Integrating community voices in the research continuum: Perspectives on a consultation service.

The Community Research Advisory Council (C-RAC) of the Johns Hopkins Institute for Clinical and Translational Research was established in 2009 to provide community-engaged research consultation services. In 2016-2017, C-RAC members and researchers were surveyed on their consultation experiences. Survey results and a 2019 stakeholder meeting proceeding helped redesign the consultation services. Transitioning to virtual consultations during COVID-19, the redesigning involved increasing visibility, providing consultation materials in advance, expanding member training, and effective communications. An increase in consultations from 28 (2009-2017) to 114 (2020-2022) was observed. Implementing stakeholder-researcher inputs is critical to holistic and sustained community-engaged research.

Von Willebrand factor assays in patients with acquired immune thrombotic thrombocytopenia purpura treated with caplacizumab.

Acquired immune thrombotic thrombocytopenic purpura (iTTP) is a rare disease with a poor prognosis if undiagnosed. It is caused by autoantibody production to the von Willebrand factor (VWF) cleaving protease, A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Caplacizumab, an immunoglobulin directed to the platelet glycoprotein Ibα receptor of VWF, has been reported to induce quicker resolution of iTTP compared to placebo. The laboratory measurement of VWF activity was significantly reduced in clinical trials of caplacizumab. Several VWF assays are available in the UK and this study investigated whether differences in VWF parameters were present in 11 patients diagnosed with iTTP and treated with daily caplacizumab. Chromogenic factor VIII activity, VWF antigen, collagen binding activity, VWF multimers and six VWF activity assays were measured prior to caplacizumab therapy and on several occasions during treatment. VWF antigen and collagen binding activity levels were normal or borderline normal in all patients. Ultra-large molecular weight multimers were present in all patients following treatment. VWF activity assays were normal or reduced during treatment, but this was reagent and patient dependant. In the unusual scenario of a caplacizumab-treated patient requiring measurement of VWF activity, it is important that laboratories understand how their local reagents perform as results cannot be predicted.

Laboratory methods for monitoring argatroban in heparin-induced thrombocytopenia.

INTRODUCTION: The Summary of Product Characteristics for the direct thrombin inhibitor argatroban states monitoring should be by activated partial thromboplastin time (APTT), with a target range of 1.5-3.0 times the patients' baseline APTT. APTT may be influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. Previous studies have shown sensitivity differences of APTT reagents to argatroban. Some recent publications have favoured the use of anti-IIa methods to determine the plasma drug concentration of argatroban. This study aims to compare the anti-IIa assays: Hemoclot thrombin inhibitor assay (HTI) and Ecarin chromogenic assay (ECA) alongside the APTT. METHODS: Residual plasma of 25 samples from 8 patients (3 with COVID-19 and HIT: n = 18, 5 with HIT: n = 7) was tested at two sites: site A: Sysmex CS5100 by HTI and APTT (Actin FS and SynthASil), and also on Stago STA Compact Max: ECA and APTT (CK Prest); and site B: Stago STA R Max 2 by ECA and APTT (Cephascreen). RESULTS: Mean APTT ratio was 1.96 (Actin FS), 1.84 (SynthASil), 1.59 (CK Prest) and 2.48 (Cephascreen). Mean argatroban concentration by HTI was 0.60 µg/mL and by ECA was 0.65 µg/mL (site A) and 0.70 µg/mL (site B). There was a poor correlation to HTI in APTT ratios (range r2  = .0235-0.4181) with stronger correlations between ECA methods to HTI (r2  = .8998 site A, r2  = .8734 site B). CONCLUSION: This study confirms previous publications on the unsuitability of APTT and expands this by being multisited and included APTT reagents that use mechanical clot detection. Both anti-IIa methods are more suitable.

Peroxiredoxin-1 Tyr194 phosphorylation regulates LOX-dependent extracellular matrix remodelling in breast cancer.

