Ocular Toxoplasmosis among Livestock Farmers and Raw Meat Handlers in Uyo, Nigeria

BACKGROUND፡ Toxoplasmosis is the commonest cause of infectious posterior uveitis in humans and can lead to blindness and low vision in both immune-competent and immunecompromised persons worldwide. The aim of this study was to determine the prevalence of Ocular Toxoplasmosis (OT) and potential risk factors among livestock farmers and raw meat handlers in Uyo.METHODS: This was a descriptive cross-sectional communitybased study involving clinical eye examination, laboratory detection of anti-Toxoplasma gondii IgG antibody and HIV testing. Participants’ other information was obtained using interviewer-administered questionnaire.RESULTS: There were 339 participants aged 15-78 (mean 34.8±11.6) years,283 (83.5%) were males 56(16.5%) were females; 189 (55.8%) tested seropositive for anti-Toxo. gondiiIgG antibodies. Eight (2.4%) had presumed ocular toxoplasmosis (POT); 6 of the 8 were seropositive for anti T.gondiiIgG antibody; and 2 of the 8 POT (25%) were HIV-seropositive. Of the 189 who were anti-T.gondiiIgG antibody seropositive, 6 (3.2%) had OT. Factors associated with OT were age (31-50 years) and female gender (P = 0.049 and 0.001, respectively). HIV infection was associated with POT (P=0.033). Most of the ocular lesions (87.5%) were unilateral and located at the posterior pole (77.7%).CONCLUSION: The prevalence of presumed ocular toxoplasmosis (POT) and ocular toxoplasmosis (OT) among livestock farmers and raw meat handlers in Uyo are 2.4% and 1.8%, respectively. Potential risk factors are being female, and persons between fourth and fifth decades of life. Awareness creation on toxoplasmosis among this occupational group is advocated

The role of honey in the treatment of type 2 diabetes mellitus: a review of literature

The use of honey in the control of hyperglycemia in patients with type 2 diabetes mellitus is a current option being explored globally. Honey bees which are named in Latin as Apis, use the collected nectar from plants to produce honey after regurgitation and digestion of nectar. Carbohydrate constitutes about 80% of the components of honey. It includes monosaccharides [fructose (37.5%) and glucose (30.6%), disaccharides (sucrose (1.6%) and maltose (2.7%)] and oligosaccharides. Natural honey also contains water (17.2%), proteins, vitamins, minerals, enzymes, acids such as flavonoids, phenolic acids and other components. Honey is rich in antioxidant content and these antioxidant compounds function as endogenous cellular antioxidant defences against free radicals in diabetes mellitus. Antioxidants have also been shown to exert a beneficial effects on blood glucose. Fructose and other bioactive constituents of honey have also been linked with amelioration of hyperglycemia. Besides the beneficial effects of honey on blood glucose, honey is widely used in the management of diabetic foot ulcers, an important complication of diabetes mellitus. The wound-healing benefits of honey are attributed to its antioxidant constituents and broad-spectrum antimicrobial activity. Though additional studies are needed, the use of honey in the management of diabetes mellitus holds much promise

Analgesic, anti-inflammatory and antipyretic activities of ethanol extract of Annona senegalensis leaves in experimental animal models

Background: This study was carried out to establish the analgesic, anti-inflammatory and antipyretic effects of the ethanol extract of Anonna senegalensis leaves in experimental animals.Methods: The analgesic activity was measured using the abdominal constriction and tail flick tests. The anti-inflammatory activity was performed using xylene and egg-albumen paw induced tests, while the antipyretic activity was measured using brewer’s yeast and 2, 4 dinitrophenol induced pyrexia tests, respectively.Results: The leaf extract at all doses used exhibited significant (p<0.05) analgesic, anti-inflammatory and antipyretic activities.Conclusions: Results show that ethanol leaf extract of Anonna senegalensis possess therapeutic potential against pains and feverish conditions, supporting the claims of its this plant as remedy for similar ailments

Hepatitis C Virus infection in apparentenly healthy individuals with family history of diabetes in Vom, Plateau State Nigeria

Hepatitis C virus (HCV) infection is an important public health problem worldwide. Its association with, and predisposing nature for diabetes mellitus (DM) has been long established. This research was carried out to determine the prevalence of Hepatitis C virus (HCV) amongst people with possible genetic predisposition to diabetes mellitus living in and around Vom, Plateau State, Nigeria. 188 subjects were screened after they filled a structured questionnaire to determine some of their demographic data, social habits and possible risk factors. 5 ml of blood was collected from each subject and sera separated out. Biotech's third generation ELISA Kit for HCV antibodies was used for the screening. Liver enzyme analysis was carried out on positive samples to determine their disease status. A prevalence of 14.36% was recorded with the highest seropositive group being those in the age bracket of 18 – 37 years. 13(13.40%) of males and 14(15.38%) of females were sero-positive. Liver enzyme analysis of sero-positive subjects showed increased levels which may imply early onset of liver damage. These result showed that these individuals could later suffer diabetes which may be triggered by their HCV infection if not treated. This is not over-looking the economic significance of their ill health, assuming they progress to cirrhotic HCV or develop hepatocelluar carcinoma due to HCV chronicity

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

TiO2 Nanoparticles Are Phototoxic to Marine Phytoplankton

Nanoparticulate titanium dioxide (TiO2) is highly photoactive, and its function as a photocatalyst drives much of the application demand for TiO2. Because TiO2 generates reactive oxygen species (ROS) when exposed to ultraviolet radiation (UVR), nanoparticulate TiO2 has been used in antibacterial coatings and wastewater disinfection, and has been investigated as an anti-cancer agent. Oxidative stress mediated by photoactive TiO2 is the likely mechanism of its toxicity, and experiments demonstrating cytotoxicity of TiO2 have used exposure to strong artificial sources of ultraviolet radiation (UVR). In vivo tests of TiO2 toxicity with aquatic organisms have typically shown low toxicity, and results across studies have been variable. No work has demonstrated that photoactivity causes environmental toxicity of TiO2 under natural levels of UVR. Here we show that relatively low levels of ultraviolet light, consistent with those found in nature, can induce toxicity of TiO2 nanoparticles to marine phytoplankton, the most important primary producers on Earth. No effect of TiO2 on phytoplankton was found in treatments where UV light was blocked. Under low intensity UVR, ROS in seawater increased with increasing nano-TiO2 concentration. These increases may lead to increased overall oxidative stress in seawater contaminated by TiO2, and cause decreased resiliency of marine ecosystems. Phototoxicity must be considered when evaluating environmental impacts of nanomaterials, many of which are photoactive

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (, , ) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types