Kenya country profile: A status check on unintended pregnancy in Kenya

Kenya’s mothers are dying at an alarming rate: a woman giving birth in Kenya has a 1 in 38 chance of dying due to inadequate reproductive health services. In response, in 2014 Kenya’s First Lady Margaret Kenyatta launched the Beyond Zero campaign to create awareness and raise funds to tackle maternal mortality and morbidity and improve child health. This brief offers six policy and programmatic recommendations to address significant sexual and reproductive health challenges highlighted throughout the report. These recommendations take into account the policy context in Kenya, which is evolving at a rapid rate in part because of the new devolution process, and increased interest and public debate surrounding maternal health and family planning. Though the Kenyan government has made key strides in improving reproductive health outcomes for its citizens, the recommendations outlined in the report would help the country move closer to achieving its reproductive health goals

Risk Factors for Triple-Negative Breast Cancer in Women Under Age 45

Little is known about the etiologic profile of triple-negative breast cancer (negative for estrogen receptor/progesterone receptor/human epidermal growth factor), a breast cancer subtype associated with high mortality and inadequate therapeutic options. We undertook this study to assess the risk for triple-negative breast cancer among women 45 years of age and younger in relation to demographic/lifestyle factors, reproductive history, and oral contraceptive use. Study participants were ascertained in two previous population-based, case-control studies. Eligible cases included all primary invasive breast cancers among women ages 20 to 45 years in the Seattle-Puget Sound area, diagnosed between January 1983 and December 1992, for whom complete data was obtained for estrogen receptor, progesterone receptor, and human epidermal growth factor status (n = 897; including n = 187 triple-negative breast cancer cases). Controls were age matched and ascertained via random digit dialing. Oral contraceptive use >/=1 year was associated with a 2.5-fold increased risk for triple-negative breast cancer (95% confidence interval, 1.4-4.3) and no significantly increased risk for non-triple-negative breast cancer (Pheterogeneity = 0.008). Furthermore, the risk among oral contraceptive users conferred by longer oral contraceptive duration and by more recent use was significantly greater for triple-negative breast cancer than non-triple-negative breast cancer (Pheterogeneity = 0.02 and 0.01, respectively). Among women /=1 year was 4.2 (95% confidence interval, 1.9-9.3), whereas there was no significantly increased risk with oral contraceptive use for non-triple-negative breast cancer among women </=40 years, nor for triple-negative breast cancer or non-triple-negative breast cancer among women 41 to 45 years of age. In conclusion, significant heterogeneity exists for the association of oral contraceptive use and breast cancer risk between triple-negative breast cancer and non-triple-negative breast cancer among young women, lending support to a distinct etiology

Improving family planning services in public health facilities to reach more women

Although Kenya has made significant progress in ensuring its citizens’ right to reproductive health, many Kenyans still lack access to or fail to use contraceptives, in part because of the lack of quality family planning (FP) services. Through the STEP UP research program, the African Population and Health Research Center developed a comprehensive country profile report that outlines the status, causes, and consequences of unintended pregnancy in Kenya. One of the most prominent findings was how important public health facilities are to reducing unmet need for FP. In order to solidify gains achieved and make further progress, concerted commitment from the Kenyan government and Ministry of Health to actively support FP services in public facilities is crucial. This policy brief makes a number of recommendations to help Kenya move forward

Invest in urban youth sexual and reproductive health to achieve a demographic dividend in Africa

The future of Africa depends on its ability to harness the potential of its young people. Making the right investments in youth—particularly those in urban areas—can enable the region to experience substantial economic growth and sustainable national development for current and future generations. This policy brief reports on a number of recommendations to help African governments and Ministries of Health and Education realize the demographic dividend; incorporate economic empowerment programs into urban programming and budget allocation; integrate training on the provision of quality and effective youth-friendly services for health workers; and revitalize school health programming

A Bitter Taste Receptor as a Novel Molecular Target on Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma

Cancer-associated fibroblasts (CAFs) execute diverse and complex functions in cancer progression. While reprogramming the crosstalk between CAFs and cancer epithelial cells is a promising avenue to evade the adverse effects of stromal depletion, drugs are limited by their suboptimal pharmacokinetics and off-target effects. Thus, there is a need to elucidate CAF-selective cell surface markers that can improve drug delivery and efficacy. Here, functional proteomic pulldown with mass spectrometry was used to identify taste receptor type 2 member 9 (TAS2R9) as a CAF target. TAS2R9 target characterization included binding assays, immunofluorescence, flow cytometry, and database mining. Liposomes conjugated to a TAS2R9-specific peptide were generated, characterized, and compared to naked liposomes in a murine pancreatic xenograft model. Proof-of-concept drug delivery experiments demonstrate that TAS2R9-targeted liposomes bind with high specificity to TAS2R9 recombinant protein and exhibit stromal colocalization in a pancreatic cancer xenograft model. Furthermore, the delivery of a CXCR2 inhibitor by TAS2R9-targeted liposomes significantly reduced cancer cell proliferation and constrained tumor growth through the inhibition of the CXCL-CXCR2 axis. Taken together, TAS2R9 is a novel cell-surface CAF-selective target that can be leveraged to facilitate small-molecule drug delivery to CAFs, paving the way for new stromal therapies

Unintended pregnancies in Kenya: A country profile

This research report presents a country profile of Kenya, and looks at differential access to and quality of family planning (FP) and abortion/post-abortion services to assess their current situation, as well the various financing and delivery mechanisms for these crucial services. Since 2000, Kenya has passed several new sexual and reproductive health (SRH) and population-related policies, including a new population and development policy that addresses rapid population growth. Results of this country profile highlight the need for further research on: 1) innovative ways through which SRH information can be brought to schools; 2) FP/SRH indicators in people living with disabilities; and 3) traditional and non-hormonal methods of contraception. The report discusses the key challenges facing reproductive health with a special focus on unintended pregnancy in Kenya and ends with policy and programmatic implications

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC