSIS: The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0-2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design. ETHICS AND DISSEMINATION: Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.

Histogenesis and Histomorphometric study of Human Fetal Small Intestine.

BACKGROUND: Intestine plays a major role for the normal growth of the fetus during the prenatal period. The process of the embryonic development is not quantified histologically. Therefore the main aim of the study was to measure the thickness of all part of the wall of the small intestine that are mucosa, submucosa and muscularis externa and to look for the appearance of the Brunner's glands and Peyer's patches in the submucosa of duodenum and ileum. METHODS: The present study was carried out on 30 fetuses of gestational ages ranging from 11-36 weeks. Ten fetuses from each trimester were used in the study. Fetal small intestine were dissected carefully, and were separated as duodenum, jejunum & ileum and fixed in formalin solution. The tissue was processed for histology and then slides were stained with Haematoxylin and Eosin. The microscopic features were noted using light microscope. RESULTS: The thickness of the mucosa, submucosa and the muscularis externa was observed to be increased in first trimester, decreased in the second trimester and again increased in the third trimester, which could be because of the increase cell turnover and the arrangement of the collagen fibers as to support the mucosa and the muscularis externa. CONCLUSION: Thus, the knowledge of the histogenesis and histomorphometry of the human fetal small intestine is crucial for the adult gastroenterologist to appreciate, because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.

A Cadaveric Report on a Giant Ureteric Stone Led Right Hydro Ureter and Severe Hydronephrosis.

BACKGROUND: The ureter shows natural constrictions in its course, and these are the potential site for the impaction of the renal calculus. Giant ureteral stones are associated with insidious growth and late presentation, often leading to renal failure. CASE PRESENTATION: In the present case, we observed a huge ureteric stone obstructing the right ureterovesical junction in a 58 year-old male cadaver. We also found hydroureter distal to the impaction of the calculus, renal damage and severe hydronephrosis on the right side. Histopathological analysis showed conditions of arterio-nephro-sclerosis and eroded ureter secondary to the calculus. Ureteric stones obstruction may result in hydroureter, hydronephrosis and progressive renal damage leading to irreversible renal function. The present case provides valuable information regarding the gross and histopathological alterations in ureteric calculi. CONCLUSION: It further enables clinicians to be armed with the knowledge of preventive approaches to educate patients with previous calculi, or those who may develop in the future.