University of Alabama at Birmingham
  • Birmingham, United States
Recent publications
Type 2 diabetes (T2D) risk is higher among non-Hispanic black (NHB) and Hispanic individuals, for reasons that are unclear. With this cross-sectional study, we tested the hypothesis that racial disparities in T2D prevalence can be partially traced to heterogeneity in etiology, as indicated by genetic subtypes that reflect distinct T2D phenotypes. Using a diverse sample of 361 US adults with T2D (69.5% women; 34.1% NHB; 13.9% Hispanic), we derived genetic risk scores (GRS) representing five distinct T2D pathophysiological pathways from 94 loci: beta-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. Genetic predisposition for insulin resistance (IR) was also assessed using a 52-SNP IR risk score. The beta-cell and proinsulin scores (as median [IQR]) were higher among NHB participants relative to NHW and Hispanics [beta-cell GRS (NHB, 0.842[0.784-0.887] vs NHW, 0.762[0.702-0.835] and Hispanic, 0.772[0.717-0.848]); proinsulin GRS (NHB, 1.006[0.973-1.070] vs NHW, 0.969[0.853-1.044] and Hispanic, 0.976[0.901-1.048])], whereas the liver/lipid and 52-SNP IR scores were higher in both NHB and Hispanic participants versus NHW [liver/lipid GRS (NHB, 1.09[0.78-1.18] and Hispanic, 0.895[0.736-1.227] vs NHW, 0.794[0.666-1.157]); 52-SNP IR GRS (NHB, 0.0095[0.009-0.010] and Hispanic, 0.0096 [0.0092-0.0101] vs NHW, 0.0090[0.0084-0.0095])]. Impaired beta-cell function may underlie T2D etiology more profoundly in NHB, whereas hepatic dysfunction, lipid metabolism abnormalities, and genetic IR contribute to T2D etiology to a greater degree in both NHB and Hispanics. Further validation of these findings may form the basis for a personalized medicine approach to prevention and treatment of T2D.
Aims/hypothesis Insulin resistance and inflammation are components of a biological framework that is hypothesised to be shared by type 2 diabetes and depression. However, depressive symptoms include a large heterogeneity of somatic and cognitive-affective symptoms, and this may obscure the associations within this biological framework. Cross-sectional and longitudinal data were used to disentangle the contributions of insulin resistance and inflammation to somatic and cognitive-affective symptoms of depression. Methods This secondary analysis used data from the Emotional Distress Sub-Study of the GRADE trial. Insulin resistance and inflammation were assessed using the HOMA-IR estimation and high-sensitivity C-reactive protein (hsCRP) levels, respectively, at baseline and at the study visits at year 1 and year 3 (HOMA-IR) and every 6 months (hsCRP) for up to 3 years of follow-up. Depressive symptoms were assessed at baseline using the Patient Health Questionnaire (PHQ-8), and a total score as well as symptom cluster scores for cognitive-affective and somatic symptoms were calculated. For the cross-sectional analyses, linear regression analyses were performed, with inflammation and insulin resistance at baseline as dependent variables. For the longitudinal analyses, linear mixed-effect regression analyses were performed, with inflammation and insulin resistance at the various time points as dependent variables. In all analyses, depressive symptoms (total score and symptom cluster scores) were the independent variables, controlled for important demographic, anthropometric and metabolic confounders. For the analysis of insulin resistance (HOMA-IR), data from 1321 participants were analysed. For the analysis of inflammation (hsCRP), data from 1739 participants were analysed. Results In cross-sectional analysis and after adjustment for potential confounders, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in HOMA-IR (p=0.007), but not with hsCRP (0.6% increase, p=0.283). The somatic symptom score was associated with a 5.8% increase in HOMA-IR (p=0.004). Single-item analyses of depressive symptoms showed that fatigue (3.6% increase, p=0.002) and increased/decreased appetite (3.5% increase, p=0.009) were significantly associated with HOMA-IR cross-sectionally. The cognitive-affective symptom score was not significantly associated with HOMA-IR at baseline. In longitudinal analyses, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in hsCRP over time (p=0.014), but not with HOMA-IR over time (0.1% decrease, p=0.564). Again, only the somatic symptom cluster was significantly associated with hsCRP over time (5.2% increase, p=0.017), while the cognitive-affective symptom score was not. Conclusion/interpretation The results highlight the associations of depressive symptoms with markers of inflammation and insulin resistance, both cross-sectionally and longitudinally, in individuals with type 2 diabetes. In particular, somatic symptoms of depression appear to be the driver of these associations, even after controlling for concomitant conditions, with a potential role for fatigue and issues with appetite. Trial registration: ClinicalTrials.gov NCT01794143 Graphical Abstract
Objective This study aims to evaluate the association between patient sex and discharge disposition as well as inpatient mortality following elective primary total hip arthroplasty (THA) for osteoarthritis (OA) in the United States. Methods This study used the 2016–2019 US National Inpatient Sample, a nationally representative dataset, to conduct a cross-sectional study. Adjusted odds ratios and 95% confidence intervals (CIs) were calculated to assess the association of sex with discharge disposition and in-hospital mortality after elective primary THA for OA, adjusting for demographics, comorbidity, social determinants of health (income, insurance payer), hospital characteristics (bed size, location/teaching status, region, control), and postprocedural complications (for mortality and discharge disposition). Results There were 1,507,085 elective primary THA hospitalizations for OA in the 2016–2019 National Inpatient Sample data. The mean age was 65.6 years, 55.7% were female, and the mean Deyo-Charlson comorbidity index score was 0.6. In multivariable-adjusted analysis, compared with male sex, female sex was associated with nonhome discharge, but not with in-hospital mortality following elective THA for OA; the adjusted odds ratios were 1.27 (95% CI, 1.25–1.29; p < 0.001) and 0.72 (95% CI, 0.46–1.13; p = 0.15), respectively. Conclusions Female sex was a risk factor for nonhome discharge, but not in-hospital mortality after elective primary THA for OA. It remains to be seen whether better patient health optimization with clinical pathways and targeted interventions in females undergoing elective primary THA can reduce the complication rate.
Background Non-cystic fibrosis bronchiectasis (NCFBE) is a disease that exhibits dilatation of airways, airflow obstruction, persistent cough, excessive sputum production, and refractory respiratory infections. NCFBE exhibits clinical and pathological manifestations similar to key features of cystic fibrosis (CF) lung disease. In CF, pathogenesis results from dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR), and diagnosis is made by demonstrating elevated sweat chloride concentrations (typically ≥60 mEq/L), two CFTR mutations known to be causal, multi-organ tissue injury, or combination(s) of these findings. Objective Based on a considerable body of evidence, we believe many patients with NCFBE have disease likely to benefit from drugs such as elexacaftor/tezacaftor/ivacaftor (ETI) that activate CFTR-dependent ion transport. ETI is currently prescribed solely for treatment of CF and has not been adequately tested or proposed for patients with NCFBE, many of whom exhibit decreased CFTR function. Accordingly, we are conducting a clinical trial of ETI in subjects carrying a diagnosis of NCFBE. Methods Participants will exhibit one disease-causing CFTR mutation and/or sweat chloride measurements of 30–59 mEq/L. Cutaneous punch biopsy or blood samples will be obtained for iPS cell differentiation into airway epithelial monolayers–which will then be tested for response to ETI. Each patient will be given CFTR modulator treatment for approximately four weeks, with monitoring of clinical endpoints that include FEV1 (forced expiratory volume in one second), sweat chloride, quality of life questionnaire, and weight. The study will evaluate response of patients with NCFBE to ETI, and test usefulness of iPSC-derived airway epithelial monolayers as a novel in vitro technology for predicting clinical benefit. Trial registration This trial is registered at clinicaltrials.gov (Identifier: NCT05743946. Date: 02/23/2023).
Objective This study aims to analyze hospitals' adoption and integration of electronic health record (EHR) metadata into their management processes. Design The study compares the rates of EHR metadata utilization across various hospitals over time. Hospitals' self‐reported use of EHR metadata is drawn from the AHA‐IT Supplements from 2018 to 2020. An analysis of metadata utilization by EHR vendors is also provided. Method The study uses Bass diffusion modeling to estimate EHR adoption parameters by fitting adoption rate data from 2018 to 2020, using Excel Solver to minimize prediction errors. The estimated internal and external influence coefficients reveal which factor primarily drives adoption, while the diffusion model enables future projection of tipping point and adoption level. Results Analysis of EHR metadata utilization rates from 2018 to 2020 find a significant trend towards the integration of this data into hospital management practices. Among health systems responding to the items of interest, 69% of them are already using EHR metadata, and it is projected that nearly all will do so by 2035. Further, metadata use varied significantly depending on the vendor. Discussion The study underscores that hospital managers' intrinsic motivations, rather than external demands, are driving EHR metadata. As innovations with greater intrinsic appeal spread more rapidly and have greater staying power, EHR metadata use will continue to grow. These trends are indicative of the growing importance of EHR metadata in management decision‐making, clinical quality improvement, and optimizing workforce efficiency. Conclusions EHR metadata holds great promise as a managerial and health service research source. The tools' utilities would be enhanced if EHR vendors created uniform metrics.
Throughout all domains of life, RNA polymerases (Pols) synthesize RNA from DNA templates, a process called transcription. During transcription, Pols require divalent metal cations for nucleotide addition and cleavage of the nascent RNA after misincorporation or polymerase stalling. Recently, several next-generation sequencing techniques have emerged to study transcription at single-nucleotide resolution in vivo. One such technique, native elongating transcript sequencing (NET-seq), allows for isolation of transcription elongation complexes associated with a specific Pol, defining polymerase occupancy on the DNA template. Originally developed to study RNA polymerase II (Pol II), NET-seq has been adapted for RNA polymerase I (Pol I) and bacterial RNA polymerase. We recently optimized Pol I NET-seq in Saccharomyces cerevisiae, however, we omitted nucleases and their metal cofactors, which are commonly used in Pol II NET-seq. Here, we investigated the effect of CaCl2 ± MNase and MnCl2 ± DNase I on Pol I occupancy. We found that exposure of Pol I to CaCl2 and MnCl2 during NET-seq caused a significant reduction in immunoprecipitation of nascent rRNA compared to the untreated control samples, with a more severe effect when incubated with MnCl2 vs. CaCl2. Surprisingly, in contrast to the Pol I results, we found that metal treatment during Pol II NET-seq did not have a significant effect on nascent transcript capture. Taken together, these observations reinforce the conclusion that transcription elongation complexes formed by Pols I and II have unique characteristics and emphasize the need to carefully consider experimental conditions deployed in all stages of nucleic acid library generation.
Black individuals have lower plasma natriuretic peptide (NP) concentrations than white individuals. However, race-based differences in the NP response to physiological perturbations are unknown. In this physiological trial (NCT#03070184), we measured the NP [mid-regional atrial NP (MR-proANP), N-terminal pro-B-type NP (NT-proBNP), and BNP] response to physiological perturbations among healthy, self-identified Black and white participants aged 18-40 years. The primary and secondary outcomes were the change in plasma NP concentrations at 6 weeks after metoprolol (initiated at 50 mg/day and doubled every 2 weeks) and standardized, aerobic exercise (70% of their maximal oxygen uptake on a salt-standardized background), respectively. Among 40 Black [median age: 27 (22, 32) years; 21 (52.5%) women] and 40 white [median age: 25 (20, 30) years; 19 (47.5%) women] participants, exercise increased MR-proANP (Black: 35%; white: 43%), NT-proBNP (Black: 11%; white: 23%), and BNP (Black: 59%; white: 61%) in both self-reported races. Exercise was associated with an increase in plasma MR-proANP (pinteraction: 0.25) and BNP (pinteraction: 0.87) concentrations which did not vary by self-reported race. However, the increase in plasma NT-proBNP concentrations were higher in white participants than in Black participants. (pinteraction: 0.04) Similarly, metoprolol therapy increased MR-proANP (Black: 18%; white: 16%), NT-proBNP (Black: 95%; white: 99%), and BNP (Black: 45%; white: 74%) in both self-reported races. The metoprolol-associated increase in plasma MR-proANP (pinteraction: 0.85), NT-proBNP (pinteraction: 0.94), and BNP (pinteraction: 0.21) concentrations were similar by self-reported race. In conclusion, the higher increase in plasma NT-proBNP concentrationsamong white patients after exercise suggests that exercise may induce significant physiological variations in NP levels. ClinicalTrials.gov ID: NCT03070184.
The desire to reduce patient morbidity has led to de-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) for breast cancer; however, the impact of such de-escalation on oncologic outcomes is unknown. We evaluated the relationship between axillary surgery type (sentinel lymph node [SLN] only vs. axillary lymph node dissection [ALND]) and 5-year outcomes in I-SPY2 trial patients from 2011 to 2022 who completed NAC and surgery. Rates of axillary recurrence (AxR), locoregional recurrence (LRR), distant recurrence-free survival (DRFS), and event-free survival (EFS) were compared. Of 1515 patients, SLN-only was performed in 804/1014 (79.3%) ypN0 patients and 127/501 (25.3%) ypN+ patients. Median follow-up time was 3.5 years. Most patients received adjuvant radiation (73.8% of ypN0 patients and 90.8% of ypN+ patients). In ypN0 cases, there was no difference between the SLN-only and ALND groups in 5-year estimated AxR (2.0% vs. 0.8%, p = 0.57), LRR (4.6% vs. 4.4%, p = 0.72), or EFS (88.3% vs. 86.4%, p = 0.09). On multivariable analysis, SLN-only was associated with better DRFS (90.8% vs. 87.9%; hazard ratio [HR] 0.54, p = 0.04). In ypN+ cases, there was no difference between the SLN-only and ALND groups in 5-year estimated AxR (5.2% vs. 3.6%, p = 0.81), LRR (7.7% vs. 14%, p = 0.13), DRFS (70.0% vs. 66.7%, p = 0.09), or EFS (70.4% vs. 63.2%, p = 0.07). With short-term follow-up, omission of ALND in selected patients was not associated with worse AxR, LRR, DRFS, or EFS in patients with ypN0 or ypN+ disease. While prospective trial results are awaited, these data suggest that ALND may not be necessary for all patients with residual nodal disease after NAC.
A fragment‐based approach has proven successful in drug design and protein assemblies, yet its potential for constructing biomaterials from simple organic building blocks remains underexplored, particularly for self‐assembly in aqueous phases, where water disrupts intermolecular hydrogen bonding. This study introduces the first case of integrating fragments from self‐assembling molecules to design a small organic molecule that forms novel hierarchical nanotubes with polymorphism. The molecule's compact design incorporates three structural motifs derived from known nanotube assemblies, enabling a hierarchical assembly process: individual molecules with two conformations form dimers, which organize into hexameric units. These hexamers further assemble into nanotubes comprising 2‐, 5‐, and 6‐protofilament fibers. The nanofibers share a nearly identical asymmetric unit—a hexameric triangular plate—with similar axial and lateral interfaces. The lateral interface, involving interactions between phosphate groups and aromatic rings, exhibits plasticity, allowing slight rotational variations between adjacent units. This adaptability facilitates the formation of diverse nanofiber architectures, showcasing the flexibility of these systems in aqueous environments. By leveraging fragments of self‐assembling molecules, this work demonstrates a straightforward strategy that combines conformational flexibility and self‐assembling fragments to construct advanced supramolecular biomaterials from small organic building blocks in aqueous settings.
Importance Transvaginal surgery is commonly performed to treat pelvic organ prolapse. Little research focuses on how sexual function relates to clitoral anatomy after vaginal surgery despite the clitoris’ role in the sexual response. Objective To determine how postoperative sexual function after vaginal surgery is associated with clitoral features (size, position, shape). Design, Setting, and Participants This was a cross-sectional ancillary study of magnetic resonance imaging (MRI) data from the Defining Mechanisms of Anterior Vaginal Wall Descent (DEMAND) study. The setting comprised 8 clinical sites in the US Pelvic Floor Disorders Network and included the MRI data of 88 women with uterovaginal prolapse previously randomized to either vaginal mesh hysteropexy or vaginal hysterectomy with uterosacral ligament suspension between 2013 and 2015. Data were analyzed between September 2021 and June 2023. Exposures Participants underwent postoperative pelvic MRI at 30 to 42 months (or earlier if reoperation was desired) between June 2014 and May 2018. Sexual activity and function at baseline (preoperatively) and 24- to 48-month follow-up (postoperatively) were assessed using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, International Urogynecological Association Revised (PISQ-IR). Clitoral features were derived from postoperative MRI-based 3-dimensional models. Main Outcomes and Measures Correlations between (1) PISQ-IR mean, subscale, and item scores and (2) clitoral size, position, and shape (principal component scores). Results A total of 82 women (median [range] age, 65 [47-79] years) were analyzed (41 received hysteropexy and 41 received hysterectomy). Postoperatively, 37 were sexually active (SA), and 45 were not SA (NSA). Among SA women, better overall postoperative sexual function (higher PISQ-IR summary score) correlated with a larger clitoral glans width (Spearman ρ = 0.37; 95% CI, 0.05-0.62; P = .03) and thickness (Spearman ρ = 0.38; 95% CI, 0.06-0.63; P = .02). Among NSA women, sexual inactivity related to postoperative dyspareunia correlated with a more lateral clitoral position (Spearman ρ = 0.45; 95% CI, 0.18-0.66; P = .002), and sexual inactivity related to incontinence/prolapse correlated with a more posterior clitoral position (Spearman ρ = −0.36; 95% CI, −0.60 to −0.07; P = .02) (farther from the pubic symphysis). Shape analysis demonstrated that poorer postoperative sexual function outcomes in SA women and sexual inactivity in NSA women correlated with a more posteriorly positioned glans, anteriorly oriented clitoral body, medially positioned crura, and lateral vestibular bulbs. Conclusions and Relevance Results of this cross-sectional study suggest that postoperative sexual function after vaginal surgery was associated with clitoral glans size, position, and shape. Results warrant prospective studies on surgery-induced changes in clitoral anatomy and sexual function.
Purpose Streptococcus pneumoniae (Spn) is the primary bacterial cause of lower respiratory tract infections (LRTI) globally, particularly impacting older adults and children. While Spn colonization in children is linked to LRTI, its prevalence, and consequences in adults with comorbidities remain uncertain. This study aims to provide novel data in that regard. Methods This prospective study of outpatient adults with chronic diseases was conducted in Colombia. Data on demographics, vaccination, and clinical history was collected in a RedCap database. Nasopharyngeal aspirate samples were examined for Spn colonization using traditional cultures and quantitative—real time polymerase chain reaction (q-rtPCR). Patients were followed for 18 months, with colonization prevalence calculated and factors influencing colonization and its impact on clinical outcomes analyzed through logistic regressions. Results 810 patients were enrolled, with 10.1% (82/810) identified as colonized. The mean (SD) age was 62 years (±15), and 48.6% (394/810) were female. Major comorbidities included hypertension (52.2% [423/810]), cardiac conditions (31.1% [252/810]), and chronic kidney disease (17.4% [141/810]). Among all, 31.6% (256/810) received the influenza vaccine in the previous year, and 10.7% (87/810) received anti-Spn vaccines. Chronic kidney disease (OR 95% CI; 2.48 [1.01–6.15], p = 0.04) and chronic cardiac diseases (OR 95% CI; 1.62 [0.99–2.66], p = 0.05) were independently associated with Spn colonization. However, colonization was not associated with the development of LRTI (OR 95%CI; 0.64 [0.14–2.79], p = 0.55) or unfavorable outcomes (OR 95% CI;1.17 [0.14–2.79], p = 0.54) during follow-up. Conclusions Chronic kidney and cardiac diseases are independently associated with Spn colonization. However, Spn colonization was not associated with LRTI/unfavorable outcomes in adult patients with chronic comorbidities in our cohort.
Objectives To assess the comparative safety of tumor necrosis factor inhibitor (TNFi), non-TNFi, and Janus kinase inhibitor (JAKi) biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) for the risk of major adverse cardiovascular events (MACE) using US administrative claims data. Methods We performed a cohort study using MerativeTM Marketscan® Research Databases (2012–2021) of individuals aged 18–64 years with RA initiating b/tsDMARD treatment. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for developing MACE within 2 years of b/tsDMARD initiation, adjusting for potential confounders. Results We included a total of 34 375 treatment exposures: 71% TNFi, 10% JAKi, 8% abatacept, 5% rituximab, and 5% IL-6i. Most individuals were female (77–84%) with a median (interquartile range) of 50 (42, 56) years. Rituximab had the highest incidence rate of MACE (196/10 000 person-years; 95% CI 126, 291), followed by IL-6i (111/10 000 person-years; 95% CI 57, 193). Multivariable analyses showed non-statistically significantly higher MACE risk with rituximab (HR 1.5; 95% CI 0.9, 2.4) and IL-6i (HR 1.3; 95% CI 0.7, 2.4) exposures but no increased risk with JAKi relative to TNFi use. Conclusion In this large nationwide study, rituximab and IL-6i users had numerically higher, but not statistically significant, MACE risk. Our data support the safety of b/tsDMARD use for RA treatment. This study was limited by short follow-up time and confounding by indication; further studies that can overcome these limitations are needed.
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Arie Nakhmani
  • Department of Electrical and Computer Engineering
Mark S Bolding
  • Department of Radiology
Cesar Acevedo-Triana
  • Graduate Biomedical Sciences (GBS)
Ichiro Nakano
  • Department of Optometry and Vision Science
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Birmingham, United States
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Ray Watts