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Background: No data exists on the breast and cervical cancer screening practices among Cambodian, Laotian, Thai, and Tongan women. In this article, we describe the efforts required to conduct a baseline survey among these non-English-speaking women using the participatory action research (PAR) approach. Methods: We tailored small population sampling techniques to each of the populations in partnership with Community Health Outreach workers. Results: A total of 1825 surveys were successfully conducted in 8 communities. Conclusion: PAR and the culturally based techniques used to conduct the survey proved successful in maintaining scientific rigor, developing true community-researcher partnership, and achieving over 99% participation. [ABSTRACT FROM AUTHOR]

Purpose: We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts., Design: Secondary analysis of 4 prospective population-based studies., Participants: We included four European-ancestry cohorts: the United States-based Nurses' Health Study, Nurses' Health Study 2, and the Health Professionals Follow-up Study and the Rotterdam Study (RS) in The Netherlands. The United States cohorts included female nurses and male health professionals ≤ 55 years of age. The RS included residents ≤ 45 years of age living in Rotterdam, The Netherlands., Methods: Polygenic risk score weights were estimated by applying the lassosum method on imputed genotype and phenotype data from the UK Biobank. This resulted in 144 020 variants, single nucleotide polymorphism and insertions or deletions, with nonzero βs that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits., Main Outcome Measures: The relative risk for POAG and Harrell's C statistic., Results: Among 1046 patients and 38 809‬ control participants, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08-5.18) times higher in the United States cohorts and 4.89 (2.93-8.17) times higher in the RS, compared with participants with median genetic risk (third quintile). Combining age, sex, intraocular pressure of more than 25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (95% CI, 0.73-0.75). Adding the PRS to this model improved the concordance to 0.82 (95% CI, 0.80-0.84). In a meta-analysis of all cohorts, patients in the highest tertile showed a larger cup-to-disc ratio at diagnosis, by 0.10 (95% CI, 0.06-0.14), and a 2.07-fold increased risk of requiring glaucoma surgery (95% CI, 1.19-3.60)., Conclusions: Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Polygenic risk scores (PRSs) likely predict risk and prognosis of glaucoma. We compared the PRS performance for primary open-angle glaucoma (POAG), defined using International Classification of Diseases (ICD) codes vs manual medical record review., Design: Retrospective cohort study., Methods: We identified POAG cases in the Mount Sinai BioMe and Mass General Brigham (MGB) biobanks using ICD codes. We confirmed POAG based on optical coherence tomograms and visual fields. In a separate 5% sample, the absence of POAG was confirmed with intraocular pressure and cup-disc ratio criteria. We used genotype data and either self-reported glaucoma diagnoses or ICD-10 codes for glaucoma diagnoses from the UK Biobank and the lassosum method to compute a genome-wide POAG PRS. We compared the area under the curve (AUC) for POAG prediction based on ICD codes vs medical records., Results: We reviewed 804 of 996 BioMe and 367 of 1006 MGB ICD-identified cases. In BioMe and MGB, respectively, positive predictive value was 53% and 55%; negative predictive value was 96% and 97%; sensitivity was 97% and 97%; and specificity was 44% and 53%. Adjusted PRS AUCs for POAG using ICD codes vs manual record review in BioMe were not statistically different (P ≥.21) by ancestry: 0.77 vs 0.75 for African, 0.80 vs 0.80 for Hispanic, and 0.81 vs 0.81 for European. Results were similar in MGB (P ≥.18): 0.72 vs 0.80 for African, 0.83 vs 0.86 for Hispanic, and 0.74 vs 0.73 for European., Conclusions: A POAG PRS performed similarly using either manual review or ICD codes in 2 electronic health record-linked biobanks; manual assessment of glaucoma status might not be necessary for some PRS studies. However, caution should be exercised when using ICD codes for glaucoma diagnosis given their low specificity (44%-53%) for manually confirmed cases of glaucoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Chemical hair relaxers are widely utilized by black women, yet little research exists on the allergens present in these products., Objective: This study aims to investigate allergen prevalence in the most popular chemical hair relaxers., Methods: We analysed 41 products from five major retailers, identifying allergens through ingredient lists and comparing them to the 2020 American Contact Dermatitis Group Core allergen series., Results: The most common contact allergens in chemical relaxers include propylene glycol, cetyl steryl alcohol, fragrance, D/L-a-tocopherol, tea tree oil and cocamidopropyl betaine., Conclusion: Understanding allergen exposure in products used by individuals with textured hair is needed for managing contact dermatitis in diverse populations. This analysis underscores the presence of potential allergens in hair relaxers, emphasizing the importance of dermatologists' awareness and patient scrutiny of ingredient lists., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: The use of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has been rapidly expanding as an alternative treatment to redo surgical aortic valve replacement (SAVR) for failed bioprosthetic valves despite limited long-term data., Objective: To assess mortality and morbidity in patients undergoing intervention for failed bioprosthetic SAVR., Design, Setting, and Participants: This was a retrospective population-based cohort analysis conducted between January 1, 2015, and December 31, 2020, with a median (IQR) follow-up time of 2.3 (1.1-4.0) years. A total of 1771 patients with a history of bioprosthetic SAVR who underwent ViV-TAVR or redo SAVR in California, New York, and New Jersey were included. Data were obtained from the California Department of Health Care Access and Information, the New York Statewide Planning and Research Cooperative System, and the New Jersey Discharge Data Collection System. Exclusion criteria included undergoing TAVR or redo SAVR within 5 years from initial SAVR, as well as infective endocarditis, concomitant surgical procedures, and out-of-state residency. Propensity matching yielded 375 patient pairs. Data were analyzed from January to December 2023., Interventions: ViV-TAVR vs redo SAVR., Main Outcomes and Measurements: The primary outcome was all-cause mortality. Secondary outcomes were stroke, heart failure hospitalization, reoperation, major bleeding, acute kidney failure, new pacemaker insertion, and infective endocarditis., Results: From 2015 through 2020, the proportion of patients undergoing ViV-TAVR vs redo SAVR increased from 159 of 451 (35.3%) to 498 or 797 (62.5%). Of 1771 participants, 653 (36.9%) were female, and the mean (SD) age was 74.4 (11.3) years. Periprocedural mortality and stroke rates were similar between propensity-matched groups. The ViV-TAVR group had lower periprocedural rates of major bleeding (2.4% vs 5.1%; P = .05), acute kidney failure (1.3% vs 7.2%; P < .001), and new pacemaker implantations (3.5% vs 10.9%; P < .001). The 5-year all-cause mortality rate was 23.4% (95% CI, 15.7-34.1) in the ViV-TAVR group and 13.3% (95% CI, 9.2-18.9) in the redo SAVR group. In a landmark analysis, no difference in mortality was observed up to 2 years (hazard ratio, 1.03; 95% CI, 0.59-1.78), but after 2 years, ViV-TAVR was associated with higher mortality (hazard ratio, 2.97; 95% CI, 1.18-7.47) as well as with a higher incidence of heart failure hospitalization (hazard ratio, 3.81; 95% CI, 1.57-9.22). There were no differences in 5-year incidence of stroke, reoperation, major bleeding, or infective endocarditis., Conclusions and Relevance: Compared with redo SAVR, ViV-TAVR was associated with a lower incidence of periprocedural complications and a similar incidence of all-cause mortality through 2 years' follow-up. However, ViV-TAVR was associated with higher rates of late mortality and heart failure hospitalization. These findings may be influenced by residual confounding and require adjudication in a randomized clinical trial.

Making data accessible to communities is essential for developing community-driven solutions to address health inequities. In this analytic essay, we highlight the importance of democratizing data for Native Hawaiians and Pacific Islanders (NHPIs)-diverse populations that historically have had little access to their data-in the context of achieving equity in health and the social drivers of health. We provide a framework for evaluating community accessibility of data, which includes concepts of data availability, salience, cost, and report back. We apply the framework to evaluate community accessibility of NHPI data from 29 federal data sources. In addition, we provide results from a survey of NHPI-serving community organizations in California conducted from December 2021 to February 2022 to assess community data needs. Findings reveal federal gaps in data accessibility, as well as NHPI community organizational needs for increased data accessibility, data saliency, and technical capacity. Furthermore, organization leads expressed concerns about data privacy, security, and misuse. We provide recommendations for data custodians to improve accessibility of timely, accurate, and robust data to support NHPI communities. ( Am J Public Health . 2024;114(S1):S103-S111. https://doi.org/10.2105/AJPH.2023.307503).

Purpose: To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum., Methods: We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments., Results: Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop., Conclusion: After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects., Design: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia., Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407)., Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses., Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma., Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (P interaction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness., Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Cu(I) 4H-imidazolate complexes are rare examples of Cu(I) complexes with chelating anionic ligands and are potent photosensitizers with unique absorption and photoredox properties. In this contribution, five novel heteroleptic Cu(I) complexes with monodentate triphenylphosphine co-ligands are investigated. As a consequence of the anionic 4H-imidazolate ligand and in contrast to comparable complexes with neutral ligands, these complexes are more stable than their homoleptic bis(4H-imidazolato)Cu(I) congeners. Here, the ligand exchange reactivity was studied by 31 P-, 19 F-, and variable temperature NMR and the ground state structural and electronic properties by X-ray diffraction, absorption spectroscopy, and cyclic voltammetry. The excited-state dynamics were investigated by femto- and nanosecond transient absorption spectroscopy. The observed differences, with respect to chelating bisphosphine bearing congeners, are often due to the increased geometric flexibility of the triphenylphosphines. These observations render the investigated complexes interesting candidates for photo(redox)reactions not accessible with chelating bisphosphine ligands., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Purpose: The purpose of this study was to describe the genetic relationship between smoking and glaucoma., Methods: We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants., Results: We identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (-0.18 mm Hg per SD, 95% confidence interval [CI] = -0.30 to -0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (-0.09 mm Hg per SD, 95% CI = -0.17 to -0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13)., Conclusions: MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma., Translational Relevance: Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.

Background: To describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm., Methods: We used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity., Results: Of 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HR OS : 0.78, 95% CI: 0.68-0.89, HR LCSS : 0.70, 95% CI: 0.60-0.81) and 3DCRT (HR OS : 0.81, 95% CI: 0.72-0.93, HR LCSS : 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71)., Conclusion: For patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In this paper, the photophysical behavior of four panchromatically absorbing, homoleptic bis(4H-imidazolato)Cu I complexes, with a systematic variation in the electron-withdrawing properties of the imidazolate ligand, were studied by wavelength-dependent time-resolved femtosecond transient absorption spectroscopy. Excitation at 400, 480, and 630 nm populates metal-to-ligand charge transfer, intraligand charge transfer, and mixed-character singlet states. The pump wavelength-dependent transient absorption data were analyzed by a recently established 2D correlation approach. Data analysis revealed that all excitation conditions yield similar excited-state dynamics. Key to the excited-state relaxation is fast, sub-picosecond pseudo-Jahn-Teller distortion, which is accompanied by the relocalization of electron density onto a single ligand from the initially delocalized state at Franck-Condon geometry. Subsequent intersystem crossing to the triplet manifold is followed by a sub-100 ps decay to the ground state. The fast, nonradiative decay is rationalized by the low triplet-state energy as found by DFT calculations, which suggest perspective treatment at the strong coupling limit of the energy gap law., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Introduction: Thyroid cancer incidence has increased substantially in the past 4 decades, estimated at 3.5% annually. Incidence is highest in white patients, yet black patients have the worst survival. Racial/ethnic differences in presentation and outcomes are hypothesized to be a result of differences in access to care. Analyses delineating the relative contribution of access to racial/ethnic survival disparities are scarce. We aimed to explore the association of delay in access to care and early/increased detection with racial/ethnic disparities in thyroid cancer survival., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2007 to 2011 for patients with a first primary thyroid cancer diagnosis and up to 5 years of follow-up. Composite scores were generated from county-level variables to capture socioeconomic status and screening habits. Kaplan-Meier analysis and Cox proportional hazards models were utilized for survival analysis., Results: We identified 46,970 patients (67% white, 7% black, 15% Hispanic, 10% Asian or Pacific Islander, and 1% unknown/other). Compared to white patients, black, Hispanic, and Asian or Pacific Islander patients were more likely to present with distant disease (3% vs 5%, 5%, and 6%, respectively; P < .001). After adjusting for sex, age, stage, subtype, tumor size, surgery, radiation, socioeconomics, and screening habits, black patients were the only race/ethnicity found to have increased odds of 5-year mortality compared to white patients (24%, P < .001)., Conclusion: Thyroid cancer survival is worst for black patients regardless of socioeconomic status or screening habits. Racial/ethnic disparities in survival are not attributable to early detection alone.

