Quenching of Single-Particle Strength in A=15 Nuclei.

Absolute cross sections for the addition of s- and d-wave neutrons to ^{14}C and ^{14}N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and proton separation energies, ΔS, is around -20 MeV for the ^{14}C+n system and +8 MeV for ^{14}N+n. The population of the 1s_{1/2} and 0d_{5/2} orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of ^{9}Be and ^{12}C. The simultaneous technique used removes many systematic uncertainties.

Left ventricular fibroma presenting as esophageal spasm: A case report.

Primary tumors of the heart are rare with fibromas most commonly identified in utero or infancy and rarely developing in adulthood. Patients with cardiac fibromas are often asymptomatic until tumor enlargement results in obstructive and nonspecific symptoms. A 39-year-old female presented with 5-year history of recurrent chest pain with functional dysphagia, indicative of esophageal spasm. Imaging identified a large left ventricular (LV) fibroma compressing the esophagus provoking esophageal spasm. The fibroma was excised measuring 51 × 39 mm. This case describes presentation with esophageal spasm, contributing a novel presentation of LV fibroma to the literature.

Retinoic acid promotes fibrinolysis and may regulate polyp formation.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells. OBJECTIVES: This study sought to determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in patients with CRSwNP and AERD. METHODS: NP tissue was collected from patients with AERD or CRSwNP, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial cells were stimulated alone or in combination with RA and IL-13 for 24 hours. RESULTS: This study observed lower retinoid levels in nasal polyps of patients with AERD than those with CRSwNP or healthy controls (P < .01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P < .01), which is consistent with lower tPA expression (P < .01). In vitro, all-trans RA upregulated tPA levels in normal human bronchial epithelial cells by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P < .01). CONCLUSIONS: RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from patients with AERD, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating patients with CRSwNP and/or AERD.

Coronary Artery Revascularization in Heart Transplant Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the primary cause of late mortality after heart transplantation. We look to provide a comprehensive review of contemporary revascularization strategies in CAV. METHODS: PubMed and Web of Science were systematically searched by 3 authors. 1,870 articles were initially screened and 24 were included in this review. RESULTS: PCI is the main revascularization technique utilized in CAV. The pooled estimates for restenosis significantly favored DES over BMS (OR 4.26; 95% CI: 2.54-7.13; p < 0.00001; I2 = 4%). There were insufficient data to quantitatively compare mortality following DES versus BMS. There was no difference in short-term mortality between CABG and PCI. In-hospital mortality was 0.0% for CABG and ranged from 0.0 to 8.34% for PCI. One-year mortality was 8.0% for CABG and 5.0-25.0% for PCI. CABG had a potential advantage at 5 years. Five-year mortality was 17.0% for CABG and ranged from 14 to 40.4% following PCI. Select measures of postoperative morbidity trended toward superior outcomes for CABG. CONCLUSION: In CAV, PCI is the primary revascularization strategy utilized, with DES exhibiting superiority to BMS regarding postoperative morbidity. Further investigation into outcomes following CABG in CAV is required to conclusively elucidate the superior management strategy in CAV.

Studies on activation and regulation of the coagulation cascade in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP. OBJECTIVE: We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS. METHODS: Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting. RESULTS: Increased levels of FXa, F1+2, and thrombin-antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue. CONCLUSION: The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.

A randomized trial comparing axillary versus innominate artery cannulation for aortic arch surgery.

BACKGROUND: Cerebral protection remains the cornerstone of successful aortic surgery; however, there is no consensus as to the optimal strategy. OBJECTIVE: To compare the safety and efficacy of innominate to axillary artery cannulation for delivering antegrade cerebral protection during proximal aortic arch surgery. METHODS: This randomized controlled trial (The Aortic Surgery Cerebral Protection Evaluation CardioLink-3 Trial, ClinicalTrials.gov Identifier: NCT02554032), conducted across 6 Canadian centers between January 2015 and June 2018, allocated 111 individuals to innominate or axillary artery cannulation. The primary safety outcome was neuroprotection per the appearance of new severe ischemic lesions on the postoperative diffusion-weighted-magnetic resonance imaging. The primary efficacy outcome was the difference in total operative time. Secondary outcomes included 30-day all-cause mortality and postoperative stroke. RESULTS: One hundred two individuals (mean age, 63 ± 11 years) were in the primary safety per-protocol analysis. Baseline characteristics between the groups were similar. New severe ischemic lesions occurred in 19 participants (38.8%) in the axillary versus 18 (34%) in the innominate group (P for noninferiority = .0009). