MicroRNA signature of stromal-epithelial interactions in prostate and breast cancers.

Stromal-epithelial communication is an absolute necessity when it comes to the morphogenesis and pathogenesis of solid tissues, including the prostate and breast. So far, signalling pathways of several growth factors have been investigated. Besides such chemical factors, non-coding RNAs such as miRNAs have recently gained much interest because of their variety and complexity of action. Prostate and breast tissues being highly responsive to steroid hormones such as androgen and estrogen, respectively, it is not surprising that a huge set of available literature critically investigated the interplay between such hormones and miRNAs, especially in carcinogenesis. This review showcases our effort to highlight hormonally-related miRNAs that also somehow perturb the regular stromal-epithelial interactions during carcinogenesis in the prostate and breast. In future, we look forward to exploring how hormonal changes in the tissue microenvironment bring about miRNA-mediated changes in stromal-epithelial interactome in carcinogenesis and cancer progression.

Calotropis procera extract inhibits prostate cancer through regulation of autophagy.

Current treatment options available for prostate cancer (PCa) patients have many adverse side effects and hence, new alternative therapies need to be explored. Anticancer potential of various phytochemicals derived from Calotropis procera has been studied in many cancers but no study has investigated the effect of leaf extract of C. procera on PCa cells. Hence, we investigated the effect of C. procera leaf extract (CPE) on cellular properties of androgen-independent PC-3 and androgen-sensitive 22Rv1 cells. A hydroalcoholic extract of C. procera was prepared and MTT assay was performed to study the effect of CPE on viability of PCa cells. The effect of CPE on cell division ability, migration capability and reactive oxygen species (ROS) production was studied using colony formation assay, wound-healing assay and 2',7'-dichlorodihydrofluorescein diacetate assay, respectively. Caspase activity assay and LDH assay were performed to study the involvement of apoptosis and necrosis in CPE-mediated cell death. Protein levels of cell cycle, antioxidant, autophagy and apoptosis markers were measured by western blot. The composition of CPE was identified using untargeted LC-MS analysis. Results showed that CPE decreased the viability of both the PCa cells, PC-3 and 22Rv1, in a dose- and time-dependent manner. Also, CPE significantly inhibited the colony-forming ability, migration and endogenous ROS production in both the cell lines. Furthermore, CPE significantly decreased NF-κB protein levels and increased the protein levels of the cell cycle inhibitor p27. A significant increase in expression of autophagy markers was observed in CPE-treated PC-3 cells while autophagy markers were downregulated in 22Rv1 cells after CPE exposure. Hence, it can be concluded that CPE inhibits PCa cell viability possibly by regulating the autophagy pathway and/or altering the ROS levels. Thus, CPE can be explored as a possible alternative therapeutic agent for PCa.

Microwave spectroscopic and computational analyses of the phenylacetylene⋯methanol complex: insights into intermolecular interactions.

The microwave spectra of five isotopologues of phenylacetylene⋯methanol complex, C6H5CCH⋯CH3OH, C6H5CCH⋯CH3OD, C6H5CCH⋯CD3OD, C6H5CCD⋯CH3OH and C6H5CCH⋯13CH3OH, have been observed through Fourier transform microwave spectroscopy. Rotational spectra unambiguously unveil a specific structural arrangement characterised by dual interactions between the phenylacetylene and methanol. CH3OH serves as a hydrogen bond donor to the acetylenic π-cloud while concurrently accepting a hydrogen bond from the ortho C-H group of the PhAc moiety. The fitted rotational constants align closely with the structural configuration computed at the B3LYP-D3/aug-cc-pVDZ level of theory. The transitions of all isotopologues exhibit doublets owing to the methyl group's internal rotation within the methanol molecule. Comprehensive computational analyses, including natural bond orbital (NBO) analysis, atoms in molecules (AIM) theory, and non-covalent interactions (NCI) index plots, reveal the coexistence of both O-H⋯π and C-H⋯O hydrogen bonds within the complex. Symmetry adapted perturbation theory with density functional theory (SAPT-DFT) calculations performed on the experimentally determined geometry provide an insight into the prominent role of electrostatic interactions in stabilising the overall structural arrangement.

Increased circulating Th17 cell populations in patients with pancreatic ductal adenocarcinoma.

T-helper 17 (Th17) cells are a subset of CD4+ helper T cells that produce interleukin 17 (IL-17) and play a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Few studies have been conducted to determine the role of Th17 cells in the tumorigenesis and development of pancreatic ductal adenocarcinoma (PDAC); however, its role is still unclear. In this study, the percentage of circulating Th17 cells and serum levels of IL-17A and IL-23 were analyzed using flow cytometry and ELISA, respectively, in 40 PDAC patients, 30 chronic pancreatitis (CP) patients and 30 healthy controls (HC). In addition, the mRNA expression levels of IL-17A, STAT3 and RORγt in tissue samples were quantified by qRT-PCR. The results showed that the percentage of circulating Th17 cells and the concentrations of serum IL-17A and IL-23 were significantly increased in PDAC patients as compared to CP and HC (P < 0.001). In addition, the higher level of IL-17A was significantly correlated with the poor overall survival of the PDAC patients. Furthermore, the frequencies of Th17 cells and IL-17A were significantly higher in stage III+IV PDAC patients versus stage I+II. A significant increase in IL-17A, STAT3 and RORγT mRNA was observed in patients with PDAC. Taken together, these findings suggest that the increased circulating Th17 cells and serum IL-17A may be involved in the development and metastasis of PDAC, and thus represent potential targets for the treatment of PDAC.

Clinical significance of Notch pathway-associated microRNA-107 in pancreatic ductal adenocarcinoma.

Background & aim: MicroRNAs associated with the Notch pathway play a critical role in the progression of pancreatic carcinoma. Our aim was to study the clinical significance of miR-107 and NOTCH2 in pancreatic ductal adenocarcinoma (PDAC). Methods: The circulating miR-107 levels in PDAC and controls were determined by qPCR. NOTCH2 protein (target) expression in tissue of PDAC, periampullary carcinoma, chronic pancreatitis and normal pancreatic tissue was assessed by immunohistochemistry. Results: The circulating miR-107 levels were found to be significantly reduced in PDAC as compared with controls. Additionally, NOTCH2 protein expression was higher in PDAC tissue as compared with controls and was clinically associated with metastasis. Conclusion: Our findings demonstrate the utility of circulating miR-107 as a potential differentiating marker in PDAC.

Comparison of High Spermatic Vessel Ligation and Low Spermatic Vessel Ligation in an Undescended Model of Rat Testis.

Aims: The aim of this study was to compare the immediate and long-term outcomes after high spermatic vessel ligation (HSVL) and low spermatic vessel ligation (LSVL) in a high undescended testis (UDT) model in rats. Materials and Methods: A prospective randomized controlled study was conducted on 24 male Wistar rats. The rats were randomly divided into three groups. Group A underwent a sham laparotomy and acted as the control. Group B underwent HSVL of both testicular vessels. Group C underwent LSVL of both testicular vessels. Each group was again subdivided into two subgroups. One sub-group underwent blood collection and testicular biopsy of both testes 24 h after the procedure to demonstrate immediate changes. Other subgroups underwent blood sample collection and testicular biopsy of both testes on day 50 following the procedure for hormonal changes and long-term changes. Results: All the testes in HSVL showed atrophy (100%) in the long term, whereas LSVL showed atrophy in 12.5% of testes, even though both groups showed adequate neovascularization. Testes in HSVL showed poor bleeding on incision at both 24 h and day 50. On histology, 75% of testes in HSVL showed complete necrosis, and 50% in LSVL showed partial necrosis at 24 h. On day 50, all the testes in HSVL (100%) showed complete necrosis with dystrophic calcification, whereas all the testes in LSVL showed normal histology with good maturation of seminiferous tubules. There was no significant difference in testosterone levels between both groups. Conclusions: Both immediate and long-term changes following LSVL showed an increase in blood flow to the testis after ligation through collaterals and reverses early ischemic changes to the testis. Given the higher testicular atrophic rate after HSVL, LSVL or at least low ligation can be preferred for the management of high intra-abdominal UDT.

Role of Procalcitonin as a Biomarker in Early Identification of Adverse Events Following Esophageal Atresia Surgery.

Introduction: Surgical complication following esophageal atresia repair is one of the several factors known to influence the final outcomes. Early identification of such complications may help in timely institution of therapeutic measures and translate into improved prognosis. Objective: The objective of this study was to evaluate the role of procalcitonin in early prediction of the adverse events after surgery in patients of esophageal atresia and the temporal relationship with clinical manifestations and other inflammatory biomarkers such as C-reactive protein (CRP). Materials and Methods: This was a prospective study on consecutive patients of esophageal atresia (n = 23). Serum procalcitonin and CRP levels were assessed at baseline (prior to surgery) and on postoperative days (POD) 1, 3, 5, 7, and 14. The trends in the biomarker values and temporal relationships of deviation in trend with the clinical and conventional laboratory parameters and patient outcomes were analyzed. Results: Baseline serum procalcitonin was elevated (n = 23; 1.7 ng/ml: min: 0.07 ng/ml-max: 24.36 ng/ml) in 18/23 (78.3%) patients. Procalcitonin nearly doubled on POD-1 (n = 22; 3.28 ng/ml: min: 0.64 ng/ml-max: 16.51 ng/ml) followed by a gradual decline. CRP was also elevated on POD-1 (three times the baseline) and depicted a delayed peak at POD-3. POD-1 procalcitonin and CRP levels correlated with survival. POD-1 procalcitonin cutoff at 3.28 ng/ml predicted mortality with a sensitivity and specificity of 100% and 57.9% (P = 0.05). Serum procalcitonin and CRP were higher for patients who sustained complications, so was the time required for hemodynamic stabilization. Procalcitonin (baseline and POD-5) and CRP (POD-3 and POD-5) values correlated with the clinical course after surgery. Baseline procalcitonin cutoff at 2.91 ng/ml predicted the possibility of a major complication with a sensitivity of 71.4% and a specificity of 93.3%. POD-5 procalcitonin cutoff at 1.38 ng/ml predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. Patients who sustained major complications depicted a change in serum procalcitonin trend 24-48 h ahead of clinical manifestation of an adverse event. Conclusions: Procalcitonin is a good indicator to identify the adverse events in neonates after surgery for esophageal atresia. The procalcitonin levels in patients who sustained a major complication depicted a reversal in trend 24-48 h of clinical manifestation. POD-1 procalcitonin correlated with survival while the baseline and POD-5 serum procalcitonin predicted the clinical course.

Epigenetic regulation of epithelial to mesenchymal transition: a trophoblast perspective.

Epigenetic changes alter the expression of genes at both pre- and post-transcriptional levels without changing their DNA sequence. Accumulating evidence suggests that such changes can modify cellular behavior and characteristics required during development and in response to various extracellular stimuli. Trophoblast cells develop from the outermost trophectoderm layer of the blastocyst and undergo many phenotypic changes as the placenta develops. One such phenotypic change is differentiation of the epithelial natured cytotrophoblasts into the mesenchymal natured extravillous trophoblasts. The extravillous trophoblasts are primarily responsible for invading into the maternal decidua and thus establishing connection with the maternal spiral arteries. Any dysregulation of this process can have adverse effects on the pregnancy outcome. Hence, tight regulation of this epithelial-mesenchymal transition (EMT) is critical for successful pregnancy. This review summarizes the recent research on the epigenetic regulation of the EMT occurring in the trophoblast cells during placental development. The functional significance of chemical modifications of DNA and histone, which regulate transcription, as well as non-coding RNAs, which control gene expression post-transcriptionally, is discussed in relation to trophoblast biology.

Association of inflammatory markers with the disease & mutation status in pancreatic cancer.

Background & objectives: Inflammation has been studied to be an important contributory factor to carcinogenesis through pro-inflammatory markers such as interleukin (IL)-6 and C-reactive protein (CRP). Furthermore, K-ras mutation is an important genetic alteration in the pathogenesis of pancreatic cancer. This study aimed to compare these inflammatory markers in pancreatic ductal adenocarcinoma (PDAC) with the diseased and healthy controls (HCs) and to check for any association between IL-6 and CRP serum levels with the disease status, survival and K-ras mutation status of PDAC patients. Methods: The study included 135 PDAC, 25 chronic pancreatitis (CP) patients and 25 HCs. The serum levels of IL-6 and CRP were detected by enzyme-linked immunosorbent assay and K-ras mutations were detected by polymerase chain reaction-restriction fragment length polymorphism technique. Results: The serum levels of both these markers were elevated in PDAC cases than that in HCs. High IL-6 levels and higher CRP levels were found to be associated with locally advanced disease, lymphatic invasion, metastasis and advanced stage of the PDAC. In patients with unresectable PDAC, higher IL-6 levels were found to be associated with the presence of K-ras mutations. Interpretation & conclusions: Higher IL-6 and CRP levels in patients with advanced PDAC suggest an important role of these inflammatory markers in tumour progression. Furthermore, the association of mutations in the K-ras gene with serum IL-6 indicates cross-talks that may contribute to the progression of the PDAC.

