Fractional extracts of Azadirachta indica leaf affect spermiogram, testosterone profile, and testis histology of rabbit bucks

The effect of fractions from a crude extract of Azadirachta indica leaves on spermatogenesis, testicular histology and testosterone concentration of New Zealand White rabbits were evaluated in this study. Twenty-five matured male New Zealand White rabbits were used for this study and were randomly assigned to five groups (A, B, C, D, and E). Group A served as the control and was administered distilled water (0.5ml); while groups B, C, D and E served as the hexane, chloroform, ethyl acetate, and butanol treated groups, respectively at the same dosage of 300 mg/kg. Semen samples were collected using an artificial vagina weekly for twelve weeks and were evaluated for volume, colour, motility, concentration, percentage live-dead ratio and morphological abnormalities. A blood sample (2ml) was also collected from each buck through venipuncture of the ear vein three times at regular intervals for the determination of testosterone concentration. Two bucks from each group were humanely sacrificed at the end of the experiment for testicular histology. Significantly lower (p<0.05) sperm motility, higher dead sperm cells, sperm abnormalities, degenerative changes, depletion and vacuolation of spermatogenic cell layers were observed in treatment group C at the end of the experiment. The present study has shown that the chloroform fraction of methanolic crude Azadirachta indica (neem) leaves extract is detrimental to sperm cells and testicular histology

Prenatal skull radiography and calvaria histogenesis in Uda and Yankasa breeds of sheep

The anterior fontanelle was opened and radiolucent in the second trimester; at the third trimester, the fontanelle began to shrink and finally closed at birth and became radiopaque. The borders of the orbit and the teeth were both radiolucent and undifferentiated at the second trimester and at the third trimester, and these regions became radiopaque at the second and third trimester, respectively. The histomorphology of the calvarium in the first-trimester foetus had three layers consisting of the mesenchymal and osteoblast cells; as the foetus ages within the second trimester, the mesenchymal cells were transformed into osteoblast, colonies, primitive bone spicules, matured bone spicules, and primitive trabeculae respective, in the third trimester, the primitive trabeculae developed into a matured trabeculae, in the day old, the matured trabeculae transforms into a primitive spongy bone. However, this process occurs earlier in Yankasa than in Uda. The histomorphology of the calvarium during foetal life is similar in the Uda and Yankasa. However, the stages of calvarium development occur earlier and faster in Yankasa than Uda of the same ages. This implies that foetal development and time of parturition could occur earlier in the Yankasa compared to the Uda breeds

Assessing the impacts of various street-level characteristics on the burden of urban burglary in Kaduna, Nigeria

Evidence suggests that crimes committed in urban environments are geographically concentrated across a range of scales, and that the variation in rates of crime within an urban space is significantly dependent on the physical environment as well as the situation in which the crime takes place. However, these assertions are typically drawn from environmental criminological studies that have focussed on Euro-American cities and western intellectual perspectives. We seek to move beyond these by focussing on a second-tier city in sub-Saharan Africa (Kaduna, Nigeria), a context for which very little literature exists. This paper therefore examines the association between a range of street characteristics and the risk of residential burglary in Kaduna for the first time. It describes a methodology for conducting a household crime victimisation survey in Nigeria, and then aggregating the information to a street-level to perform a population-based ecological study. It integrates street network analysis and statistical modelling techniques in order to provide novel estimates for factors that may increase the risk of burglary such as street accessibility metrics (e.g. connectivity, betweenness and closeness centrality), segment length, socioeconomic status and business activities. Finally, the article provides a discussion on the plausibility and implication of findings within the sub-Saharan African context

Frequently Encountered Animal Diseases at Animal Hospital Birnin Kebbi, Kebbi State - Nigeria

Data from the clinical record of the Animal Hospital Birnin Kebbi was used to determine the frequency of occurrence of various diseases of animals from February 2009 to January 2010. A total of 794 cases were presented. 155 (19.5%) for routine check and vaccination, while the bulk 639 (80.5%)were presented as a result of disease conditions. Diseases diagnosed include; helminthoses 141(22%), followed by fowl pox 65(10.2%), lousiness 61(9.5%), traumatic injuries 46(7.2%), enteritis 32(5.0%), upper respiratory tract infection 29(4.5%), mite/mange 24(3.8%), septicemia22(3.4%), bloat 19(3.0%), and abscess 17(2.7%). Other moderately occurring, disorders included dystocia & post partum complications 14(2.2%) each, mal-directed horn/hooves 12(1.9%), tick infestation 10(1.6%), coccidiosis 9(1.4%), fracture 8(1.3%), hernia, PPR, pregnancy toxemia & castration 7(1.1%) each. Poisoning, infectious coryza, arthritis, rumen impaction & vaginal prolapse were 6(0.9%) each, pneumonia and mastitis 5(0.8%) each. The less occurring disorders included urinarytract infection, Gumboro disease, black leg, abortion, paraphimosis & dog bite 4(0.6%) each. Rhinitis & chronic respiratory diseases 3(0.5%) each, Foot and Mouth disease, New castle disease, cowdriosis, and hygroma numbering 2(0.3%) each. The least occurring disorders were Fowltyphoid, dislocation, trypanasomosis, pyometra, orf, stomatitis, grass tetany, canine distemper, atresia ani and rectal prolapse 1(0.2%) case each. Information generated can be useful to Government agencies involved in formulating policies and guidelines for prevention andcontrol of animal diseases

Using item response theory to explore the psychometric properties of extended matching questions examination in undergraduate medical education