Topic: This systematic review and meta-analysis summarizes the existing evidence for the association of alcohol use with intraocular pressure (IOP) and open-angle glaucoma (OAG)., Clinical Relevance: Understanding and quantifying these associations may aid clinical guidelines or treatment strategies and shed light on disease pathogenesis. The role of alcohol, a modifiable factor, in determining IOP and OAG risk also may be of interest from an individual or public health perspective., Methods: The study protocol was preregistered in the Open Science Framework Registries (https://osf.io/z7yeg). Eligible articles (as of May 14, 2021) from 3 databases (PubMed, Embase, Scopus) were independently screened and quality assessed by 2 reviewers. All case-control, cross-sectional, and cohort studies reporting a quantitative effect estimate and 95% confidence interval (CI) for the association between alcohol use and either IOP or OAG were included. The evidence for the associations with both IOP and OAG was qualitatively summarized. Effect estimates for the association with OAG were pooled using random effects meta-analysis. Studies not meeting formal inclusion criteria for systematic review, but with pertinent results, were also appraised and discussed. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework., Results: Thirty-four studies were included in the systematic review. Evidence from 10 studies reporting an association with IOP suggests that habitual alcohol use is associated with higher IOP and prevalence of ocular hypertension (IOP > 21 mmHg), although absolute effect sizes were small. Eleven of 26 studies, comprising 173 058 participants, that tested for an association with OAG met inclusion criteria for meta-analysis. Pooled effect estimates indicated a positive association between any use of alcohol and OAG (1.18; 95% confidence interval [CI], 1.02-1.36; P = 0.03; I 2  = 40.5%), with similar estimates for both prevalent and incident OAG. The overall GRADE certainty of evidence was very low., Conclusions: Although this meta-analysis suggests a harmful association between alcohol use and OAG, our results should be interpreted cautiously given the weakness and heterogeneity of the underlying evidence base, the small absolute effect size, and the borderline statistical significance. Nonetheless, these findings may be clinically relevant, and future research should focus on improving the quality of evidence., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The intense absorption of light to covering a large part of the visible spectrum is highly desirable for solar energy conversion schemes. To this end, we have developed novel anionic bis(4H-imidazolato)Cu(I) complexes (cuprates), which feature intense, panchromatic light absorption properties throughout the visible spectrum and into the NIR region with extinction coefficients up to 28,000 M -1  cm -1 . Steady-state absorption, (spectro)electrochemical and theoretical investigations reveal low energy (Vis to NIR) metal-to-ligand charge-transfer absorption bands, which are a consequence of destabilized copper-based donor states. These high-lying copper-based states are induced by the σ-donation of the chelating anionic ligands, which also feature low energy acceptor states. The optical properties are reflected in very low, copper-based oxidation potentials and three ligand-based reduction events. These electronic features reveal a new route to panchromatically absorbing Cu(I) complexes., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Cu(I) 4 H -imidazolato complexes are excellent photosensitizers with broad and intense light absorption properties, based on an earth-abundant metal, and hold great promise as photosensitizers in artificial photosynthesis and for accumulation of redox equivalents. In this study, the excited-state relaxation dynamics of three novel heteroleptic Cu(I) 4 H -imidazolato complexes with phenyl, tolyl, and mesityl side groups are systematically investigated by femtosecond and nanosecond time-resolved transient absorption spectroscopy and theoretical methods, complemented by steady-state absorption spectroscopy and (spectro)electrochemistry. After photoexcitation into the metal-to-ligand charge transfer (MLCT) and intraligand charge transfer absorption band, fast (0.6-1 ps) intersystem crossing occurs into the triplet MLCT manifold. The triplet-state population relaxes via the geometrical planarization of the N -aryl rings on the Cu(I) 4 H -imidazolato complexes. Depending on the initial Franck-Condon state, the remaining small singlet state population relaxes into two geometrically distinct minima geometries with similar energy, S 1/2,relax and S 3/4,relax . Subsequent ground-state recovery from S 1/2,relax and internal conversion from S 3/4,relax to S 1/2,relax take place on a 100 ps time scale. The internal conversion can be understood as hole transfer from a d yz -orbital to a d xz -orbital, which is accompanied with the structural reorganization of the coordination environment. Generally, the photophysical processes are determined by the steric hindrance of the side groups on the ligands. And the excited singlet-state pathways are dependent on the excitation wavelength.

Research demonstrates that instructing patients to have a full bladder for pelvic radiotherapy results in highly variable bladder volumes at daily treatment. We aimed to determine bladder volume variation in patients with intact cervical cancer treated with intensity-modulated radiotherapy (IMRT) on an empty bladder and estimate the difference in radiation dose to the small bowel compared to treating on a full bladder. We identified 29 patients treated with IMRT from 2010 to 2013 who underwent 2 planning computed tomography (CT) scans, 1 with a full bladder followed by 1 with an empty bladder. Interfractional variation in bladder volume was measured using 782 daily cone beam computed tomography (CBCT) scans. To estimate dose to small bowel, radiation plans were created on both empty and full bladder CT scans using an automated knowledge-based planning modeling program. Mean bladder volume with empty bladder instructions was 67 ± 26 cc compared to 91 ± 43 cc for no bladder instructions and 154 ± 54 cc for full bladder instructions (p < 0.001). There was a significant reduction in the absolute bladder volume variation in patients given empty bladder instructions compared to full bladder instructions (p < 0.05) The intraclass correlation coefficient showed low reliability of bladder filling across all groups (p = 0.6). The average bowel V45 for the empty bladder plans was 188 cc, compared to 139 cc for the full bladder plans (p < 0.05). More plans created on an empty bladder exceeded Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) guidelines but this was not significant (31% vs 14%, p = 0.12). Reliability of bladder volume at the time of radiation treatment is low, regardless of bladder filling instructions, although an empty bladder reduces absolute variation in bladder volume. Radiation planning on an empty bladder predicts a larger volume of small bowel receiving 45 Gy compared to a full bladder, although bowel dose on average is still within QUANTEC guidelines (V45 < 195 cc)., (Copyright © 2018 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Background: With over 66 million Americans who speak over 350 languages other than English at home, we sought to examine attitudes and behaviors of neurology clinicians and staff when communicating across language differences., Methods: We conducted an electronic-enabled cross-sectional survey of clinicians and patient services coordinators working at an academic neurology outpatient clinic. Questions focused on professional medical interpreter (PMI) services usage, satisfaction, and perceived barriers to utilization., Results: A total of 82/235 (35%) neurology clinicians and 24/52 (46%) coordinators met the study eligibility criteria. Most clinicians (96%) reported seeing at least 1 non-English-speaking patient and using PMI services (85%) in the last month. Most commonly self-reported interpretation modalities were face-to-face PMI services (39%) and patients' family members or friends (28%). Perceived barriers to using PMI included time constraints (60%) and lack of available face-to-face PMI (51%). Among patient services coordinators, 33% reported consistently asking patients their preferred language and 50% if they needed a PMI for appointments. Most respondents (77% clinicians and 71% coordinators) were satisfied with PMI services. Recommendations included having more available face-to-face PMI, greater coordinated efforts to preschedule PMI, and more education on the effective use of PMI., Conclusions: More than 70% of outpatient neurology clinicians and patient services coordinators were satisfied with PMI. However, their perceived barriers and reported practices suggest a need for updated policies and education to improve the use of PMI services.

A comprehensive understanding of how the molecular structure influences the electronic coupling is crucial in optimizing (supra) molecular assemblies for photoinduced electron transfer. Here, we report that the electronic coupling underlying electron transfer from a phenothiazine donor to a photoexcited Ru(tpy)2 acceptor is modulated by substitution of the second (remote) tpy-ligand.

Objective: To determine the accuracy and safety of pin placement for lateral vertebral stabilization to the reference dorsal stabilization., Study Design: A randomized noninferiority trial., Sample Population: Twenty Greyhound cadaveric lumbar spines (L1-L6)., Methods: One hundred and fifty-nine lumbar vertebral pins placed in 80 vertebrae were assessed; these pins were distributed approximately equally between the dorsal and lateral approaches, and between 2 surgeons. Pin angle accuracy, bone purchase distance, and distances from pin to the spinal canal and the aorta were measured for each pin., Results: The lateral approach was superior for pin angle accuracy and bone purchase. The mean angle of deviation was 15.3° with the dorsal approach and 7.0° with the lateral approach. The mean bone purchase was 16.7 mm with the dorsal approach and 22.2 mm with the lateral approach. Pins were placed at a mean of 2.3 mm from the spinal canal with the dorsal approach and 1.7 mm with the lateral approach. Pins were placed at a mean of 3.8 mm from the aorta with the dorsal approach and 8.0 mm with the lateral approach. The percentage of pins breaching the spinal canal was 14% with the dorsal approach and 19% with the lateral approach. Fourteen percent of pins placed via the dorsal approach breached the aorta, whereas no pins placed via the lateral approach breached the aorta., Conclusion: Relative to the dorsal approach, the lateral approach improves angle accuracy, bone purchase, and distance between pins, and the aorta and is noninferior with regards to the distance between pins and the spinal canal., (© 2017 The American College of Veterinary Surgeons.)

Identifying the sequence polymorphisms underlying complex trait variation is a key goal of genetics research, since knowing the precise causative molecular events allows insight into the pathways governing trait variation. Genetic analysis of complex traits in model systems regularly starts by constructing QTL maps, but generally fails to identify causative sequence polymorphisms. Previously we mapped a series of QTL contributing to resistance to nicotine in a Drosophila melanogaster multiparental mapping resource and here use a battery of functional tests to resolve QTL to the molecular level. One large-effect QTL resided over a cluster of UDP-glucuronosyltransferases, and quantitative complementation tests using deficiencies eliminating subsets of these detoxification genes revealed allelic variation impacting resistance. RNAseq showed that Ugt86Dd had significantly higher expression in genotypes that are more resistant to nicotine, and anterior midgut-specific RNA interference (RNAi) of this gene reduced resistance. We discovered a segregating 22-bp frameshift deletion in Ugt86Dd , and accounting for the InDel during mapping largely eliminates the QTL, implying the event explains the bulk of the effect of the mapped locus. CRISPR/Cas9 editing of a relatively resistant genotype to generate lesions in Ugt86Dd that recapitulate the naturally occurring putative loss-of-function allele, leads to a large reduction in resistance. Despite this major effect of the deletion, the allele appears to be very rare in wild-caught populations and likely explains only a small fraction of the natural variation for the trait. Nonetheless, this putatively causative coding InDel can be a launchpad for future mechanistic exploration of xenobiotic detoxification., (Copyright © 2017 Highfill.)

Background: Very little is known about the burden of asthma in Vietnamese American children. Prior data have suggested that the burden of childhood asthma is significant for this population, although they seem to underutilize Western healthcare for unclear reasons., Objectives: To gain insight into the perceptions of the burden, health needs, and traditional health beliefs regarding childhood asthma in the Vietnamese American community in Orange County, CA. Additionally, to foster and build sustainable relationships with the community and to ensure that our research process is mutually rewarding for all stakeholders., Methods: Using a community-based participatory research (CBPR) approach, we initiated the formation of the Vietnamese Children's Asthma Project (VCAP) and used focus groups of various community stakeholders as a platform to gather information, give basic asthma education, and build relationships., Results: A total of 66 people participated in the focus groups: 26 parents, 20 Vietnamese American physicians, 12 school nurses, and 8 school-community liaisons (SCLs). Overall, all participants believe that asthma is a significant problem and that language is a barrier to healthcare access for the Vietnamese community. We learned that academic achievement is a high priority for Vietnamese parents and associating better asthma control with improved academic performance may be a way to improve asthma education and adherence with therapy. We also found that although healthcare providers believe that parental traditional beliefs contribute to non-adherence to Western therapies, Vietnamese American parents report that they prefer to use Western medications to treat their children's asthma., Conclusions: Through the use of CBPR and the development of VCAP, we successfully conducted focus groups to assess the Vietnamese American perception of the burden of childhood asthma in their community and to gauge their receptivity to participate in further studies about childhood asthma and receptivity to subsequent interventions.

Mounting evidence indicates that community health workers (CHWs) contribute to improved behavioral and health outcomes and reductions in health disparities. We provide an overview (based on grantee reports and community action plans) that describe CHW contributions to 22 Racial and Ethnic Approaches to Community Health (REACH) programs funded by the Centers for Disease Control and Prevention from 2007 to 2012, offering additional evidence of their contributions to the effectiveness of community public health programs. We then highlight how CHWs helped deliver REACH U.S. community interventions to meet differing needs across communities to bridge the gap between health care services and community members, build community and individual capacity to plan and implement interventions addressing multiple chronic health conditions, and meet community needs in a culturally appropriate manner. The experience, skills, and success gained by CHWs participating in the REACH U.S. program have fostered important individual community-level changes geared to increase health equity. Finally, we underscore the importance of CHWs being embedded within these communities and the flexibility they offer to intervention strategies, both of which are characteristics critical to meeting needs of communities experiencing health disparities. CHWs served a vital role in facilitating and leading changes and will continue to do so., (© 2014 Society for Public Health Education.)

Background: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time., Methods: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden., Findings: In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania., Interpretation: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cancer patient navigation (PN) programs have been shown to increase access to and utilization of cancer care for poor and underserved individuals. Despite mounting evidence of its value, cancer patient navigation is not universally understood or provided. We describe five PN programs and the range of tasks their navigators provide across the cancer care continuum (education and outreach, screening, diagnosis and staging, treatment, survivorship, and end-of-life). Tasks are organized by their potential to make cancer services understandable, available, accessible, affordable, appropriate, and accountable. Although navigators perform similar tasks across the five programs, their specific approaches reflect differences in community culture, context, program setting, and funding. Task lists can inform the development of programs, job descriptions, training, and evaluation. They also may be useful in the move to certify navigators and establish mechanisms for reimbursement for navigation services.

Objectives: We identified key elements required for a training curriculum for Southeast Asian community-based health navigators (CBHNs), who help low-income, immigrant Cambodian, Laotian, Thai, and Vietnamese women negotiate cultural and systemic barriers to breast cancer screening and care in the United States., Methods: We gathered the perspectives of 3 groups: CBHNs, community members, and their providers. We conducted 16 focus groups with 110 women representing different stages of the cancer care continuum and in-depth interviews with 15 providers and 10 navigators to identify the essential roles, skills, and interpersonal qualities that characterize successful CBHNs., Results: The most important areas identified for training CBHNs were information (e.g., knowing pertinent medical information and how to navigate resources), logistics (transportation, interpretation), and affective interpersonal skills (understanding the language and cultural beliefs of patients, communicating with providers, establishing trust)., Conclusions: CBHNs serve a crucial role in building trust and making screening practices culturally meaningful, accessible, usable, and acceptable. Future research should focus on developing training curricula, policies, resources, and funding to better maximize the expertise and services that CBHNs provide and to expand our findings to other underserved communities.

Asian American Pacific Islander (AAPI) groups have low rates of breast and cervical cancer screening. This study examined knowledge, attitudes, and beliefs (KABs) regarding breast and cervical cancer on AAPI women. A cross-sectional survey of 1,808 AAPI women was included. Descriptive statistics and chi-square tests were provided and 55.3%, 68.6%, and 71.9% had received mammograms, clinical breast exam, and Pap smears, respectively. KABs on breast and cervical cancer varied between the four ethnic groups. Understanding the KABs toward cancer screening among AAPI women holds promise for identifying barriers to early detection and could aid in the creation of interventions.

Breast and cervical cancers are the second and fourth leading causes of cancer death among Asian and Pacific Islander women. Despite screening exams that can detect these cancers early and increase survival, racial and ethnic populations continue to be disproportionately affected. This study examined the sources of information and their impacts on cancer screening compliance among native Hawaiians in Orange County, California. A community-based participatory research approach was used to conceive, design, implement, and analyze data. A relatively small proportion of the study's native Hawaiian women were compliant with recommended breast and cervical cancer screenings, and their screening rates were below the national Healthy People 2010 standards. Knowledge of screening procedures, seeking advice from a doctor, and obtaining information from internet medical sites were associated with higher rates of compliance with cancer-screening procedures.

We examined whether the impact of medical interpretation services was associated with the receipt of a mammogram, clinical breast exam, and Pap smear. We conducted a large cross-sectional study involving four Asian American and Pacific Islander (AAPI) communities with high proportions of individuals with limited English proficiency (LEP). Participants were recruited from community clinics, churches and temples, supermarkets, and other community gathering sites in Northern and Southern California. Among those that responded, 98% completed the survey rendering a total of 1,708 AAPI women. In a series of multivariate logistic regression models, it was found that women who typically used a medical interpreter had a greater odds of having received a mammogram (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.21, 2.83), clinical breast exam (OR = 3.03; 95% CI = 1.82, 5.03), and a Pap smear (OR = 2.34; 95% CI = 1.38, 3.97) than those who did not usually use an interpreter. The study provides support for increasing language access in healthcare settings. In particular, medical interpreters may help increase the utilization of breast and cervical cancer screening among LEP AAPI women.