BACKGROUND: Peroxiredoxin 1 (PRDX1) belongs to an abundant family of peroxidases whose role in cancer is still unresolved. While mouse knockout studies demonstrate a tumour suppressive role for PRDX1, in cancer cell xenografts, results denote PRDX1 as a drug target. Probably, this phenotypic discrepancy stems from distinct roles of PRDX1 in certain cell types or stages of tumour progression. METHODS: We demonstrate an important cell-autonomous function for PRDX1 utilising a syngeneic mouse model (BALB/c) and mammary fibroblasts (MFs) obtained from it. RESULTS: Loss of PRDX1 in vivo promotes collagen remodelling known to promote breast cancer progression. PRDX1 inactivation in MFs occurs via SRC-induced phosphorylation of PRDX1 TYR194 and not through the expected direct oxidation of CYS52 in PRDX1 by ROS. TYR194-phosphorylated PRDX1 fails to bind to lysyl oxidases (LOX) and leads to the accumulation of extracellular LOX proteins which supports enhanced collagen remodelling associated with breast cancer progression. CONCLUSIONS: This study reveals a cell type-specific tumour suppressive role for PRDX1 that is supported by survival analyses, depending on PRDX1 protein levels in breast cancer cohorts.

The peroxidase PRDX1 inhibits the activated phenotype in mammary fibroblasts through regulating c-Jun N-terminal kinases.

BACKGROUND: Reactive oxygen species (ROS), including hydrogen peroxide, drive differentiation of normal fibroblasts into activated fibroblasts, which can generate high amounts of hydrogen peroxide themselves, thereby increasing oxidative stress in the microenvironment. This way, activated fibroblasts can transition into cancer-associated fibroblasts (CAFs). METHODS: Mammary fibroblasts from either female 8 weeks old PRDX1 knockout and wildtype mice or Balb/c mice were studied for characteristic protein expression using immunofluorescence and immunoblotting. Cancer-associated fibroblasts was examined by transwell migration and invasion assays. The binding of PRDX1 to JNK1 was assessed by co-immuneprecipitation and JNK regulation of CAF phenotypes was examined using the JNK inhibitor SP600125. Extracellular hydrogen peroxide levels were measured by chemiluminescence via the reaction between hypochlorite and luminol. Statistical analyses were done using Students t-test. RESULTS: We show here PRDX1 activity as an essential switch in regulating the activated phenotype as loss of PRDX1 results in the development of a CAF-like phenotype in mammary fibroblasts. We also show that PRDX1 regulates JNK kinase signaling thereby inhibiting CAF-like markers and CAF invasion. Inhibition of JNK activity reduced these behaviors. CONCLUSIONS: These data suggest that PRDX1 repressed the activated phenotype of fibroblasts in part through JNK inhibition which may present a novel therapeutic option for CAF-enriched cancers such as breast cancer.

Redoxins as gatekeepers of the transcriptional oxidative stress response.

Transcription factors control the rate of transcription of genetic information from DNA to messenger RNA, by binding specific DNA sequences in promoter regions. Transcriptional gene control is a rate-limiting process that is tightly regulated and based on transient environmental signals which are translated into long-term changes in gene transcription. Post-translational modifications (PTMs) on transcription factors by phosphorylation or acetylation have profound effects not only on sub-cellular localization but also on substrate specificity through changes in DNA binding capacity. During times of cellular stress, specific transcription factors are in place to help protect the cell from damage by initiating the transcription of antioxidant response genes. Here we discuss PTMs caused by reactive oxygen species (ROS), such as H2O2, that can expeditiously regulate the activation of transcription factors involved in the oxidative stress response. Part of this rapid regulation are proteins involved in H2O2-related reduction and oxidation (redox) reactions such as redoxins, H2O2 scavengers described to interact with transcription factors. Redoxins have highly reactive cysteines of rate constants around 6-10-1 s-1 that engage in nucleophilic substitution of a thiol-disulfide with another thiol in inter-disulfide exchange reactions. We propose here that H2O2 signal transduction induced inter-disulfide exchange reactions between redoxin cysteines and cysteine thiols of transcription factors to allow for rapid and precise on and off switching of transcription factor activity. Thus, redoxins are essential modulators of stress response pathways beyond H2O2 scavenging capacity.

A Peroxidase Peroxiredoxin 1-Specific Redox Regulation of the Novel FOXO3 microRNA Target let-7.

Precision in redox signaling is attained through posttranslational protein modifications such as oxidation of protein thiols. The peroxidase peroxiredoxin 1 (PRDX1) regulates signal transduction through changes in thiol oxidation of its cysteines. We demonstrate here that PRDX1 is a binding partner for the tumor suppressive transcription factor FOXO3 that directly regulates the FOXO3 stress response. Heightened oxidative stress evokes formation of disulfide-bound heterotrimers linking dimeric PRDX1 to monomeric FOXO3. Absence of PRDX1 enhances FOXO3 nuclear localization and transcription that are dependent on the presence of Cys31 or Cys150 within FOXO3. Notably, FOXO3-T32 phosphorylation is constitutively enhanced in these mutants, but nuclear translocation of mutant FOXO3 is restored with PI3K inhibition. Here we show that on H2O2 exposure, transcription of tumor suppressive miRNAs let-7b and let-7c is regulated by FOXO3 or PRDX1 expression levels and that let-7c is a novel target for FOXO3. Conjointly, inhibition of let-7 microRNAs increases let-7-phenotypes in PRDX1-deficient breast cancer cells. Altogether, these data ascertain the existence of an H2O2-sensitive PRDX1-FOXO3 signaling axis that fine tunes FOXO3 activity toward the transcription of gene targets in response to oxidative stress. Antioxid. Redox Signal. 28, 62-77.

A Dietary Intervention in Urban African Americans: Results of the "Five Plus Nuts and Beans" Randomized Trial.

INTRODUCTION: Unhealthy diets, often low in potassium, likely contribute to racial disparities in blood pressure. We tested the effectiveness of providing weekly dietary advice, assistance with selection of higher potassium grocery items, and a $30 per week food allowance on blood pressure and other outcomes in African American adults with hypertension. DESIGN: We conducted an 8-week RCT with two parallel arms between May 2012 and November 2013. SETTING/PARTICIPANTS: We randomized 123 African Americans with controlled hypertension from an urban primary care clinic in Baltimore, Maryland, and implemented the trial in partnership with a community supermarket and the Baltimore City Health Department. Mean (SD) age was 58.6 (9.5) years; 71% were female; blood pressure was 131.3 (14.7)/77.2 (10.5) mmHg; BMI was 34.5 (8.2); and 28% had diabetes. INTERVENTION: Participants randomized to the active intervention group (Dietary Approaches to Stop Hypertension [DASH]-Plus) received coach-directed dietary advice and assistance with weekly online ordering and purchasing of high-potassium foods ($30/week) delivered by a community supermarket to a neighborhood library. Participants in the control group received a printed DASH diet brochure along with a debit account of equivalent value to that of the DASH-Plus group. MAIN OUTCOME MEASURES: The primary outcome was blood pressure change. Analyses were conducted in January to October 2014. RESULTS: Compared with the control group, the DASH-Plus group increased self-reported consumption of fruits and vegetables (mean=1.4, 95% CI=0.7, 2.1 servings/day); estimated intake of potassium (mean=0.4, 95% CI=0.1, 0.7 grams/day); and urine potassium excretion (mean=19%, 95% CI=1%, 38%). There was no significant effect on blood pressure. CONCLUSIONS: A program providing dietary advice, assistance with grocery ordering, and $30/week of high-potassium foods in African American patients with controlled hypertension in a community-based clinic did not reduce BP. However, the intervention increased consumption of fruits, vegetables, and urinary excretion of potassium.

Public infrastructure disparities and the microbiological and chemical safety of drinking and surface water supplies in a community bordering a landfill.

The historically African-American Rogers-Eubanks community straddles unincorporated boundaries of two municipalities in Orange County, North Carolina, and predates a regional landfill sited along its border in 1972. Community members from the Rogers-Eubanks Neighborhood Association (RENA), concerned about deterioration of private wells and septic systems and a lack of public drinking water and sewer services, implemented a community-driven research partnership with university scientists and community-based organizations to investigate water and sewer infrastructure disparities and the safety of drinking and surface water supplies. RENA drafted memoranda of agreement with partners and trained community monitors to collect data (inventory households, map water and sewer infrastructure, administer household water and sewer infrastructure surveys, and collect drinking and surface water samples). Respondents to the surveys reported pervasive signs of well vulnerability (100%) and septic system failure (68%). Each 100-m increase in distance from the landfill was associated with a 600 most probable number/100 mL decrease in enterococci concentrations in surface water (95% confidence interval = -1106, -93). Pervasive private household water and sewer infrastructure failures and poor water quality were identified in this community bordering a regional landfill, providing evidence of a need for improved water and sanitation services.

Enhancing fire department home visiting programs: results of a community intervention trial.

This study evaluates the impact of an enhanced fire department home visiting program on community participation and installation of smoke alarms, and describes the rate of fire and burn hazards observed in homes. Communities were randomly assigned to receive either a standard or enhanced home visiting program. Before implementing the program, 603 household surveys were completed to determine comparability between the communities. During a 1-year intervention period, 171 home visits took place with 8080 homes. At baseline, 60% of homes did not have working smoke alarms on every level, 44% had unsafe water temperatures, and 72% did not have carbon monoxide alarms. Residents in the enhanced community relative to those in the standard community were significantly more likely to let the fire fighters into their homes (75 vs 62%). Among entered homes, those in the enhanced community were significantly more likely to agree to have smoke alarms installed (95 vs 92%), to be left with a working smoke alarm on every level of the home (84 vs 78%), and to have more smoke alarms installed per home visited (1.89 vs 1.74). The high baseline rates of home hazards suggest that fire department home visiting programs should take an "all hazards" approach. Community health workers and community partnerships can be effective in promoting fire departments' fire and life safety goals. Public health academic centers should partner with the fire service to help generate evidence on program effectiveness that can inform decision making about resource allocation for prevention.

The effectiveness of a short food frequency questionnaire in determining vitamin D intake in children.

Previous studies have found a high prevalence of vitamin D deficiency in children, yet few validated dietary vitamin D assessment tools are available for use in children. Our objective was to determine whether a short food frequency questionnaire (SFFQ) can effectively assess vitamin D intake in children. Vitamin D intake ascertained by a SFFQ was compared with assessments by a previously validated long food frequency questionnaire (LFFQ) in a population of 296 healthy 6- to 14-y-old children (54% male, 60% African American) from Pittsburgh, PA. The questionnaires were completed at two points 6 mo apart. Median reported daily vitamin D intake from the SFFQ (baseline: 380 IU, follow-up: 363 IU) was higher than the LFFQ (255 IU and 254 IU, respectively). Reported median dairy intake, including milk, cheese, and yogurt, was 3.7 cups/day, which meets the USDA recommendation for children. Vitamin D intake reported by the 2 questionnaires was modestly correlated at baseline and follow-up (r = 0.35 and r = 0.37, respectively; p < 0.001). These associations were stronger in Caucasians (r = 0.48 and r = 0.49, p < 0.001) than in African Americans (r = 0.27 and r = 0.31; p = 0.001). The sensitivity of the SFFQ for predicting daily vitamin D intake, defined as intake of ≥ 400 IU on both the SFFQ and LFFQ, was 65%. Specificity, defined as intake of < 400 IU on both questionnaires, was 42%. Vitamin D requirements may not be met despite adequate consumption of dairy products. The SFFQ was found to be a modestly valid and sensitive tool for dietary assessment of vitamin D intake in children.

Relation between malodor, ambient hydrogen sulfide, and health in a community bordering a landfill.

BACKGROUND: Municipal solid waste landfills are sources of air pollution that may affect the health and quality of life of neighboring communities. OBJECTIVES: To investigate health and quality of life concerns of neighbors related to landfill air pollution. METHODS: Landfill neighbors were enrolled and kept twice-daily diaries for 14d about odor intensity, alteration of daily activities, mood states, and irritant and other physical symptoms between January and November 2009. Concurrently, hydrogen sulfide (H(2)S) air measurements were recorded every 15-min. Relationships between H(2)S, odor, and health outcomes were evaluated using conditional fixed effects regression models. RESULTS: Twenty-three participants enrolled and completed 878 twice-daily diary entries. H(2)S measurements were recorded over a period of 80d and 1-h average H(2)S=0.22ppb (SD=0.27; range: 0-2.30ppb). Landfill odor increased 0.63 points (on 5-point Likert-type scale) for every 1ppb increase in hourly average H(2)S when the wind was blowing from the landfill towards the community (95% confidence interval (CI): 0.29, 0.91). Odor was strongly associated with reports of alteration of daily activities (odds ratio (OR)=9.0; 95% CI: 3.5, 23.5), negative mood states (OR=5.2; 95% CI: 2.8, 9.6), mucosal irritation (OR=3.7; 95% CI=2.0, 7.1) and upper respiratory symptoms (OR=3.9; 95% CI: 2.2, 7.0), but not positive mood states (OR=0.6; 95% CI: 0.2, 1.5) and gastrointestinal (GI) symptoms (OR=1.0; 95% CI: 0.4, 2.6). CONCLUSIONS: Results suggest air pollutants from a regional landfill negatively impact the health and quality of life of neighbors.

Faculty beliefs, perceptions, and level of community involvement in their research: a survey at one urban academic institution.

Health researchers are increasingly interested in how best to engage communities in their health-related research studies. To help determine how researchers have interacted with community members in their research, we conducted a survey of full-time faculty from the Johns Hopkins Medical Institutions regarding researchers' beliefs and experiences with community-based research. Approximately 41% of respondents who conducted human subject studies had enrolled local residents in their research. Researchers whose studies were based in the surrounding community were significantly more likely to involve community members in all stages of their research (e.g., selection of the problem, project planning, data collection, interpretation and dissemination of results, or developing an intervention) than were faculty whose studies enrolled community members as research participants but whose studies were not set in the community. Over 90% of all faculty respondents agree that community involvement improves the relevance of their research, although almost 60% had not done so. Most faculty value community involvement, but they want more institutional support for such activities and they seek better skills to involve community. Few studies have surveyed researchers who enroll community members as research participants to document practices regarding community involvement in the research process. Given that the majority (73.6%) of faculty responded that they intend to include local residents in their upcoming studies, future research to evaluate interventions designed to facilitate community involvement, especially in the inner city, would help stakeholders identify best practices for involving and engaging communities in health research.

Effect of intensified diet education on serum phosphorus and knowledge of pediatric peritoneal dialysis patients.

OBJECTIVE: To investigate the effect of intensive diet education on the knowledge and serum phosphorus levels of pediatric peritoneal dialysis (PD) patients and their parents. DESIGN: Interventional study using a pre-post design and convenience sample. SETTING: The study was performed in a pediatric PD clinic. PATIENTS: Sixteen patients ranging in age from 9 to 21 years and their parents. INTERVENTION: Patients routinely receive a review of laboratory results and a review of foods to limit. For the study, two additional education sessions were conducted. The additional phosphorus education to participants included a computer-based jeopardy game, handouts, education magnets and a hands-on learning activity. A 20 question before-and-after knowledge test was administered to the patients and parents separately. MAIN OUTCOME MEASURES: Change in serum phosphorus levels and the difference in pre and post knowledge test scores for both patients and parents. RESULTS: There was a significant increase in parent (p=0.003) and patient knowledge (p<0.001). There was a decrease in serum phosphorus from 2.3+/-0.68mmol/L to 2.16+/-0.58mmol/L (7.13+/-2.1mg/dL to 6.68+/-1.8mg/dL), but this change was not statistically significant (p=0.256). CONCLUSION: Intensive education regarding phosphorus led to improved patient and family knowledge in pediatric PD patients. Although increased knowledge did not result in a significant decrease in serum phosphorus, there was a slight decrease indicating some clinical relevance. Therefore, pediatric PD patients may benefit from intensive on-going diet education sessions.

Increasing social communication in persons with dementia.

