tbuckley/cabot-search huggingface dataset:
Correspondence on ‘Which factors are associated with bone marrow oedema suspicious of axial spondyloarthritis as detected by MRI in the sacroiliac joints and the spine in the general population?’
Authors: Chun-Lin Su, Jhih-Wei Chen, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2021)

We have read with great interest the work by Xenofon Baraliakos.1 The authors evaluated the presence of bone marrow oedema (BME) in spinal and sacroiliac joint (SIJ) MRIs of 793 patients, and analysed its clinical predictors. This study identified that HLA-B27 +, delivery during the last year in female adult, high body mass index (BMI) and presence of back pain in the last 3 months were strongly associated with the extent of SIJ BME, while age and physically demanding work were the predictors for spinal BME. We agree with the hypothesis that mechanic strain such as delivery, high BMI and physically demanding work contribute to BME since multiple other researches also report the same results,2 3 and interestingly, unlike previous studies,4 high-sensitivity C reactive protein (hsCRP) is found not associated with SIJ-BME in this study. However, we believe that at least three points should be discussed to integrate these new results and help guiding further development of predictive …
Abstract 15314: Gene Therapy With Pellino1 Improves Perfusion and Decreases Tissue Loss in an Flk-1 Heterozygous Murine Limb Ischemia Model But Fails in Mapkapkinase 2 Knockout Mice
Authors: Diego Accorsi, Mahesh Thirunavukkarasu, Gopi Ukani, Mark Youssef, Santosh Swaminathan, J. Alexander Palesty, Nilanjana Maulik
Journal: Circulation (2020)

Introduction: Peripheral vascular disease (PVD) is a major cause of morbidity in the US. Vascular endothelial growth factor (VEGF) induces angiogenesis through Fetal-Liver Kinase-1 (Flk-1 or VEGFR-2), an endothelial tyrosine kinase receptor which activates a downstream signaling cascade involving MAPKAPKinase2 (MK2). We have demonstrated poorer recovery in hind limb ischemia models using Flk-1 +/- and MK2 -/- knockout mice compared to wild type mice. We also demonstrated overespression of Pellino1 (Peli1), an E3 Ligase, can attenuate ischemic damage and increase neovascularization and survivability of ischemic myocardium and skin flaps. Therefore, in this study we aim to show if Peli1 gene therapy can help rescue function in Flk-1 +/- and MK2 -/- after femoral artery ligation. Methods: 8-12 week-old Flk-1 +/- and MK2 -/- mice were subjected to femoral artery ligation of the right hind limb and treated with either adenovirus carrying Peli1 (Ad.Peli1) or LacZ (Ad.LacZ), for a total of 4 groups: Flk-1 +/- Ad.LacZ, Flk-1 +/- Ad.Peli1, MK2 -/- Ad.LacZ and MK2 -/- Ad.Peli1. Perfusion was assessed with laser Doppler imaging preop and on days 0, 3, 7, 14, 21 and 28. Extent of limb ischemia was also quantified using a standardized scoring scale (0 = no ischemia, to 8 = full limb amputation). Results: Perfusion was significantly higher in the Flk-1 +/- Ad.Peli1 group compared to Flk-1 +/- Ad.LacZ on days 7 (0.19±0.03 vs 0.08±0.02), 14 (0.41±0.07 vs 0.09±0.03), 21 (0.33±0.05 vs 0.14±0.05) and 28 (0.31±0.05 vs 0.15±0.02) (n=9-15, p&lt;0.05). The level of ischemia (ischemic score) was significantly lower in the Flk-1 +/- Ad.Peli1 group when compared to Flk-1 +/- Ad.LacZ on days 3 (1.89±0.56 vs 4.88±0.85), 7 (2.11±0.54 vs 5.69±0.92), 14 (2.18±0.52 vs 6.31±1.02), 21 (1.83±0.58 vs 6.50±1.05) and 28 (1.67±0.62 vs 6.50±1.05) (n=8-9, p&lt;0.05). There was no difference in perfusion or ischemic score between the MK2 -/- Ad.Peli1 and MK2 -/- Ad.LacZ groups. Values are mean +/- SEM. Conclusions: Treatment with Ad.Peli1 resulted in improved perfusion and decreased tissue ischemia in Flk-1 +/- mice. These results were not paralleled in MK2 -/- mice suggesting that Peli1 acts upstream to MK2 but downstream of VEGF/Flk-1. Overall, Peli1 gene therapy is a promising candidate in the management of PVD.
Abstract 17025: Myeloid Rage Protects From Insulin Resistance in Mice Fed High Fat Diet
Authors: Lakshmi Arivazhagan, Henry Ruiz, Robin Wilson, Laura Frye, Ravichandran Ramasamy, Ann Marie SCHMIDT
Journal: Circulation (2020)