Objectives: We examined trends in smoking prevalence from 2002 through 2006 in 4 Asian communities served by the Racial and Ethnic Approaches to Community Health (REACH) intervention., Methods: Annual survey data from 2002 through 2006 were gathered in 4 REACH Asian communities. Trends in the age-standardized prevalence of current smoking for men in 2 Vietnamese communities, 1 Cambodian community, and 1 Asian American/Pacific Islander (API) community were examined and compared with nationwide US and state-specific data from the Behavioral Risk Factor Surveillance System., Results: Prevalence of current smoking decreased dramatically among men in REACH communities. The reduction rate was significantly greater than that observed in the general US or API male population, and it was greater than reduction rates observed in the states in which REACH communities were located. There was little change in the quit ratio of men at the state and national levels, but there was a significant increase in quit ratios in the REACH communities, indicating increases in the proportions of smokers who had quit smoking., Conclusions: Smoking prevalence decreased in Asian communities served by the REACH project, and these decreases were larger than nationwide decreases in smoking prevalence observed for the same period. However, disparities in smoking prevalence remain a concern among Cambodian men and non-English-speaking Vietnamese men; these subgroups continue to smoke at a higher rate than do men nationwide.

The Pacific Islander (PI) community suffers disproportionately from illnesses and diseases, including diabetes, heart disease and cancer. While there are tremendous health needs within the PI community, there are few health care providers from the community that exist to help address these particular needs. Many efforts have focused on health care workforce diversity to reduce and eliminate health disparities, but few have examined the issues faced in the health care work force pipeline. Understanding educational attainment among PI young adults is pivotal in speaking to a diverse health care workforce where health disparities among Pacific Islanders (PIs) may be addressed. This paper provides an in-depth, qualitative assessment of the various environmental, structural, socio-economic, and social challenges that prevent PIs from attaining higher education; it also discusses the various needs of PI young adults as they relate to psychosocial support, retention and recruitment, and health career knowledge and access. This paper represents a local, Southern California, assessment of PI young adults regarding educational access barriers. We examine how these barriers impact efforts to address health disparities and look at opportunities for health and health-related professionals to reduce and care for the high burden of illnesses and diseases in PI communities.

Genetic studies have identified a number of proteins required for the internalization of biosynthetic and endocytic cargo proteins transported to the multivesicular body (MVB). We have developed a cell-free reaction that recapitulates the internalization of a yeast biosynthetic membrane cargo protein, carboxypeptidase S (CPS), into the interior of an endosome. A recombinant form of CPS containing a biotinylation site from an Escherichia coli protein is accumulated in a vps27 yeast mutant blocked in the MVB internalization event. Endosomes isolated from the vps27 mutant are exposed to E. coli biotin ligase, which acts on only those CPS molecules with a cytosol-exposed N-terminal domain. Internalization of biotin-tagged CPS is measured by the detection of trypsin-inaccessible, membrane-protected species. Biotinylated CPS internalization requires ATP and functional forms of Vps27p and Vps4p and depends on the availability of an exposed lysine residue critical for CPS ubiquitylation.

We determined hepatitis B virus (HBV) testing and vaccination levels and factors associated with testing and vaccination among Vietnamese- and Cambodian-Americans. We also examined factors associated with healthcare professional (HCP)-patient discussions about HBV. We analyzed 2006 Racial and Ethnic Approaches to Community Health (REACH) 2010 Risk Factor Survey data from four US communities. We used logistic regression to identify variables associated with HBV vaccination, testing, and HCP-patient discussions about HBV. Of the 2,049 Vietnamese- and Cambodian-American respondents, 60% reported being tested for HBV, 35% reported being vaccinated against hepatitis B, and 36% indicated that they had discussed HBV with a HCP. Cambodian-Americans were less likely than Vietnamese-Americans to have been tested for HBV, while respondents with at least a high school diploma were more likely to have been tested for HBV. Respondents born in the US, younger individuals, and respondents with at least some college education were more likely to have been vaccinated against hepatitis B. HBV testing and vaccination remain suboptimal among members of these populations. Culturally sensitive efforts that target Vietnamese- and Cambodian-Americans for HBV testing and vaccination are needed to identify chronic carriers of HBV, prevent new infections, and provide appropriate medical management. HCPs that serve these populations should be encouraged to discuss HBV with their patients.

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared with other rat CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the nuclear factor-kappa B (NF-kappaB) signaling cascade including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and inhibitor of kappa B alpha (IkappaBalpha) in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS.

In recent years, there has been a growing number of programs employing health navigators to assist underserved individuals in overcoming barriers to obtaining regular and quality health care. This article describes the perspectives and experiences of community-based health navigators in the Cambodian and Laotian communities involved in a REACH 2010 project to reduce health disparities in breast and cervical cancer among Pacific Islander and Southeast Asian communities in California. These community health navigators, who have extensive training and knowledge about the cultural, historical, and structural needs and resources of their communities, are well equipped to build trusting relationships with community members traditionally ignored by the mainstream medical system. By comparing the different social support roles and intervention strategies employed by community health navigators in diverse communities, we can better understand how these valuable change agents of the health workforce are effective in improving health access and healthy behaviors for underserved communities.

Background: Addressing cancer health disparities constitutes a national priority in this country, with funding for Pacific Islander efforts initiated 7 years ago by the National Cancer Institute. In 2005, the Weaving an Islander Network for Cancer Awareness, Research and Training (WINCART) was launched in Southern California by a collaboration of community and university organizations to build upon past efforts to decrease cancer health disparities for Chamorros, Native Hawaiians, Marshallese, Samoans and Tongans., Methods: To assess community organizational capacity to participate in collaborative cancer control for Pacific Islanders, a strengths, weaknesses, opportunities, and threats (SWOT) analysis was undertaken. Two staff members per community organization (CBO) performed the SWOT analyses, with grids analyzed for commonalities and differences between all organizations., Results: Staff informants provided many examples of what they perceived as organizational strengths and weaknesses with regards to promoting cancer control for their respective Pacific Islander populations. CBO strengths included strong leadership and extensive community experience. Challenges included limited resources, lack of staff skills in some areas, and difficulty in recruiting volunteers. In addition, many external opportunities and threats to cancer control promotion were identified., Conclusion: Results from the SWOT analyses have been used to identify topics for community organizational trainings and supports within WINCART, with the goals of increasing their participation in the development and implementation of collaborative, community-university driven efforts to decrease cancer disparities for Pacific Islanders in Southern California.

Community-based participatory research (CPBR) represents a growing research approach for addressing health disparities disfavoring members of racial/ethnic minorities and other underserved populations in the U.S. While such endeavors are often guided by explicit principles regarding the relationships between communities and universities, few studies have reported on the development or strength of such relationships. This paper describes the methods and preliminary results of a cross-sectional analysis of the ties between community and university organizations in a CBPR network to address cancer disparities between Pacific Islanders in Southern California and the general population. These analyses afford a means of representing the collaborative relationships and may enhance tracking improvements in CBPR links for cancer education, research, and training. Such tracking will help concerned parties understand how academic and community groups collaborate and coordinate their efforts to reach shared and overlapping goals.

Cancer is a leading cause of death for Asians and Pacific Islanders in the United States, but education and research efforts addressing the needs ofPacific Islanders in the continental U.S. is sparse. The purpose of this paper is to describe the development of a community-based participatory research network dedicated to addressing cancer health disparities among Chamorros, Marshallese, Native Hawaiians, Samoans and Tongans in Southern California. Community-based organizations (CBO) comprise the focus of the network, and their efforts have included increasing cancer-related awareness in their communities, developing capacities regarding cancer control, and initiating collaborative research efforts with academic partners. First year processes and outcomes are described, and specific examples are given from two CBO partners.

Purified QnrA blocked ciprofloxacin inhibition of topoisomerase IV, just as QnrA was previously found to prevent quinolone inhibition of DNA gyrase. With a gel displacement assay, tagged QnrA was shown to bind to topoisomerase IV and its subunits in a reaction that did not depend on the presence of DNA, quinolone, or ATP.

Quinolone resistance normally arises by mutations in the chromosomal genes for type II topoisomerases and by changes in the expression of proteins that control the accumulation of quinolones inside bacteria. A novel mechanism of plasmid-mediated quinolone resistance was recently reported that involves DNA gyrase protection by a pentapeptide repeat family member called Qnr. This family includes two other members, McbG and MfpA, that are also involved in resistance to gyrase inhibitors. Purified Qnr-His(6) was shown to protect Escherichia coli DNA gyrase directly from inhibition by ciprofloxacin. Here we have provided a biochemical basis for the mechanism of quinolone resistance. We have shown that Qnr can bind to the gyrase holoenzyme and its respective subunits, GyrA and GyrB. The binding of Qnr to gyrase does not require the presence of the complex of enzyme, DNA, and quinolone, since binding occurred in the absence of relaxed DNA, ciprofloxacin, or ATP. We hypothesize that the formation of Qnr-gyrase complex occurs before the formation of the cleavage complex. Furthermore, there was a decrease in DNA binding by gyrase when the enzyme interacted with Qnr. Therefore, it is possible that the reaction intermediate recognized by Qnr is one early in the gyrase catalytic cycle, in which gyrase has just begun to interact with DNA. Quinolones bind later in the catalytic cycle and stabilize a ternary complex consisting of the drug, gyrase, and DNA. By lowering gyrase binding to DNA, Qnr may reduce the amount of holoenzyme-DNA targets for quinolone inhibition.

During the last 25 years, numerous studies have been conducted to promote breast cancer and cervical cancer screening. Most of these studies focused on individual-level factors predicting screening, but we are unaware of any that directly examined community and ecological influences. The goal of this project, Promoting Access to Health for Pacific Islander and Southeast Asian Women (PATH for Women), was to increase community capacity for breast and cervical cancer screening and follow up in Los Angeles and Orange counties. We focused on Southeast Asian and Pacific Islander women because, although they have the lowest rates for cancer, compared to all other ethnic groups, relatively few programs have specifically targeted Asian-American and Pacific Islander (AAPI) women to promote and sustain screening practices. The PATH for Women project involved a partnership between 5 community-based organizations and 2 universities, and included 7 Asian-American and Pacific Islander communities: Cambodians, Chamorros, Laotians, Thais, Tongans, Samoans, and Vietnamese. In this paper, we share our experiences in developing a Geographic Information System (GIS)-mapping evaluation component that was used to explore availability and accessibility to culturally responsive breast and cervical cancer screening services for Southeast Asian and Pacific Islander women in all 7 communities. We describe the methods used to develop the maps, and present the preliminary findings that demonstrate significant geographic and language barriers to accessing healthcare providers, services for breast and cervical cancer screening, and follow up, in each of the communities. Finally, we discuss implications for programs designed to promote breast and cervical screening and policy education.

The mechanism of tumor necrosis factor (TNF)-induced nonapoptotic cell death is largely unknown, although the mechanism of TNF-induced apoptosis has been studied extensively. In wild-type mouse embryonic fibroblast cells under a caspase-inhibited condition, TNF effectively induced cell death that morphologically resembled necrosis. In this study, we utilized gene knockout mouse embryonic fibroblasts cells and found that tumor necrosis factor receptor (TNFR) I mediates TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical components of the signaling cascade of this TNF-induced necrotic cell death. Inhibitors of NF-kappaB facilitated TNF-induced necrotic cell death, suggesting that NF-kappaB suppresses the necrotic cell death pathway. JNK, p38, and ERK activation seem not to be required for this type of cell death because mitogen-activated protein kinase inhibitors did not significantly affect TNF-induced necrotic cell death. In agreement with the previous reports that the reactive oxygen species (ROS) may play an important role in this type of cell death, the ROS scavenger butylated hydroxyanisole efficiently blocked TNF-induced necrotic cell death. Interestingly, during TNF-induced necrotic cell death, the cellular ROS level was significantly elevated in wild type, but not in RIP(-/-), TRAF2(-/-), and FADD(-/-) cells. These results suggest that RIP, TRAF2, and FADD are crucial in mediating ROS accumulation in TNF-induced necrotic cell death.