An in vitro comparative evaluation of casein phosphopeptide-amorphous calcium phosphate fluoride, tricalcium phosphate and grape seed extract on remineralization of artificial caries lesion in primary enamel.

OBJECTIVES: To evaluate and compare the remineralization potential of casein phosphopeptide-amorphous calcium phosphate fluoride, tricalcium phosphate and grape seed extract on artificial caries lesions in primary enamel. STUDY DESIGN: A sample of 40 non-carious, primary molar teeth was collected and cut in longitudinal sections into three equal halves. Those 120 samples were divided into four equal groups. Group A: Sections treated with casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF), Group B: Sections treated with tricalcium phosphate, Group C: Sections treated with grape seed extract Group D: Sections treated with deionized water (control group). Samples were evaluated for change in surface characteristics, mineral content using Scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX) and microhardness using Vicker's microhardness tester. Cavitated lesions were evaluated for Cone beam computer tomography to obtain baseline data post remineralization. RESULTS: The remineralization potential of grape seed extract was found to be greater compared to tricalcium phosphate followed by CPP-ACPF. CONCLUSION: All the three groups viz. CPP-ACPF, tricalcium phosphate and grape seed extract showed remineralization under the in vitro pH cycling model, while grape seed extract group showed significantly greater remineralization compared to the CPP-ACPF and tricalcium phosphate groups.

Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry.

BACKGROUND: In 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia. OBJECTIVE: To compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment. METHODS: A cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing. RESULTS: Between 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ2 73.14, p<0.001). Of 883 tumors tested, 242 (27%) showed loss of mismatch repair protein expression. In 2015, 30 (26%) tumors of 117 tested showed loss of mismatch repair protein expression. During the 4 years of universal screening, 13 (1.5%) of 883 patients screened were diagnosed with Lynch syndrome compared with 2 (1.7%) of 117 in 2015 (Fisher's exact test 0.04, p=0.69). In 2015, 11 (37%) of 30 patients with loss of mismatch repair protein expression were not referred for genetic assessment compared with 36 (17%) of 209 patients in the universal screening group (χ2 6.28, p=0.02). No cases of Lynch syndrome were diagnosed in patients aged over 70 years. CONCLUSIONS: Universal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

Triiodothyronine stimulates steroid and VEGF production in murine Leydig cells via cAMP-PKA pathway.

Thyroid hormones affect testicular development as well as functions like spermatogenesis and steroidogenesis, thereby influencing male fertility. Our group earlier showed that the stimulatory role of the thyroid hormone, T3 , on the production of vascular endothelial growth factor (VEGF) by murine Leydig cells is mediated by steroids and hypoxia-inducible factor-1 (HIF-1α). The current study further defines the signalling pathway(s) utilised by T3 to stimulate the production of steroids, VEGF and HIF-1α in mouse Leydig tumour cell line (MLTC-1). Specific inhibitors for different signalling molecules were used to study the role of cyclic AMP (cAMP), and its downstream mediators. Expression of VEGF and HIF-1α mRNA were measured by quantitative RT-PCR; VEGF secretion by ELISA; steroid secretion by radioimmunoassay and HIF-1α protein levels by western blotting. Inhibitors of adenylate cyclase (AC), protein kinase A (PKA), sarcoma kinase (SrcK), phosphoinositide 3-kinase (PI3K) and MAP kinase kinase (MEK1/2) abolished the T3 -induced increase in VEGF mRNA and protein levels. The same signalling molecules also mediated the increased production of steroids and HIF-1α protein in response to T3 . Therefore, it was concluded that T3 stimulates steroid secretion and HIF-1α protein in MLTC-1 cells through the AC-cAMP-PKA-PI3K-MEK pathway, which in turn stimulate VEGF production.

Publisher Correction: Survival analysis of Rural Clinical School of Western Australia graduates: the long-term work of building a long-term rural medical workforce.

In the original publication of this article [1], an error occurred during the publication of this article in Table 2.

New landmarks for ideal positioning of syndesmotic screw: a computerised tomography based analysis and radiographic simulation.

