Evaluating Racial Disparities in Implementation and Monitoring of a Remote Blood Pressure Program in a Pregnant Population-A Retrospective Cohort Study.

Background: Whether remote blood pressure (BP) monitoring can decrease racial disparities in BP measurement during pregnancy and the postpartum period remains unclear. This study evaluated whether Black and White patients enrolled in the Connected Maternity Online Monitoring (CMOM) program showed improvements in BP ascertainment and interval. Methods: A retrospective cohort of 3,976 pregnant patients enrolled in CMOM were compared to matched usual care patients between January 2016 and September 2022 using electronic health record data. The primary outcomes were BP ascertainment (number of BP measurements) and BP interval (time between BP measurements) during pregnancy and the postpartum period. The proportion of patients with a hypertensive disorder of pregnancy who checked their BP within 7 days of discharge following delivery was also assessed. Results: Enrollment in CMOM was lower among Black patients than White patients (42.1% vs 54.7%, P<0.0001). Patients in the CMOM group had more BP measurements than patients in the usual care group during pregnancy (rate ratio=1.78, 95% CI 1.74-1.82) and the postpartum period (rate ratio=1.30, 95% CI 1.23-1.37), with significant improvements for both Black and White patients enrolled in CMOM compared to patients in usual care. The CMOM intervention did not result in an improvement in 7-day postpartum adherence to checking BP for Black patients (risk ratio=1.03, 95% CI 0.94-1.11) as it did for White patients (risk ratio=1.09, 95% CI 1.01-1.17). Conclusion: Remote BP monitoring programs are a helpful tool to improve the frequency of BP measurements and shorten intervals between measurements during the prenatal and postpartum periods for all patients. Future evaluation is needed to determine the barriers to offering the program to and enrolling Black patients.

The Impact of Post-Myocardial Infarction (MI) Depression on Cardiovascular-Related Hospitalizations.

Routine depression screening and subsequent treatment in post-myocardial infarction (MI) patients may lead to improved cardiac outcomes. However, screening for depression is not a standard of post-MI care. Though the American Heart Association (AHA) published an advisory recommending routine depression screening in post-MI patients, there is conflicting evidence on the benefit that routine depression screening has on cardiovascular outcomes. The purpose of this study is to compare the occurrence of cardiovascular-related readmissions in post-MI patients diagnosed with depression versus post-MI patients not diagnosed with depression. This retrospective cohort study analyzed the incidence of cardiovascular-related readmissions and mortality in adult post-MI patients diagnosed with depression within 1 year compared to those not diagnosed with depression within a year. Those diagnosed with depression were more likely to experience a subsequent cardiovascular-related hospitalization within 2 years of MI than those not diagnosed with depression (52.6% vs 28.7%; odds ratio [OR], 3.19; 95% CI 2.33-4.38). There was no difference between groups in the incidence of in-hospital mortality.

Increasing myocardial edema is associated with greater microvascular obstruction in ST-segment elevation myocardial infarction.

Microvascular obstruction (MVO) frequently develops after ST-elevation myocardial infarction (STEMI) and is associated with increased mortality and adverse left ventricular remodeling. We hypothesized that increased extravascular compressive forces in the myocardium that arise from the development of myocardial edema because of ischemia-reperfusion injury would contribute to the development of MVO. We measured MVO, infarct size, and left ventricular mass in patients with STEMI (n = 385) using cardiac MRI 2 to 3 days following successful percutaneous coronary intervention and stenting. MVO was found in 57% of patients with STEMI. The average infarct size was 45 ± 29 g. Patients with MVO had significantly greater infarct size and reduced left ventricular (LV) function (P < 0.01) compared with patients without MVO. Patients with MVO had significantly greater LV mass than patients without MVO and there was a linear increase in MVO with increasing LV mass (P < 0.001). Myocardial edema by T2-weighted imaging increased with increasing LV mass and patients with MVO had significantly greater myocardial edema than patients without MVO (P < 0.01). Patients with MVO had significantly greater left ventricular end-diastolic pressure (LVEDP) than patients without MVO (P < 0.05). In a cohort of patients with STEMI who underwent primary percutaneous intervention, we observed that MVO increased linearly with increasing LV mass and was associated with increased myocardial edema and higher LVEDP. These observations support the concept that extravascular compressive forces in the left ventricle may increase with increasing ischemic injury and contribute to the development of MVO.NEW & NOTEWORTHY Patients with STEMI (n = 385) had cardiac MRIs 2 to 3 days following reperfusion with primary PCI to determine the relationship between myocardial edema, LV mass, and MVO. We observed that MVO increased linearly with LV mass and that myocardial edema measured by T2-imaging also increased linearly with LV mass. Patients with MVO had greater edema and LVEDP than subjects without MVO. These findings suggest that myocardial edema which arises from ischemia-reperfusion injury may result in extravascular compression of the microcirculation manifested as MVO on cardiac MRI.

An Electronic Health Record Tool Increases Genetic Counseling Referral of Individuals at Hereditary Cancer Risk: An Intervention Study.

INTRODUCTION: There is widespread under-identification of individuals at hereditary cancer risk despite national guidelines calling for screening. We evaluated the utilization of a tool embedded in the electronic health record (EHR) to assist primary care providers in screening patients for cancer genetic counseling referral. METHODS: We designed BestPractice Advisories linked to a Genetic Cancer Screening Tool (GCST) in EpicCare Ambulatory. The GCST identifies individuals for evaluation for BRCA1/2, Lynch syndrome, and other risk mutations due to personal and family history. We tested the tool in a 7-week intervention in adult wellness visits at two clinics, one urban and one rural. RESULTS: Out of 687 eligible patients, the screening survey was completed for 469 (67%), and of these, 150 (32%) screened positive for a personal and/or family history meeting genetic counseling referral criteria. Of individuals screening positive, a referral order was placed for 20 (13%). GCST screen-positive rate varied by patient gender but not race or age. Referral rate varied by provider and clinic but was not significantly affected by patient demographics. In the previous year over an equivalent date range, 0.1% of wellness visits (1 of 1,086) led to a referral, and this rate increased to 2.1% (22 of 1,062) during the intervention. The proportion of providers referring patients also increased, from 3.8% (1 of 26) to 42.3% (11 of 26). DISCUSSION/CONCLUSION: Genetic counseling referral of individuals at hereditary cancer risk was increased by use of an EHR-integrated tool. These findings add evidence for the benefit of clinical decision support for cancer genetic risk screening in primary care.

HER2 Testing Characteristics Can Predict Residual Cancer Burden following Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer.

OBJECTIVES: The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC. METHODS: A retrospective chart review was conducted with Stage I-III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated. RESULTS: 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining (p < 0.0001), lower HER2 FISH copies (p < 0.0001), and lower HER2/CEP17 ratios (p = 0.0015) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories. CONCLUSIONS: HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.

Effects of Germline Pathogenic Variants, Cancer Subtypes, Tumor-related Characteristics, and Pregnancy-associated Diagnosis on Outcomes.

BACKGROUND: Although breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC. MATERIALS AND METHODS: This was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS. RESULTS: With mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing. CONCLUSIONS: Similar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.

Myocardial Work Index: A Novel Method for Assessment of Myocardial Function in South Asian Recreational Athletes.

PURPOSE: We used a novel noninvasive method based on speckle-tracking echocardiography to evaluate myocardial performance in South Asian recreational athletes who completed a half marathon. METHODS: Transthoracic echocardiography was performed on 24 recreational athletes 48 hours before they took part in a half marathon (premarathon), within 2 hours of half marathon completion (postmarathon), and 72 hours after completion. Clinical, laboratory, and echocardiographic variables were collected. Speckle-tracking echocardiography was performed in all subjects to characterize myocardial mechanics. RESULTS: Mean age of participants was 41.8 ± 7.4 years, and 23 (95.8%) were male. No subject had a prior history of coronary artery disease. Significant changes in pre- and postmarathon values suggested myocardial injury, including an increase in mean brain natriuretic peptide (BNP), an increase in left atrial volume, and an overall reduction in peak left ventricular global longitudinal strain. All subjects had a similar value of global work index, the average myocardial work, premarathon. Global work index did not change in 11 patients (Group 1), and global work index increased in 13 patients (Group 2) immediately postmarathon. Group 2 patients were noted to have higher heart rate, lower end-diastolic and end-systolic volumes, and higher BNP levels, suggesting myocardial stress. CONCLUSIONS: South Asian athletes completing a half marathon exhibited two different responses to the cardiac stress of the half marathon, as outlined by the use of myocardial work indices, a novel method for assessing cardiac performance.

Tablet vs. station-based laptop ultrasound devices increases internal medicine resident point-of-care ultrasound performance: a prospective cohort study.

BACKGROUND: Point-of-care ultrasound (POCUS) is becoming an important part of internal medicine (IM) residency training. Achieving competency requires performing a large volume of clinical exams which can be difficult within the constraints of residency. Often-cited barriers include insufficient resident time and the interruption of daily workflow. Despite availability of hospital station-based laptop ultrasound machines, we hypothesized that the addition of ward team-based tablet ultrasound devices would lower barriers and increase clinical POCUS volume within an IM residency POCUS curriculum at a 670-bed, quaternary care, teaching hospital. IM resident POCUS volumes and characteristics during an 18-mo. baseline (station-based laptop devices only) period were compared to matched months during the intervention (station-based + tablet). RESULTS: Total patients examined with POCUS by 6 inpatient resident teams during the 18-mo. baseline and intervention periods were 1386 and 1853, respectively. Patients examined per month increased during the intervention by 34% (77 vs. 103, p = 0.002). The number of areas (e.g., abdominal, cardiac) and items (e.g., bladder, pericardial effusion) examined per month increased by 27% (p = 0.021) and 23% (p = 0.073), respectively. CONCLUSIONS: A combined program infrastructure of station-based laptop and "in-the-pocket" tablet ultrasound devices lowered common POCUS barriers of inadequate time and workflow disruption for IM residents and resulted in a meaningful increase of exams within a longitudinal residency-based training program where station-based laptop devices already existed.

Noninvasive biomarker-based risk stratification for development of new onset atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Postoperative atrial fibrillation (PoAF) is a common complication after cardiac surgery. A pre-existing atrial substrate appears to be important in postoperative development of dysrhythmia, but its preoperative estimation is challenging. We tested the hypothesis that a combination of clinical predictors, noninvasive surrogate markers for atrial fibrosis defining abnormal left atrial (LA) mechanics, and biomarkers of collagen turnover is superior to clinical predictors alone in identifying patients at-risk for PoAF. METHODS: In patients without prior AF undergoing coronary artery bypass grafting, concentrations of biomarkers reflecting collagen synthesis and degradation, extracellular matrix, and regulatory microRNA-29s were determined in serum from preoperative blood samples and correlated to atrial fibrosis extent, alteration in atrial deformation properties determined by 3D speckle-tracking echocardiography, and AF development. RESULTS: Of 90 patients without prior AF, 34 who developed PoAF were older than non-PoAF patients (72.04 ± 10.7 y; P = 0.043) with no significant difference in baseline comorbidities, LA size, or ventricular function. Global (P = 0.007) and regional longitudinal LA strain and ejection fraction (P = 0.01) were reduced in PoAF vs. non-PoAF patients. Preoperative amino-terminal-procollagen-III-peptide (PIIINP) (103.1 ± 39.7 vs. 35.1 ± 19.3; P = 0.041) and carboxy-terminal-procollagen-I-peptide levels were elevated in PoAF vs. non-PoAF patients with a reduction in miR-29 levels and correlated with atrial fibrosis extent. Combining age as the only significant clinical predictor with PIIINP and miR-29a provided a model that identified PoAF patients with higher predictive accuracy. CONCLUSIONS: In patients without a previous history of AF, using age and biomarkers of collagen synthesis and regulation, a noninvasive tool was developed to identify those at risk for new-onset PoAF.

Secular Trend in the Use and Implementation of Impella in High-Risk Percutaneous Coronary Intervention and Cardiogenic Shock: A Real-World Experience.

OBJECTIVES: Cardiogenic shock carries high mortality despite advancements in therapeutic interventions. Impella (Abiomed) is a mechanical circulatory support device that is being increasingly used in cardiogenic shock patients. Impella is also utilized in high-risk patients undergoing percutaneous coronary intervention (PCI). We review the trend of Impella use at a single tertiary-care center, retrospectively analyze the outcomes, and discuss the increasing use of this device in the United States. METHODS: This a retrospective, observational study of Impella use for two indications, cardiogenic shock and high-risk PCI, at a tertiary-care center. The primary endpoint was the yearly implant rate of Impella and the secondary endpoint was periprocedural complications and major adverse cardiovascular events at 30 days. RESULTS: Forty-four Impella devices were implanted between 2008 and June of 2017. The rate of Impella implantation has significantly increased since its introduction in our facility in 2008. The most common complication was acute renal dysfunction (23%) followed by vascular complications (20%). Mortality at 30 days was 75% in the cardiogenic shock group and 11% in the high-risk PCI group. CONCLUSION: The use of the Impella device as a mechanical circulatory support has increased since its introduction, although its acceptance rate remains low. Despite its theoretical hemodynamic advantage, the outcome in cardiogenic shock patients remains poor.

Inappropriate usage of selected antimicrobials: Comparative residue proportions in rural and urban beef in Uganda.

INTRODUCTION: In most developing countries like Uganda, antimicrobials including ß-lactams and tetracyclines are used indiscriminately in livestock. When livestock get sick and treatment is necessary, some producers and veterinarians use these drugs with minimal controls to prevent residues from occurring in the beef sent to markets. This study was done to determine the presence of drug residues above acceptable limits of two commonly used antimicrobials in Uganda's rural and urban beef. METHODS: A cross-sectional study was conducted of 134 cattle carcasses from eight different slaughter slabs over twelve weeks. This study entailed 81 samples of rural and 53 samples of urban origin. To enable detailed analysis these samples were categorized according to age (maturity), breed, and sex. For each of the 134 carcasses, three samples of liver, kidney and muscle were taken and homogeneously mixed into one sample, which was tested for ß-lactam and tetracycline drug residues. RESULTS: The results were statistically significant for ß-lactam levels (χ2 = 22.10, df = 10, p = 0.0146) with average concentration (µg/kg) of 2.93:29.3 (rural: urban), though not for tetracycline levels (χ2 = 3.594, df = 10, P = 0.9638) with average concentration (µg/kg) of 5.028:12.83 (rural: urban). Age (maturity) had significant effect at all values of antibiotic level (F(1, 68) = 5.06, p = 0.0278). Age effect was extremely significant (F(1, 68) = 15.51, p = 0.0002). CONCLUSION: A significant difference existed in drug residue proportions of ß-lactam and tetracycline antimicrobials among Uganda's rural and urban beef. A significant difference also occured in drug residue proportions of these two commonly used antimicrobials related to age (maturity), but neither breed, nor sex, of Uganda's rural and urban beef.

Contemporary practice pattern of revascularization in a large tertiary care referral center in non-ST elevation myocardial infarction: A propensity-matched 10-year experience.

OBJECTIVES: We sought to compare the effects of early versus delayed percutaneous coronary intervention (PCI) on the outcomes at 1 year in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: Prompt reperfusion in NSTEMI remains controversial. Randomized studies have shown conflicting results regarding the benefits of early intervention versus delayed intervention (defined as intervention performed within 24 hr vs. 24-72 hr of presentation, respectively). This study was conducted to determine the clinical outcomes post PCI in a large tertiary care center. METHODS: A propensity-matched group of 1,640 NSTEMI patients [62.4% males (n = 1,023), median age 65 years] was studied for a composite of death, myocardial infarction (MI), stroke, and heart failure in 1 year as a primary endpoint after PCI. Patients were divided into an early intervention group (EIG) and delayed intervention group (DIG). Timing of PCI was determined by the treating interventional cardiologist. RESULTS: The primary outcome was significantly lower in the EIG than DIG (20.4% vs. 24.9%, P = 0.029), which was mainly derived from mortality benefit in the EIG. There was no difference in occurrence of death, MI, stroke, or heart failure between the groups at 30 days. CONCLUSIONS: An earlier PCI in patients with NSTEMI is associated with a significant reduction in the composite outcome of death, MI, heart failure, or stroke at 1 year compared with delayed PCI. Based on this large cohort of patients from a real-world referral center, contemporary reperfusion practices in NSTEMI may need to be re-examined with a bias toward early intervention.

Diagnostic accuracy of bicuspid aortic valve by echocardiography.

BACKGROUND: Echocardiography is regarded as the gold standard for diagnosis of bicuspid aortic valve (BAV), yet diagnostic accuracy has been evaluated previously only in single-center studies. We systematically evaluated the accuracy of BAV diagnosis in a large healthcare system of multiple echocardiography laboratories. METHODS AND RESULTS: Aurora Health Care is a multihospital, multi-clinic system across the state of Wisconsin encompassing 33 inpatient and outpatient echocardiography laboratories with 39 cardiologist readers and 72 sonographers. As all laboratories store echocardiograms in one database, we queried all patients with "bicuspid aortic valve" diagnosis on echocardiography. Echocardiograms were classified as "BAV" or "possible BAV" based on initial reader confidence. An expert review panel categorized each as BAV, no BAV, or Indeterminate. Of the 745 cases identified, 589 (79.1%, initial reader interpretation: n = 494 "BAV," n = 95 "possible") were BAV. A high level of agreement (84%) was present in BAV diagnosis. There were 156 (20.9%) echocardiograms that were no BAV (8.4%) or Indeterminate (12.4%). We identified three common reasons for misdiagnosis: poor image quality (n = 70, 44.9%), leaflet calcium (n = 44, 28.2%), and oblique axis imaging (n = 33, 21.1%). A clear reason for misclassification was not elucidated in nine cases (n = 9, 5.7%). CONCLUSIONS: This is the first study to evaluate BAV accuracy across a community health system with multiple echocardiography laboratories and a heterogeneous group of readers and sonographers. We establish a high degree of accuracy of echocardiography in BAV diagnosis and draw attention to common echocardiographic pitfalls that lead to BAV misclassification, highlighting opportunities for education and quality improvement.

Clinical Features and Prognosis of Type 2 Myocardial Infarction in Acutely Decompensated Diabetic Patients.

BACKGROUND: After the introduction of the universal definition of myocardial infarction, the incidence and diagnosis of type 2 myocardial infarction have risen dramatically, yet there are no clear guidelines on clinical management. Diabetic patients are at high risk for developing type 2 myocardial infarction when admitted in a decompensated state, and they are also at high risk for future cardiovascular events. METHODS: We performed a retrospective analysis of 1058 patients admitted with diabetic ketoacidosis or hyperosmolar hyperglycemic state between 2011 and 2016. Patients were included if they had cardiac troponin I measured within 24 hours of admission, were older than 18 years of age, and had no evidence of acute coronary syndrome on admission. Baseline characteristics, admission laboratory test results, major adverse cardiovascular events, cardiac stress testing, and coronary angiography data up to 1 year after admission were reviewed. Patients were categorized into 2 groups: those with and those without type 2 myocardial infarction. The study had 2 endpoints: mortality and major adverse cardiac events (MACE) at 1 year and an abnormal result on stress test or coronary angiography at 1 year. RESULTS: Of the 845 patients who met the inclusion criteria, 133 patients (15%) had type 2 myocardial infarction on admission. Patients with type 2 myocardial infarction were at a significantly higher risk for mortality and MACE at 1 year than those without. Patients with type 2 myocardial infarction were also at higher risk for developing an abnormal result on stress test or coronary angiography within 1 year of admission as compared with those without type 2 myocardial infarction (40% vs 24%; odds ratio 2; P = .0699). CONCLUSION: Acutely decompensated diabetic patients with type 2 myocardial infarction are at increased risk for death and MACE. These patients may also be at risk for undiagnosed coronary artery disease.

Marked respiratory-related fluctuations in left ventricular outflow tract gradients in hypertrophic obstructive cardiomyopathy: an observational study.

Aims: Left ventricular outflow (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM) is dynamic and sensitive to many variables that affect left ventricular preload, afterload, and contractility. The haemodynamic effect of normal respiration on LVOT obstruction has not been described. Methods and results: We examined 20 patients with HCM who were noted to have phasic respiratory variation of LVOT obstruction on initial transthoracic 2D echocardiogram and Doppler examination. LVOT gradients were re-examined with simultaneous recording of a respirometer. LVOT gradients varied widely during the respiratory cycle; peak gradients were uniformly lowest during inspiration (50.8 mmHg + 25.6) and highest during expiration (90.1 mmHg + 41.8). On average, there was 82.4% ± 39.1 (P ≤ 0.0001) incremental change from inspiration to expiration, in the severity of LVOT obstruction. In 11 patients with mitral annulus inflow, LV inflow (preload) was decreased during inspiration. In 16 patients with isovolumic relaxation time and ejection time measurements, decreased left atrial filling pressure was noted during inspiration, consistent with decreased LVOT obstruction. When compared with a control group of 20 HCM patients who did not have respiratory variation, the study group patients were more overweight (mean body mass index cases 35.1 ± 7.3 vs. control group 29.1 ± 5.1, P = 0.0045) and more likely to have sleep-disordered breathing (n = 15 study group, n = 5 control group). Conclusions: Counterintuitive respiratory-related fluctuations in LVOT gradients were observed in this case series of 20 HCM patients. These findings challenge traditional haemodynamic teaching and demonstrate the contribution of LV transmural pressure to LVOT obstruction in certain HCM patients.

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation.

Mitochondria are critical for maintaining normal cardiac function, and a deficit in mitochondrial energetics can lead to the development of the substrate that promotes atrial fibrillation (AF) and its progression. However, the link between mitochondrial dysfunction and AF in humans is still not fully defined. The aim of this study was to elucidate differences in the functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes and oxidative stress in right atrial tissue from patients without (non-AF) and with AF (AF) who were undergoing open-heart surgery and were not significantly different for age, sex, major comorbidities, and medications. The overall functional activity of the electron transport chain (ETC), NADH:O2 oxidoreductase activity, was reduced by 30% in atrial tissue from AF compared with non-AF patients. This was predominantly due to a selective reduction in complex I (0.06 ± 0.007 vs. 0.09 ± 0.006 nmol·min(-1)·citrate synthase activity(-1), P = 0.02) and II (0.11 ± 0.012 vs. 0.16 ± 0.012 nmol·min(-1)·citrate synthase activity(-1), P = 0.003) functional activity in AF patients. Conversely, complex V activity was significantly increased in AF patients (0.21 ± 0.027 vs. 0.12 ± 0.01 nmol·min(-1)·citrate synthase activity(-1), P = 0.005). In addition, AF patients exhibited a higher oxidative stress with increased production of mitochondrial superoxide (73 ± 17 vs. 11 ± 2 arbitrary units, P = 0.03) and 4-hydroxynonenal level (77.64 ± 30.2 vs. 9.83 ± 2.83 ng·mg(-1) protein, P = 0.048). Our findings suggest that AF is associated with selective downregulation of ETC activity and increased oxidative stress that can contribute to the progression of the substrate for AF.

Isolation and characterization of shiga toxin-producing escherichia coli serogroups O26, O45, O103, O111, O113, O121, O145, and O157 shed from range and feedlot cattle from postweaning to slaughter.

Cattle are the main reservoirs for Shiga toxin-producing Escherichia coli (STEC) strains. E. coli O26, O45, O103, O111, O121, O145, and O157 are among the STEC serogroups that cause severe foodborne illness and have been declared as adulterants by the U.S. Department of Agriculture, Food Safety and Inspection Service. The objectives of this study were (i) to estimate the prevalence of non-O157 STEC and E. coli O157 in naturally infected beef cows and in steer calves at postweaning, during finishing, and at slaughter and (ii) to test non-O157 STEC isolates for the presence of virulence genes stx1, stx2, eaeA, and ehlyA. Samples were collected from study animals during multiple sampling periods and included fecal grabs, rectal swabs, and midline sponge samples. Laboratory culture, PCR, and multiplex PCR were performed to recover and identify E. coli and the virulence genes. The prevalence of non-O157 STEC (serogroups O26, O45, O103, O111, O121, O113, and O145) fecal shedding ranged from 8% (4 of 48 samples) to 39% (15 of 38 samples) in cows and 2% (1 of 47 samples) to 38% (9 of 24 samples) in steer calves. The prevalence of E. coli O157 fecal shedding ranged from 0% (0 of 38 samples) to 52% (25 of 48 samples) in cows and 2% (1 of 47 samples) to 31% (15 of 48 samples) in steer calves. In steer calves, the prevalence of non-O157 STEC and E. coli O157 was highest at postweaning, at 16% (15 of 96 samples) and 23% (22 of 96 samples), respectively. Among the 208 non-O157 STEC isolates, 79% (164 isolates) had stx1, 79% (165 isolates) had stx2, and 58% (121 isolates) had both stx1 and stx2 genes. The percentage of non-O157 STEC isolates encoding the eaeA gene was low; of the 165 isolates tested, 8 (5%) were positive for eaeA and 135 (82%) were positive for ehlyA. Findings from this study provide further evidence of non-O157 STEC shedding in beef cows and steer calves particularly at the stage of postweaning and before entry into the feedlot.

Prevalence and antimicrobial susceptibility of virulent and avirulent multidrug-resistant Escherichia coli isolated from diarrheic neonatal calves.

OBJECTIVE: To determine the prevalence of selected virulence genes and the antimicrobial susceptibility of multidrug-resistant (MDR) Escherichia coli isolated from diarrheic neonatal calves. SAMPLE: 97 E coli isolates from diarrheic neonatal calves. PROCEDURES: E coli isolates were tested via PCR assay for 6 virulence genes and susceptibility to 17 drugs belonging to 9 classes. A 2-sample test of proportions was used to make comparisons between proportions of virulent and avirulent MDR isolates. RESULTS: 23 of 97 (23.7%) isolates were virulent, and 74 (76.3%) were avirulent. Of the 23 virulent isolates, 15 (65.2%) were positive for K99, 14 (60.9%) for F41, 12 (52.2%) for STa, 9 (39.1%) for Stx1, 6 (26.1%) for intimin, and 0 (0%) for Stx2. Twenty of 23 (87.0%) virulent isolates expressed ≥ 2 virulence genes, and 3 of 23 (13.0%) were positive for 1 virulence factor. Eight of 23 (34.8%) virulent isolates expressed STa, K99, and F41, whereas 1 of 23 (4.4%) was positive for STa, F41, intimin, and Stx1. The second most frequent gene pattern was Stx1 and intimin. Twenty of 23 (87.0%) virulent isolates were MDR; the highest prevalence of resistance was recorded for the macrolide-lincosides, followed by the tetracyclines and penicillins. Also, 17 of 23 (74.0%) virulent isolates were resistant to sulfadimethoxine, and 10 of 23 (43.5%) were resistant to trimethoprim-sulfamethoxazole. Additionally, 60 of 74 (81.0%) avirulent isolates were MDR. CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence of multidrug resistance was comparable for virulent and avirulent E coli isolated from diarrheic neonatal calves. Cephalosporins and aminoglycosides had reasonable susceptibility.

Proteomic analysis of multidrug resistant Escherichia coli strains from scouring calves.

A number of researchers have used chemical inhibitors that target membrane efflux pumps as an experimental treatment strategy for multidrug resistant (MDR) bacterial infections. However, most of these compounds are toxic in vertebrate animals. The present research was therefore done to describe expression dynamics of drug resistance-associated Escherichia coli proteins that could serve as novel drug targets. Proteomes of MDR and antimicrobial susceptible (AS) E. coli were studied in two dimensional (2-D) polyacrylamide gels and liquid chromatography-mass spectrometry (LC-MS) was performed on proteins of interest. The number of recovered peptides per protein was used to elucidate the amounts of target proteins expressed in MDR and AS E. coli strains. Eight proteins that may be potentially involved in mechanisms of drug resistance were analyzed and identified by LC-MS. These were grouped into membrane porins (TolC, OmpA, OmpC, Nmpc Precursor), proteins involved in microbial protein synthesis (EF-Ts, EF-Tu, RpsA) and Dps, a protein of unknown location and function. Experimental data demonstrated variability in the expression patterns and quantities of the four porins (TolC, OmpA, OmpC, Nmpc precursor), the three microbial protein synthesis associated proteins (EF-Ts, EF-Tu and RpsA), and Dps which has been previously associated with drug resistance. While variability was seen in quantities and expression patterns of some of the proteins of interest, the present data falls short of determining the suitability of these proteins as novel drug targets. Further studies are required to explore how these proteins could be targeted for drug development.

Factors associated with pastoral community knowledge and occurrence of mycobacterial infections in human-animal interface areas of Nakasongola and Mubende districts, Uganda.

BACKGROUND: Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens whose role in human and animal disease is increasingly being recognized. Major concerns are their role as opportunistic pathogens in HIV/AIDS infections. The role of open natural water sources as source and livestock/wildlife as reservoirs of infections to man are well documented. This presents a health challenge to the pastoral systems in Africa that rely mostly on open natural water sources to meet livestock and human needs. Recent study in the pastoral areas of Uganda showed infections with same genotypes of NTM in pastoralists and their livestock. The aim of this study was to determine the environmental, animal husbandry and socio-demographic factors associated with occurrence and the pastoral community knowledge of mycobacterial infections at the human-environment-livestock/wildlife interface (HELI) areas in pastoral ecosystems of Uganda. METHODS: Two hundred and fifty three (253) individuals were subjected to a questionnaire survey across the study districts of Nakasongola and Mubende. Data were analyzed using descriptive statistics and multivariable logistic regression analysis. RESULTS: Humans sharing of the water sources with wild animals from the forest compared to savannah ecosystem (OR = 3.3), the tribe of herding pastoral community (OR = 7.9), number of rooms present in household (3-5 vs. 1-2 rooms) (OR = 3.3) were the socio-demographic factors that influenced the level of knowledge on mycobacterial infections among the pastoral communities. Tribe (OR = 6.4), use of spring vs. stream water for domestic use (OR = 4.5), presence of sediments in household water receptacle (OR = 2.32), non separation of water containers for drinking and domestic use (OR = 2.46), sharing of drinking water sources with wild animals (OR = 2.1), duration of involvement of >5 yrs in cattle keeping (OR = 3.7) and distance of household to animal night shelters (>20 meters) (OR = 3.8) were significant socio-demographic factors associated with the risk of occurrence of mycobacterioses among the pastoral communities in Uganda. CONCLUSION: The socio-demographic, environmental and household related factors influence the risk of occurrence as well as pastoralists' knowledge of mycobacterial infections in the pastoral households at the human-environment-livestock/wildlife pastoral interface areas of Uganda.