Evaluation of cadmium toxicity and its association with iron on the gonads of female rats

Cadmium has been identified as one of the endocrine-disrupting chemicals. Several studies on heavy metals focus on individual metals neglecting the fact that they occur in association with other metals in the environment, a situation that can affect the toxic capacity of each metal. The current study was therefore designed to examine the possible influence of iron (Fe) on cadmium (Cd) toxicity in the gonad of female rats. Twenty adult female albino rats used in this study were divided into four groups. The groups were designated as group A-control (rats administered Cd-free water), group B rats were exposed to Cd-tainted water, group C rats were exposed to Fe-tainted water and group D rats were exposed to combined Cd+Fe tainted water. The treatments were done daily for four weeks. At the end of 4 weeks of exposure, there was significant increase in ovary CAT activity of rats exposed to Cd+Fe when compared to the control. The malondialdehyde (MDA) level in ovary of rats exposed to Fe only was significantly increased (p≤0.05) relative to the control. Similarly, there was a significant increase in serum cholesterol level of rats exposed to Cd+Fe simultaneously when compared to the Cd only and Fe only treated groups. The levels of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were significantly increased (p≤0.05) in sera of rats exposed to Cd only, Fe only and Cd+Fe when compared to the control. The levels of estradiol were significantly decreased in all the treated groups relative to control. The level of testosterone was significantly increased (p≤0.05) in Cd+Fe group relative to the control. Histological study revealed atretic and disintegrating follicles in ovary of rats exposed to Cd only and combined Cd+Fe. The results from this study suggest that cadmium only as well as combined cadmium and iron are responsible for the biochemical changes induced in the ovary. The presence of Cd caused oxidative stress in the ovary and an imbalance in serum levels of the reproductive hormones analyzed. Since Cd only was able to cause the changes observed and similar changes was also observed in presence of iron, it can therefore be suggested that Cd is responsible for the changes since iron was unable to ameliorate its effect. Findings from histological examination of the ovaries that there was profound disintegration with follicular damage appear to corroborate the biochemical observation made in this study. In conclusion, it appears that cadmium in the presence of iron can still exhibit its gonadal toxicity without antagonism or synergism with iron as shown in the rats exposed via water

Nonlinear control model and operational support system for the Kainji Hydroelectric Power System

Over the past years, hydropower model and control were largely based on classical and linear transfer function, this was motivated by the available control system design techniques that were available and the desire to simplify the design procedure. Such a model is inadequate for dynamic study and design of hydropower station in the presence of uncertainties in the water head, discharge rate, elastic water effect, traveling wave effect, large variation power output and frequency. This research, therefore, focuses on developing a nonlinear model for the Kainji hydroelectric power station. The model relies on the energy conversion principles, inflows, discharge, evaporation rate and number of units on busbar. The parameters of the model were also estimated, and the model validated with an error within +1.4% to -3.6%. The model is expected to be used to determine the optimal control policies for the operation of the station and the release of water to the downstream.Keywords: Hydroelectric Power, Inflow, Model, Operating Head, Turbo-alternato

A steepest descent algorithm for the optimal control of a cascaded hydropower system

Optimal power generation along the cascaded Kainji-Jebba hydroelectric power system had been very difficult to achieve. The reservoirs operating heads are being affected by possible variation in impoundments upstream, stochastic factors that are weather-related, availability of the turbo-alternators and power generated at any time. Proposed in this paper, is an algorithm for solving the optimal release of water on the cascaded hydropower system based on steepest descent method. The uniqueness of this work is the conversion of the infinite dimensional control problem to a finite one, the introduction of clever techniques for choosing the steepest descent step size in each iteration and the nonlinear penalty embedded in the procedure. The control algorithm was implemented in an Excel VBA® environment to solve the ormulated Lagrange problem within an accuracy of 0.03%. It is recommended for use in system studies and control design for the optimal power generation in the cascaded hydropower system

Design and Construction of an Arduino - Based Solar Power Parameter-Measuring System with Data Logger

Accurate monitoring and measurement of solar photovoltaic panel parameters are important for solar power plant analysis to evaluate the performance and predict the future energy generation. There are always challenges of getting such data readily available due to huge amount of money to be spent on state of the art equipment or the purchase of reliable satellite weather data. This study aimed at the development of a cost-effective parameter-measuring system for a solar photovoltaic panel using Arduino microprocessor board. The systems measure five parameters, including voltage, current, light intensity, temperature, and pressure. The hardware circuit was designed to link different sensors with the Arduino board and the measured data were in turn were documented into a computer for further analysis. The accuracy of the constructed device was ascertained by comparing the measured parameters with that of conventional standard measuring instruments which shows good agreement. The measured parameters show that the output energy generation from solar photovoltaic panel largely depends on the solar irradiance and temperatur

Evaluation of circulating transcript analysis (NETest) in small intestinal neuroendocrine neoplasms after surgical resection

PURPOSE: Surgical resection is the only effective curative strategy for small intestinal neuroendocrine neoplasms (SINENs). Nevertheless, the evaluation of residual disease and prediction of disease recurrence/progression remains a problematic issue. METHODS: We evaluated 13 SINENs that underwent surgical resection of the primary tumour and/or mesenteric mass. Patients were divided in three groups: (a) Group 1: SINENs that underwent resection with curative intent, (b) Group 2: SINENs treated with resection in the setting of metastatic disease, which remained stable and (c) Group 3: SINENs treated with resection in the setting of metastatic disease, with evidence of any progression at follow-up. NETest and chromogranin A were measured pre-operatively and post-operatively during a 22-month median follow-up period and compared with imaging studies. NETest score <20% was determined as normal, 20-40% low, 41-79% intermediate and ≥80% high score. RESULTS: NETest score was raised in all (100%) SINENs pre-operatively. Surgery with curative intent resulted in NETest score reduction from 78.25 ± 15.32 to 25.25 ± 1.75 (p < 0.05). Low NETest scores post-operatively were evident in all cases without clinical evidence of residual disease (Group 1). However, the low disease activity score suggested the presence of microscopic residual disease. In three cases (75%) with stable disease (Group 2) the NETest score was low consistent with indolent disease. In the progressive disease group (Group 3), a high NETest score was present in three cases (60%) and an intermediate NETest score in the remainder (40%). CONCLUSIONS: Blood NETest scores accurately identified SINENs and were significantly decreased by curative surgery. Monitoring NETest post-operatively may facilitate management by identifying the presence of residual/progressive disease

Clinicopathological correlations of mesenteric fibrosis and evaluation of a novel biomarker for fibrosis detection in small bowel neuroendocrine neoplasms

PURPOSE: Mesenteric fibrosis (MF) in small intestinal neuroendocrine neoplasms (SINENs) is often associated with significant morbidity and mortality. The detection of MF is usually based on radiological criteria, but no previous studies have attempted a prospective, multidimensional assessment of mesenteric desmoplasia to determine the accuracy of radiological measurements. There is also a lack of non-invasive biomarkers for the detection of image-negative MF. METHODS: A multidimensional assessment of MF incorporating radiological, surgical and histological parameters was performed in a prospective cohort of 34 patients with SINENs who underwent primary resection. Pre-operative blood samples were collected in 20 cases to evaluate a set of five profibrotic circulating transcripts-the "fibrosome"-that is included as an "omic" component of the NETest. RESULTS: There was a significant correlation between radiological and surgical assessments of MF (p < 0.05). However, there were several cases of image-negative MF. The NETest-fibrosome demonstrated an accuracy of 100% for the detection of microscopic MF. CONCLUSIONS: The detection of MF by radiological criteria has limitations. The NETest-fibrosome is a promising biomarker for fibrosis detection and further validation of these results would be needed in larger, multicentre studies

COVID-19 and vertical transmission: assessing the expression of ACE2 / TMPRSS2 in the human fetus and placenta to assess the risk of SARS-CoV-2 infection

Background: While pregnant women have been identified as a potentially at-risk group concerning COVID-19 infection, little is known regarding the susceptibility of the fetus to infection. Co-expression of ACE2 and TMPRSS2 has been identified as a pre-requisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown. Methods: We performed a retrospective analysis of single cell data repositories. This data was then validated at both gene and protein level by performing qRT-PCR and two-colour immunohistochemistry on a library of second-trimester human fetal tissues. Findings: TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels, only in the fetal intestine and kidney and is not expressed in the fetal lung. The placenta is also negative for the two proteins both during development and at term. Interpretation: This dataset indicates that the lungs are unlikely to be a viable route of SARS-CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the GI tract is likely to be susceptible to infection due to its high co-expression of both proteins, as well as its exposure to potentially infected amniotic fluid

Transcriptomic Profiling of In Vitro Tumor-Stromal Cell Paracrine Crosstalk Identifies Involvement of the Integrin Signaling Pathway in the Pathogenesis of Mesenteric Fibrosis in Human Small Intestinal Neuroendocrine Neoplasms.

Aim: Analysis of the pathophysiology of mesenteric fibrosis (MF) in small intestinal neuroendocrine tumors (SI-NETs) in an in vitro paracrine model and in human SI-NET tissue samples. Methods: An indirect co-culture model of SI-NET cells KRJ-I and P-STS with stromal cells HEK293 was designed to evaluate the paracrine effects on cell metabolic activity, gene expression by RT2 PCR Profilers to analyse cancer and fibrosis related genes, and RNA sequencing. The integrin signaling pathway, a specific Ingenuity enriched pathway, was further explored in a cohort of human SI-NET tissues by performing protein analysis and immunohistochemistry. Results: RT Profiler array analysis demonstrated several genes to be significantly up- or down-regulated in a cell specific manner as a result of the paracrine effect. This was further confirmed by employing RNA sequencing revealing multiple signaling pathways involved in carcinogenesis and fibrogenesis that were significantly affected in these cell lines. A significant upregulation in the expression of various integrin pathway - related genes was identified in the mesenteric mass of fibrotic SI-NET as confirmed by RT-qPCR and immunohistochemistry. Protein analysis demonstrated downstream activation of the MAPK and mTOR pathways in some patients with fibrotic SI-NETs. Conclusion: This study has provided the first comprehensive analysis of the crosstalk of SI-NET cells with stromal cells. A novel pathway - the integrin pathway - was identified and further validated and confirmed in a cohort of human SI-NET tissue featured by a dual role in fibrogenesis/carcinogenesis within the neoplastic fibrotic microenvironment

DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification.

AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology that resolved 17/22 and 15/21, respectively, where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach