African American communities disproportionately bear the burden of complications of diabetes. Early intervention can significantly improve the prognosis. Progress in overcoming disparities has been partially impaired by mistrust between the African American community and researchers. For this reason, minority men are often underrepresented in biomedical research studies that serve as the basis for the development of biomarkers for diagnosis and therapeutics. Overcoming this disparity calls for the development of culturally sensitive approaches that leverage partnerships with health care providers in minority serving clinics. A unique level of trust exists between African American communities and Historically Black Colleges and Universities (HBCUs). HBCU's are thus in a unique position to develop partnerships with clinical researchers to increase participation of African American men in research to promote healthy living and develop biomarkers for diseases that disproportionately affect their communities. In the current study, North Carolina A&T State University, one of the largest HBCU's in North Carolina, has partnered with the Cone Health Community Health and Wellness Center to build infrastructure to engage African American men in community participatory research. The research is designed to: (i) empower African American men to prevent and/or manage diabetes in order to prevent progression to complications, such as diabetic nephropathy and (ii) to increase collection of biological samples from African American men for biomarker development. Diabetic nephropathy (DN) is the most common complication of diabetes and is the leading cause of end stage renal disease. With the rising incidences of obesity, diabetes is becoming an epidemic in the African American community. While efforts are being made to develop biomarkers for early diagnosis of DN, participation of African American men in these studies has been minimal. By partnering with a community clinic that serves uninsured and underinsured patients, many of whom are from minority ethnic groups, we were able to engage diabetic African American men in biomedical research and collect biological samples for development of biomarkers of diabetic nephropathy. These samples will be subjected to proteomic and metabolomics analysis to identify biomarkers of diabetic nephropathy representative of the African American male population. Support or Funding Information NIH/NIHMD #U54MD008621 Sub‐Award # HU‐14004NIH/NIHMD U54MD008621 Sub‐Award # HU‐150006
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.
Chronic kidney disease is the most common complication of diabetes. Without interventions, diabetic kidney disease (DKD) progresses to end stage renal disease (ESRD). In the United States, minority ethnic groups (e.g. African Americans) are disproportionately burdened by DKD. While genetic factors contribute to the disparities in DKD, little is known about the underlying cellular and molecular mechanisms. Several studies have shown that inflammation plays a role in the pathophysiology of DKD and the fibrosis observed in diabetic nephropathy. The goal of the current study was to determine the association between specific inflammation markers and diabetic kidney injury in diabetic African American men, an underrepresented sub‐population with high risk for diabetes and DKD. To this end, diabetic patients with (n=21) and without (n=88) diagnosed kidney disease were recruited at the Cone Health Community Health and Wellness Center in Greensboro, NC. Age‐matched, non‐diabetic subjects (n=81) served as controls. Assays for albumin and creatinine were used for biochemical assessment of kidney function. The diabetic patients were then stratified into three groups based on their albumin to creatinine ratios (ACR); normoalbuminuria (ACR<30 mg/g), microalbuminuria (30 mg/g<ACR<300 mg/g), and macroalbuminuria (ACR>300 mg/g). Enzyme‐linked immunosorbent assays were used to measure the plasma and urinary levels of five inflammatory markers; two markers of system‐wide markers (adiponectin and C‐reactive protein (CRP)); and three markers involved in renal inflammation (tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), intercellular cell adhesion molecule‐1 (ICAM‐1)). Plasma levels of the pro‐inflammatory cytokines TNF‐α and IL‐6 were significantly higher in diabetic patients with micro‐ and macroalbuminuria when compared to non‐diabetic controls and diabetic patients with normoalbuminuria. Urinary levels for ICAM‐1 and the anti‐inflammatory cytokine, adiponectin, were higher in diabetic patients with macroalbuminuria than the other three groups. Plasma CRP was elevated in diabetic subjects compared to non‐diabetic controls, but did not correlate with the extent of diabetic kidney injury. In contrast, urinary ICAM‐1, plasma TNF‐α, and plasma adiponectin had moderate positive correlations with ACR. The plasma levels for ICAM‐1, IL‐6, and CRP were not significantly correlated with the ACR. The data suggest that certain inflammation pathways play a role in the pathogenesis of DKD in African American men. Support or Funding Information This 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 .
Diabetic nephropathy (DN) is a progressive kidney disease caused by damage to the capillaries in the kidneys' glomeruli due to changes in glomerular hemodynamics, causing renal lesions and fibrosis. Oxidative stress and inflammatory responses represent underlying causes for developing chronic kidney damage. Treatment outcomes for DN are poor because many patients with DN are diagnosed late due to lack of clinical tests based on sensitive biomarkers. Monocyte chemoattractant protein‐1 (MCP‐1) is a major promoter of inflammation, renal injury, and fibrosis in diabetic nephropathy. In the United States, minority ethnic communities bear a disproportionate burden of complications of diabetes and are at a higher risk of developing end stage renal disease. Participation in biomedical research by African American men is especially low due to historical mistrust with the research institutions. The objective of this study is to assess correlations between biomarkers of kidney injury and indicators of inflammation among three groups of African American men: 1) diabetic patients without DN, 2) diabetic patients with diagnosed DN, and 3) non‐diabetic controls. Fasting blood and urine samples were collected from patients recruited through a community health clinic. Surveys were administered to establish patient profiles and family history. Enzyme‐linked immunosorbent assays (ELISA) were used to determine the levels of plasma MCP‐1 and the levels of three biomarkers of kidney injury, namely, cystatin C, neutrophil gelatinase‐associated lipocalin (NGAL), and kidney injury molecule 1 (KIM‐1). The data were analyzed by 2‐way ANOVA. The data showed that the levels of serum cystatin C were significantly higher in patients with diagnosed DN compared to non‐diabetic controls (p<0.01). Additionally, diabetic patients showed a significant increase in serum cystatin C levels relative to the non‐diabetic controls (p<0.05). In contrast, urine cystatin C levels were significantly lower in patients with DN compared to the other two groups. Plasma NGAL levels were significantly higher in patients with DN compared to both non‐diabetic and diabetic patients (p<0.01). However, there was no significant difference in the levels of urine KIM‐1 among the three groups. In conclusion, serum MCP‐1 exhibited higher levels in patients with DN compared to both diabetic patients and non‐diabetic controls (p<0.0001). The significant increase in serum MCP‐1 levels suggests that inflammation is an underlying cause of kidney injury in African American men who have DN. Furthermore, the data suggest that a significant number of diabetic African American men may have undiagnosed kidney injury as shown by elevated cystatin C levels. Support or Funding Information This study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Award # HU140004 and sub‐award #HU150006.
We report Stenotrophomonas maltophilia as a cause of Gradenigo’s syndrome, a rare complication of suppurative otitis media (OM). The clinical triad of sixth nerve palsy, OM and pain in the distribution of trigeminal nerve constitute the diagnosis of Gradenigo’s syndrome. Common organisms that have been recovered include; Group A Streptococcus, Pneumococcus, Staphylococcus, Pseudomonas aeruginosa and Mycobacterium tuberculosis. Our aim is to report the first case of Gradenigo’s syndrome caused by S. maltophilia, an aerobic, non-fermentative, Gram-negative bacterium which causes uncommon but difficult to treat infections in humans. Rare pathogens such as S. maltophilia should be included in the differential diagnosis of organisms causing complicated non-responding OM even if the host is immunocompetent.
Diabetic nephropathy (DN), the most common complication of diabetes, develops in about one‐third of diabetic patients. The prevalence of diabetes is higher in ethnic minorities, affecting approximately 13% of African Americans, 9.5% of Hispanics, and 15% of Native Americans, primarily with type 2 diabetes. African‐American men are underrepresented in research studies used to develop biomarkers for diagnosis and early detection of DN. Previous studies have developed more sensitive and reliable proteomic markers of kidney injury, which include neutrophil gelatinase‐associated lipocalin (NGAL), cystatin C, and kidney injury molecule‐1 (KIM‐1). Accumulating evidence suggests that transforming growth factor β1 (TGF‐β 1 ) is involved in the development of renal scarring. Meanwhile, adiponectin is an adipokine that has been shown to have reno‐protective effects through AMPK‐activated pathways, resulting in the prevention of albuminuria. The goal of the current study was to determine the correlation between proteomic biomarkers of kidney injury, adiponectin, and TGF‐β1 in African American men with diabetes. To this end, fasting blood and urine samples were collected from African American men aged 18 to 62 years. Three groups were compared, namely: diabetics (n=43), diabetics with diagnosed diabetic nephropathy (n=7), and non‐diabetic controls (n=28). Enzyme‐linked immunosorbent assays (ELISA) were used to determine the plasma and urine levels of proteomic markers of kidney injury (creatinine, cystatin C, NGAL, and KIM‐1), as well as the levels of adiponectin, and TGF‐β1. The data were analyzed by 2‐way ANOVA (GraphPad Prism). Plasma NGAL levels were significantly higher in patients with diagnosed DN when compared to diabetics without kidney injury and non‐diabetic controls (p≤0.01). Similarly, plasma cystatin C levels were significantly higher in patients with DN when compared to non‐diabetic controls and diabetics without known kidney injury (p≤0.01). Diabetic patients had a modest but significant increase in plasma cystatin C when compared to non‐diabetic controls (p≤0.05). In contrast, the urinary cystatin C levels were lower in all diabetic patients when compared to non‐diabetic controls. There was no significant difference in urine creatinine levels among the non‐diabetic and diabetic patients evaluated. There was a significant increase in urinary adiponectin levels in patients with DN when compared to non‐diabetic controls and diabetic patients without known kidney injury (p≤0.01). A modest increase in adiponectin was also observed in diabetic patients without DN when compared to non‐diabetic controls. However, there was no significant difference in TGF‐β1 levels between the three groups analyzed. Our data shows an increase in plasma cystatin C levels in diabetic African American men. This increase may be indicative of early onset of kidney disease, suggesting that cystatin C could be a suitable marker for early diagnosis of DN. The data also shows that adiponectin and/or adiponectin‐mediated pathways may play a role in the progression of DN in African American men. Support or Funding Information This study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Awards # HU140004 and HU150006. Ava Boston is supported by the RISE program under NIH/NIGMS Grant # R25GM076162 to Goldie S Byrd
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<30 mg/g), only the macroalbuminuria (ACR>300 mg/g) and not the microalbuminuria (300 mg/g>ACR>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 Information This 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 .
African Americans are disproportionately burdened by diabetic kidney disease (DKD). However, little is known about the cellular and molecular mechanisms underlying the onset and progression of DKD in this population. The goal of the current study was to determine the association between specific inflammation markers and kidney injury in diabetic African American men. To this end, we recruited diabetic patients either with (n = 20) or without (n = 87) diagnosed kidney disease along with age-matched nondiabetic controls (n = 81). Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFR) were used for biochemical assessment of kidney function. We then measured plasma and urinary levels of seven inflammatory markers, including adiponectin, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), interleukin-6 (IL-6), and intercellular cell adhesion molecule-1 (ICAM-1). Plasma levels of TNF-α, TNFR1, and TNFR2 were significantly higher in diabetics with macroalbuminuria compared to nondiabetic controls and diabetics with normoalbuminuria or microalbuminuria. Likewise, urinary levels of ICAM-1 were higher in diabetics with macroalbuminuria compared to the other groups. Indeed, urinary ICAM-1, plasma TNF-α, and adiponectin had moderate positive correlations with UACR while plasma TNFR1 and TNFR2 levels were strongly correlated with kidney injury, indicated by multiple biomarkers of kidney injury. In contrast, though plasma CRP was elevated in diabetic subjects relative to nondiabetic controls, its levels did not correlate with kidney injury. Together, these data suggest that inflammation, particularly that mediated by the TNF-α/NF-κB signaling axis, may play a role in the pathogenesis of DKD in African American men.
This study was conducted to determine the fungi associated with persistent cough in immunocompromised patients attending Jos University Teaching Hospital (JUTH) and Vom Christian Hospital both in Plateau State. Hundred (100) immunocompromised patients with persistent cough were selected by random sampling. The sputum samples were collected and assayed for fungi using standard methods. The degree of disparity was analyzed using statistical method. Four different fungi were isolated from sputum of 37 (37%) immunocompromised patient with persistent cough, with Candida albicans been the highest 18 (48.6%) followed by Aspergillus niger 12 (32.4%), Cryptococcus neoformans 5 (13.5%) and Penicilium species 2(5.4%). Male subjects 22 (22%) were more susceptible to fungi associated cough than female 15(15%) with significant difference (P value 0.026). HIV, Tuberculosis and co-infection of both (HIV and TB) and prolong use of antibiotics were more predisposing factor associated with fungi related cough. These isolates were tested on 5 antifungal drugs. Ketoconazole and intraconazole were most susceptible to 83.8% of isolates, Amphotericin B had 54.1% susceptible while Griseofulvin and Vericonazole were 18.9% susceptible to the isolates. However, in managing the immunocompromised patient, there is a need for antifungal prophylaxis and sending of sample of immunocompromised host with persistent cough not only for bacteriological analysis but also mycological evaluation.
