Publications by authors named "Rachel Miller"

471 Publications

Clinical Outcomes of Molecular Tumor Boards: A Systematic Review.

JCO Precis Oncol 2021 Jul 9;5. Epub 2021 Jul 9.

Markey Cancer Center, University of Kentucky, Lexington, Kentucky.

We conducted this systematic review to evaluate the clinical outcomes associated with molecular tumor board (MTB) review in patients with cancer.

Methods: A systematic search of PubMed was performed to identify studies reporting clinical outcomes in patients with cancer who were reviewed by an MTB. To be included, studies had to report clinical outcomes, including clinical benefit, response, progression-free survival, or overall survival. Two reviewers independently selected studies and assessed quality with the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group or the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies depending on the type of study being reviewed.

Results: Fourteen studies were included with a total of 3,328 patients with cancer. All studies included patients without standard-of-care treatment options and usually with multiple prior lines of therapy. In studies reporting response rates, patients receiving MTB-recommended therapy had overall response rates ranging from 0% to 67%. In the only trial powered on clinical outcome and including a control group, the group receiving MTB-recommended therapy had significantly improved rate of progression-free survival compared with those receiving conventional therapy.

Conclusion: Although data quality is limited by a lack of prospective randomized controlled trials, MTBs appear to improve clinical outcomes for patients with cancer. Future research should concentrate on prospective trials and standardization of approach and outcomes.
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http://dx.doi.org/10.1200/PO.20.00495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277300PMC
July 2021

Can we prevent chronic osteoarthritis pain? A view from the bench.

Osteoarthritis Cartilage 2021 Oct 7. Epub 2021 Oct 7.

Division of Rheumatology, Rush University Medical Center, Chicago IL. Electronic address:

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http://dx.doi.org/10.1016/j.joca.2021.10.001DOI Listing
October 2021

Molecular Tumor Board Review and Improved Overall Survival in Non-Small-Cell Lung Cancer.

JCO Precis Oncol 2021 29;5. Epub 2021 Sep 29.

Markey Cancer Center, University of Kentucky, Lexington, KY.

With the introduction of precision medicine, treatment options for non-small-cell lung cancer have improved dramatically; however, underutilization, especially in disadvantaged patients, like those living in rural Appalachian regions, is associated with poorer survival. Molecular tumor boards (MTBs) represent a strategy to increase precision medicine use. UK HealthCare at the University of Kentucky (UK) implemented a statewide MTB in January 2017. We wanted to test the impact of UK MTB review on overall survival in Appalachian and other regions in Kentucky.

Methods: We performed a case-control study of Kentucky patients newly diagnosed with non-small-cell lung cancer between 2017 and 2019. Cases were reviewed by the UK MTB and were compared with controls without UK MTB review. Controls were identified from the Kentucky Cancer Registry and propensity-matched to cases. The primary end point was the association between MTB review and overall patient survival.

Results: Overall, 956 patients were included, with 343 (39%) residing in an Appalachian region. Seventy-seven (8.1%) were reviewed by the MTB and classified as cases. Cox regression analysis showed that poorer survival outcome was associated with lack of MTB review (hazard ratio [HR] = 8.61; 95% CI, 3.83 to 19.31; < .0001) and living in an Appalachian region (hazard ratio = 1.43; 95% CI, 1.17 to 1.75; = .004). Among individuals with MTB review, survival outcomes were similar regardless of whether they lived in Appalachia or other parts of Kentucky.

Conclusion: MTB review is an independent positive predictor of overall survival regardless of residence location. MTBs may help overcome some health disparities for disadvantaged populations.
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http://dx.doi.org/10.1200/PO.21.00210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492377PMC
September 2021

The role of Sociodemographic factors on goal achievement in a community-based diabetes prevention program behavioral lifestyle intervention.

BMC Public Health 2021 Oct 2;21(1):1783. Epub 2021 Oct 2.

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, 5135 Public Health, 130 De Soto Street, Pittsburgh, PA, 15261, USA.

Background: The Diabetes Prevention Program (DPP) behavioral lifestyle intervention was effective among a diverse sample of adults with prediabetes. Demonstrated effectiveness in translated versions of the DPP lifestyle intervention (such as Group Lifestyle Balance, DPP-GLB) led to widescale usage with national program oversight and reimbursement. However, little is known about the success of these DPP-translation programs across subgroups of sociodemographic factors. This current effort investigated potential disparities in DPP-translation program primary goal achievement (physical activity and weight) by key sociodemographic factors.

Methods: Data were combined from two 12-month community-based DPP-GLB trials among overweight/obese individuals with prediabetes and/or metabolic syndrome. We evaluated change in weight (kilograms and percent) and activity (MET-hrs/week) and goal achievement (yes/no; ≥5% weight loss and 150 min per week activity) after 6 and 12 months of intervention within and across subgroups of race/ethnicity (non-Hispanic white, non-Hispanic black), employment status, education, income, and gender.

Results: Among 240 participants (85%) with complete data, most sociodemographic subgroups demonstrated significant weight loss. However, non-Hispanic white lost more weight at both 6 and 12 months compared to non-Hispanic black participants [median weight loss (IQR), 6 months: 5.7% (2.7-9.0) vs. 1.5% (1.2-7.5) p = .01 and 12 months: 4.8% (1.1-9.6) vs. 1.1% (- 2.0-3.7) p = .01, respectively]. In addition, a larger percentage of non-Hispanic white demonstrated a 5% weight loss at 6 and 12 months. Employment was significantly related to 12-month weight loss, with retired participants being the most successful. Men, participants with graduate degrees, and those with higher income were most likely to meet the activity goal at baseline and 12 months. Differences in physical activity goal achievement across gender, education, and income groups were significant at baseline, attenuated after 6 months, then re-emerged at 12 months.