A sample of 752 resistant Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli strains from 70 sites in 25 U.S. states and the District of Columbia was examined for transmissibility of resistance to ceftazidime and the nature of the plasmid-mediated beta-lactamase involved. Fifty-nine percent of the K. pneumoniae, 24% of the K. oxytoca, and 44% of the E. coli isolates transferred resistance to ceftazidime. Plasmids encoding AmpC-type beta-lactamase were found in 8.5% of the K. pneumoniae samples, 6.9% of the K. oxytoca samples, and 4% of the E. coli samples, at 20 of the 70 sites and in 10 of the 25 states. ACT-1 beta-lactamase was found at eight sites, four of which were near New York City, where the ACT-1 enzyme was first discovered; ACT-1 beta-lactamase was also found in Massachusetts, Pennsylvania, and Virginia. FOX-5 beta-lactamase was also found at eight sites, mainly in southeastern states but also in New York. Two E. coli strains produced CMY-2, and one K. pneumoniae strain produced DHA-1 beta-lactamase. Pulsed-field gel electrophoresis and plasmid analysis suggested that AmpC-mediated resistance spread both by strain and plasmid dissemination. All AmpC beta-lactamase-containing isolates were resistant to cefoxitin, but so were 11% of strains containing transmissible SHV- and TEM-type extended-spectrum beta-lactamases. A beta-lactamase inhibitor test was helpful in distinguishing the two types of resistance but was not definitive since 24% of clinical isolates producing AmpC beta-lactamase had a positive response to clavulanic acid. Coexistence of AmpC and extended-spectrum beta-lactamases was the main reason for these discrepancies. Plasmid-mediated AmpC-type enzymes are thus responsible for an appreciable fraction of resistance in clinical isolates of Klebsiella spp. and E. coli, are disseminated around the United States, and are not so easily distinguished from other enzymes that mediate resistance to oxyimino-beta-lactams.

Although quinolone resistance usually results from chromosomal mutations, recent studies indicate that quinolone resistance can also be plasmid mediated. The gene responsible, qnr, is distinct from the known quinolone resistance genes and in previous studies seemed to be restricted to Klebsiella pneumoniae and Escherichia coli isolates from the University of Alabama in Birmingham, where this resistance was discovered. In Shanghai, the frequency of ciprofloxacin resistance in E. coli has exceeded 50% since 1993. Seventy-eight unique ciprofloxacin-resistant clinical isolates of E. coli from Shanghai hospitals were screened for the qnr gene by colony blotting and Southern hybridization of plasmid DNA. Conjugation experiments were done with azide-resistant E. coli J53 as a recipient with selection for plasmid-encoded antimicrobial resistance (chloramphenicol, gentamicin, or tetracycline) and azide counterselection. qnr genes were sequenced, and the structure of the plasmid DNA adjacent to qnr was analyzed by primer walking with a sequential series of outward-facing sequencing primers with plasmid DNA templates purified from transconjugants. Six (7.7%) of 78 strains gave a reproducible hybridization signal with a qnr gene probe on colony blots and yielded strong signals on plasmid DNA preparations. Quinolone resistance was transferred from all six probe-positive strains. Transconjugants had 16- to 250-fold increases in the MICs of ciprofloxacin relative to that of the recipient. All six strains contained qnr with a nucleotide sequence identical to that originally reported, except for a single nucleotide change (CTA-->CTG at position 537) encoding the same amino acid. qnr was located in complex In4 family class 1 integrons. Two completely sequenced integrons were designated In36 and In37. Transferable plasmid-mediated quinolone resistance associated with qnr is thus prevalent in quinolone-resistant clinical strains of E. coli from Shanghai and may contribute to the rapid increase in bacterial resistance to quinolones in China.

Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance. Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. We have cloned the plasmid-quinolone resistance gene, termed qnr, and found it in an integron-like environment upstream from qacE Delta 1 and sulI. The gene product Qnr was a 218-aa protein belonging to the pentapeptide repeat family and shared sequence homology with the immunity protein McbG, which is thought to protect DNA gyrase from the action of microcin B17. Qnr had pentapeptide repeat domains of 11 and 28 tandem copies, separated by a single glycine with a consensus sequence of A/C D/N L/F X X. Because the primary target of quinolones is DNA gyrase in Gram-negative strains, we tested the ability of Qnr to reverse the inhibition of gyrase activity by quinolones. Purified Qnr-His(6) protected Escherichia coli DNA gyrase from inhibition by ciprofloxacin. Gyrase protection was proportional to the concentration of Qnr-His(6) and inversely proportional to the concentration of ciprofloxacin. The protective activity of Qnr-His(6) was lost by boiling the protein and involved neither quinolone inactivation nor independent gyrase activity. Protection of topoisomerase IV, a secondary target of quinolone action in E. coli, was not evident. How Qnr protects DNA gyrase and the prevalence of this resistance mechanism in clinical isolates remains to be determined.

Most antituberculosis drugs appear to be safe for use with breastfeeding. These agents are excreted in breast milk at relatively small concentrations. No adverse effects have been reported to date. The percentages of the therapeutic dose of antituberculosis agents that potentially may be delivered to the nursing infants range from 0.05% to 28%. Currently isoniazid, rifampin, ethambutol, streptomycin (first-line agents), kanamycin and cycloserine (second-line agents) are the only agents considered by the AAP to be compatible with breastfeeding. Unfortunately, there are still no clear data on the safety of pyrazinamide, ethionamide, and capreomycin during breastfeeding. If the mother chooses to breastfeed, it may be prudent to examine the infant for signs and symptoms of toxicity. In infants requiring treatment with antituberculosis agents, it is important to use therapeutic doses since drug concentrations in breast milk are not adequate as effective therapy for treatment or prevention. However, dosing at the lower end of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid) to decrease the risk of toxicity.