NCoR repression of LXRs restricts macrophage biosynthesis of insulin-sensitizing omega 3 fatty acids.

Macrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and ω3 fatty acids. Remarkably, the increased ω3 fatty acid levels primarily inhibit NF-κB-dependent inflammatory responses by uncoupling NF-κB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies.

Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses.

Inflammation and macrophage foam cells are characteristic features of atherosclerotic lesions, but the mechanisms linking cholesterol accumulation to inflammation and LXR-dependent response pathways are poorly understood. To investigate this relationship, we utilized lipidomic and transcriptomic methods to evaluate the effect of diet and LDL receptor genotype on macrophage foam cell formation within the peritoneal cavities of mice. Foam cell formation was associated with significant changes in hundreds of lipid species and unexpected suppression, rather than activation, of inflammatory gene expression. We provide evidence that regulated accumulation of desmosterol underlies many of the homeostatic responses, including activation of LXR target genes, inhibition of SREBP target genes, selective reprogramming of fatty acid metabolism, and suppression of inflammatory-response genes, observed in macrophage foam cells. These observations suggest that macrophage activation in atherosclerotic lesions results from extrinsic, proinflammatory signals generated within the artery wall that suppress homeostatic and anti-inflammatory functions of desmosterol.

A pragmatic randomized trial of mailed fecal immunochemical testing to increase colorectal cancer screening among low-income and minoritized populations.

BACKGROUND: Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. METHODS: A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant. RESULTS: Among 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals). CONCLUSIONS: A regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

OPTN/SRTR 2022 Annual Data Report: Vascularized Composite Allograft.

This year's chapter on vascularized composite allograft (VCA) encompasses reviews of data collected from 2014 (when VCA was included in the Final Rule) through 2022. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and has remained consistent from the prior report. The data continue to be limited by sample size, with trends persistently demonstrating a predominance of White males in the young/middle-aged population as both donors and recipients for nonuterus VCA transplants, and White women younger than 35 years as the predominant recipients of uterus transplant. Similar to the 2021 report, there were only eight failed uterus grafts and one failed nonuterus VCA graft reported from 2014 through 2022. Standardization of definitions of success and failure as well as outcome measures for the different VCA types remain unmet needs in VCA transplantation.

Mental health and social connection among older lesbian and bisexual women.

OBJECTIVE: To assess differences in psychosocial and mental health outcomes between older lesbian and bisexual women compared to heterosexual women. DESIGN: Cross sectional study. SETTING: The study was carried out in the California Teachers Study, a prospective cohort study. PARTICIPANTS: Self-identified heterosexual (n = 35,846), lesbian (n = 710), and bisexual (n = 253) women 50 years of age and older were enrolled. MEASUREMENTS: Validated questionnaires were used to measure social connection, overall happiness, and depression. Logistic regression modeling was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing lesbian and bisexual women separately to heterosexual women in relation to psychosocial and mental health outcomes. RESULTS: After controlling for age and marital status, older bisexual women were significantly more likely to report lack of companionship (OR = 2.00; 95% CI, 1.30-3.12) and feeling left out (OR = 2.33; 95% CI, 1.36-3.97) compared to older heterosexual women. The odds of reporting feeling isolated from others was significantly higher in lesbian (OR = 1.56; 95% CI, 1.06-2.30) and bisexual women (OR = 2.30; 95% CI, 1.37-3.87) than in heterosexual women. The OR (95% CI) for reporting not being very happy overall was 1.96 (CI, 1.09-3.52) in bisexual women and 1.40 (0.92-2.14) in lesbian women compared to heterosexual women. The likelihood of reporting diagnosed depression was significantly higher in lesbian women (OR = 1.65; 95% CI, 1.38-1.97) and bisexual women (OR = 2.21; 95% CI, 1.67-2.93) compared to heterosexual women. CONCLUSION: Inclusion of lesbian and bisexual women in aging research is essential to understand their unique mental and other health needs, including those specific to bisexual women.

Multiple courses of intralesional collagenase injections for Peyronie disease: a retrospective analysis.