Introduction: Obesity is a major global health problem, with over one third of adults in the US classified as obese. Obesity often leads to a state of insulin resistance (IR), type 2 diabetes (T2D) and its complications. We previously showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and IR, as whole body and adipocyte-specific Ager (gene encoding RAGE) deleted mice fed a high fat diet (HFD) were significantly protected from weight gain and IR. Here, we hypothesize that myeloid RAGE contributed to IR upon HFD feeding. Methods: We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager flox/flox and adipocyte and myeloid-specific (Double Knockouts) AdipoQCre(-/+)LyzMCre(+/+).Ager flox/flox deletion of Ager and LysMCre mice were used as control. Mice were fed either standard chow (LFD) or HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and composition, glucose and insulin sensitivity and whole body glucose metabolism by hyperinsulinemic-euglycemic clamp studies. Results: After 3 months HFD, there were no significant differences in body mass, body composition, food intake, energy expenditure and physical activity of the MDR mice vs. controls. Similar findings were observed in mice fed LFD. However, surprisingly, in HFD-fed mice, insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies showed decreased insulin sensitivity and insulin action in the MDR vs. control mice, indicating that the MDR mice were more insulin resistant. The Double Knockout (myeloid/adipocyte) Cre (+) mice were more glucose tolerant and insulin sensitive compared to MDR mice, showing that deletion of Ager in the adipocytes rescued the adverse effects of Ager deletion in myeloid cells. Conclusions: Myeloid Ager protects from IR in mice fed HFD. Furthermore, in MDR mice, concomitant adipocyte-specific deletion of Ager rescues these mice from IR and, at the same time, reduces HFD-induced adiposity. The mechanisms underlying these findings are under active investigation.
Abstract #5224: Cytogenetic evaluation and biochemical analysis of malathion induced toxicity in Sprague-Dawley rats
Authors: Pamela Moore, Anita Patlolla, Paul Tchounwou
Journal: Cancer Research (2009)

Malathion is a commonly used organophosphate pesticide that is considered relatively safe due to its low mammalian toxicity. Malathion functions by inhibiting cholinesterase (ChE) enzymes of the nervous system in both vertebrate and invertebrate organisms. The inactivation and modulation of these enzymes is therefore a useful indicator of exposure. The main objective of this study was to further elucidate the in vivo genotoxic potential of malathion using chromosome aberration, mitotic index, and modulation of enzyme activity as toxicological endpoints in bone marrow cells and blood serum of Sprague-Dawley rats. Four groups of four male rats each weighing approximately 60±2g, were injected intraperitoneally once a day for five days with doses of 2.5, 5, 10 and 20mg/kg BW of malathion dissolved in 1%DMSO. The control group was given 1%DMSO. All the animals were sacrificed at the end of the treatment period. Chromosome preparation was obtained using standard protocols. Blood specimens were immediately collected using heparinized syringes; cholinesterase, aspartate and alanine aminotransferase, alkaline and acid phosphatase (ChE, AST, ALT, ALP, ACP) were detected and quantified in serum samples by spectrophotometry (405nm). The mean frequency of induced structural chromosomal aberrations in bone marrow cells were 1.33±0.57, 5.3±2.5, 7.6±2.1, 11.3±1.5, and 17±2 for malathion doses of 0, 2.5, 5, 10, and 20mg/kg BW, respectively. It was also found that the mitotic index significantly decreased as the malathion dose increased. Mitotic indices of 18.4±0.75, 16.1±0.98, 14.1±0.96, 8.87±0.4, and 5.87±0.66 were recorded for malathion doses of 0, 2.5,5,10 and 20mg/kg BW, respectively. Further findings indicated a depression in ChE activity due to malathion treatment. ChE activity of 1376±119, 1286±119, 1286±159, 792±460, 747±506, and 628±97 U/L were recorded for malathion doses 0, 2.5, 5, 10 and 20mg/kg BW, respectively. There was also a significant increase in AST, ALT, ALP and ACP enzyme activity in the blood specimens. In summary, malathion exposure significantly increased the number of structural chromosome aberrations (CA), decreased mitotic index (MI), initiated a depression in ChE activity, and caused the modulation of enzyme activities (AST, ALT, ALP, ACP) in treated groups when compared with control groups. Biochemical analysis was further proven to be an accurate technique to determine the toxic effects of malathion, therefore acting as important biomarkers of effect to this compound.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5224.
Risk Factors for Incident Fracture in Older Adults With Type 2 Diabetes: The Framingham Heart Study
Authors: Alyssa B. Dufour, Douglas P. Kiel, Setareh A. Williams, Richard J. Weiss, Elizabeth J. Samelson
Journal: Diabetes Care (2021)

OBJECTIVE To identify risk factors for fracture in type 2 diabetes. RESEARCH DESIGN AND METHODS This prospective study included members of the Framingham Original and Offspring Cohorts. Type 2 diabetes was defined as fasting plasma glucose &amp;gt;125 mg/dL or use of type 2 diabetes therapy. We used repeated-measures Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% CIs for associations between potential predictors and incidence of fragility fracture. RESULTS Participants included 793 individuals with type 2 diabetes. Mean ± SD age was 70 ± 10 years; 45% were women. A total of 106 incident fractures occurred over 1,437 observation follow-up intervals. Fracture incidence increased with age (adjusted HRs 1.00, 1.44 [95% CI 0.65, 3.16], and 2.40 [1.14, 5.04] for &amp;lt;60, 60–70, and &amp;gt;70 years, respectively; Ptrend = 0.02), female sex (2.23 [1.26, 3.95]), HbA1c (1.00, 2.10 [1.17, 3.75], and 1.29 [0.69, 2.41] for 4.45–6.46% [25–47 mmol/mol], 6.50–7.49% [48–58 mmol/mol], and 7.50–13.86% [58–128 mmol/mol]; Ptrend =0.03), falls in past year (1.00, 1.87 [0.82, 4.28], and 3.29 [1.34, 8.09] for no falls, one fall, and two or more falls; Ptrend =0.03), fracture history (2.05 [1.34, 3.12]), and lower grip strength (0.82 [0.69, 0.99] per 5-kg increase). Femoral neck bone mineral density, BMI, smoking, physical function, chronic diseases, medications, and physical function were not associated with fracture incidence. CONCLUSIONS Prior falls, fractures, low grip strength, and elevated HbA1c are risk factors for fractures in older adults with type 2 diabetes. Evaluation of these factors may improve opportunities for early intervention and reduce fractures in this high-risk group.
Flexible partial shifts should be made to work
Authors: E. O'Neill
Journal: BMJ (1995)

EDITOR,--The new deal on junior doctors' hours arose out of an agreement signed in 1990, the government having been forced to address the issue of hours of work by a sustained campaign of publicity by junior doctors over the proceeding 3 years. Under the terms of the new deal no doctors should work more than 56 hours, whatever their working pattern. Set in the context of a maximum average of 72 hours on call, this obviously implies periods of rest.1 Despite the rantings of Christopher Wong this is not a new policy.1 2

The …
Abstract P060: Plasma Osteocalcin And Incident Diabetes Mellitus: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Jeffrey R Misialek, Elizabeth R Stremke, Elizabeth Selvin, Sanaz Sedaghat, James S Pankow, Pamela L Lutsey
Journal: Circulation (2021)

Introduction: Diabetes is a major risk factor for cardiovascular disease. Osteocalcin is a vitamin K-dependent, bone-derived hormone that functions as an endocrine regulator of energy metabolism, male fertility, and cognition. Early studies of endocrine effects of osteocalcin have shown that genomic deletion of osteocalcin in mice resulted in a diabetic phenotype (i.e. glucose intolerance, and insulin resistance). However, results from clinical studies have shown mixed associations between blood levels of osteocalcin and risk of incident type 2 diabetes mellitus. Hypothesis: Lower values of plasma osteocalcin would be associated with an increased risk of diabetes. Methods: A total of 11,557 ARIC participants without diabetes at baseline were followed from ARIC visit 3 (1993-1995) through 2018. Diabetes cases were identified through self-report on annual and semi-annual follow-up phone calls. Plasma osteocalcin data was measured using an aptamer-based proteomic profiling platform (SomaLogic). We used Cox regression to evaluate the association of quintiles of plasma osteocalcin and incident diabetes. The primary model adjusted for age, sex, and race-center. Results: Participants were age 60 ± 5.6 years at visit 3, 56% identified as female, 21% identified as Black. There were 3,031 incident diabetes cases over a median follow-up of 17.9 years. Mean ± SD was 10.053 ± 0.775. When comparing the highest quintile of plasma osteocalcin (values 10.42 to 14.66) to the lowest quintile (values 9.03 to 9.52), there was no association with incident diabetes (HRs [95% CIs]: 0.92 [0.81, 1.02]). There was also no significant trend across the quintiles (p = 0.19). Results were similar when adjusting for additional potential confounders, and when limiting the follow-up time to 10 years. Conclusions: These data do not support the hypothesis that total plasma osteocalcin, as measured by Somalogic proteomic panel, is a biomarker associated with diabetes risk. It is possible that total plasma or serum osteocalcin and/or other isoforms of osteocalcin protein (i.e. gamma carboxylated or uncarboxylated osteocalcin) measured via other validated methodologies may be linked to diabetes.
Abstract 15774: Site Variation and Early Outcomes for Coronary Revascularization in Patients Undergoing TAVR in Northern New England
Authors: Michael N Young, Harold L Dauerman, David J Malenka, Michael P Robich, Rony Lahound, James T Devries, Alexander Iribarne, James M Flynn, Patrick Magnus, Yi-Ling Huang, Cathy S Ross, David W Butzel
Journal: Circulation (2020)

Introduction: It is unclear whether or not percutaneous coronary intervention (PCI) prior to transcatheter aortic valve replacement (TAVR) yields an incremental benefit to patients with concomitant coronary artery disease (CAD). Hypothesis: We hypothesized that unprotected left main (LM) or proximal left anterior descending artery (pLAD) PCI conducted prior to TAVR is not associated with improved post-procedural clinical outcomes in a Northern New England patient population. Methods: We performed a retrospective study of 2,729 patients undergoing TAVR at 6 medical centers in Northern New England from 2012-2018. From this cohort, we identified patients with unprotected LM &gt;50% and/or pLAD &gt;70% CAD (n=160). We analyzed site variability and compared early outcomes of patients who underwent PCI ≤60 days before TAVR to those who did not. Results: Across 6 hospitals, there was significant variation in the use of PCI before TAVR (range 50%-76%, p for trend=0.361); this variation did not correlate with site TAVR volumes. In this 160 patient cohort, 36.2% had isolated LM&gt;50% and 76% had pLAD&gt;70% disease. The comparator groups were well-matched with respect to age, sex, and medical complexity. There were no significant differences between PCI and non-PCI groups with respect to early mortality, MI, or stroke after TAVR (Table). Conclusion: There is significant variation in revascularization practices before TAVR. The routine performance of unprotected LM or pLAD PCI before TAVR does not affect early post-valve outcomes in patients of Northern New England.
Abstract 15561: Incremental Prognostic Value of Biventricular Longitudinal Strain and Hs-tni in Covid-19 Patients
Authors: Mingxing XIE, Wei Sun, yanting zhang, CHUN WU, Yuji Xie, Li Zhang, Cynthia C. Taub
Journal: Circulation (2020)

Background: Myocardial strain derived from two-dimensional speckle-tracking echocardiography (2D-STE) has been shown to be more sensitive to detect early ventricular dysfunction than conventional echocardiography. However, the study about the prognostic value of biventricular longitudinal strain in coronavirus disease 2019 (COVID-19) is still scarce. Aims: We aimed to evaluate the prognostic value of biventricular longitudinal strain and its combination with high-sensitivity troponin I (hs-TNI) in COVID-19 patients. Methods: We enrolled a total of 160 COVID-19 patients who underwent both echocardiogram and hs-TNI testing. The cardiac structure, function and myocardial strain were compared between patients with and without elevated hs-TNI levels. Left ventricular longitudinal strain (LV LS) and right ventricular free wall longitudinal strain (RVFWLS) were determined by 2D-STE. Results: Compared with patients with normal hs-TNI levels, patients with elevated hs-TNI levels had diminished LV diastolic function, larger right-heart chamber, higher proportion of pulmonary hypertension, lower LV LS and RVFWLS. During a median follow-up of 60 days, 23 patients died. The multivariant analysis revealed LV LS and RVFWLS [Odd ratio (confidence interval): 1.533 (1.131-2.079); P =0.006; 1.267 (1.101-1.794), P =0.021, respectively] both were the independent predictors of higher mortality. Further, receiver-operating characteristic analysis revealed that the accuracy for predicting death was greater for the combination of hs-TNI levels with LV LS than separate LV LS (AUC: 0.93 vs 0.77, P =0.001), and for the combination of hs-TNI levels with RVFWLS than RVFWLS alone (AUC: 0.92 vs 0.83, P =0.041). Conclusion: Our study highlights that the combination of ventricular longitudinal strain with hs-TNI can provide a higher accuracy for predicting mortality in COVID-19 patients, which may enhance risk stratification in COVID-19 patients.
Oral Temperature of Noninfected Hospitalized Patients
Authors: Sidra L. Speaker, Elizabeth R. Pfoh, Matthew A. Pappas, Bo Hu, Michael B. Rothberg
Journal: JAMA (2021)

seropositive for N-protein IgG, the levels of S-protein IgG antibody were significantly higher than among the 60 without prior COVID-19 (P < .001)and were not statistically significantly different from the 36 who had a positive RT-PCR result and were seropositive for N-protein IgG (P = .26;Figure).Discussion | This preliminary study suggests that a single dose of BNT162b2 vaccine may be sufficient to obtain a high level of S-protein IgG antibody in nursing home residents previously diagnosed with COVID-19 based on RT-PCR results.This is in line with results based on IgG to spike trimer and neutralization antibody titers reported among health care workers with prior COVID-19 (diagnosed using SARS-CoV-2 IgG). 2 Measuring S-protein IgG antibody levels just before the second vaccine dose could be useful in determining whether a second dose is required in individuals whose infection history is unknown.This could limit possible adverse effects related to reactogenicity in previously infected patients and spare precious vaccine doses.
Exposure to corticosteroids in pregnancy is associated with adverse perinatal outcomes among infants of mothers with inflammatory bowel disease: results from the PIANO registry
Authors: Florence-Damilola Odufalu, Millie Long, Kirk Lin, Uma Mahadevan
Journal: Gut (2021)

Objective Active inflammatory bowel disease (IBD) during pregnancy may require the use of corticosteroids. The aim of this study was to investigate the impact of in utero corticosteroid exposure on adverse pregnancy outcomes, congenital malformations, infections and neurocognitive development among offspring of mothers with IBD. Design Using the prospective Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry, data were collected at each trimester, delivery; and in the 12 months post partum. Bivariate statistics and multivariate logistic regression models compared pregnancy outcomes by corticosteroid exposure. Results A total of 1490 mothers with IBD were enrolled, with 1431 live births recorded. Corticosteroid use was associated with increased risk of preterm birth, small for gestational age, low birth weight (LBW), intrauterine growth restriction and neonatal intensive care unit (NICU) admission. On adjusted multivariate models, corticosteroid use was associated with preterm birth (OR 1.79, 95% CI 1.18 to 2.73), LBW (OR 1.76, 95% CI 1.07 to 2.88) and NICU admission (OR 1.54, 95% CI 1.03 to 2.30). Late corticosteroid use (second and/or third trimester) was associated with serious infections at 9 and 12 months (4% vs 2% and 5% vs 2%, respectively, p=0.03 and p=0.001). There were five newborns with in utero corticosteroid exposure born with orofacial clefts versus one without corticosteroid exposure. Developmental milestones were similar across corticosteroid exposure groups. Conclusion In this prospective pregnancy registry, offspring of women exposed to corticosteroids during pregnancy were more likely to have adverse pregnancy outcomes. This emphasises the importance of controlling disease activity before and during pregnancy with steroid-sparing therapy.