PURPOSE: A lack of specific intra-operative markers for accurate positioning of the syndesmotic screw can result in its malpositioning. Knowledge of the axial orientation of the syndesmosis can help in reducing this risk of malpositioning of the syndesmotic screw. In this CT-based study, we investigated the axial relationships of intact syndesmoses with various rigid bony landmarks around the ankle joint that were independent of foot and horizontal plane. METHODS: We analyzed 126 CT-based studies of uninjured normal ankle joints and defined the following bony landmarks: posteromedial and posterolateral surface of the distal tibia, bimalleolar tips, and anterior and posterior extents of both malleoli. Axial differences between coronal plane through the central axis of syndesmosis and modified coronal planes through these bony landmarks were then measured. Software-based lateral radiographs were created with the reference coronal plane for each radiograph being kept perpendicular to the plane of the viewing screen. RESULTS: The mean axial differences parting the syndesmotic axis from the modified coronal planes based on distal tibial posteromedial surface, distal tibial posterolateral surface, bimalleolar tips, anterior bimalleolar extents, and posterior bimalleolar extents were - 3.15°, 13.73°, 4.10°, 11.95°, and 12.24°, respectively. With the exception of the posterolateral surface of the distal tibia, all other bony landmarks were radiologically identifiable in the majority of cases. CONCLUSION: Our study attempts to provide a solution to the issues related to malpositioning of the syndesmotic screw by providing new bony landmarks that can be clinically and fluoroscopically used for syndesmotic-screw positioning. The relationships of bimalleolar tips, anterior and posterior bimalleolar extents, and the posteromedial surface can be reliably used as landmarks for directing syndesmotic screws.

Agreement and Predictors of Discordance of 6 Visual Field Progression Algorithms.

PURPOSE: To determine the agreement of 6 established visual field (VF) progression algorithms in a large dataset of VFs from multiple institutions and to determine predictors of discordance among these algorithms. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Visual fields from 5 major eye care institutions in the United States were analyzed, including a subset of eyes with at least 5 Swedish interactive threshold algorithm standard 24-2 VFs that met our reliability criteria. Of a total of 831 240 VFs, a subset of 90 713 VFs from 13 156 eyes of 8499 patients met the inclusion criteria. METHODS: Six commonly used VF progression algorithms (mean deviation [MD] slope, VF index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort, and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's κ coefficient. Bivariate and multivariate analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms. RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (κ range, 0.12-0.52). Based on at least 4 algorithms, 11.7% of eyes progressed. Major predictors of discordance or lack of agreement among algorithms were more depressed initial MD (P < 0.01) and older age at first available VF (P < 0.01). A greater number of VFs (P < 0.01), more years of follow-up (P < 0.01), and eye care institution (P = 0.03) also were associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrated that existing algorithms have limited agreement and that agreement varies with clinical parameters, including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying big-data results to individual practices.

Regioselective Nitration of N-Alkyl Anilines using tert-Butyl Nitrite under Mild Condition.

Regioselective ring nitration of N-alkyl anilines is reported using tert-butyl nitrite. The reactions proceed efficiently with a wide range of substrates providing synthetically useful N-nitroso N-alkyl nitroanilines in excellent yields which can be easily converted into N-alkyl phenylenediamines and N-alkyl nitroanilines using Zn-AcOH and HCl/MeOH, respectively.

Survival analysis of Rural Clinical School of Western Australia graduates: the long-term work of building a long-term rural medical workforce.

BACKGROUND: Deficits in the rural medical workforce is an international issue. In Australia, The Rural Clinical School intervention is effective for initial recruitment of rural doctors. However, the extent of survival is not yet established. This paper summarises rural survival over a 10-year period. METHODS: Rural Clinical School graduates of Western Australia were surveyed annually, 2006-2015, and post Graduate Years (PGY) 3-12 included. Survival was described as "tours of service", where a tour was either a period of ≥1 year, or a period of ≥2 weeks, working rurally. A tour ended with a rural work gap of ≥52 weeks. Considering each exit from urban as an event, semi-parametric repeated measures survival models were fitted. RESULTS: Of 468 graduates, using the ≥2 weeks definition, 239 PGY3-12 graduates spent at least one tour rurally (average 61.1, CI 52.5-69.7 weeks), and a total length of 14,607 weeks. Based on the tour definition of ≥1 year, 120 graduates completed at least one tour (average 1.89, 1.69-2.10 years), and a total of 227 years' rural work. For both definitions, the number of tours increased from one to four by PGY10/11, giving 17,786 total weeks (342 years) across all PGYs for the ≥2 weeks tour definition, and 256 years total for ≥1 year. Significantly more graduates exited from urban work for the 2007-09 middle cohort compared with 2010-11 (HR 1.876, p = 0.022), but no significant difference between 2002 and 06 and 2010-11. Rural origin, age and gender were not statistically significant. CONCLUSIONS: PGY3-12 RCS graduates contributed substantially to the rural workforce: 51% did so by short rotations, while 26% contributed whole years of service. There was an apparent peak in entry and survival for the middle cohort and decline thereafter, likely attributable to lack of advanced/specialist vocational training. These data indicate a real commitment to rural practice by RCS graduates, and the need for rural vocational training as a key element of a successful rural survival strategy.