BACKGROUND: In the original clinical trials evaluating intralesional collagenase Clostridium histolyticum for Peyronie disease (PD), treatment protocols were limited to 8 injections. AIM: We sought to describe our single-center experience with the use of multiple rounds (>8 injections) of intralesional collagenase in patients with PD. METHODS: We conducted a retrospective analysis of all patients with PD receiving intralesional collagenase injections at our institution from October 2015 through December 2020. Some patients who completed 1 round of treatment elected to undergo additional rounds (16 or 24 injections) based on persistent curvature and presence of penile plaque. Clinical improvement was defined as a 20% reduction in penile curvature from the start of a given round of treatment to the end of that round of treatment. We measured erect penile curvature before and after each round and collected demographics, medical and surgical history, curvature outcomes, and treatment-related adverse events. OUTCOME: The primary outcome was the reduction in penile curvature after multiple rounds of treatment with intralesional collagenase injections in patients with PD. RESULTS: A total of 330 patients underwent intralesional collagenase injections for PD, of whom 229 completed at least 8 injections and underwent pre- and posttreatment erect penile goniometry. An overall 42.8% (98/229), 38.6% (22/57), and 12.5% (1/8) of patients achieved clinical improvement after 1 round of therapy (8 injections), 2 rounds (16 injections), and 3 rounds (24 injections), respectively. Mean degree and mean percentage improvement of penile curvature for the start and end of each round of treatment were 8.3° and 16.4% (after 1 round), 7.2° and 16.8% (after 2 rounds), and 3.3° and 8.1% (after 3 rounds). Bruising was the most common complication, with an incidence of at least 50% in each round. CLINICAL IMPLICATIONS: Knowledge of patient responses to multiple rounds of intralesional collagenase injections may help guide physicians in management and counseling of patients regarding PD treatment options. STRENGTHS AND LIMITATIONS: This is the first study to evaluate multiple rounds (>8 injections) of intralesional collagenase for PD. Limitations include retrospective analysis and smaller sample size among patients undergoing 3 rounds (24 injections). CONCLUSION: For patients who did not achieve clinical improvement after 1 round of treatment, an additional round may be beneficial. However, no real improvement was observed for patients undergoing a third round.

Toxicity Impacts on Human Adipose Mesenchymal Stem/Stromal Cells Acutely Exposed to Aroclor and Non-Aroclor Mixtures of Polychlorinated Biphenyl.

Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We investigated how exposure to Aroclor 1016 and Aroclor 1254, as well as a newly characterized non-Aroclor mixture that resembles the PCB profile found in cabinets, Cabinet Mixture, affects adipose MSC growth, viability, and function in vitro. We found that exposure to all three mixtures resulted in two distinct types of toxicity. At PCB concentrations >20 µM, the majority of MSCs die, while at 1-10 µM, MSCs remained viable but display numerous alterations to their phenotype. At these sublethal concentrations, the MSC rate of expansion slowed and morphology changed. Further assessment revealed that PCB-exposed MSCs had impaired adipogenesis and a modest decrease in immunosuppressive capabilities. Thus, exposure to PCB mixtures found in schools negatively impacts the health and function of adipose MSCs. This work has implications for human health due to MSCs' role in supporting the growth and maintenance of adipose tissue.

Temperature and Fungicide Sensitivity in Three Prevalent Phytophthora Species Causing Phytophthora Root Rot in Rhododendron.

Temperature is an important environmental variable affecting Phytophthora spp. biology. It alters the ability of species to grow, sporulate, and infect their plant host, and it is also important in mediating pathogen responses to disease control measures. Average global temperatures are increasing as a consequence of climate change, yet there are few studies that compare the effects of temperature on Phytophthora spp. that are important to the nursery industry. To address this, we conducted a series of experiments to evaluate how temperature affects the biology and control of three soilborne Phytophthora spp. prevalent in the nursery industry. In the first set of experiments, we evaluated the mycelial growth and sporulation of several Phytophthora cinnamomi, P. plurivora, and P. pini isolates at temperatures ranging from 4 to 42°C for different amounts of time (0 to 120 h). In the second set of experiments, we evaluated the response of three isolates of each species to the fungicides mefenoxam and phosphorous acid at temperatures ranging from 6 to 40°C. Results showed that each species responds differently to temperature, with P. plurivora having the greatest optimal temperature (26.6°C), P. pini the least (24.4°C), and P. cinnamomi was intermediate between the two (25.3°C). P. plurivora and P. pini had the lowest minimum temperatures (approximately 2.4°C) compared with P. cinnamomi (6.5°C), while all three species had a similar maximum temperature (approximately 35°C). When tested against mefenoxam, all three species were generally more sensitive to mefenoxam at cool temperatures (6 to 14°C) than at warmer temperatures (22 to 30°C). P. cinnamomi was also more sensitive to phosphorous acid at cool temperatures (6 to 14°C). However, both P. plurivora and P. pini tended to be more sensitive to phosphorous acid at warmer temperatures (22 to 30°C). These findings help define the temperatures at which these pathogens will be the most damaging and help delineate the temperatures at which fungicides should be applied for maximum efficacy.

Minimizing Costs for Dorsal Wrist Ganglion Treatment: A Cost-Minimization Analysis.

PURPOSE: Dorsal wrist ganglions are treated commonly with aspiration, or open or arthroscopic excision in operating room (OR) or procedure room (PR) settings. As it remains unclear which treatment strategy is most cost-effective in yielding cyst resolution, our purpose was to perform a formal cost-minimization analysis from the societal perspective in this context. METHODS: A microsimulation decision analytic model evaluating 5 treatment strategies for dorsal wrist ganglions was developed, ending in either resolution or a single failed open revision surgical excision. Strategies included immediate open excision in the OR, immediate open excision in the PR, immediate arthroscopic excision in the OR, or 1 or 2 aspirations before each of the surgical options. Recurrence and complications rates were pooled from the literature for each treatment type. One-way sensitivity and threshold analyses were performed. RESULTS: The most cost-minimal strategy was 2 aspiration attempts before open surgical excision in the PR setting ($1,603 ± 1,595 per resolved case), followed by 2 aspirations before open excision in the OR ($1,969 ± 2,165 per resolved case). Immediate arthroscopic excision was the costliest strategy ($6,539 ± 264 per resolved case). Single aspiration preoperatively was more cost-minimal than any form of immediate surgery ($2,918 ± 306 and $4,188 ± 306 per resolved case performed in the PR and OR, respectively). CONCLUSIONS: From the societal perspective, performing 2 aspirations before surgical excision in the PR setting was the most cost-minimal treatment strategy, although in reference to surgeons who do not perform this procedure in the PR setting, open excision in the OR was nearly as cost-effective. As patient preferences may preclude routinely performing 2 aspirations, performing at least 1 aspiration before surgical excision improves the cost-effectiveness of dorsal wrist ganglions treatment. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic Decision Analysis II.

Improved survival in cervical cancer patients receiving care at National Cancer Institute-designated cancer centers.

BACKGROUND: Locally advanced cervical cancer (CC) remains lethal in the United States. We investigate the effect of receiving care at an National Cancer Institute-designated cancer center (NCICC) on survival. METHODS: Data for women diagnosed with CC from 2004 to 2016 who received radiation treatment were extracted from the California Cancer Registry (n = 4250). Cox proportional hazards regression models assessed whether (1) receiving care at NCICCs was associated with risk of CC-specific death, (2) this association remained after multivariable adjustment for age, race/ethnicity, and insurance status, and (3) this association was explained by receipt of guideline-concordant treatment. RESULTS: Median age was 50 years (interquartile range [IQR] 41-61 years), with median follow-up of 2.7 years (IQR 1.3-6.0 years). One-third of patients were seen at an NCICC, and 29% died of CC. The hazard of CC-specific death was reduced by 20% for those receiving care at NCICCs compared with patients receiving care elsewhere (HR = .80; 95% CI, 0.70-0.90). Adjustment for guideline-concordant treatment and other covariates minimally attenuated the association to 0.83 (95% CI, 0.74-0.95), suggesting that the survival advantage associated with care at NCICCs may not be due to receipt of guideline-concordant treatment. CONCLUSIONS: This study demonstrates survival benefit for patients receiving care at NCICCs compared with those receiving care elsewhere that is not explained by differences in guideline-concordant care. Structural, organizational, or provider characteristics and differences in patients receiving care at centers with and without NCI designation could explain observed associations. Further understanding of these factors will promote equality across oncology care facilities and survival equity for patients with CC.