Conclusions: The DPP-GLB was effective in promoting weight loss and helped to alleviate disparities in physical activity levels after 6 months. Despite overall program success, differences in weight loss achievement by race/ethnicity were found and disparities in activity re-emerged after 12 months of intervention. These results support the need for intervention modification providing more tailored approaches to marginalized groups to maximize the achievement and maintenance of DPP-GLB behavioral goals.

Trial Registration: NCT01050205 , NCT02467881 .
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http://dx.doi.org/10.1186/s12889-021-11844-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487523PMC
October 2021

The Role of Childhood Asthma in Obesity Development: A Nationwide U.S. Multi-cohort Study.

Epidemiology 2021 Sep 20. Epub 2021 Sep 20.

Department of Preventive Medicine, University of Southern California, Los Angeles, CA Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD Department of Civil and Environmental Engineering, Northeastern University, Boston, MA Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston MA Department of Pediatrics, Hackensack Meridian School of Medicine, Nutley NJ and the Albert Einstein College of Medicine, Bronx, NY Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN Departments of Pediatrics and Medicine, The University of Chicago, Chicago, IL University of Colorado, Anschutz Medical Campus, Aurora, CO Nell Hodgson Woodruff School of Nursing and Department of Family & Preventive Medicine, Emory University, Atlanta, GA Avera Research Institute, Sioux Falls, SD Kaiser Permanente Northern California Division of Research Department of Psychology The George Washington University, Washington, DC Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA University of California, Davis, School of Medicine, CA Geisel School of Medicine, Dartmouth College, Hanover, NH Department of Pediatrics & Environmental and Occupational Health Sciences, University of Washington, WA Department of Psychiatry and Human Behavior and Department of Pediatrics, Brown Alpert Medical School and Women and Infants Hospital, Providence, RI. Department of Education, University of Oregon, Eugene, OR Division of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY Department of Pediatrics, Oregon Health and Science University, Portland, OR Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY Departments of Psychiatry, Psychology, Neuroscience and Obstetrics and Gynecology, University of Rochester, NY Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT Division of Allergy, Immunology, and Pulmonary Medicine, Department of PediatricsSt. Louis Children's Hospital, Washington University School of Medicine St. Louis, MO Departments of Pediatrics, Environmental Medicine and Population Health, New York University School of Medicine, NY Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY Department of Internal Medicine, University of Utah, Salt Lake City, UT Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY.

Rationale: Asthma and obesity often co-occur. It has been hypothesized that asthma may contribute to childhood obesity onset.

Objectives: To determine if childhood asthma is associated with incident obesity and examine the role of asthma medication in this association.

Methods: We studied 8716 children between ages 6-18.5 years who were non-obese at study entry participating in 18 U.S. cohorts of the Environmental influences on Child Health Outcomes program (among 7299 children with complete covariate data mean [SD] study entry age=7.2 [1.6] years and follow-up=5.3 [3.1] years).

Measurements And Main Results: We defined asthma based on caregiver report of provider diagnosis. Incident obesity was defined as the first documented body mass index ≥95th percentile for age and sex following asthma status ascertainment. Over the study period, 26% of children had an asthma diagnosis and 11% developed obesity. Cox proportional hazards models with sex-specific baseline hazards were fitted to assess the association of asthma diagnosis with obesity incidence. Children with asthma had a 23% (95%CI: 4%, 44%) higher risk for subsequently developing obesity compared to those without asthma. A novel mediation analysis was also conducted to decompose the total asthma effect on obesity into pathways mediated and not mediated by asthma medication use. Use of asthma medication attenuated the total estimated effect of asthma on obesity by 64% (excess HR:-0.64 [95%CI:-1.05,-0.23]).

Conclusions: This nationwide study supports the hypothesis that childhood asthma is associated with later risk of obesity. Asthma medication may reduce this association and merits further investigation as a potential strategy for obesity prevention among children with asthma.
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http://dx.doi.org/10.1097/EDE.0000000000001421DOI Listing
September 2021

THE BLEEDING RISK TREATMENT PARADOX AT THE PHYSICIAN 1 AND HOSPITAL LEVEL: IMPLICATIONS FOR REDUCING BLEEDING IN PATIENTS UNDERGOING PCI.

Am Heart J 2021 Sep 17. Epub 2021 Sep 17.

The Duke Clinical Research Institute, Durham, NC.

Background: Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: "bleeding risk-treatment paradox" (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients' bleeding risk (i.e., exhibit a RTP) have higher bleeding rates.

Methods: We examined 28,005 PCIs from the NCDR CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention (TRI), bivalirudin (BIV), and vascular closure devices (VCDs). Patients' predicted bleeding risk was based on NCDR CathPCI bleeding model and categorized as low (<2.0%), moderate (2.0-6.4%), or high (≥6.5%) risk tertiles. BAS use was considered risk-concordant if: at least one BAS was used for moderate risk; two BAS were used for high risk and bivalirudin or VCDs were not used for low risk. Absence of risk-concordant BAS use was defined as RTP. We analyzed inter-hospital and inter-physician variation in RTP, and the association of RTP with post-PCI bleeding.

Results: Amongst 28,005 patients undergoing PCI by 103 physicians at seven hospitals, RTP was observed in 12,035 (43%) patients. RTP was independently associated with a higher likelihood of bleeding even after adjusting for predicted bleeding risk, mortality risk and potential sources of variation (OR 1.66, 95%CI 1.44-1.92, P<0.001). A higher prevalence of RTP strongly and independently correlated with worse bleeding rates, both at the physician-level (Wilk's Lambda 0.9502, F-value 17.21, p<0.0001) and the hospital-level (Wilk's Lambda 0.9899, F-value 35.68, p<0.0001). All the results were similar in a subset of PCIs conducted since 2015 - a period more reflective of the contemporary practice.

Conclusions: Bleeding RTP is a strong, independent predictor of bleeding. It exists at the level of physicians and hospitals: those with a higher rate of RTP had worse bleeding rates. These findings not only underscore the importance of recognizing bleeding risk upfront and using BAS in a risk-aligned manner, but also inform and motivate national efforts to reduce PCI-related bleeding.
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http://dx.doi.org/10.1016/j.ahj.2021.08.021DOI Listing
September 2021

Indoor Environmental Factors May Modify the Response to Mouse Allergen Reduction Among Mouse-Sensitized and Exposed Children with Persistent Asthma.

J Allergy Clin Immunol Pract 2021 Sep 8. Epub 2021 Sep 8.

Departments of Population Health and Pediatrics, Dell Medical School at University of Texas at Austin, Austin, Texas.

Background: Whether concomitant home exposures modify the effectiveness of mouse allergen reduction among mouse-sensitized children with asthma is unknown.

Objective: To determine whether a lower baseline home mouse allergen level, lower particulate matter 10 μ or less (PM), and the absence of sensitization and exposure to other indoor allergens are associated with greater improvements in asthma associated with mouse allergen reduction.

Methods: A secondary analysis of a randomized clinical trial of a home mouse allergen intervention was performed to examine the effect of 3 indoor factors on the relationship between mouse allergen reduction and a range of asthma outcomes.

Results: Participants (N = 297) were predominantly minority (78% African American, 22% Hispanic) and publicly insured (88%). Higher baseline mouse allergen levels were associated with a greater response to mouse allergen reduction for several symptom and exacerbation outcomes. Lower indoor PM levels were associated with a greater response to mouse allergen reduction for several symptom outcomes, but not exacerbation outcomes. Overall, sensitization and exposure to other indoor allergens did not appear to modify the effect of mouse allergen reduction.

Conclusions: In this population of predominantly low-income children with persistent asthma and mouse sensitization, mouse allergen reduction was associated with improvements in asthma, especially among those with high baseline mouse allergen exposure. Lower indoor PM was associated with greater improvements in asthma symptoms.
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http://dx.doi.org/10.1016/j.jaip.2021.08.031DOI Listing
September 2021

Personal Exposure to Black Carbon at School and Levels of Fractional Exhaled Nitric Oxide in New York City.

Environ Health Perspect 2021 Sep 8;129(9):97005. Epub 2021 Sep 8.

Division of Pediatric Pulmonary, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, USA.

Background: Schools are often located near traffic sources, leading to high levels of exposure to traffic-related air pollutants, including black carbon (BC). Thus, the school environment could play in a significant role in the adverse respiratory health of children.

Objectives: Our objective was to determine associations between personal BC levels at school and airway inflammation [i.e., fractional exhaled nitric oxide (FeNO)] in school-age children. We hypothesized that higher school BC (SBC) would be associated with higher FeNO.

Methods: Children 9-14 years of age in New York City (NYC) () wore BC monitors for two 24-h periods over a 6-d sampling period, repeated 6 months later. SBC was defined as the average personal BC concentrations measured during NYC school hours (i.e., 0830-1430 hours). FeNO was measured following each 24-h BC monitoring period. Multivariable linear regression in generalized estimating equation models were used to examine associations between SBC and FeNO. Results are presented as percentage difference (PD) in FeNO.

Results: Personal BC at school was associated with higher FeNO ( higher FeNO per BC (95% CI: 1.31, 13.9), ]. Compared with BC exposure during school, a smaller PD in FeNO was observed in association with BC exposure while commuting to and from school [ (95% CI: 0.70, 13.3), ]. Personal BC in non-school environments and residential BC were not associated with FeNO (). A significant association between personal BC at school and FeNO was observed among children with seroatopy who did not have asthma [ (95% CI: 4.81, 40.9), ].

Discussion: Schools may be important sources of BC exposure that contribute to airway inflammation in school-age children. Our results provide rationale for interventions that target improved air quality in urban schools and classrooms. https://doi.org/10.1289/EHP8985.
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http://dx.doi.org/10.1289/EHP8985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425518PMC
September 2021

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance.

Biomedicines 2021 Aug 16;9(8). Epub 2021 Aug 16.

Department of Pharmacy Practice & Science, University of Kentucky College of Pharmacy, 540 Healthy Kentucky Research Building, 760 Press Avenue, Lexington, KY 40539-0596, USA.

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects ( = 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K-Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance.
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http://dx.doi.org/10.3390/biomedicines9081021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394135PMC
August 2021

Data driven patterns of nutrient intake and coronary artery disease risk in adults with type 1 diabetes.

J Diabetes Complications 2021 Oct 4;35(10):108016. Epub 2021 Aug 4.

University of Pittsburgh Graduate School of Public Health, Department of Epidemiology, United States of America. Electronic address:

Aims: Dietary intake provides a potential intervention target to reduce the high risk for coronary artery disease (CAD) in type 1 diabetes. This effort aimed to identify patterns of nutrient intake in young/middle-aged adults with type 1 diabetes and to examine associations between those patterns and development of CAD.

