Genetic Assessment of Hyperuricemia and Gout in Asian, Native Hawaiian, and Pacific Islander Subgroups of Pregnant Women: Biospecimens Repository Cross-Sectional Study

Background Gout, an inflammatory condition, is characterized by the precipitation of monosodium urate crystals (MSU) in or around distal joints. The latter is caused by chronic hyperuricemia (HU)—high urate levels in the blood. Genetic variations in urate transporters play a significant role in determining urate levels within the human body, rendering some racial and ethnic groups more or less susceptible to developing either HU or gout. This study aims to estimate the frequencies of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups, using biorepository DNA samples. Methods The biospecimens repository at the University of Hawai’i provided DNA samples of consented post-partum women of Japanese, Filipino, Korean, Native Hawaiian, Samoan, and Marshallese descent. The DNA was previously extracted from maternal blood and genotyped at the Genomics and Bioinformatics Shared Resource, Cancer Center (Honolulu, HI). Nine urate genes: ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1, were selected due to their significant association with HU and gout risk. Hardy–Weinberg Equilibrium (HWE) for genotype frequencies was assessed, using the Chi-Square test with p \u3c 0.006 for statistical significance. Allele frequencies in our study were then compared to EUR from the 1000 Genomes Project Database Phase III, using Chi-square or Fisher\u27s exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p \u3c 0.006 for statistical significance. Results Our study involved 1059 post-partum women 18-year-old or older who self-reported their respective race and ethnicity, including Asian, Native Hawaiian, and Pacific Islander ancestry. The Asian subgroups included Japanese, Filipino, and Korean. The Pacific Islander subgroups included Marshallese and Samoan. None of the study participants had a history of gout. We excluded the PDZK1 gene from the final analysis due to its deviation from HWE (p \u3c 0.006) across all the population subgroups, with eight loci remaining for cross-subgroup comparisons. Compared to EUR, the genetic polymorphism frequencies were significantly different-8/8 in Japanese, 6/8 in Korean, 6/8 in Filipino, 8/8 in Samoan, 6/8 in Native Hawaiian, and 6/8 in Marshallese. HU and gout risk alleles indices were 8, 6, 5, 5, 4, and 4 in Japanese, Filipino, Korean, Samoan, Marshallese, and Native Hawaiian, respectively. The percentage of cumulative risk alleles was 100% in both Japanese and Filipino, followed by 83.5% in Korean. Conclusions Compared to EUR, Asian subgroups, particularly Japanese, Filipino, and Korean, had the highest percentage of the cumulative uric acid risk alleles. These results could partly explain the increased risk of developing gout among some Asian ancestral subgroups compared to EUR

What can obstetrician/gynecologists do to support abortion access?

AbstractUnsafe abortion causes approximately13% of all maternal deaths worldwide, with higher rates in areas where abortion access is restricted. Because safe abortion is so low risk, if all women who needed an abortion could access safe care, this rate would drop dramatically. As women’s health providers and advocates, obstetrician/gynecologists can support abortion access. By delivering high-quality, evidence-based care ourselves, supporting other providers who perform abortion, helping women who access abortion in the community, providing second-trimester care, and improving contraceptive uptake, we can decrease morbidity and mortality from unsafe abortion

Vascular Regeneration by Local Growth Factor Release Is Self-Limited by Microvascular Clearance

Background— The challenge of angiogenesis science is that stable sustained vascular regeneration in humans has not been realized despite promising preclinical findings. We hypothesized that angiogenic therapies powerfully self-regulate by dynamically altering tissue characteristics. Induced neocapillaries increase drug clearance and limit tissue retention and subsequent angiogenesis even in the face of sustained delivery. Methods and Results— We quantified how capillary flow clears fibroblast growth factor after local epicardial delivery. Fibroblast growth factor spatial loading was significantly reduced with intact coronary perfusion. Penetration and retention decreased with transendothelial permeability, a trend diametrically opposite to intravascular delivery, in which factor delivery depends on vascular leak, but consistent with a continuum model of drug transport in perfused tissues. Model predictions of fibroblast growth factor sensitivity to manipulations of its diffusivity and transendothelial permeability were validated by conjugation to sucrose octasulfate. Induction of neocapillaries adds pharmacokinetic complexity. Sustained local fibroblast growth factor delivery in vivo produced a burst of neovascularization in ischemic myocardium but was followed by drug washout and a 5-fold decrease in fibroblast growth factor penetration depth. Conclusions— The very efficacy of proangiogenic compounds enhances their clearance and abrogates their pharmacological benefit. This self-limiting property of angiogenesis may explain the failures of promising proangiogenic therapies.National Institutes of Health (U.S.) (Grant R01 GM 49039

Progestin-only contraceptives: effects on weight

Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception, implants, and oral contraceptives. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users