Communication difficulties between caregivers and persons with dementia (PWDs) may increase stress, resulting in behavior problems. Kitwood's theory of dementia care suggests that successful collaborative communication increases well-being and quality of life in PWDs. This study aimed to determine if individualized communication prescriptions (ways interviewers might facilitate collaborative communication) are effective for doing so. Ten PWDs were interviewed; individualized communication prescriptions developed then implemented in a second interview. No increase in number of words used by PWDs occurred in interview 2; however, PWDs' words per topic significantly increased and number of topics needed to sustain a 15-minute conversation significantly decreased in the second interview. Systematic, individualized communication strategies may encourage PWDs to express their needs, preferences, and ideas.

"You've got to understand community": community perceptions on "breaking the disconnect" between researchers and communities.

BACKGROUND: Community-based participatory research (CBPR) is a growing approach to research yet its implementation does not come without challenges. Incorporating CBPR may be especially difficult for large academic medical institutions where research is conducted by different stakeholders operating under different paradigms. The Environmental Justice Partnership (EJP) is a community-academic partnership that sought to understand and address these challenges. OBJECTIVES: To know how to effectively foster collaboration between a large academic medical center and its surrounding urban community, the EJP sought to understand community stakeholders' views on research, the research process, and how to improve researcher-community collaborations. METHODS: This study used a qualitative approach to gather information from residents and representatives from community-based organizations (CBOs) and city agencies. The data are from 17 semistructured interviews and 8 focus groups (n = 80) conducted from October 2003 to May 2004. RESULTS: Respondents emphasized the importance of disseminating research findings, working closely with the community before research starts and throughout the study, and listening to community members' priorities and needs. Those with personal research experience had more positive attitudes about research than respondents who had not been in research. CONCLUSIONS: Academic institutions need to make greater effort to involve communities regularly in their community-based research to identify community priorities and concerns. Institutions may want to develop strategies for their affiliated researchers to facilitate partnership building. Especially for large academic institutions in urban settings, such efforts may help to bridge distance between researchers and community to promote the shared goal of improved public health.

Predicting in-hospital falls: development of the Scott and White Falls Risk Screener.

Falling is the most common hospital accident, and up to 15% of fallers sustain a serious injury. This study focused on developing a simple, practical fall risk screener using routine admission and daily in-hospital stay data. A case-control design was used. Logistic regression identified individual characteristics associated with an increased risk of a fall. Four variables were identified: history of falls, ambulation assistance, disoriented, and bowel control problems, creating a fall risk model with 70% sensitivity and 57% specificity.

Prevalence of metabolic syndrome risk factors among young adult Asian Indians.

Metabolic syndrome has a high prevalence within the U.S population. Asian Indians have a greater prevalence of the chronic diseases associated with this syndrome compared to Caucasians. This study aimed to determine the prevalence of risk factors of metabolic syndrome in young adult Asian Indians. Behavioral risk factors, dietary intake, and anthropometric measurements were assessed on all study participants (n=50). The mean BMI was 23.2 and 20.4, waist circumference was 87 and 79 cm, and percent body fat was 16 and 26% for males and females, respectively. Macronutrient contributions to the total energy intake were: carbohydrate 55% for males and females, protein 14 and 12% for males and females respectively, and total fat 31 and 33% for males and females, respectively. Using the definition of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, ATP III), these Asian Indians did not appear to be at high risk for developing metabolic syndrome. However, using the newly proposed recommendations for Asian Indians, the results suggest that this group may be at risk for developing metabolic syndrome.

Recommendations for nutrition interventions with overweight African-American adolescents and young adults at the Atlanta Job Corps Center.

Focus groups were used to gain insight into the nutrition-related attitudes and motivations of overweight African-American adolescents and young adults enrolled in the Atlanta Job Corps Center in preparation for designing an effective and culturally appropriate nutrition intervention for this population. Eighteen students and 18 staff members participated in six different focus groups. Focus group themes suggest that an intervention with this target group should address overeating, proper diet composition, emotional eating, long-term consequences of a poor diet, group work, and incentives. Limiting food portions, offering healthy, appealing food choices, and displaying nutritional content of foods in the cafeteria were also suggested. It was also suggested that the intervention should be ongoing and led by someone who is patient, supportive, and has overcome an overweight problem. An intervention based on these recommendations can be specifically tailored to this target group and, potentially, be effective in changing dietary behaviors and lifestyle.