Copper promoted N-alkylation of sulfoximines with alkylboronic acid under mild conditions.

The copper meditated N-methylation of sulfoximines using methylboronic acid is reported. The reactions provide excellent yields in a short span of time under mild conditions. The optimized conditions were also found to be suitable for the N-alkylation of sulfoximine with different alkylboronic acids. In addition, N-methylation and cyclopropylation of the bioactive l-methionine sulfoximine derivative was demonstrated under standard reaction conditions.

Opting for rural practice: the influence of medical student origin, intention and immersion experience.

OBJECTIVE: To compare the influence of rural background, rural intent at medical school entry, and Rural Clinical School (RCS) participation on the likelihood of later participation in rural practice. DESIGN: Analysis of linked data from the Medical School Outcomes Database Commencing Medical Students Questionnaire (CMSQ), routinely collected demographic information, and the Australian Health Practitioner Regulation Agency database on practice location. SETTING AND PARTICIPANTS: University of Western Australia medical students who completed the CMSQ during 2006-2010 and were practising medicine in 2016. MAIN OUTCOME MEASURES: Medical practice in rural areas (ASGC-RAs 2-5) during postgraduate years 2-5. RESULTS: Full data were available for 508 eligible medical graduates. Rural background (OR, 3.91; 95% CI, 2.12-7.21; P < 0.001) and experience in an RCS (OR, 1.93; 95% CI, 1.05-3.54; P = 0.034) were significant predictors of rural practice in the multivariate analysis of all potential factors. When interactions between intention, origin, and RCS experience were included, RCS participation significantly increased the likelihood of graduates with an initial rural intention practising in a rural location (OR, 3.57; 95% CI, 1.25-10.2; P = 0.017). The effect of RCS participation was not significant if there was no pre-existing intention to practise rurally (OR, 1.38; 95% CI, 0.61-3.16; P = 0.44). CONCLUSION: For students who entered medical school with the intention to later work in a rural location, RCS experience was the deciding factor for realising this intention. Background, intent and RCS participation should all be considered if medical schools are to increase the proportion of graduates working rurally.

Prognostic significance of plasma matrix metalloprotease-2 in pancreatic cancer patients.

BACKGROUND & OBJECTIVES: Pancreatic cancer has a propensity for wide stromal invasion. Matrix metalloprotease-2 (MMP-2) is a protease that degrades the peri-tumoural tissue and helps in tumour dissemination. Thus, this study was aimed to assess any association of plasma MMP-2 levels with clinicopathological parameters and survival of patients with pancreatic cancer. METHODS: Plasma samples from 127 pancreatic cancer patients were analyzed for MMP-2 levels by ELISA. Survival and other clinicopathological parameters of patients were analyzed for any correlation with plasma MMP-2 levels. RESULTS: The mean MMP-2 levels in pancreatic cancer patients were 560.3±222.0 ng/ml which were significantly elevated compared to chronic pancreatitis patients (P<0.001) and healthy individuals (P<0.05). The plasma levels of MMP-2 significantly correlated with tissue expression of this protease (P=0.004). However, MMP-2 levels did not exhibit any association either with clinicopathological parameters or with survival. INTERPRETATION & CONCLUSIONS: Elevated MMP-2 levels were observed in blood of pancreatic cancer patients which correlated with its tissue expression. However, these levels did not associate with survival or any clinicopathological parameters of patients. Further studies need to be done to confirm the prognostic/ clinical significance of MMP-2 in cancer patients before and after surgery.