Prevalence In African Americans Research Articles

Door-To-Door Video-Enhanced Prevalence Study of Tourette Disorder Among African Americans

ABSTRACT Tourette syndrome (TS) affects about 0.5% of the population worldwide, but only sparse and conflicting data exist on TS prevalence among minority samples. Here we used VISITTS (a survey preceded by a short video showing tic phenomenology) and community outreach to provide estimates of tic disorder prevalence in African Americans. Community health workers (CHWs) left flyers at households in a predominantly minority neighborhood and approached people at a community health fair. Of 606 such contacts, 222 individuals agreed to discuss the study. Of these, 70% enrolled, of whom 82% identified as Black and 64% female. The VISITTS was well received. Lifetime prevalence of TS or another chronic tic disorder (TS/CTD) was 3.2%, and 31% endorsed any lifetime simple tic. The number of enrolled Black participants is remarkable compared to earlier TS studies, allowing one of the first prevalence estimates in this population (TS 2.3%, TS/CTD 3.9%). Tic disorders were endorsed only by Black respondents, though the small White sample precluded statistical comparison. Women had higher rates than men of TS (M:F = 0:1) and of any lifetime simple tic (M:F = 0.85), differing significantly from the expected 4:1 ratio (p = .009 and p < .001, respectively). For TS/CTD the ratio was 1.2:1 (p > .15). We conclude that VISITTS is a feasible tic screening tool in a minority population, that CHW community outreach increases enrollment of Black participants, that TS/CTD is no less common in this population, and that tics were as common in female as in male respondents.

Abstract P125: Tissue Specific Regulation Of The Cardiac And Renal Endothelin System In A Lupus-prone Mouse Model

Systemic Lupus Erythematosus (SLE), the most common form of lupus autoimmune disease, disproportionally affects women (9:1) with high prevalence in African Americans. Numerous studies report elevated endothelin-1 (ET-1) in the plasma of patients with lupus and demonstrate increased ET-1 contribution to various pathological cardiovascular complications including hypertension, cardiac hypertrophy, and heart failure in lupus patients. However, few studies explored the relative roles and regulation of the cardiac and renal ET systems in lupus-associated cardiovascular complications. We hypothesized that immune modulation and acceleration of lupus by a toll-like receptor 7/8 agonist, Resiquimod, would lead to tissue-specific regulation of the ET system in both the kidney and heart in lupus-prone mice. To investigate this, female lupus-prone B6.Nba2 mice were subjected to bi-weekly treatment with the Resiquimod (R848; 100ug/30ul; n=4) or vehicle control (Acetone; n=5) for one month and subsequently studied for 12 weeks. At 16 weeks post-treatment (30 weeks old), heart and kidneys were collected, and the ET system was analyzed by RT-PCR, immunoblotting, and immunohistochemistry. R848 treatment significantly increased cardiac but not kidney expression of ET-1 (19.90 ± 1.36 vs. 7.65 ± 0.54 pg/mg; p=0.02 compared to controls (6.10 ± 1.64 vs. 4.95 ± 0.55 pg/mg; p&gt;0.05). Furthermore, R848 treated mice had no significant effect on cardiac endothelin receptor A (ET A ) nor endothelin receptor B (ET B ) expression at both the RNA and protein levels (p&gt;0.05 for all). Interestingly, renal ET B RNA expression was reduced (0.08 vs. 1.62; p &lt;0.05), while ET A expression was unchanged (p &gt; 0.05) with R848. The same trend was observed at the protein level by immunoblotting and immunohistochemistry (p&gt;0.05) Our results provide evidence that lupus acceleration with TLR7/8 activation in B6.Nba2 mice differentially regulates tissue-specific ET systems in the heart and kidney, potentially contributing to the tissue specific dysfunction found in lupus. These findings suggest that our model offers an opportunity to identify cardiac and renal contributions to lupus complications, and specifically determine the cell-specific regulation of ET biosynthesis and signaling.

Admixture mapping of peripheral artery disease in a Dominican population reveals a putative risk locus on 2q35.

Peripheral artery disease (PAD) is a form of atherosclerotic cardiovascular disease, affecting ∼8 million Americans, and is known to have racial and ethnic disparities. PAD has been reported to have a significantly higher prevalence in African Americans (AAs) compared to non-Hispanic European Americans (EAs). Hispanic/Latinos (HLs) have been reported to have lower or similar rates of PAD compared to EAs, despite having a paradoxically high burden of PAD risk factors; however, recent work suggests prevalence may differ between sub-groups. Here, we examined a large cohort of diverse adults in the BioMe biobank in New York City. We observed the prevalence of PAD at 1.7% in EAs vs. 8.5% and 9.4% in AAs and HLs, respectively, and among HL sub-groups, the prevalence was found at 11.4% and 11.5% in Puerto Rican and Dominican populations, respectively. Follow-up analysis that adjusted for common risk factors demonstrated that Dominicans had the highest increased risk for PAD relative to EAs [OR = 3.15 (95% CI 2.33-4.25), p < 6.44 × 10-14]. To investigate whether genetic factors may explain this increased risk, we performed admixture mapping by testing the association between local ancestry and PAD in Dominican BioMe participants (N = 1,813) separately from European, African, and Native American (NAT) continental ancestry tracts. The top association with PAD was an NAT ancestry tract at chromosome 2q35 [OR = 1.96 (SE = 0.16), p < 2.75 × 10-05) with 22.6% vs. 12.9% PAD prevalence in heterozygous NAT tract carriers versus non-carriers, respectively. Fine-mapping at this locus implicated tag SNP rs78529201 located within a long intergenic non-coding RNA (lincRNA) LINC00607, a gene expression regulator of key genes related to thrombosis and extracellular remodeling of endothelial cells, suggesting a putative link of the 2q35 locus to PAD etiology. Efforts to reproduce the signal in other Hispanic cohorts were unsuccessful. In summary, we showed how leveraging health system data helped understand nuances of PAD risk across HL sub-groups and admixture mapping approaches elucidated a putative risk locus in a Dominican population.

Prevalence and Risk Factors of New-onset Diabetes after Transplant in East Africans.

Very little is known about the prevalence of new-onset diabetes after transplant (NODAT) in sub-Saharan and Eastern Africans. Most of the data are related to African Americans and to North and South Africans. The aims of this study were to examine the prevalence of NODAT in Sudanese renal transplant recipients, compare it with the published literature, and identify the risk factors for developing NODAT. In total, 150 patients who received a living-related kidney transplant between January 2015 and January 2016 were included in this study. Patients with diabetic nephropathy and pretransplant diabetes were excluded. Follow-up was for 2 years after the transplant. The variables studied were age, sex, body mass index, a family history of diabetes mellitus (DM), pretransplant steroid therapy, dyslipidemia, and hepatitis C virus infection. Twenty- three patients (15.3%) developed NODAT during the study period. The mean age of the patients who developed NODAT was 39 ± 14 years, and the mean time to develop NODAT was 5.78 ± 5.9 months. In the multivariate analysis, the risk factors for developing NODAT were a family history of DM (P = 0.01) and pretransplant steroid therapy (P = 0.01). The prevalence of NODAT in this study was 15.3%, which is in line with the reported literature from North Africa. However, it was significantly lower than the reported prevalence in African Americans.

Disparities in cancer prevalence in African Americans: A United States population study 2021.

6531 Background: African-Americans (AA) have the highest incidence and death rates from cancer and the shortest survival of all racial groups in the USA, as reiterated by the American Cancer Society’s Cancer Facts and Figures for AA from 2019. We studied cancer prevalence in AA compared to Caucasians, focusing on patients with above-normal Body Mass Index (BMI). Methods: Data was collected from Explorys, IBM, a national database including over 73 million patients. Patients were divided based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race (Caucasians and AA), and BMI (18.5 - &lt; 25 and ≥ 25.0 kg/m2). The odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in AA compared to Caucasians were calculated with P values &lt;0.001 considered significant. Results: N: Normal BMI EW: Excess weight (Females) C: Caucasian S: Significant NS: Non-significant. Conclusions: Our results show a significantly lower than expected prevalence of screenable cancers in AA compared to Caucasians, diverging widely from established incidence rates. The difference was more remarkable in pre-Medicare age (&lt; 65 years) and excess weight patients. These disparities are concerning for a compromised healthcare access contributing to underdiagnosis of cancer or shorter survival among AA in the US.[Table: see text]

Clinical and Sociodemographic Profile of Patients With Thyroid Storm: A National Inpatient Sample Database Analysis

Background: Thyroid storm (TS) is a rare, life-threatening disease that is associated with significant mortality. The clinical outcome of these patients has not been evaluated in general practice on a national scale. Our study aimed to find the clinical characteristics and outcomes of patients admitted to community hospitals with TS using the National Inpatient Sample (NIS) database. Methods: We conducted a retrospective study of adult patients (>=18 years of age) diagnosed with primary and secondary TS from the NIS database from 2012 to 2014. The NIS is the largest all-payer inpatient care database in the United States, containing data on more than seven million hospital stays each year. Statistical analysis performed included Chi-Square test, Wilcoxon two-sample test, Fisher’s exact test and multiple logistic regression with a p-value<0.05 considered significant. Results: In total, 2,163 hospitalizations with TS were identified. The incidence of TS in hospitalized patients was 11.96 per 100,000 hospitalizations. Compared to all other adult hospitalizations reported over the same period, admission with TS was significantly associated with a higher prevalence in African Americans (31.4% vs 14.7%, p<0.001) as well as concomitant blood diseases (31.4% vs 21.9%, p<0.001), drug use disorder (11.4% vs 8.4%, p<0.001), electrolyte disturbance (36.9% vs 23.8%, p<0.001), and psychosis (38.1% vs 28.5%, p<0.001). Admission with TS was associated with lower prevalence of concomitant cancer (2.5% vs 4.9%, p<0.001) and renal disease (5.6% vs 12.2%, p<0.001), along with a higher risk of death during hospitalization (3.9% vs 2.2%, p<0.001). There was no significant association between TS and GI disease, cardiovascular disease, pulmonary disease or rheumatoid arthritis. Admission with TS was associated with longer average length of stay (TS median: 4 days, Non-TS: 3 days, p<0.001) and higher total hospital charge (TS median: $27,360, Non-TS: $24,346, p<0.001). Additionally, TS had a higher incidence in urban populations with large hospitals.Overall, inpatient mortality rate was 3.9%. For those with TS, the odds of inpatient death were greater for age group 30-59 compared to <30 (OR 2.916, p=0.026), age group >60 compared to <30 (OR 3.157, p=0.022), males (OR 2.20, p<0.001), those with cancer (OR 6.42, p<0.001), those with electrolyte disturbance (OR 6.12, p<0.001) and those with a neurologic disorder (OR 2.46, p=0.002). Admitted patients with a concomitant psychological disorder had lower odds of death (OR 0.38, p=0.03). Conclusions: This study identified clinical characteristics associated with TS-related admission including female gender, age 30-59, Caucasian race, and urban populations. Higher mortality was associated with patients 30-59 years and >60 years of age, electrolyte disturbances, blood disease, weight loss, paralysis, cancer, renal disease, and male gender.

Genetic architecture of type 2 diabetes and its shared genetic component with low birth weight in African Americans.

Recent large-scale multiancestry efforts has contributed to our knowledge of the hereditary basis of type 2 diabetes (T2D). The present review will summarize findings of the genetic basis of T2D in African Americans, a population group with a disproportionate burden of this disease. To date, >400 risk genetic variants have been found to be associated with the risk of T2D across populations of different ancestries. Although these findings are based on primarily European-ancestry populations, most of the identified loci show similar associations in African Americans. Ancestry-specific analyses including genome-wide associations studies (GWAS) in African Americans, Africans; as well as admixture mapping scans in African Americans have identified additional risk variants and genomic loci associate with the risk of T2D. These efforts have also uncovered new genetic links between low birth weight and T2D. In particular, admixture mapping approaches have identified a shared genetic ancestry component of both phenotypic traits in African Americans. Recent findings have helped us to better understand the genetic basis of T2D in African Americans. Of particular interest are new genetic discoveries linking low birth weight and T2D, two conditions with a much higher prevalence in African Americans compared to U.S. whites. Continuing work, including large-scale sequencing efforts would add to our knowledge of the genetic architecture of T2D in African Americans, as well as genetic links with other conditions.

Origins and History of the Minimal Model of Glucose Regulation.

It has long been hoped that our understanding of the pathogenesis of diabetes would be helped by the use of mathematical modeling. In 1979 Richard Bergman and Claudio Cobelli worked together to find a “minimal model” based upon experimental data from Bergman’s laboratory. Model was chosen as the simplest representation based upon physiology known at the time. The model itself is two quasi-linear differential equations; one representing insulin kinetics in plasma, and a second representing the effects of insulin and glucose itself on restoration of the glucose after perturbation by intravenous injection. Model would only be sufficient if it included a delay in insulin action; that is, insulin had to enter a remote compartment, which was interstitial fluid (ISF). Insulin suppressed endogenous glucose output (by liver) slowly. Delay proved to be due to initial suppression of lipolysis; resultant lowering of free fatty acids reduced liver glucose output. Modeling also demanded that normalization of glucose after injection included an effect of glucose itself on glucose disposal and endogenous glucose production – these effects were termed “glucose effectiveness.” Insulin sensitivity was calculated from fitting the model to intravenous glucose tolerance test data; the resulting insulin sensitivity index, SI, was validated with the glucose clamp method in human subjects. Model allowed us to examine the relationship between insulin sensitivity and insulin secretion. Relationship was described by a rectangular hyperbola, such that Insulin Secretion x Insulin Sensitivity = Disposition Index (DI). Latter term represents ability of the pancreatic beta-cells to compensate for insulin resistance due to factors such as obesity, pregnancy, or puberty. DI has a genetic basis, and predicts the onset of Type 2 diabetes. An additional factor was clearance of insulin by the liver. Clearance varies significantly among animal or human populations; using the model, clearance was shown to be lower in African Americans than Whites (adults and children), and may be a factor accounting for greater diabetes prevalence in African Americans. The research outlined in the manuscript emphasizes the powerful approach by which hypothesis testing, experimental studies, and mathematical modeling can work together to explain the pathogenesis of metabolic disease.

Lack of association between acute stroke, post-stroke dementia, race, and β-amyloid status

IntroductionStroke and Alzheimer disease share risk factors and often co-occur, and both have been reported to have a higher prevalence in African Americans as compared to non-Hispanic whites. However, their interaction has not been established. The objective of this study was to determine if preclinical Alzheimer disease is a risk factor for stroke and post-stroke dementia and whether racial differences moderate this relationship. MethodsThis case-control study was analyzed in 2019 using retrospective data from 2007 to 2013. Participants were adults age 65 and older with and without acute ischemic stroke. Recruitment included word of mouth and referrals in Saint Louis, MO, with stroke participants recruited from acutely hospitalized patients and non-stroke participants from community living older adults who were research volunteers. Our assessment included radiologic reads of infarcts, microbleeds, and white matter hyperintensitites (WMH); a Pittsburgh Compound B PET measure of cortical β-amyloid binding; quantitative measures of hippocampal and WMH volume; longitudinal Mini Mental State Examination (MMSE) scores; and Clinical Dementia Rating (CDR) 1 year post-stroke. ResultsA total of 243 participants were enrolled, 81 of which had a recent ischemic stroke. Participants had a mean age of 75, 57% were women, and 52% were African American. Cortical amyloid did not differ significantly by race, stroke status, or CDR post-stroke. There were racial differences in MMSE scores at baseline (mean 26.8 for African Americans, 27.9 for non-Hispanic whites, p = 0.03), but not longitudinally. African Americans were more likely to have microbleeds (32.8% vs 22.6%, p = 0.04), and within the acute stroke group, African Americans were more likely to have small infarcts (75.6% vs 56.8%, p = 0.049). ConclusionPreclinical Alzheimer disease did not show evidence of being a risk factor for stroke nor predictive of post-stroke dementia. We did not observe racial differences in β-amyloid levels. However, even after controlling for several vascular risk factors, African Americans with clinical stroke presentations had greater levels of vascular pathology on MRI.

An epistatic interaction between pre-natal smoke exposure and socioeconomic status has a significant impact on bronchodilator drug response in African American youth with asthma

BackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables.ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 233 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to quantify interaction effects using an information-theory metric known as Information Gain (IG). We performed analyses in the full dataset and in sex-stratified subsets. Our analyses identified several interaction models significantly, and suggestively, associated with BDR. The strongest interaction significantly associated with BDR was a pairwise interaction between pre-natal smoke exposure and socioeconomic status (full dataset IG: 2.78%, p = 0.001; female IG: 7.27%, p = 0.004)). Sex-stratified analyses yielded divergent results for females and males, indicating the presence of sex-specific effects.ConclusionsOur study identified novel interaction effects significantly, and suggestively, associated with BDR in African American children with asthma. Notably, we found that all of the interactions identified by ViSEN were “pure” interaction effects, in that they were not the result of strong main effects on BDR, highlighting the complexity of the network of biological and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods, thus emphasizing the importance of employing statistical methods optimized to detect both additive and non-additive interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.

Yoga versus Aerobic Exercise: An Alternative Intervention for Neuropathic Pain Among African Americans with Diabetes

In today’s world, the prevalence of African Americans (AA) with diabetes continues to grow as it is becoming an epidemic. As of 2012, AA adults are two times more likely to be diagnosed with diabetes. Diabetes is most closely associated with being overweight/obese and around 50%–75% of AA that are older than 20 years of age fall into this category. With this disease comes many challenges not only mentally but physically that can decrease the quality of life in individuals that live with this condition. Often times pharmacological management of diabetes is introduced to patients as a means of controlling symptoms, such as neuropathic pain, without discussion of alternative methods. Commonly, side effects of these medicines introduce new problems that are then managed with more medications; this contributes to the rising opioid crisis in the United States. Therefore, alternative methods such as yoga should be employed. Current evidence suggests yoga has many beneficial effects to individuals with diabetes including decreased neuropathic pain. Although this evidence exists for the majority of the population in the United States, few studies have been conducted on AAs using yoga as a means to decrease neuropathic pain. The purpose of this study was to conduct a systematic review regarding neuropathic pain in the AA population and how yoga may be a better alternative to treating this pain versus aerobic exercise only. Using a variety of databases such as PubMed, Google Scholar, and EBSCO Host, studies were reviewed and ranked according to the Oxford Center for Evidence‐Based Medicine. Distal symmetric polyneuropathy (DSPN) is a common neuropathy among individuals with diabetes and this neuropathy can cause pain in the upper and lower distal extremities due to damage of small and large myelinated nerve fibers. While aerobic exercise is commonly used and has shown positive results in helping decrease neuropathic pain as well as promote regrowth of nerve fibers, research shows that yoga can be used as an alternative method for reducing blood glucose levels as well as improvements in nerve conduction velocities leading to a reduction in neuropathic pain. In conclusion, our research provided evidence as to why AA populations should be encouraged to participate in yoga as an effective means of providing relief of neuropathic pain.

Association of salvage cryoablation with decreased utilization of androgen deprivation therapy for recurrent prostate cancer after radiotherapy.

358 Background: Cryoablation is an established treatment for recurrent prostate cancer after primary radiotherapy, but outcomes data are mostly limited to uncontrolled case series. We assessed salvage cryoablation efficacy with a comparative analysis in a large national cohort. Methods: Patients with clinically localized prostate cancer treated with primary radiotherapy from 2000 to 2015 were identified in the Veterans Affairs Informatics and Computing Infrastructure (VINCI) dataset. Prostate-specific antigen (PSA) recurrence was defined as nadir + 2 ng/mL. Inclusion criteria included availability of serial PSA measures for ≥ 3 years after completion of radiotherapy and PSA &lt; 10 ng/mL at recurrence. Salvage cryotherapy was identified with procedure- and fee-based billing codes. Chi square and Wilcoxon analysis was utilized for descriptive statistics; and Kaplan Meier analyses for time to androgen deprivation therapy (ADT). Results: Among 35,502 patients who underwent primary radiotherapy, 4,391 (12.3%) developed biochemical recurrence a median (IQR) of 4.5 (2.7, 6.9) years after treatment. Of these, 3889 (88.9%) had PSA &lt; 10 ng/mL at time of recurrence, of whom 95 (2.4%) underwent salvage cryoablation. Cryoablation patients were younger at initial diagnosis (60 years versus 65 years, p &lt; 0.01); had a lower pre-treatment PSA (6.6 ng/mL versus 7.8 ng/mL, p &lt; 0.01); and had a lower PSA nadir (0.04 ng/mL versus 0.19 ng/mL, p&lt;0.01). There were no between-group differences for clinical stage at initial diagnosis (p = 0.22) or African American prevalence (34.7% versus 29%, p =0.27). After recurrence, median (IQR) follow-up for those who did and did not receive cryoablation was 9.1 (7.2, 9.11) and 8.1 (5.4, 10.9) years, respectively. Cryoablation patients were less likely to receive ADT (40% versus 55%, p &lt; 0.01); and, among those who did, time to ADT from recurrence was significantly longer compared to those who did not receive cryoablation (15.5 months versus 5.8 months, p&lt;0.01). Conclusions: Salvage cryoablation is associated with decreased utilization of ADT in patients with biochemical recurrence after radiation.

The Relationship between Tobacco Retailer Density and Neighborhood Demographics in Ohio

Studies from various parts of the country suggest that tobacco-related health disparities are exacerbated by disparities in the distribution of tobacco retailers (convenience stores, tobacco shops, etc.). The purpose of the present study was to use advanced spatial modeling techniques for count data to estimate current disparities in tobacco retailer density in Ohio. We identified and geocoded 11,392 tobacco retailers in Ohio. Next, we obtained census tract-level information on race/ethnicity, poverty, and age and obtained county-level information on whether an area was Urban, Suburban, or Rural. Finally, we used negative binomial generalized linear models, adapted for residual spatial dependence, to determine the association between per capita tobacco retailer density and demographic characteristics-summarized by adjusted rate ratios. There were more (from 1.4-1.9 times as many) retailers per capita in high-poverty, vs. low-poverty tracts. Poverty also interacted with age: the association between high poverty and high retailer density was stronger for tracts with a low youth population. Density was also greater in tracts with a high (vs. low) prevalence of African Americans (1.1 times as many) and Hispanics (1.2 times as many). Finally, density was generally greater in rural (vs. suburban or urban) tracts, although the effect was modified by a three-way interaction: density was particularly high for rural tracts that also had both a high prevalence of poverty and a low youth population. Overall, our findings indicate that Ohio's vulnerable populations are exposed to a greater per capita density of tobacco retailers. There is a need for state and local-level tobacco control policies that will improve equity and reduce health disparities.

Body Composition Remodeling and Incident Mobility Limitations in African Ancestry Men.

Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry. Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.

Undiagnosed Kidney Injury in Uninsured and Underinsured Diabetic African American Men and Putative Role of Meprin Metalloproteasses in Renal Pathology

Diabetes is a leading cause of chronic kidney disease. African Americans are disproportionately burdened by diabetic kidney disease (DKD) and end stage renal disease (ESRD). Disparities in DKD have genetic and socioeconomic components, yet its prevalence in African Americans is not adequately studied. The current study evaluated undiagnosed DKD in uninsured and underinsured African American men in Greensboro, North Carolina. Participants consisted of three groups: non‐diabetic controls, diabetic patients without known kidney disease, and diabetic patients with diagnosed DKD. Our data reveal undiagnosed kidney injury in a significant proportion of the diabetic patients, based on urinary albumin to creatinine ratio (ACR) which is the gold standard clinical test for DKD. The sensitivity of multiple other kidney injury biomarkers, namely kidney injury molecule‐1 (KIM‐1), cystatin C, and neutrophil gelatinase‐associated lipocalin (NGAL), were also tested in the current study through comparison to ACR. Compared with the normoalbuminuria group (ACR&lt;30 mg/g), only the macroalbuminuria (ACR&gt;300 mg/g) and not the microalbuminuria (300 mg/g&gt;ACR&gt;30 mg/g) group showed increased plasma levels for cystatin C, and increased urinary levels for KIM‐1, cystatin C and NGAL. Also, for plasma, plasma KIM‐1 showed higher levels in the microalbuminuria group than the normoalbuminuria group. In summary, plasma KIM‐1 showed the highest sensitivity in response to increased ACR in the African American subpopulation in our study. We also found the urinary levels of two metalloproteases, meprin A and meprin B, and two of their targets, nidogen‐1 and monocytes chemoattractant protein‐1, increased with severity of kidney injury, which suggests a role for meprin metalloproteases in the pathophysiology of DKD in this subpopulation. Our study has overall revealed undiagnosed kidney injury in a significant proportion of uninsured and underinsured diabetic African American men in the City of Greensboro, North Carolina, and demonstrates a need for more aggressive tests to assess kidney injury in uninsured diabetic patients to facilitate early diagnosis and targeted interventions that could slow progression to ESRD.Support or Funding InformationThis study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Awards # HU140400 (to RHN and EMO) and HU150006 (to EMO and SHH); and the NIH/NIGMS Award Number SC3GM102049 to EMO.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Undiagnosed Kidney Injury in Uninsured and Underinsured Diabetic African American Men and Putative Role of Meprin Metalloproteases in Diabetic Nephropathy.

Diabetes is the leading cause of chronic kidney disease. African Americans are disproportionately burdened by diabetic kidney disease (DKD) and end stage renal disease (ESRD). Disparities in DKD have genetic and socioeconomic components, yet its prevalence in African Americans is not adequately studied. The current study used multiple biomarkers of DKD to evaluate undiagnosed DKD in uninsured and underinsured African American men in Greensboro, North Carolina. Participants consisted of three groups: nondiabetic controls, diabetic patients without known kidney disease, and diabetic patients with diagnosed DKD. Our data reveal undiagnosed kidney injury in a significant proportion of the diabetic patients, based on levels of both plasma and urinary biomarkers of kidney injury, namely, urinary albumin to creatinine ratio, kidney injury molecule-1, cystatin C, and neutrophil gelatinase-associated lipocalin. We also found that the urinary levels of meprin A, meprin B, and two kidney meprin targets (nidogen-1 and monocytes chemoattractant protein-1) increased with severity of kidney injury, suggesting a potential role for meprin metalloproteases in the pathophysiology of DKD in this subpopulation. The study also demonstrates a need for more aggressive tests to assess kidney injury in uninsured diabetic patients to facilitate early diagnosis and targeted interventions that could slow progression to ESRD.

Abstract 5568A: A network based analysis for the treatment of triple negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically-accepted targets for tailored therapy, warranting the need for candidate biomarkers. Methods: BiomarkerBase, a biomarker knowledgebase developed by Amplion uses a comprehensive list of synonyms to identify biomarkers registered in the records of clinical trials via the government website clinicaltrials.gov. Under each of the registered breast cancer biomarkers (with the exceptions of HER2, ER, and PR), sub-searches were conducted for clinical trials that explicitly used TNBC (or the full name, triple negative breast cancer) in the title of the biomarkers’ studies. Of note, most trials in this review were completed phase II or III. The selected candidate biomarkers were classified into four FDA biomarker categories (surrogate, prognostic, predictive, or pharmacodynamic (PD)) as well as by location (blood/plasma, cell surface, cytoplasm, or nucleus). Current literature about the biomarkers was further examined using PubMed. There, we sought to find papers that studied how the biomarkers may interact. These markers were further organized into a “cellular protein network” that demonstrates potential connectivity. Results: Blood biomarkers include VEGF/VEGFR and IL-8; cell surface biomarkers include EGFR, IGFBP, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA/AKT/mTOR-related metabolites (GPC, PCh, Lactate/ glucose), pPKM2, F1,6BP, SPHK1, STAT1/IRF2BP2, S6, p4E-BP1, SUV39H1, PTEN, and ALDH1; and nucleus biomarkers include BRCA1, the glucocorticoid receptor (GR), TP53, and Ki67. Table 1 provides an overview of the examined surrogate, prognostic, predictive, and PD biomarkers in TNBC in addition to current literature found in PubMed that provides support for their potential use. Conclusion: To date, there are no clinically-validated biomarkers for TNBC, which has hindered the development of tailored therapy for both chemosensitive and refractory TNBC. Before validation and use of these biomarkers occurs, stringent-clinical criteria must be met first. The list and cellular protein network provided is an inventory and reference point for promising biomarkers for breakthrough, targeted therapies in TNBC. Citation Format: Brett A. Fleisher, Sihem Ait-Oudhia. A network based analysis for the treatment of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5568A. doi:10.1158/1538-7445.AM2017-5568A

Changing Trends in Age, Gender, Racial Distribution and Inpatient Burden of Achalasia.

BackgroundAchalasia is an idiopathic esophageal motility disorder characterized by dysphagia, regurgitation, chest discomfort and weight loss. The aim of this study was to evaluate the temporal trends in demographic variables, interventions, and inpatient burden in achalasia-related hospitalizations.MethodsWe evaluated the National Inpatient Sample Database (NIS) for all patients in whom achalasia (ICD-9 code: 530.0) was the principal discharge diagnosis from 1997 to 2013. Data regarding the patient demographics, number of hospitalizations, length of stay, associated hospital costs and temporal trends over the study period were obtained.ResultsIn 1997, there were 2,493 admissions with a principal discharge diagnosis of achalasia as compared to 5,195 in 2013 with an average increase of 4% per year (P < 0.001). In 1997, the proportion of patients under 65 years of age was 53.8% versus 60.1% in 2013. Increasing prevalence in African Americans was noted (11.1% to 17.1%). Inflation-adjusted hospital charges related to achalasia showed a mean increase of $2,521 per year (P < 0.001). There was an increase in Heller myotomy procedures over the study period (P < 0.001).ConclusionsThe number of hospitalizations for achalasia and associated costs has significantly increased significantly over the last 16 years in the United States with disproportionate increase in patients under 65 years of age and racial minorities. Further research on cost-effective evaluation and management of achalasia is required.

Current advances in biomarkers for targeted therapy in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD) and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-8); cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the gluco-corticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC.

Hydrochlorothiazide Induced Lichen Planus in the Emergency Department

Lichen planus (LP) is a mucocutaneous inflammatory disease that involves papulosquamous eruption of the skin, scalp, nails, and mucous membranes. This uncommon condition has a higher prevalence in African Americans and females. Women accounts for 50% of cutaneous LP (CLP) and 60% to 75% of oral LP (OLP) cases. Diagnosis is centered around clinical presentation. Patient evaluation requires a comprehensive physical examination to identify any potential sites of involvement. LP is usually described by the “Six P’s”: planar, purple, polygonal, pruritic, papules, and plaques. Drug-induced LP, or lichenoid drug reactions, is uncommon and usually indiscernible from other forms of LP. Lichenoid drug reactions exhibit parakeratosis, dermal infiltrates of eosinophils, or perivascular lymphocytic infiltrates affecting the reticular dermis. An extended time interval between the initiation of drug to the onset of symptoms usually does not exclude potential diagnosis of a lichenoid drug reaction. We describe a case of hydrochlorothiazide-induced LP without prolonged exposure to sunlight diagnosed in the emergency department (ED). In this case, a pharmacist-conducted medication reconciliation played an integral role in accurately recognizing this adverse drug reaction. Our case report adds to the limited available literature on the topic, most of which originated more than 30 years ago.