tbuckley/cabot-search huggingface dataset:
Evaluation of Occupational Exposure Limits for Heat Stress in Outdoor Workers — United States, 2011–2016
Authors: Aaron W. Tustin, Glenn E. Lamson, Brenda L. Jacklitsch, Richard J. Thomas, Sheila B. Arbury, Dawn L. Cannon, Richard G. Gonzales, Michael J. Hodgson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Heat stress, an environmental and occupational hazard, is associated with a spectrum of heat-related illnesses, including heat stroke, which can lead to death. CDC's National Institute for Occupational Safety and Health (NIOSH) publishes recommended occupational exposure limits for heat stress (1). These limits, which are consistent with those of the American Conference of Governmental Industrial Hygienists (ACGIH) (2), specify the maximum combination of environmental heat (measured as wet bulb globe temperature [WBGT]) and metabolic heat (i.e., workload) to which workers should be exposed. Exposure limits are lower for workers who are unacclimatized to heat, who wear work clothing that inhibits heat dissipation, and who have predisposing personal risk factors (1,2). These limits have been validated in experimental settings but not at outdoor worksites. To determine whether the NIOSH and ACGIH exposure limits are protective of workers, CDC retrospectively reviewed 25 outdoor occupational heat-related illnesses (14 fatal and 11 nonfatal) investigated by the Occupational Safety and Health Administration (OSHA) from 2011 to 2016. For each incident, OSHA assessed personal risk factors and estimated WBGT, workload, and acclimatization status. Heat stress exceeded exposure limits in all 14 fatalities and in eight of 11 nonfatal illnesses. An analysis of Heat Index data for the same 25 cases suggests that when WBGT is unavailable, a Heat Index screening threshold of 85°F (29.4°C) could identify potentially hazardous levels of workplace environmental heat. Protective measures should be implemented whenever the exposure limits are exceeded. The comprehensive heat-related illness prevention program should include an acclimatization schedule for newly hired workers and unacclimatized long-term workers (e.g., during early-season heat waves), training for workers and supervisors about symptom recognition and first aid (e.g., aggressive cooling of presumed heat stroke victims before medical professionals arrive), engineering and administrative controls to reduce heat stress, medical surveillance, and provision of fluids and shady areas for rest breaks.
Abstract 16862: Afterload-Induced Myocardial Fibrosis is Promoted by TRIF-Dependent Inflammation
Authors: Stephan H Schirmer, Stephanie I Bettink, Andrej Kazakov, Christina Körbel, Michael Böhm, Ulrich Laufs
Journal: Circulation (2012)

Background: Inflammation contributes to myocardial and vascular remodeling. The role of TIR-domain-containing adapter-inducing interferon-s (TRIF) and interferon regulatory factor-3 (IRF3)-dependent inflammatory signaling during myocardial hypertrophy is incompletely understood.  Methods and results: Afterload-induced myocardial remodeling was induced by trans-aortic constriction (TAC) in C57Bl/6J wildtype (WT) and TRIF-/- mice. Left ventricular (LV) mRNA-expression of MyD88-dependent inflammatory cytokines (TNFalpha, IL6) was upregulated 7 days after TAC in both strains, while TRIF-dependent cytokines (CXCL10, CXCL11, RANTES) and pathway molecules (IRF3) remained unchanged in TRIF-/- mice. Furthermore, knockout mice showed reduced CD3 T-cell (8.1±1.3-fold vs. sham, p   Conclusion:  TRIF-dependent signaling plays an important role in the regulation of fibrosis and capillarisation during pressure overload-dependent cardiac remodeling in mice. Further studies are ongoing to evaluate particularly diastolic LV function in this model and to investigate molecular effects of TRIF inhibition of fibrogenesis and angiogenesis.
Effect of Natriuretic Peptide Family on the Oxidized LDL–Induced Migration of Human Coronary Artery Smooth Muscle Cells
Authors: MasakazuKohno, KojiYokokawa, KenichiYasunari, HiroakiKano, MiekoMinami, MakikoUeda, JunichiYoshikawa
Journal: Circulation Research (1997)

