Factors Associated with Treatment Success among Pulmonary Tuberculosis and HIV Co-infected Patients in Oyo State, South West-Nigeria

Background The co-existence of Tuberculosis (TB) and Human immunodeficiency Virus (HIV) is  known to increase morbidity and mortality in patients. The determinants of treatment success in TBHIV co-infection are not yet well studied. Such information can help optimise treatment and reduce morbidity and mortality.Objective To determine factors associated with antitubercular treatment success among TB I HIV coinfected patients.Methods A cross sectional study was carried out in fifty  three DOT clinics and treatment centres  using tuberculosis patient's records from January 2009 to December 2010 in Oyo state, Nigeria. The study population consisted of 7905 tuberculosis patients. Information on variables of interest were obtained with the use of data extraction forms. Chi-square and logistic regression were used to test the relationship between TB I HIV coinfection and socio-demographic variables, clinical characteristics and treatment success.Results Prevalence ofTB I HIV co-infection was found to be 14.2%. Patients with TB-HIV co-infection  were younger and more likely to be females. There were statistically significant association between treatment success and gender, marital status and patient point of care. After adjusting for other variables, it was found that patients receiving treatment in private facilities were independently less likely to be successfully treated compared with those receiving care in Public facilities. Female patients were also independently more likely to have better treatment outcome than male.Conclusion In addition to patients' point of care, gender of the patients can adversely impact on their treatment success. Efforts from the government to strengthening the private public mix, health education and media awareness on adherence to treatment to improve treatment success should be intensified in the country.Keywords: Tube rc ulosis; Human immunodeficiency virus, Directly observe therapy short-course;  Treatment success, Coinfection

Mucin-Grafted Polyethylene Glycol Microparticles Enable Oral Insulin Delivery for Improving Diabetic Treatment

In this study, different ratios of mucin-grafted polyethylene-glycol-based microparticles were prepared and evaluated both in vitro and in vivo as carriers for the oral delivery of insulin. Characterization measurements showed that the insulin-loaded microparticles display irregular porosity and shape. The encapsulation efficiency and loading capacity of insulin were >82% and 18%, respectively. The release of insulin varied between 68% and 92% depending on the microparticle formulation. In particular, orally administered insulin-loaded microparticles resulted in a significant fall of blood glucose levels, as compared to insulin solution. Subcutaneous administration showed a faster, albeit not sustained, glucose fall within a short time as compared to the polymeric microparticle-based formulations. These results indicate the possible oral delivery of insulin using this combination of polymers.Tertiary Education Trust Fund (TETFUND)–National Research Fund (NFR)Ministerio de Ciencia, Innovación y Universidade

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases

Improving the Bearing Strength of Sandy Loam Soil Compressed Earth Block Bricks Using Sugercane Bagasse Ash

The need for affordable and sustainable alternative construction materials to cement in developing countries cannot be underemphasized. Compressed Earth Bricks have gained acceptability as an affordable and sustainable construction material. There is however a need to boost its bearing capacity. Previous research show that Sugarcane Bagasse Ash as a soil stabilizer has yielded positive results. However, there is limited research on its effect on the mechanical property of Compressed Earth Brick. This current research investigated the effect of adding 3%, 5%, 8% and 10% Sugarcane Bagasse Ash on the compressive strength of compressed earth brick. The result showed improvement in its compressive strength by 65% with the addition of 10% Sugarcane Bagasse Ash

The Fire Service for the Removal of a Metallic Penile Constricting Device: A Ready Help When All Else Fail

The placement of a constricting device around the penis is a urologic emergency. Though injuries from constricting penile devices are generally rare, they may be associated with serious complications. There is no standard modality for the removal of penile constricting devices and the management of the patient can therefore prove to be a formidable challenge to the urologist. Timely intervention is always important in preventing complications especially penile gangrene. Depending on the type of device used along with the duration and severity of penile constriction caused, significant resourcefulness may be required in the treatment of the patient. Achieving a timely and successful outcome may require a multidisciplinary approach involving equipment only available with the fire service or other agencies. We report the case of a 30-year-old man with a background psychiatric illness who had his penile constricting device removed under conscious sedation in the emergency room with the aid of a power driven arc saw from the fire service with a successful outcome

Abstract 2320: Evaluating a polygenic risk score for breast cancer in women of African ancestry