Methods: Principal component analysis was used to derive nutrient intake patterns among 514 individuals with childhood-onset (<17 years old) type 1 diabetes aged 18+ years and free of CAD (defined as CAD death, myocardial infarction, revascularization, ischemia, or study physician diagnosed angina). Cox models were used to assess the association between nutrient patterns and CAD incidence over 30-years of follow-up.

Results: Three nutrient principal components (PC) were identified: PC1 (high caffeine and saccharin intake), PC2 (high alcohol and caffeine, lower intake of essential nutrients) and PC3 (higher fiber/micronutrients, low alcohol). In unadjusted Cox models, only PC1 (negatively) and PC2 (positively) were associated with CAD risk. These associations were no longer significant after adjusting for diabetes duration.

Conclusions: Important dietary components underlying the three patterns identified may have been influenced by diabetes duration or age. Future research can continue to explore patterns of nutrient intake over time and CAD development in type 1 diabetes.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.108016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434996PMC
October 2021

Klamath Tribal Response to the Pandemic of COVID-19 Among Klamath Tribal Community in Oregon, USA.

Glob Adv Health Med 2021 15;10:21649561211034470. Epub 2021 Jul 15.

Department of Surgery and Cancer, Imperial College London, London, UK.

Introduction: Socially-disadvantaged populations are more at risk of contracting COVID-19 than those with access to better medical facilities. We looked at responses of Klamath Tribes in Oregon, USA to mitigate spread of COVID-19 in a community with a higher incidence of obesity, diabetes and coronary heart disease, compared to the general US population. This study reports on Klamath Tribes response to COVID-19 March -September 2020.

Methods: Klamath Tribes Tribal Health and Family Services established a COVID-19 Incident Management Team (IMT), instituting creative programs including a Walk-In Testing Center, implementing strict infection control protocols and regular sharing of information on the pandemic and prevalence of COVID-19 amongst Klamath Tribes. All COVID-19 tests were documented with positive cases isolated and people with high risk exposures quarantined and provided with wrap-around medical and social services until recovered or past quarantine time period.

Results: A total of 888 (12%) tribal members were tested for COVID1-19 between March to September 2020; 50 were found positive for COVID-19, giving a test positivity rate of 5.6% (Male - 6.3%; Female - 5.2%). No deaths have been reported amongst the local Klamath Tribes and other American Indians/Alaska Native (AI/AN) population served by the tribe.

Conclusion: Despite the fact that structural inequities including income disparities have shaped racial and ethnic impact of epidemics around the world, the timely response, establishment of partnerships and proactive control of the epidemic resulted in minimal impact among the Klamath Tribal and other AI/AN populations served by the tribal facilities.
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http://dx.doi.org/10.1177/21649561211034470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287354PMC
July 2021

Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality.

Front Genet 2021 16;12:706902. Epub 2021 Jul 16.

Laboratory of Inflammatory Skin Diseases, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

A major component of COVID-19 severe respiratory syndrome is the patient's immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4 T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium ( < 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 ( = 0.11), unless evaluated in the asthmatic strata ( = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived ( < 0.001), as well as in the asthmatic strata only ( < 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19.
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http://dx.doi.org/10.3389/fgene.2021.706902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324177PMC
July 2021

A Comparison of Activity Participation between Children with and without Asthma.

Open J Occup Ther 2021 ;9(3)

Columbia University Medical Center - USA.

Background: Asthma affects approximately 6 million children in the United States and can greatly impact quality of life and occupational engagement. Although occupational therapists are well-equipped to address participation limitations, insufficient evidence exists to support the role of occupational therapists in asthma treatment.

Method: The purpose of this study was to further understand the occupational limitations experienced by children with asthma. We also explored a dual diagnosis of asthma and obesity. The participants included children with (n = 84) and without (n = 63) asthma living in New York City. The Child Behavior Checklist, Youth Self Report, Brief Respiratory Questionnaire, and accelerometer data were used to examine occupational participation.

Results: Although accelerometry data demonstrated that children with asthma were equally as active as their non-asthmatic peers, the participants with asthma perceived themselves as participating more in sedentary occupations and were less likely to be members of sports teams. They also had more missed school days and nights of troubled sleep. The children with both asthma and obesity reported the highest level of activity limitations.

Conclusion: This study illustrates specific limitations experienced by children with asthma and supports the need for occupational therapy intervention. Future studies are needed to design and assess interventions that will support the addition of occupational therapists to multidisciplinary asthma treatment teams.
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http://dx.doi.org/10.15453/2168-6408.1813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311949PMC
January 2021

Risk of Breakthrough SARS-CoV-2 Infections in Adult Transplant Recipients.

Transplantation 2021 Jul 23. Epub 2021 Jul 23.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA Department of Medicine, Division of Infectious Disease, University of Miami Miller School of Medicine, Miami, Florida, USA Department of Nephrology and Hypertension, Rabin Medical Center, Petah-Tikva, Israel Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA Transplant Institute, NYU Langone Health, New York, New York, USA Department of Internal Medicine, Division of Infectious Diseases, Virginia Commonwealth University Health, Richmond, Virginia, USA Department of Surgery, Columbia University College of Physicians & Surgeons, New York, New York, USA Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Clinical Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia Department of Medicine, Division of Infectious Diseases, Duke University, Durham, North Carolina, USA Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA Avera Medical Group Nephrology, Sioux Falls, South Dakota, USA Department of Transplant, Mayo Clinic, Jacksonville, Florida, USA Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Virginia Transplant Center at Henrico Doctors' Hospital, Henrico, Virginia, USA Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA Department of Medicine, Division of Infectious Diseases & Global Public Health, University of California San Diego, San Diego, California, USA Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé publique (iPLESP), APHP, Hôpital Pitié-Salpêtrière, Paris, France.

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http://dx.doi.org/10.1097/TP.0000000000003907DOI Listing
July 2021

Association of Coding Variants in Hydroxysteroid 17-beta Dehydrogenase 14 () with Reduced Progression to End Stage Kidney Disease in Type 1 Diabetes.

J Am Soc Nephrol 2021 Oct 14;32(10):2634-2651. Epub 2021 Jul 14.

Research Division, Joslin Diabetes Center, Boston, Massachusetts.

Background: Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of ESKD in individuals with type 1 diabetes at advanced kidney disease stage.

Methods: Gene-based exome array analyses of 15,449 genes in five large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time to ESKD, testing the top gene in a sixth cohort (=2372/1115 events all cohorts) and replicating in two retrospective case-control studies (=1072 cases, 752 controls). Deep resequencing of the top associated gene in five cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models.

Results: Protein coding variants in the hydroxysteroid 17- dehydrogenase 14 gene (), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (=4196; value=3.3 × 10). The gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other CKD-associated renal pathologies.

Conclusions: gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.
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http://dx.doi.org/10.1681/ASN.2020101457DOI Listing
October 2021

Circulating Free Fatty Acid and Phospholipid Signature Predicts Early Rapid Kidney Function Decline in Patients With Type 1 Diabetes.

Diabetes Care 2021 Sep 8;44(9):2098-2106. Epub 2021 Jul 8.

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI

Objectives: Patients with type 1 diabetes (T1D) exhibit modest lipid abnormalities as measured by traditional metrics. This study aimed to identify lipidomic predictors of rapid decline of kidney function in T1D.

Research Design And Methods: In a case-control study, 817 patients with T1D from three large cohorts were randomly split into training and validation subsets. Case was defined as >3 mL/min/1.73 m per year decline in estimated glomerular filtration rate (eGFR), while control was defined as <1 mL/min/1.73 m per year decline over a minimum 4-year follow-up. Lipids were quantified in baseline serum samples using a targeted mass spectrometry lipidomic platform.

Results: At individual lipids, free fatty acid (FFA)20:2 was directly and phosphatidylcholine (PC)16:0/22:6 was inversely and independently associated with rapid eGFR decline. When examined by lipid class, rapid eGFR decline was characterized by higher abundance of unsaturated FFAs, phosphatidylethanolamine (PE)-Ps, and PCs with an unsaturated acyl chain at the sn1 carbon, and by lower abundance of saturated FFAs, longer triacylglycerols, and PCs, PEs, PE-Ps, and PE-Os with an unsaturated acyl chain at the sn1 carbon at eGFR ≥90 mL/min/1.73 m. A multilipid panel consisting of unsaturated FFAs and saturated PE-Ps predicted rapid eGFR decline better than individual lipids (C-statistic, 0.71) and improved the C-statistic of the clinical model from 0.816 to 0.841 ( = 0.039). Observations were confirmed in the validation subset.

Conclusions: Distinct from previously reported predictors of GFR decline in type 2 diabetes, these findings suggest differential incorporation of FFAs at the sn1 carbon of the phospholipids' glycerol backbone as an independent predictor of rapid GFR decline in T1D.
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http://dx.doi.org/10.2337/dc21-0737DOI Listing
September 2021

The Impact of a Yearlong Diabetes Prevention Program-Based Lifestyle Intervention on Cardiovascular Health Metrics.

J Prim Care Community Health 2021 Jan-Dec;12:21501327211029816

University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.

Introduction: The American Heart Association created "Life's Simple Seven" metrics to estimate progress toward improving US cardiovascular health in a standardized manner. Given the widespread use of federally funded Diabetes Prevention Program (DPP)-based lifestyle interventions such as the Group Lifestyle Balance (DPP-GLB), evaluation of change in health metrics within such a program is of national interest. This study examined change in cardiovascular health metric scores during the course of a yearlong DPP-GLB intervention.

Methods: Data were combined from 2 similar randomized trials offering a community based DPP-GLB lifestyle intervention to overweight/obese individuals with prediabetes and/or metabolic syndrome. Pre/post lifestyle intervention participation changes in 5 of the 7 cardiovascular health metrics were examined at 6 and 12 months (BMI, blood pressure, total cholesterol, fasting plasma glucose, physical activity). Smoking was rare and diet was not measured.

Results: Among 305 participants with complete data (81.8% of 373 eligible adults), significant improvements were demonstrated in all 5 risk factors measured continuously at 6 and 12 months. There were significant positive shifts in the "ideal" and "total" metric scores at both time points. Also noted were beneficial shifts in the proportion of participants across categories for BMI, activity, and blood pressure.

Conclusion: AHA-metrics could have clinical utility in estimating an individual's cardiovascular health status and in capturing improvement in cardiometabolic/behavioral risk factors resulting from participation in a community-based translation of the DPP lifestyle intervention.
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http://dx.doi.org/10.1177/21501327211029816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274083PMC
August 2021

The Wnt/PCP formin Daam1 drives cell-cell adhesion during nephron development.

Cell Rep 2021 Jul;36(1):109340

Program in Genes and Development, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Department of Pediatrics, Pediatric Research Center, UTHealth McGovern Medical School, Houston, TX 77030, USA; Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Program in Biochemistry and Cell Biology, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA. Electronic address:

E-cadherin junctions facilitate assembly and disassembly of cell contacts that drive development and homeostasis of epithelial tissues. In this study, using Xenopus embryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/planar cell polarity (PCP) formin Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin-based intercellular adhesion. Using live imaging, we show that Daam1 localizes to newly formed cell contacts in the developing nephron. Furthermore, analyses of junctional filamentous actin (F-actin) upon Daam1 depletion indicate decreased microfilament localization and slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional E-cadherin, mediated by Daam1's formin homology domain 2 (FH2). Finally, we establish that Daam1 signaling promotes organized movement of renal cells. This study demonstrates that Daam1 formin junctional activity is critical for epithelial tissue organization.
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http://dx.doi.org/10.1016/j.celrep.2021.109340DOI Listing
July 2021

Mitochondrial calcium uniporter deletion prevents painful diabetic neuropathy by restoring mitochondrial morphology and dynamics.

Pain 2021 Jul 2. Epub 2021 Jul 2.

Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, Department of Internal Medicine, Rush Medical College, Chicago, IL, USA.

Abstract: Painful diabetic neuropathy (PDN) is an intractable complication affecting 25% of diabetic patients. PDN is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, resulting in calcium overload, axonal degeneration, and loss of cutaneous innervation. The molecular pathways underlying these effects are unknown. Using high-throughput and deep-proteome profiling, we found that mitochondrial fission proteins were elevated in DRG neurons from mice with PDN induced by a high-fat diet (HFD). In vivo calcium imaging revealed increased calcium signaling in DRG nociceptors from mice with PDN. Furthermore, using electron microscopy, we showed that mitochondria in DRG nociceptors had fragmented morphology as early as two weeks after starting HFD, preceding the onset of mechanical allodynia and small-fiber degeneration. Moreover, preventing calcium entry into the mitochondria, by selectively deleting the mitochondrial calcium uniporter (MCU) from these neurons restored normal mitochondrial morphology, prevented axonal degeneration, and reversed mechanical allodynia in the HFD mouse model of PDN. These studies suggest a molecular cascade linking neuropathic pain to axonal degeneration in PDN. In particular, nociceptor hyperexcitability and the associated increased intracellular calcium concentrations could lead to excessive calcium entry into mitochondria mediated by the MCU, resulting in increased calcium-dependent mitochondrial fission and ultimately contributing to small-fiber degeneration and neuropathic pain in PDN. Hence, we propose that targeting calcium entry into nociceptor mitochondria may represent a promising effective and disease-modifying therapeutic approach for this currently intractable and widespread affliction. Moreover, these results are likely to inform studies of other neurodegenerative disease involving similar underlying events.
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http://dx.doi.org/10.1097/j.pain.0000000000002391DOI Listing
July 2021

An update on targets for treating osteoarthritis pain: NGF and TRPV1.

Curr Treatm Opt Rheumatol 2020 Sep 6;6(3):129-145. Epub 2020 May 6.

Division of Rheumatology, Rush University Medical Center, Chicago, IL.

Purpose Of Review: a)Osteoarthritis (OA) is the most common form of arthritis, and pain is the primary symptom of the disease, yet analgesic options for treating OA pain remain limited. In this review, we aimed to give an update on the current clinical and preclinical studies targeting two pathways that are being investigated for treating OA pain: the nerve growth factor (NGF) pathway and the transient receptor potential vanilloid-1 (TRPV1) pathway.

Recent Findings: b)Antibodies against NGF, small molecule inhibitors of TrkA, TRPV1 agonists, and TRPV1 antagonists are all in different stages of clinical and pre-clinical testing for the treatment of OA pain. NGF antibodies have shown efficacy in the primary endpoints tested compared to placebo, however, rapidly progressive OA has been consistently observed in a subset of patients and the cause remains unclear. TRPV1 agonists have also demonstrated reduced pain with no serious adverse events - the most common adverse events include a burning or warming sensation upon administration.

Summary: c)Targeting the NGF and TRPV1 pathways appear effective for reducing OA pain, but further work is needed to better understand which patients may benefit most from these treatments. The anti-NGF antibody tanezumab and the TRPV1 agonist CNTX-4975 have both received fast-track designation from the FDA for the treatment of OA pain.
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http://dx.doi.org/10.1007/s40674-020-00146-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223492PMC
September 2020

Impact of Maintenance Session Attendance and Early Weight Loss Goal Achievement on Weight Loss Success in a Community-Based Diabetes Prevention Program Intervention.

Sci Diabetes Self Manag Care 2021 Aug 25;47(4):279-289. Epub 2021 Jun 25.

Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.

Purpose: The purpose of this study was to examine how maintenance session attendance and 6-month weight loss (WL) goal achievement impacted 12-month 5% WL success in older adults participating in a community-based Diabetes Prevention Program (DPP) lifestyle intervention.

Methods: Data were combined from 2 community trials that delivered the 12-month DPP-based Group Lifestyle Balance (GLB) to overweight/obese adults (mean age = 62 years, 76% women) with prediabetes and/or metabolic syndrome. Included participants (n = 238) attended ≥4 core sessions (months 0-6) and had complete data on maintenance attendance (≥4 of 6 sessions during months 7-12) and 6- and 12-month WL (5% WL goal, yes/no). Multivariate logistic regression was used to estimate the odds of 12-month 5% WL associated with maintenance attendance and 6-month WL. Associations between age (Medicare-eligible ≥65 vs <65 years) and WL and attendance were examined.

Results: Both attending ≥4 maintenance sessions and meeting the 6-month 5% WL goal increased the odds of meeting the 12-month 5% WL goal. For those not meeting the 6-month WL goal, maintenance session attendance did not improve odds of 12-month WL success. Medicare-eligible adults ≥65 years were more likely to meet the 12-month WL goal (odds ratio = 3.03, 95% CI, 1.58-5.81) versus <65 years.

Conclusions: The results of this study provide important information regarding participant attendance and WL for providers offering DPP-based lifestyle intervention programs across the country who are seeking Medicare reimbursement. Understanding Medicare reimbursement-defined success will allow these providers to focus on and develop strategies to enhance program effectiveness and sustainability.
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http://dx.doi.org/10.1177/26350106211023990DOI Listing
August 2021

Exploring the evidence for epigenetic regulation of environmental influences on child health across generations.

Commun Biol 2021 06 22;4(1):769. Epub 2021 Jun 22.

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, UNC Chapel Hill, Chapel Hill, NC, USA.

Environmental exposures, psychosocial stressors and nutrition are all potentially important influences that may impact health outcomes directly or via interactions with the genome or epigenome over generations. While there have been clear successes in large-scale human genetic studies in recent decades, there is still a substantial amount of missing heritability to be elucidated for complex childhood disorders. Mounting evidence, primarily in animals, suggests environmental exposures may generate or perpetuate altered health outcomes across one or more generations. One putative mechanism for these environmental health effects is via altered epigenetic regulation. This review highlights the current epidemiologic literature and supporting animal studies that describe intergenerational and transgenerational health effects of environmental exposures. Both maternal and paternal exposures and transmission patterns are considered, with attention paid to the attendant ethical, legal and social implications.
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http://dx.doi.org/10.1038/s42003-021-02316-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219763PMC
June 2021

Vishniacozyma victoriae (syn. Cryptococcus victoriae) in the homes of asthmatic and non-asthmatic children in New York City.

J Expo Sci Environ Epidemiol 2021 Jun 5. Epub 2021 Jun 5.

Office of the Director, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV, USA.

Background: Indoor environments contain a broad diversity of non-pathogenic Basidiomycota yeasts, but their role in exacerbating adverse health effects has remained unclear.

Objective: To understand the role of Vishniacozyma victoriae exposure and its impact on human health.

Methods: A qPCR assay was developed to detect and quantify an abundant indoor yeast species, Vishniacozyma victoriae (syn. Cryptococcus victoriae), from homes participating in the New York City Neighborhood Asthma and Allergy Study (NAAS). We evaluated the associations between V. victoriae, housing characteristics, and asthma relevant health endpoints.

Results: V. victoriae was quantified in 236 of the 256 bedroom floor dust samples ranging from less than 300-45,918 cell equivalents/mg of dust. Higher concentrations of V. victoriae were significantly associated with carpeted bedroom floors (P = 0.044), mean specific humidity (P = 0.004), winter (P < 0.0001) and spring (P = 0.001) seasons, and the presence of dog (P = 0.010) and dog allergen Can f 1 (P = 0.027). V. victoriae concentrations were lower in homes of children with asthma vs. without asthma (P = 0.027), an association observed only among the non-seroatopic children.
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http://dx.doi.org/10.1038/s41370-021-00342-4DOI Listing
June 2021

A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.

Biochem Biophys Res Commun 2021 Jul 28;563:31-39. Epub 2021 May 28.

Department of Genetics, University of Texas MD Anderson Cancer Center, Houston TX, 77030, USA; University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston TX, 77030, USA. Electronic address:

Vertebrate beta-catenin plays a key role as a transducer of canonical-Wnt signals. We earlier reported that, similar to beta-catenin, the cytoplasmic signaling pool of p120-catenin-isoform1 is stabilized in response to canonical-Wnt signals. To obtain a yet broader view of the Wnt-pathway's impact upon catenin proteins, we focused upon plakophilin3 (plakophilin-3; Pkp3) as a representative of the plakophilin-catenin subfamily. Promoting tissue integrity, the plakophilins assist in linking desmosomal cadherins to intermediate filaments at desmosome junctions, and in common with other catenins they perform additional functions including in the nucleus. In this report, we test whether canonical-Wnt pathway components modulate Pkp3 protein levels. We find that in common with beta-catenin and p120-catenin-isoform1, Pkp3 is stabilized in the presence of a Wnt-ligand or a dominant-active form of the LRP6 receptor. Pkp3's levels are conversely lowered upon expressing destruction-complex components such as GSK3β and Axin, and in further likeness to beta-catenin and p120-isoform1, Pkp3 associates with GSK3beta and Axin. Finally, we note that Pkp3-catenin trans-localizes into the nucleus in response to Wnt-ligand and its exogenous expression stimulates an accepted Wnt reporter. These findings fit an expanded model where context-dependent Wnt-signals or pathway components modulate Pkp3-catenin levels. Future studies will be needed to assess potential gene regulatory, cell adhesive, or cytoskeletal effects.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252864PMC
July 2021

Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?

BMC Cancer 2021 May 20;21(1):580. Epub 2021 May 20.

Division of Medical Oncology, University of Kentucky, Lexington, KY, USA.

Background: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models.

Methods: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval.

Results: Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3-20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0-11).

Conclusions: Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.
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http://dx.doi.org/10.1186/s12885-021-08315-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139143PMC
May 2021

A distributed geospatial approach to describe community characteristics for multisite studies.

J Clin Transl Sci 2021 Feb 5;5(1):e86. Epub 2021 Feb 5.

Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
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http://dx.doi.org/10.1017/cts.2021.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111696PMC
February 2021

Neuroimmune interactions and osteoarthritis pain: focus on macrophages.

Pain Rep 2021 9;6(1):e892. Epub 2021 Mar 9.

Division of Rheumatology, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.

Bidirectional interactions between the immune system and the nervous system are increasingly appreciated as playing a pathogenic role in chronic pain. Unraveling the mechanisms by which inflammatory pain is mediated through communication between nerves and immune cells may lead to exciting new strategies for therapeutic intervention. In this narrative review, we focus on the role of macrophages in the pathogenesis of osteoarthritis (OA) pain. From regulating homeostasis to conducting phagocytosis, and from inducing inflammation to resolving it, macrophages are plastic cells that are highly adaptable to their environment. They rely on communicating with the environment through cytokines, growth factors, neuropeptides, and other signals to respond to inflammation or injury. The contribution of macrophages to OA joint damage has garnered much attention in recent years. Here, we discuss how macrophages may participate in the initiation and maintenance of pain in OA. We aim to summarize what is currently known about macrophages in OA pain and identify important gaps in the field to fuel future investigations.
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http://dx.doi.org/10.1097/PR9.0000000000000892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108586PMC
March 2021

Pediatric Asthma Incidence Rates in the United States from 1980 to 2017.

J Allergy Clin Immunol 2021 May 6. Epub 2021 May 6.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.

Background: Few studies have examined longitudinal asthma incidence rates (IRs) from a public health surveillance perspective.

Objective: Our aim was to calculate descriptive asthma IRs in children over time with consideration for demographics and parental asthma history.

Methods: Data from 9 US birth cohorts were pooled into 1 population covering the period from 1980 to 2017. The outcome was earliest parental report of a doctor diagnosis of asthma. IRs per 1,000 person-years were calculated.

Results: The racial/ethnic backgrounds of the 6,283 children studied were as follows: 55% European American (EA), 25.5% African American (AA), 9.5% Mexican-Hispanic American (MA) and 8.5% Caribbean-Hispanic American (CA). The average follow-up was 10.4 years (SD = 8.5 years; median = 8.4 years), totaling 65,291 person-years, with 1789 asthma diagnoses yielding a crude IR of 27.5 per 1,000 person-years (95% CI = 26.3-28.8). Age-specific rates were highest among children aged 0 to 4 years, notably from 1995 to 1999, with a decline in EA and MA children in 2000 to 2004 followed by a decline in AA and CA children in 2010 to 2014. Parental asthma history was associated with statistically significantly increased rates. IRs were similar and higher in AA and CA children versus lower but similar in EA and MA children. The differential rates by sex from birth through adolescence principally resulted from a decline in rates among males but relatively stable rates among females.

Conclusions: US childhood asthma IRs varied dramatically by age, sex, parental asthma history, race/ethnicity, and calendar year. Higher rates in the 0- to 4-year-olds group, particularly among AA/CA males with a parental history of asthma, as well as changes in rates over time and by demographic factors, suggest that asthma is driven by complex interactions between genetic susceptibility and variation in time-dependent environmental and social factors.
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http://dx.doi.org/10.1016/j.jaci.2021.04.027DOI Listing
May 2021

Protective Football Headgear and Peripheral Visuomotor Ability in NCAA Football Athletes: The Role of Facemasks and Visors.

J Funct Morphol Kinesiol 2021 Apr 8;6(2). Epub 2021 Apr 8.

Department of Kinesiology, Samford University, Birmingham, AL 35229, USA.

The purpose of this investigation was to determine the effects of varying facemask reinforcement and visor tint on peripheral visuomotor abilities in collegiate football players. Division I NCAA football players ( = 14) completed two peripheral visuomotor experiments: (1) Varying facemask reinforcement, (2) Varying visor tinting. In experiment 1, participants were tested under the following conditions: baseline (no helmet; BL), helmet + light (HL), helmet + medium (HM), helmet + heavy (HH), and helmet + extra heavy (HXH) reinforced facemasks. In experiment 2, participants were tested under the following conditions: baseline (no helmet; BL), helmet only (HO), helmet + clear (HCV), helmet + smoke-tinted (HSV), and helmet + mirror-tinted (HMV) visors. For each condition, a 60 s peripheral visuomotor test was completed on a Dynavision D2 visuomotor board. For experiment 1, the BL peripheral reaction time (PRT) was faster than all facemask conditions ( < 0.05). Furthermore, PRT was impaired with the HXH compared to HL ( < 0.001), HM ( < 0.001), and HH ( = 0.001). Both HH and HXH resulted in the potentiation of PRT impairments in the outermost and inferior peripheral visual areas ( < 0.05). In experiment 2, BL PRT was faster than all helmeted conditions ( < 0.05). Additionally, PRT was slower in HSV ( = 0.013) and HMV ( < 0.001) conditions compared to HO. HMV resulted in slower PRT in all peripheral areas ( < 0.05) while PRT was impaired only in outer areas for HSV ( < 0.05). Wearing protective football headgear impairs peripheral visuomotor ability. Lighter reinforced facemasks and clear visors do not appear to exacerbate impairment. However, heavier reinforced facemasks and tinted visors further decrease visuomotor performance in outer and inferior visual areas, indicating a potential need for considerations of on-field player performance and safety.
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http://dx.doi.org/10.3390/jfmk6020034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167592PMC
April 2021
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