Abstract The migration of medial smooth muscle cells (SMCs) into the intima is proposed to be an important process of intimal thickening in atherosclerotic lesions. The present study examined the possible effect of a novel endothelium-derived relaxing peptide, C-type natriuretic peptide (CNP), on oxidized low-density lipoprotein (LDL)–induced migration of cultured human coronary artery SMCs by the Boyden’s chamber method. The effect of CNP was compared with that of atrial and brain natriuretic peptides (ANP and BNP, respectively). Oxidized LDL stimulates SMC migration in a concentration-dependent manner between 20 and 200 μg/mL. This stimulation was chemotactic in nature but was not chemokinetic. By contrast, native LDL was without significant activity. CNP-22 clearly inhibited SMC migration stimulated with 200 μg/mL oxidized LDL in a concentration-dependent manner between 10−9 and 10−6 mol/L. ANP-(1-28) and BNP-32 also inhibited oxidized LDL–induced SMC migration at concentrations of 10−7 and 10−6 mol/L,...
Outcomes in Catheter Ablation of Ventricular Tachycardia in Dilated Nonischemic Cardiomyopathy Compared With Ischemic Cardiomyopathy
Authors: BorislavDinov, LukasFiedler, RobertSchönbauer, AndreasBollmann, SaschaRolf, ChristopherPiorkowski, GerhardHindricks, ArashArya
Journal: Circulation (2014)

Background—Data on the outcomes of ventricular tachycardia (VT) ablation in nonischemic dilated cardiomyopathy (NIDCM) are insufficient. The Heart Center of Leipzig VT (HELP-VT) study was conducted prospectively to compare outcomes after radiofrequency catheter ablation of VT in patients with NIDCM compared with ischemic cardiomyopathy (ICM). Methods and Results—Two hundred twenty-seven patients, 63 with NIDCM and 164 with ICM, presenting with sustained VT were ablated with radiofrequency catheter ablation. Noninducibility of any clinical and nonclinical VT was achieved in 66.7% of NIDCM and in 77.4% of ICM patients. Ablation of the clinical VT only was achieved in 18.3% of ICM and in 22.2% of NIDCM patients. There was no statistically significant difference in short-term outcomes between the 2 groups. At the 1-year follow-up, VT-free survival in NIDCM was 40.5% compared with 57% in ICM. In univariate analysis, the hazard ratio for VT recurrence was significantly higher for NIDCM (1.62; 95% confidence int...
Abstract 939: Galpha-i Signaling in Neural Crest Cells is Required for Normal Migration of Cardiac Neural Crest Cells, Cardiac Development, and Survival
Authors: Kathleen M Ruppel, Hiroshi Kataoka, Michelle Iwaki, Ivo Cornelissen, Shaun R Coughlin
Journal: Circulation (2007)

G protein coupled receptors (GPCRs) have long been known to play crucial roles in transducing environmental signals to the adult cardiovascular system. In recent years, the roles of G protein-mediated signaling pathways in orchestrating the interactions of different tissues during cardiovascular development have become increasingly evident. To analyze the role of G protein signaling pathways in vivo we have generated mice where the function of the heterotrimeric G alpha subunit Gai can be ablated in a cell type specific manner utilizing the Cre-loxP system. We have mated these mice to two different neural crest-specific Cre lines in order to probe the effects of loss of Gai mediated signaling on the ability of neural crest cells (NCC) to contribute to the developing outflow tract and aortic arch arteries. METHODS: We have generated mice that express the Gai-inhibiting pertussis toxin S1 subunit (PTX) from the ROSA26 locus in a Cre recombination dependent manner (ROSA-PTX mice). These were mated to mice expressing either the Wnt1 Cre or P0 Cre transgene. Wnt1Cre is active in both premigratory and migratory NCC, whereas P0Cre is active only in migratory NCC and their derivatives. RESULTS: P0Cre-ROSA-PTX mice were normal at birth and demonstrated no structural heart defects. In contrast, Wnt1Cre-ROSA-PTX mice were present in normal numbers at late gestation but died perinatally due in part to cardiac outflow tract defects. Excision reporter and in situ hybridization studies suggest this is secondary to a delay/blockage of cardiac NCC migration into the developing outflow tract. NCC migration into the pharyngeal arches was unaffected in these mice and no craniofacial, thymic, or aortic arch abnormalities were observed. CONCLUSIONS: These results indicate that Gai-mediated signaling is required in premigratory or early migratory cardiac NCC for normal development of the outflow tract. In contrast, endothelin A receptor knockout mice (currently the only GPCR knock out with a neural crest phenotype) are thought to exhibit defects of postmigratory NCC function. RNA profiling of NCC for GPCRs involved in this Gai-dependent pathway has revealed several potential candidate receptors, including orphan receptors. Further analysis of these receptors is underway.
Pathological bases and clinical impact of long noncoding RNAs in prostate cancer: a new budding star
Authors: Tao Xu, Chang-ming Lin, Shu-qi Cheng, Jie Min, Li Li, Xiao-ming Meng, Cheng Huang, Lei Zhang, Zi-yu Deng, Jun Li
Journal: Molecular Cancer (2018)

Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides. Recent advances in the non-protein coding part of human genome analysis have discovered extensive transcription of large RNA transcripts that lack coding protein function, termed non-coding RNA (ncRNA). It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in diverse diseases are not yet fully understood. Thus, it is anticipated that more efforts should be made to clarify the lncRNA world. Moreover, accumulating evidence has demonstrated that many lncRNAs are dysregulated in prostate cancer (PC) and closely related to tumorigenesis, metastasis, and prognosis or diagnosis. In this review, we will briefly outline the regulation and functional role of lncRNAs in PC. Finally, we discussed the potential of lncRNAs as prospective novel targets in PC treatment and biomarkers for PC diagnosis.
Subclonal evolution in disease progression from MGUS/SMM to multiple myeloma is characterised by clonal stability
Authors: Ankit K. Dutta, J. Lynn Fink, John P. Grady, Gareth J. Morgan, Charles G. Mullighan, Luen B. To, Duncan R. Hewett, Andrew C. W. Zannettino
Journal: Leukemia (2018)

Multiple myeloma (MM) is a largely incurable haematological malignancy defined by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow. Clonal heterogeneity has recently been established as a feature in MM, however, the subclonal evolution associated with disease progression has not been described. Here, we performed whole-exome sequencing of serial samples from 10 patients, providing new insights into the progression from monoclonal gammopathy of undetermined significance (MGUS) and smouldering MM (SMM), to symptomatic MM. We confirm that intraclonal genetic heterogeneity is a common feature at diagnosis and that the driving events involved in disease progression are more subtle than previously reported. We reveal that MM evolution is mainly characterised by the phenomenon of clonal stability, where the transformed subclonal PC populations identified at MM are already present in the asymptomatic MGUS/SMM stages. Our findings highlight the possibility that PC extrinsic factors may play a role in subclonal evolution and MGUS/SMM to MM progression.
Electroacupuncture for Painful Diabetic Peripheral Neuropathy: A Multicenter, Randomized, Assessor-Blinded, Controlled Trial
Authors: Kyung-Min Shin, Seunghoon Lee, Eun Yong Lee, Cheol-Hong Kim, Jung Won Kang, Cham Kyul Lee, Bok-Nam Seo, Ae-Ran Kim, So-Young Jung, Ojin Kwon, Sun-Mi Choi
Journal: Diabetes Care (2018)

Painful diabetic peripheral neuropathy (PDN) is one of the most common complications of diabetes. In patients with PDN, greater pain intensity leads to poorer quality of life, sleep, function, and work productivity (1–3). According to the clinical practice guideline, electrical stimulation is probably effective and should be considered for the treatment of PDN (evidence level B) (4). The aim of this study is to evaluate the effectiveness and safety of electroacupuncture (EA) for the management of PDN in patients with type 2 diabetes.

This multicenter, randomized, assessor-blinded, controlled trial was conducted between June 2014 and March 2016 at four centers in South Korea (clinical trial reg. no. KCT0001135, https://cris.nih.go.kr). A total of 126 participants with a ≥6-month history of PDN and a mean weekly pain score of ≥4 on the Pain Intensity Numerical Rating Scale (PI-NRS) were randomly assigned in a 1:1 ratio to an EA group ( n = 63) or control group ( n = 63). Randomization was performed by using a computer-generated random code, and allocation concealment was achieved using sequentially numbered, opaque sealed envelopes. The participants in the EA group received EA treatment with a mixed current of 2 Hz/120 Hz at 12 acupuncture points (bilateral Zusanli [ST36], Xuanzhong [GB39], Yinlingquan [SP9], Sanyinjiao [SP6], Taichong …
Abstract 14650: A Monoclonal Antibody to a Sodium Pump Inhibitor Marinobufagenin Reversed Aortic Remodeling and Stiffness in Normotensive Rats on a High Salt Intake
Authors: Yulia Grigorova, Wen Wei, Valentina Zernetkina, Ondrej Juhasz, Edward Lakatta, Olga Fedorova, Alexei Bagrov
Journal: Circulation (2014)

Background: Marinobufagenin (MBG), an endogenous cardiotonic steroid, is a Na/K-ATPase inhibitor and a vasoconstrictor. Previously it was demonstrated, that administration of 3E9 anti-MBG-antibody (mAb) reduced blood pressure (BP) and reversed left ventricular fibrosis in animal models of salt-sensitive hypertension and nephropathy. In the present study we investigated whether mAb alleviates BP and vascular remodeling in normotensive rats on a high salt intake. Methods: Wistar rats (5 months old) received normal salt diet (CTRL; n=8) or high salt intake (2% NaCl in drinking water) for 4 weeks. Rats on a high salt were administered vehicle (SALT; n=8) or mAb (50 ug/kg) (SALT-AB; n=8) 3 times during the last week of a high salt diet. BP was measured at baseline, after 3 and 4 weeks of experiment. Na/K-ATPase activity was measured in erythrocytes. Aortas were weighed, and were used to study sensitivity to the vasorelaxant effect of sodium nitroprusside (SNP), and for the histochemistry analysis of collagen deposition. Renal 24-hr MBG excretion was measured at week 4. Results: In SALT vs. CTRL, in the absence of BP changes, elevated levels of MBG (14.1±1.1 vs. 9.0±1.6 pmol/24hr, p&lt;0.05) were associated with inhibition of erythrocyte Na/K-ATPase (12.6±0.3 vs. 14.2±0.35 μmol Pi/ml/hr, p&lt;0.05), increased aortic weights (217±15 vs. 158±9 mg/kg BW, p&lt;0.01), increased levels of collagen in aorta (2.5-fold; p&lt;0.05), and compromised SNP vasorelaxant effect in aortic explants (EC50=167±19.3 nM vs. 99±2.0 nM; P&lt;0.01). Antibody treatment in SALT-AB vs. SALT increased Na/K-ATPase activity (13.93±0.54 μmol Pi/ml/hr, p&lt;0.05), reduced the aortic weight (180±12 mg/kg; P&lt;0.05) and collagen deposition 3-fold (P&lt;0.05), and restored the vasorelaxation of aortic rings by SNP to the levels in CTRL (70±1.5 nM, p&lt;0.01). Conclusion: These findings for the first time demonstrated that in normotensive rats on a high salt intake heightened MBG levels induced vascular fibrosis and impairment of vasorelaxation in the absence of blood pressure changes. Immunoneutralization of MBG reversed these changes. Thus, high dietary NaCl intake in normotensive animals can stimulate vascular fibrosis via pressure-independent/ MBG-dependent mechanisms, and this remodeling is reversible.
Deceased Donation in Uterus Transplantation Trials: Novelty, Consent, and Surrogate Decision Making
Authors: Nicola Jane Williams
Journal: The American Journal of Bioethics (2018)

In my 2016 paper “Should Deceased Donation be Morally Preferred in Uterus Transplantation Trials?” I explored a number of the ethical concerns and questions posed by the use of living donors in ute...
Discordance between Oncotype Dx and Saint Gallen criteria, Adjuvant!, NCCN 2011 guidelines, and initial physician treatment recommendation.
Authors: Allan Andresson Lima Pereira, Fernando Costa Santini, Andrea Kazumi Shimada, Ellen Caroline Nascimento, Artur Katz, Max S. Mano
Journal: Journal of Clinical Oncology (2012)

e11014 Background: The Oncotype Dx recurrence score (RS) assay quantifies the risk of distant recurrence (rDR) and its use has increased despite the lack of prospective studies. Methods: This is a cross sectional retrospective study of consecutive patients (PTS) from our institution with histologically confirmed invasive breast cancer who underwent surgery with curative intent and in whom Oncotype was performed. The main objectives were to compare (1) the predicted rDR by RS and Adjuvant! (2) Risk allocation by RS and St Gallen Criteria, (3) chemotherapy indication according to RS results and NCCN guidelines and (4) to evaluate the impact of RS results on the recommendation of adjuvant chemotherapy (aCT). Results: Between October/2006-June/2011, 74 PTS were evaluated. Forty seven (63,5%) were EC IA and all had estrogen receptor positive; axillary lymph node involvement was seen in 19 PTS (13 micro and 6 macrometastasis). The rDR by RS was low in 50 PTS (67%), intermediate in 19 (26%) and high in 5 (7%). According to Saint Gallen, 7 (9%), 51 (69%) and 14 PTS (19%) were classified as low, intermediate and high risk, respectively. There was a statistical significant discordance between risk allocation according to RS and Saint Gallen (Kappa coefficient=-0.002; p=0.971). Among the 55 node-negative PTS, there was also a statistical significant discordance between the predicted average rDR, obtained from Oncotype, and Adjuvant! with median risk of 8,5% vs 15,7%, respectively (p = 0.00001 rank sum Mann Whitney test). The NCCN 2011 would have indicated aCT to 62 PTS. Among 55 classified as low and high risk by RS, the NCCN would have indicated aCT to 46 PTS. In other words, 89% (41) of PTS who would receive aCT by NCCN were classified as low risk by RS, with a statistically significant discordance (Kappa coefficient=0.035, p=0.328). Conclusions: Oncotype changed the medical management in 28 (55%) of 51 PTS in which the initial intention of the physician was known. Of these, 93% were spared aCT. We found no statistical significant concordance among the Saint Gallen, Adjuvant! or NCCN guidelines with Oncotype Dx. The rDR may be overestimated by clinicopathological-based classifications.
Characteristics of Patients for Whom Benznidazole Was Released Through the CDC-Sponsored Investigational New Drug Program for Treatment of Chagas Disease — United States, 2011–2018
Authors: Barbara L. Herwaldt, Cindy P. Dougherty, Christopher K. Allen, Julian P. Jolly, Megan N. Brown, Patricia Yu, Yon Yu
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Chagas disease (also known as American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi (1,2). Vectorborne transmission via skin or mucosal contact with the feces of infected triatomine bugs mainly occurs in rural areas of Latin America but has been reported in the southern United States (3). The parasite also is transmissible congenitally and via blood transfusion, organ transplantation, and accidental laboratory exposures. The two drugs used for treating Chagas disease are benznidazole and nifurtimox (1,2), which have been used in Latin America since the 1970s and 1960s, respectively. In the absence of commercially available drugs approved by the Food and Drug Administration (FDA), benznidazole and nifurtimox have been available exclusively through CDC, under Investigational New Drug (IND) treatment protocols. On August 29, 2017, FDA approved a benznidazole product (Chemo Research, SL, in care of Exeltis*) for treatment of Chagas disease (4), which became commercially available on May 14, 2018. Therefore, effective May 14, 2018, benznidazole is no longer available through the CDC-sponsored IND program. This report summarizes selected characteristics of patients for whom CDC released benznidazole through that program from October 2011, when the IND went into effect, until mid-May 2018. The majority of the 365 patients included in intention-to-treat analyses were chronically infected adults who were born and became infected in Latin America. Physician requests for benznidazole should now be directed to the drug company Exeltis.† The CDC-sponsored IND for nifurtimox remains in effect to provide an alternative therapeutic option to benznidazole when clinically appropriate. CDC will continue to provide reference diagnostic testing for T. cruzi infection and teleconsultative services regarding Chagas disease.
Abstract 14945: The Release of Cardiac Necrosis Biomarkers in Patients Without Myocardial Infarction After On-Pump Surgical Revascularization. A Study of Cardiac Magnetic Resonance Imaging
Authors: Fernando T Oikawa, Whady Hueb, Leandro M Costa, Rodrigo M Vieira de Melo, Paulo C Rezende, Cibele L Garzillo, Eduardo G Lima, Cesar H Nomura, Alexandre V Villa, Alexandre C Hueb, Jose A Ramires, Roberto Kalil Filho
Journal: Circulation (2016)

Introduction: The lack of a correlation of myocardial infarction after coronary artery bypass surgery (type V MI) with electrocardiographic abnormalities is quite complex, creating numerous controv...
Three ways to make replication mainstream
Authors: Morton Ann Gernsbacher
Journal: Behavioral and Brain Sciences (2018)

Zwaan et al. argue convincingly that replication needs to be more mainstream. Here, I suggest three practices for achieving that goal: Incremental Replications, which are built into each experiment in a series of experiments; Reciprocal Replications, which are reciprocal arrangements of co-replications across labs; and Didactic Replications, which are replications used for training.