Antimullerian hormone and obesity: insights in oral contraceptive users

The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women

Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia

available in PMC 2015 October 30A “one material fits all” mindset ignores profound differences in target tissues that affect their responses and reactivity. Yet little attention has been paid to the role of diseased tissue on material performance, biocompatibility, and healing capacity. We assessed material-tissue interactions with a prototypical adhesive material based on dendrimer/dextran and colon as a model tissue platform. Adhesive materials have high sensitivity to changes in their environment and can be exploited to probe and quantify the influence of even subtle modifications in tissue architecture and biology. We studied inflammatory colitis and colon cancer and found not only a difference in adhesion related to surface chemical interactions but also the existence of a complex interplay that determined the overall dendrimer/dextran biomaterial compatibility. Compatibility was contextual, not simply a constitutive property of the material, and was related to the extent and nature of immune cells in the diseased environment present before material implantation. We then showed how to use information about local alterations of the tissue microenvironment to assess disease severity. This in turn guided us to an optimal dendrimer/dextran formulation choice using a predictive model based on clinically relevant conditions.National Institutes of Health (U.S.) (NIH grant R01 GM-49039)Deshpande Center for Technological Innovatio

Medical abortion offered in pharmacy versus clinic-based settings

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To compare the safety and efficacy of medical abortion offered in pharmacy settings with clinic‐based medical abortion

Can initial vaginal bleeding patterns in etonogestrel implant users predict subsequent bleeding in the first 2 years of use?

ObjectivesTo evaluate if a simple method for characterizing vaginal bleeding patterns in etonogestrel contraceptive implant users can predict subsequent patterns and bleeding-related discontinuation over the first 2 years of use.Study designWe reanalyzed phase 3 study bleeding data for non-breastfeeding participants from the United States, Europe, Russia and Chile during the first 2 years of implant use to characterize and correlate bleeding patterns. We used 90-day reference periods with period 1.1 starting at Day 29 and ending at Day 118. We dichotomized bleeding patterns as "favorable" (amenorrhea, infrequent bleeding and normal frequency bleeding without prolonged bleeding) or "unfavorable' (prolonged and/or frequent bleeding) and tracked user groups based on these bleeding patterns in reference period 1.1 through Year 1 and from Year 1 through Year 2, respectively.ResultsWe evaluated data from 537 and 428 women with up to 1 and 2 years use, respectively. Of the 325 (60.5%) women with favorable bleeding in reference period 1.1, 275 (84.6%) reported favorable bleeding also in reference period 2, 197 (60.6%) reported favorable bleeding throughout Year 1, and favorable bleeding in 75-85% of reference periods in Year 2. Among 212 (39.5%) women with unfavorable bleeding in reference period 1.1, 118 (55.7%) continued with unfavorable bleeding in reference period 2, while about 40%-50% reported favorable patterns in RP 2, 3 and/or 4. Initial favorable bleeding resulted in lower discontinuation rates than initial unfavorable bleeding in years 1 (3.7% vs 12.7%, p≪.0001) and 2 (2.5% vs 16.5%, p≪.0001).ConclusionImplant users with favorable bleeding in the first reference period are likely to continue with favorable bleeding over the next 2 years. Initial bleeding patterns predict overall continuation rates in years 1 and 2. Implications Statement When evaluating vaginal bleeding in any 90-day reference period over 2 years of etonogestrel implant use, approximately 80% of women with favorable and 40% with unfavorable bleeding patterns will have favorable bleeding in the next reference periods. These findings can facilitate counseling regarding bleeding for women using the etonogestrel implant

Academic Health Science Centres as Vehicles for Knowledge Mobilisation in Australia? A Qualitative Study

Background Despite increasing investments in academic health science centres (AHSCs) in Australia and an expectation that they will serve as vehicles for knowledge translation and exchange, there is limited empirical evidence on whether and how they deliver impact. The aim of this study was to examine and compare the early development of four Australian AHSCs to explore how they are enacting their impact-focused role. Methods A descriptive qualitative methodology was employed across four AHSCs located in diverse health system settings in urban and regional locations across Australia. Data were collected via semi-structured interviews with 15 academic, industry and executive board members of participating AHSCs. The analysis combined inductive and deductive elements, with inductive categories mapped to deductive themes corresponding to the study aims. Results AHSCs in Australia are in an emergent state of development and are following different pathways. Whilst varied approaches to support research translation are apparent, there is a dominant focus on structure and governance, as opposed to action-oriented roles and processes to deliver strategic goals. Balancing collaboration and competition between partners presents a challenge, as does identifying appropriate ways to evaluate impact. Conclusion The early stage of development of AHSCs in Australia presents an important opportunity for formative learning and evaluation to optimise their enactment of knowledge mobilisation processes for impact

Mobilising knowledge in (and about) Academic Health Science Centres : boundary spanning, inter-organisational governance and systems thinking

Academic Health Science Centres (AHSCs), also termed Research Translation Centres (RTCs) in Australia, are organisations that aim to promote the integration of research, health professional education, and health service delivery to improve translation and innovation in Australia’s health system. In 2020, we published a study on how people, processes and systems were being organised within Australian AHSCs to enable knowledge to be mobilised for impact