BACKGROUND: As assessment has been shown to direct learning, it is critical that the examinations developed to test clinical competence in medical undergraduates are valid and reliable. The use of extended matching questions (EMQ) has been advocated to overcome some of the criticisms of using multiple-choice questions to test factual and applied knowledge. METHODS: We analysed the results from the Extended Matching Questions Examination taken by 4th year undergraduate medical students in the academic year 2001 to 2002. Rasch analysis was used to examine whether the set of questions used in the examination mapped on to a unidimensional scale, the degree of difficulty of questions within and between the various medical and surgical specialties and the pattern of responses within individual questions to assess the impact of the distractor options. RESULTS: Analysis of a subset of items and of the full examination demonstrated internal construct validity and the absence of bias on the majority of questions. Three main patterns of response selection were identified. CONCLUSION: Modern psychometric methods based upon the work of Rasch provide a useful approach to the calibration and analysis of EMQ undergraduate medical assessments. The approach allows for a formal test of the unidimensionality of the questions and thus the validity of the summed score. Given the metric calibration which follows fit to the model, it also allows for the establishment of items banks to facilitate continuity and equity in exam standards

Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression

<p>Abstract</p> <p>Background</p> <p>Microsatellite instability (MSI) refers to mutations in short motifs of tandemly repeated nucleotides resulting from replication errors and deficient mismatch repair (MMR). Colorectal cancer with MSI has characteristic biology and chemosensitivity, however the molecular basis remains unclarified. The association of MSI and MMR status with outcome and with thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression in colorectal cancer were evaluated.</p> <p>Methods</p> <p>MSI in five reference loci, MMR enzymes (hMSH2, hMSH6, hMLH1 and hPMS2), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) expression were assessed in paraffin embedded tumor specimens, and associated with outcome in 340 consecutive patients completely resected for colorectal cancer stages II-IV and subsequently receiving adjuvant 5-fluorouracil therapy.</p> <p>Results</p> <p>MSI was found in 43 (13.8%) tumors. Absence of repair protein expression was assessed in 52 (17.0%) tumors, which had primarily lost hMLH1 in 39 (12.7%), hMSH2 in 5 (1.6%), and hMSH6 in 8 (2.6%) tumors. In multivariate analysis MSI (instable) compared to MSS (stable) tumors were significantly associated with lower risk of recurrence (hazard ratio (HR) = 0.3; 95% CI: 0.2–0.7; P = 0.0007) and death (HR = 0.4; 95% CI: 0.2–0.9; P = 0.02) independently of the TS and DPD expressions. A direct relationship between MSI and TS intensity (P = 0.001) was found, while there was no significant association with DPD intensity (P = 0.1).</p> <p>Conclusion</p> <p>The favourable outcome of MSI colorectal carcinomas is ascribed mainly to the tumor biology and to a lesser extent to antitumor response to 5-fluorouracil therapy. There is no evidence that differential TS or DPD expression may account for these outcome characteristics.</p

Molecular Pathological Classification of Colorectal Cancer

Colorectal cancer (CRC) shows variable underlying molecular changes with two major mechanisms of genetic instability: chromosomal instability and microsatellite instability. This review aims to delineate the different pathways of colorectal carcinogenesis and provide an overview of the most recent advances in molecular pathological classification systems for colorectal cancer. Two molecular pathological classification systems for CRC have recently been proposed. Integrated molecular analysis by The Cancer Genome Atlas project is based on a wide-ranging genomic and transcriptomic characterisation study of CRC using array-based and sequencing technologies. This approach classified CRC into two major groups consistent with previous classification systems: (1) ∼16 % hypermutated cancers with either microsatellite instability (MSI) due to defective mismatch repair (∼13 %) or ultramutated cancers with DNA polymerase epsilon proofreading mutations (∼3 %); and (2) ∼84 % non-hypermutated, microsatellite stable (MSS) cancers with a high frequency of DNA somatic copy number alterations, which showed common mutations in APC, TP53, KRAS, SMAD4, and PIK3CA. The recent Consensus Molecular Subtypes (CMS) Consortium analysing CRC expression profiling data from multiple studies described four CMS groups: almost all hypermutated MSI cancers fell into the first category CMS1 (MSI-immune, 14 %) with the remaining MSS cancers subcategorised into three groups of CMS2 (canonical, 37 %), CMS3 (metabolic, 13 %) and CMS4 (mesenchymal, 23 %), with a residual unclassified group (mixed features, 13 %). Although further research is required to validate these two systems, they may be useful for clinical trial designs and future post-surgical adjuvant treatment decisions, particularly for tumours with aggressive features or predicted responsiveness to immune checkpoint blockade

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy

Lack of EGF receptor contributes to drug sensitivity of human germline cells

Germline mutations have been associated with generation of various types of tumour. In this study, we investigated genetic alteration of germline tumours that affect the drug sensitivity of cells. Although all germline tumour cells we tested were hypersensitive to DNA-damaging drugs, no significant alteration was observed in their DNA repair activity or the expression of DNA repair proteins. In contrast, germline tumours expressed very low level of epidermal growth factor receptor (EGFR) compared to drug-resistant ovarian cancer cells. An immunohistochemical analysis indicated that most of the primary germline tumours we tested expressed very low level of EGFR. In accordance with this, overexpression of EGFR in germline tumour cells showed an increase in drug resistance, suggesting that a lack of EGFR, at least in part, contributes to the drug sensitivity of germline tumours