Acute Lower Back Pain after Intralesional Injection of Collagenase Clostridium histolyticum for Peyronie's Disease.

PURPOSE: The safety label for collagenase Clostridium histolyticum was updated to include postinjection acute lower back pain as an adverse event observed with intralesional therapy for Peyronie's disease. Incidence and causality are unknown. We assessed frequencies and temporal associations for this adverse event in a large cohort. MATERIALS AND METHODS: Data on all men undergoing collagenase injections for Peyronie's disease at our institution from October 2015 through December 2020 were retrospectively assessed. The study included 330 patients, 300 completing at least 1 full course (8 injections). Measured outcomes included incidence and timing of back pain, and associations with demographics and comorbidities. RESULTS: Of 330 patients, 19 (5.8%) experienced at least 1 episode of postinjection acute lower back pain. Of 300 who completed at least 1 full course of 8 injections, 4 (1.3%) reported back pain within the 8-injection course. A subset underwent additional rounds (16 or 24 injections). Back pain increased to 8.7% (13/149) during a second round, 6.9% (3/43) during a third. No association was found with age, diabetes or back pain history. Most cases occurred shortly after injection; all were self-limited or resolved with a single dose of ketorolac. CONCLUSIONS: This single-center, retrospective analysis suggests that intralesional collagenase injections for Peyronie's disease may cause acute lower back pain in up to 6% of patients. Patients may benefit from counseling regarding this risk. Incidence rises with additional rounds of treatment. Prospective safety data regarding >8 injections do not exist. No patient had long-term sequelae of back pain.

Engagement With HIV and COVID-19 Prevention: Nationwide Cross-sectional Analysis of Users on a Geosocial Networking App.

BACKGROUND: Geosocial networking (GSN) apps play a pivotal role in catalyzing sexual partnering, especially among men who have sex with men. OBJECTIVE: To quantify the prevalence and disparities in disclosure of pre-exposure prophylaxis (PrEP) use and COVID-19 vaccination among GSN app users, mostly men who have sex with men, in the United States. METHODS: Web-based Grindr profiles from the top 50 metropolitan areas as well as the 50 most rural counties in the United States by population were randomly sampled. Grindr provides an option to disclose current PrEP use (HIV positive, HIV negative, or HIV negative with PrEP use). The free text in all profiles was analyzed, and any mention of COVID-19 vaccination was recorded. Multivariable logistic regression to assess independent associations with PrEP disclosure and COVID-19 vaccination was performed. Imputation analyses were used to test the robustness of the results. RESULTS: We evaluated 1889 urban and 384 rural profiles. Mean age among urban profiles was 32.9 (SD 9.6) years; mean age among rural profiles was 33.5 (SD 12.1) years (P=.41). Among the urban profiles, 16% reported being vaccinated against COVID-19 and 23% reported PrEP use compared to 10% and 8% in rural profiles, respectively (P=.002 and P<.001, respectively). Reporting COVID-19 vaccination (adjusted odds ratio [aOR] 1.7, 95% CI 1.2-2.4), living in an urban center (aOR 3.2, 95% CI 1.8-5.7), and showing a face picture as part of the Grindr profile (aOR 4.0, 95% CI 2.3-7.0) were positively associated with PrEP disclosure. Self-identified Black and Latino users were less likely to report PrEP use (aOR 0.6, 95% CI 0.4-0.9 and aOR 0.5, 95% CI 0.4-0.9, respectively). Reporting PrEP use (aOR 1.7, 95% CI 1.2-2.4), living in an urban center (aOR 2.5, 95% CI 1.4-4.5), having a "discreet" status (aOR 1.6, 95% CI 1.0-2.5), and showing a face picture (aOR 2.7, 95% CI 1.5-4.8) were positively associated with reporting COVID-19 vaccination on their profile. Users in the southern United States were less likely to report COVID-19 vaccination status than those in the northeast United States (aOR 0.6, 95% CI 0.3-0.9). CONCLUSIONS: Variations in PrEP disclosure are associated with race, whereas COVID-19 vaccination disclosure is associated with geographic area. However, rural GSN users were less likely to report both PrEP use and COVID-19 vaccination. The data demonstrate a need to expand health preventative services in the rural United States for sexual minorities. GSN platforms may be ideal for deployment of preventative interventions to improve access for this difficult-to-reach population.

Is Disease Induced by Flooding Representative of Nursery Conditions in Rhododendrons Infected with Phytophthora cinnamomi or P. plurivora?

The degree of flooding commonly used to induce disease in Phytophthora root rot studies rarely occurs in container nurseries. Instead, over-irrigation and poor drainage result in plants periodically sitting in shallow pools of water. Rhododendron plants were grown in a noninfested substrate or substrate infested with Phytophthora cinnamomi or P. plurivora to determine whether root rot induced by flooding represents disease that occurs under simulated nursery conditions when plants are in a shallow pool of water (saucers), or are allowed to freely drain and maintained at ∼75% container capacity (CC). Generally P. cinnamomi caused more disease than P. plurivora, and all water treatments were conducive to root rot. In experiment 1, the amount of disease caused by flooding was similar to that in the saucer treatment (75% CC not tested) while in experiment 2, flooding often caused more rapid and severe disease than the saucer or 75% CC treatment. Pathogens differed in their response to water treatments. P. cinnamomi caused more disease in treatments with >90% substrate moisture for either a short (flood) or long duration (saucer), while P. plurivora was less capable of causing disease when soil moisture was maintained >90% than when substrate moisture was maintained at a more moderate level (flood, 75% CC). Our results indicate that it is not necessary to flood plants to induce disease under experimental conditions and that disease induced by flooding can represent disease in container nurseries when containers are in pools of water or maintained at ∼75% CC. In addition, our results suggest that P. cinnamomi is a more aggressive pathogen than P. plurivora in nursery conditions where drainage is poor; however, both species are capable of causing a similar amount of disease under more typical irrigation management.

Cost Assessment of Plating Versus Tension Band Wiring Constructs for Treating Mayo Type 2A Olecranon Fractures.

PURPOSE: Tension band wiring (TBW) or plating may be used for fixation with similar clinical outcomes for adults with displaced Mayo 2A olecranon fractures. The primary hypothesis is that total direct costs (TDCs) for surgery are lower for TBW than plating. Our secondary hypothesis is that combined surgical TDCs are lower for TBW even with a 100% rate of subsequent tension band hardware removal and a 0% rate of plate removal. METHODS: Patients who underwent TBW or plating of an isolated unilateral Mayo 2A olecranon fracture between July 2011 and January 2020 at a single academic medical center were identified. Then, TDC for each surgery on plate fixation, TBW, and hardware removal was obtained and converted to 2020 US dollars using information technology cost tools provided by our institution. Finally, relative TDCs were compared between plate fixation and TBW groups using univariate and multivariable generalized estimating equations with log-link. RESULTS: Of the 97 included patients, the mean age was 50 ± 21 years, and 48% were female. Tension band wiring and plate fixation were performed on 18% (17/97) and 82% (80/97) of male and female patients, respectively. Demographics were similar between groups, although the finding that plate fixation cost 2.6 times that of TBW within the index surgery was significant in the multivariable model, independent of potential confounders (coefficient 2.55, 95% confidence interval: 2.09-3.10). Additionally, mean TDC remained significantly greater for plate fixation even under the hypothetical situation where 100% TBW were removed, and the plate removal rate was 0% (cost difference 181%). CONCLUSIONS: Using TBW relative to plate fixation may improve the cost of care for operative Mayo 2A olecranon fractures. Furthermore, this finding was robust to the rate of hardware removal. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic and Decision Analyses III.

Online Readability Analysis: Mohs Micrographic Surgery Postsurgical Wound Care.

OBJECTIVE: Although various treatment modalities exist for skin cancer care, Mohs micrographic surgery (MMS) is one of the most effective and cosmetically sensitive surgical techniques. The readability of online informational materials specifically related to MMS postsurgical wound care is extremely relevant for patients given the high rates of skin cancer in the US and the number of patients utilizing the internet for information. METHODS: Investigators conducted Google searches to evaluate the current state of readability on MMS postsurgical wound care using the specific keywords "healing after Mohs surgery" and "wound care Mohs surgery." The readabilities of individual websites were analyzed using the WebFX online software. Health-specific click-through rate was used to select the number of samples assessed. RESULTS: Based on the 33 unique websites evaluated, the aggregate readability of online MMS postsurgical wound care materials was 11.3, corresponding to an 11th-grade reading level by US standards. CONCLUSIONS: Although this level of readability is an improvement in online MMS postsurgical wound care information relative to prior literature, there is still considerable work to be done by the dermatologic community in improving the readability of online patient materials regarding MMS.

Progesterone-induced blocking factor improves blood pressure, inflammation, and pup weight in response to reduced uterine perfusion pressure (RUPP).

Preeclampsia (PE) is characterized by new-onset hypertension in association with elevated natural killer (NK) cells and inflammatory cytokines, which are likely culprits for decreased fetal weight during PE pregnancies. As progesterone increases during normal pregnancy, it stimulates progesterone-induced blocking factor (PIBF). PIBF has been shown to decrease inflammation and cytolytic NK cells, both of which are increased during PE. We hypothesized that PIBF reduces inflammation as a mechanism to improve hypertension in the preclinical reduced uterine perfusion pressure (RUPP) rat model of PE. PIBF (2.0 µg/mL) was administered intraperitoneally on gestational day 15 to either RUPP or normal pregnant (NP) rats. On day 18, carotid catheters were inserted. Mean arterial blood pressure (MAP) and samples were collected on day 19. MAP in NP rats (n = 11) was 100 ± 2 mmHg and 105 ± 3 mmHg in NP + PIBF rats (n = 8) and 122 ± 1 mmHg in RUPP rats (n = 10), which improved to 110 ± 2 mmHg in RUPP + PIBF rats (n = 11), P < 0.05. Pup weight was 2.4 ± 0.1 g in NP, 2.5 ± 0.1 g in NP + PIBF, 1.9 ± 0.1 g in RUPP, and improved to 2.1 ± 0.1 g in RUPP + PIBF rats. Circulating and placental cytolytic NK cells, IL-17, and IL-6 were significantly reduced while IL-4 and T helper (TH) 2 cells were significantly increased in RUPP rats after PIBF administration. Importantly, vasoactive pathways preproendothelin-1, nitric oxide, and soluble fms-Like tyrosine Kinase-1 (sFlt-1) were normalized in RUPP + PIBF rats compared with RUPP rats, P < 0.05. Our findings suggest that PIBF normalized IL-4/TH2 cells, which was associated with improved inflammation, fetal growth restriction, and blood pressure in the RUPP rat model of PE.

Between-population differences in constitutive and infection-induced gene expression in threespine stickleback.

Vertebrate immunity is a complex system consisting of a mix of constitutive and inducible defences. Furthermore, host immunity is subject to selective pressure from a range of parasites and pathogens which can produce variation in these defences across populations. As populations evolve immune responses to parasites, they may adapt via a combination of (1) constitutive differences, (2) shared inducible responses, or (3) divergent inducible responses. Here, we leverage a powerful natural host-parasite model system (Gasterosteus aculeatus and Schistochephalus solidus) to tease apart the relative contributions of these three types of adaptations to among-population divergence in response to parasites. Gene expression analyses revealed limited evidence of significant divergence in constitutive expression of immune defence, and strong signatures of conserved inducible responses to the parasite. Furthermore, our results highlight a handful of immune-related genes which show divergent inducible responses which may contribute disproportionately to functional differences in infection success or failure. In addition to investigating variation in evolutionary adaptation to parasite selection, we also leverage this unique data set to improve understanding of cellular mechanisms underlying a putative resistance phenotype (fibrosis). Combined, our results provide a case study in evolutionary immunology showing that a very small number of genes may contribute to genotype differences in infection response.

Evaluating the benefits of a rapport-based approach to investigative interviews: A training study with law enforcement investigators.

Objective: The purpose of this study was to test the effectiveness of a rapport-based approach to interviewing that includes productive questioning skills, conversational rapport, and relational rapport-building tactics. Hypotheses: We predicted that training police investigators in a rapport-based approach would significantly increase the use of rapport-based tactics and that such tactics would directly influence the interviewee's perceptions of rapport and indirectly lead to increased cooperation and disclosure of information. Method: We trained federal, state, and local law enforcement investigators (N = 67) in the use of evidence-based interviewing techniques. Both before and after this training, investigators interviewed semi cooperative subjects (N = 125). Interviews were coded for the use of various interview tactics, as well as subjects' disclosure. Participants also completed a questionnaire regarding their perceptions of the interviewer and their decision to cooperate with the interviewer. Results: Evaluations of the training were positive, with high ratings of learning, preparedness to use tactics, and likelihood of use following the training. In posttraining interviews, investigators significantly increased their use of evidence-based tactics, including productive questioning, conversational rapport, and relational rapport-building tactics. Structural equation modeling demonstrated that investigators' use of the evidence-based interview tactics was directly associated with increased perceptions of rapport and trust and indirectly associated with increased cooperation and information disclosure. Conclusions: We demonstrated that rapport-based interview tactics could be successfully trained and that using such tactics can facilitate perceptions of rapport and trust, reduce individuals' resistance to cooperate, and increase information yield. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Epidemiology, Risk Factors, and Nonsurgical Treatment of Injuries Related to Endurance Running.

ABSTRACT: Running is a popular form of exercise that is easily accessible to various populations; endurance running, defined as distances beyond 5 km, continues to grow within the sport. Endurance running-related injuries are common in the lower extremities and are primarily overuse related. A multitude of risk factors for injury exist, including extrinsic factors, such as running distance and frequency, and intrinsic factors, such as biomechanics and nutrition status. Training and rehabilitation techniques vary with a general focus on strengthening and gradual increase in activity, but evidence is mixed, and it is difficult to generalize programs across different running populations. Management of specific running groups, including youth runners, is an area in which additional research is needed. New treatments, such as orthobiologics and wearable technology, have promising potential to optimize performance and recovery and minimize injury. However, they need to be further evaluated with high-quality studies.

Age-related differences in breast cancer mortality according to race/ethnicity, insurance, and socioeconomic status.

BACKGROUND: We assessed breast cancer mortality in older versus younger women according to race/ethnicity, neighborhood socioeconomic status (nSES), and health insurance status. METHODS: The study included female breast cancer cases 18 years of age and older, diagnosed between 2005 and 2015 in the California Cancer Registry. Multivariable Cox proportional hazards modeling was used to generate hazard ratios (HR) of breast cancer specific deaths and 95% confidence intervals (CI) for older (60+ years) versus younger (< 60 years) patients separately by race/ethnicity, nSES, and health insurance status. RESULTS: Risk of dying from breast cancer was higher in older than younger patients after multivariable adjustment, which varied in magnitude by race/ethnicity (P-interaction< 0.0001). Comparing older to younger patients, higher mortality differences were shown for non-Hispanic White (HR = 1.43; 95% CI, 1.36-1.51) and Hispanic women (HR = 1.37; 95% CI, 1.26-1.50) and lower differences for non-Hispanic Blacks (HR = 1.17; 95% CI, 1.04-1.31) and Asians/Pacific Islanders (HR = 1.15; 95% CI, 1.02-1.31). HRs comparing older to younger patients varied by insurance status (P-interaction< 0.0001), with largest mortality differences observed for privately insured women (HR = 1.51; 95% CI, 1.43-1.59) and lowest in Medicaid/military/other public insurance (HR = 1.18; 95% CI, 1.10-1.26). No age differences were shown for uninsured women. HRs comparing older to younger patients were similar across nSES strata. CONCLUSION: Our results provide evidence for the continued disparity in Black-White breast cancer mortality, which is magnified in younger women. Moreover, insurance status continues to play a role in breast cancer mortality, with uninsured women having the highest risk for breast cancer death, regardless of age.