Abstract Background: A polygenic risk score (PRS) for breast cancer including 313 common variants developed by the Breast Cancer Association Consortium (BCAC) has been demonstrated to identify women who are at high risk of developing breast cancer [odds ratio (OR 95%CI) = 1.61 (1.57-1.65) per SD] in women of European ancestry. In the present study, we examined the performance of the 313-variant PRS and a PRS including 179 variants reaching genome-wide significance in previous genome-wide association studies (GWAS), in women of African ancestry. Methods: We assembled genotype data for women of African ancestry from 28 breast cancer studies, including a total of 9,241 cases and 10,193 controls. We constructed the 179-variant and 313-variant PRSs with relative risk weights for each variant estimated in women of European ancestry in BCAC. The associations between the two PRSs and overall, ER+ and ER- breast cancer risk were estimated using logistic regression adjusting for age, study site and principal components. Discriminatory accuracy of the PRSs was evaluated using the receiver operating characteristic curve (AUROC). We then recalibrated the 179-variant PRS by replacing index variants with variants in each region that better captured risk in women of African ancestry and used relative risk weights estimated in women of African ancestry. We also assessed PRS performance by age (<55 versus ≥ 55 years). Results: Both the 179 and 313- variant PRSs were significantly associated with overall, ER+ and ER- breast cancer risk, with odds ratios (OR) per standard deviation of 1.21~1.37 and AUROCs ranging from 0.57 to 0.59. The 179-variant PRS outperformed in ER- cancer [1.31(1.24,1.37) per SD] while the 313-SNP PRS was better for overall [1.27(1.23,1.31) per SD] and ER+ cancer [1.37(1.32,1.43) per SD]. For overall breast cancer, compared to women with average risk (40th-60th PRS percentiles), women in the top decile of PRS had a 1.54 (95% CI: 1.38, 1.72)-fold increased risk. The performance of the recalibrated 179-variant PRS was not improved (average AUROC=0.56). The PRS ORs did not differ significantly across age strata (P-value for age interaction = 0.63). Conclusion: Our study shows that both 179 and 313 variant PRS stratify breast cancer risk in women of African ancestry, with attenuated performance compared to that reported in European and in Latina populations. Future work is needed to improve breast cancer risk stratification for women of African ancestry. Citation Format: Zhaohui Du, Guimin Gao, Babatunde Adedokun, Thomas Ahearn, Kathryn L. Lunetta, Gary Zirpoli, Melissa Troester, Edward A. Ruiz-Narváez, Stephen Haddad, Jonine Figueroa, Esther M. John, Leslie Bernstein, Wei Zheng, Jennifer J. Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. Bandera, Sue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Song Yao, Temidayo O. Ogundiran, Oladosu A. Ojengbede, William Blot, Katherine L. Nathanson, Anselm Hennis, Barbara Nemesure, Stefan Ambs, Lara E. Sucheston-Campbell, Jeannette T. Bensen, Stephen J. Chanock, Andrew F. Olshan, Christine B. Ambrosone, David V. Conti, Olufunmilayo I. Olopade, Julie R. Palmer, Montserrat Garcia-Closas, Dezheng Huo, Christopher A. Haiman. Evaluating a polygenic risk score for breast cancer in women of African ancestry [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2320

Abstract 4613: Cross-ancestry genome-wide association study identifies six new loci for breast cancer in women of African and european ancestry

Abstract Background: Over 180 genetic variants have been identified as risk loci for breast cancer. However, most loci were discovered using European ancestry populations. As some common susceptibility loci are shared across populations, we aim to discover new risk loci for breast cancer using a cross-ancestry genome-wide association study (GWAS) approach. Methods: Data from five GWAS studies in women of African ancestry with a combined sample size of 9241 cases and 10192 controls were used to generate pooled breast cancer risk estimates in a fixed effect meta-analysis, and this served as the discovery dataset. Summary statistics from the GWAS conducted in European ancestry populations (Breast Cancer Association Consortium, 122977 cases and 105974 controls) served as the validation dataset. The variants that were associated with breast cancer risk at P 500kb away from known breast cancer risk loci. Conditional on the lead index variants, we searched for additional signals in each locus using multivariable logistic regression. Analyses were done separately for ER-positive, ER-negative and overall breast cancer risk. Results: We discovered four novel loci for overall breast cancer risk (1p13.3, 5q31.1, 15q24, and 15q26.3) and two novel loci for ER-negative breast cancer (1q41 and 7q11.23) at the genome-wide significance level of P < 5 × 10−8. Three index single nucleotide polymorphism (SNPs) lie within introns of genes (KCNK2, C5orf56, and SIN3A) and the other index SNPs are located in intergenic regions (close to GSTM4 and AMPD2, CASTOR2, and the antisense DNA RP11-168G16.2). The direction of the associations was consistent between the GWASs of African and European descendants. At the 15q24 locus, we found an additional SNP (in the intron of the SCAMP2 gene) to be independently associated with overall breast cancer risk. Conclusions: We have identified six new risk loci that may contribute to better prediction of breast cancer risk in African ancestry populations and provide new insights into mechanisms of breast cancer carcinogenesis. Replication of these loci in multiple populations and functional studies can help to identify causal variants. Citation Format: Babatunde Adedokun, Zhaohui Du, Guimin Gao, Thomas Ahearn, Kathryn L. Lunetta, Gary Zirpoli, Jonine Figueroa, Esther M. John, Leslie Bernstein, Wei Zheng, Jennifer J. Hu, Regina G. Ziegler, Sarah Nyante, Elisa V. Bandera, Sue A. Ingles, Michael F. Press, Sandra L. Deming, Jorge L. Rodriguez-Gil, Song Yao, Temidayo O. Ogundiran, Oladosu Ojengbede, William Blot, Melissa Troester, Katherine L. Nathanson, Anselm Hennis, Barbara Nemesure, Stefan Ambs, Lara E. Sucheston-Campbell, Jeannette T. Bensen, Stephen J. Chanock, Andrew F. Olshan, Christine B. Ambrosone, David V. Conti, Olufunmilayo I. Olopade, Montserrat Garcia-Closas, Julie R. Palmer, Christopher A. Haiman, Dezheng Huo. Cross-ancestry genome-wide association study identifies six new loci for breast cancer in women of African and european ancestry [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4613