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ObjectivesBlack women disproportionately experience STIs (including HIV/AIDS), gender-based violence, substance misuse and mental health conditions. Addressing a gap in syndemic research, we characterised comorbidity overlap within the context of sociostructural inequities and adverse childhood experiences (ACEs) among black women in Baltimore, Maryland.MethodsBetween 2015 and 2018, black women (n=305) were recruited from STI clinics in Baltimore, Maryland. Among those with complete survey data (n=230), we conducted a latent class analysis to differentiate women based on their profile of the following syndemic comorbidities: STIs, adult sexual victimisation, substance misuse and mental health disorders. We then examined the association between ACEs and syndemic latent class membership.ResultsThirty-three percent of women experienced three to nine ACEs before age 18 years, and 44% reported four to six comorbidities. The two-class latent class solution demonstrated the best fit model, and women were categorised in either class 1 (past-year STI; 59%) or class 2 (syndemic comorbidities; 41%). Women in class 2 were more likely to report unstable housing (10% vs 3%) and identify as bisexual/gay (22% vs 10%) than women in class 1. ACEs were significantly associated with an increased likelihood of class 2 membership.ConclusionsThis study reinforces the importance of screening for ACEs and offering trauma-informed, integrated care for black women with syndemic comorbidities. It also highlights the critical nature of tailoring interventions to improve sociostructural equity, preventing and reducing syndemic development.

Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors.Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors.Results:In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA.Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.

Supplementary Tables S1-S2 from In vivo Knockdown of the Androgen Receptor Results in Growth Inhibition and Regression of Well-Established, Castration-Resistant Prostate Tumors

Purpose:We performed a systematic review comparing the incidence of infectious complications following transperineal ultrasound-guided prostate biopsy (TPB) in cases utilizing antibiotic prophylaxi...

Background This study examined the associations between feminine gender ideologies (i.e., socially constructed attitudes and beliefs of women’s appropriate behavior and roles) and the syndemic comorbidities of harmful alcohol use, sexual violence, and sexually transmitted infections (STI), which disproportionately affect Black women. Methods Black women, aged 18–44 (n = 305) were recruited from STI clinics in Baltimore, MD into a retrospective cohort study. A survey assessed feminine gender ideologies using a measure of hyperfemininity and sexual hyperfemininity (subscale of sexual domains), harmful drinking (AUDIT), lifetime STI (Y/N and count), and syndemic burden (no burden [0−1 morbidity] and syndemic burden [2−3 comorbidities]). Multivariable regression models identified correlates of harmful drinking, STI, and syndemic burden. The analytic sample included (n = 231) women with complete data. Results Nearly half of our sample reported high hyperfemininity and high sexual hyperfemininity, 23% reported harmful drinking, 39% experienced sexual violence as an adult, and 74% reported a lifetime STI. High sexual hyperfemininity (Adjusted Odds Ratio [AOR] = 1.94, 95% Confidence Interval [CI]: 1.00–3.76) and sexual violence (AOR = 2.82, 95%CI: 1.43–5.58) were associated with greater odds of harmful drinking. Experiencing sexual violence in adulthood was associated with an increased count of lifetime STIs (Adjusted Incidence Rate Ratio [AIRR] = 1.33, 95%CI: 1.06–1.68). Syndemic burden affected 41% of our sample. High sexual hyperfemininity was associated with experiencing syndemic burden in unadjusted models (OR = 1.98, 95%CI: 1.16–3.37), but was not significant after controlling for confounders. Conclusions Interventions to reduce harmful drinking and STIs among Black women in the U.S. should address sexual gender ideologies and sexual violence.

Biomarkers are a useful tool for the investigation of chronic kidney disease (CKD), although the design, analytical tools and outcomes used in many biomarker studies are suboptimal. In part, this situation might reflect a lack of appreciation of the nature of different biomarkers. A particular biomarker could, for example, be implicated in the pathogenesis of CKD because it is a physiological risk factor for declining kidney function, an indicator of impaired kidney function, or a marker of ongoing injury within the kidney. Such risk factors enable us to understand the process of disease and to identify treatment targets. By contrast, risk markers enable us to distinguish persons who will or will not develop CKD, even though the markers themselves are not required to be modifiable by (or directly involved in) the disease process. Accurate prediction of CKD risk will probably require a combination of biomarkers of several types, however. This Review offers a conceptual framework for interpreting the results of studies evaluating biomarkers of declining kidney function and incident CKD.

The identification of a selective CDK2, 7, 9 inhibitor 4 with improved permeability is described. Compound 4 exhibits comparable CDK selectivity profile to SNS-032, but shows improved permeability and higher bioavailability in mice.

Background. Accu lturation affects health, but it has never been studied with kidney disease. Methods. W e studied the association of language spoken at home, generation and birth place with kidney function among Hispanics and Chinese in the Multi-Ethnic Study of Atherosclerosis (n = 2999). Kidney function was determined by cystatin C (eGFRcys) and albumin/creatinine ratio (ACR). We evaluated mediators in models: Model 1 = age, sex,income, education; Model 2 = Model 1 + behaviors; and Model 3 = Model 1 + comorbidities. Results. A mong Hispanics, speaking mixed Spanish/ English was significantly associated with lower eGFRcys (−2 .83 mL/min/1.73 m 2 , −5.69–0.04) and higher ACR (RD 40%, 17–68%) compared with speaking Spanish only; this was mildly attenuated by behaviors (−2.2 9, −5.33–0.75; RD 42%, 18–72%) but not comorbidities (−3.04, −5.83 to −0.23); RD 35%, 14–59%). US-born Hispanics had lower eGFRcys compared with foreign-born Hispanics [1.83 mL/min/1.73 m 2 lower (0.97–1.31) for Generation 1; 1.37 mL/min/1.73 m 2 lower (0.75–1.57) for Generation ≥2]. In contrast, Chinese who spoke any English had higher eGFRcys (2.53, 95% CI: −1. 70–6.78), but similar ACR (RD −5%, 95% CI: −26–23%) compared with those speaking Chinese only, but associations were not statistically significant. Conclusion. Hi gher acculturation was associated with worse kidney function in Hispanics, mediated perhaps by behavioral factors but not comorbidities. Associations may be in the opposite direction among Chinese. Future studies are needed to elucidate these mechanisms.

Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors. Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors. Results: In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA. Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.

Modifications of the isonipecotic acid fragment of SNS-032 results in analogs which are more permeable and lower effluxed than SNS-032. The enantiomerically pure synthesis and the in vivo profile of analog 20 is described.

We report two women with glutaric acidemia type I in whom the diagnosis was unsuspected until a low carnitine level was found in their newborn children. Both mothers had low carnitine in plasma. In the first, organic acid analysis was only done after fibroblast studies revealed normal carnitine uptake. Having learned from the first family, organic acid analysis was done immediately in the mother of family 2. In both, the plasma acylcarnitine profile was normal but both excreted the metabolites typical of their disorder. One of the women was a compound heterozygote for distinct mutations in the glutaric acid dehydrogenase gene, whereas the second was either homozygous or hemizygous for a mutation in Exon 6 of the gene.

The Supplemental Security Income (SSI) and Temporary Assistance for Needy Families (TANF) programs serve overlapping target groups. SSI serves adults and children with disabilities from low-income families, while TANF serves low-income families with children. Consequently, policy changes in one program can affect the other. The target group for Aid to Families with Dependent Children (AFDC), TANF's predecessor, also overlapped with SSI's target group. Many have anticipated that the replacement of AFDC with TANF in August 1996 would eventually increase SSI participation as TANF recipients with disabilities sought SSI benefits to avoid TANF work requirements and time limits.

While people with disabilities often say that a loss of public health insurance is a deterrent to work, it is rare to find situations in which they might actually exhibit such a behavioral response to a change in access. Expansions in the income threshold for SSI work incentives program (Sections 1619(a) and (b)) provide an opportunity to observe such a response. Section 1619(b) allows SSI recipients to maintain Medicaid eligibility even if their income is above the level that makes them ineligible for SSI payments. If earnings increase beyond the 1619(b) threshold, however, the person loses their SSI and Medicaid eligibility. Section 1619(b) income thresholds vary significantly across states and over time. Stapleton and Tucker (2000) use the variation in Section 1619(b) income thresholds to examine the employment, earnings and program participation patterns of SSI recipients who have incomes near the threshold level for their state. They find strong evidence that many SSI recipients restrain their earnings to stay below the 1619(b) threshold. It is important to note, however, that the findings only provide evidence on the behavior of a small portion of the population with disabilities (i.e., SSI recipients who work). Nonetheless, this evidence seems to provide strong empirical support for the hypothesis that lack of access to health insurance is an important work disincentive for people with disabilities. They also find that 1619(b) participation varies significantly from month to month. Consequently, cross-sectional estimates on the share of SSI recipients participating in 1619(b) significantly understate the share of SSI recipients who ever participate. These findings are consistent with previous findings that cross-sectional estimates of employment tend to understate multi-period employment patterns for the broader population with disabilities.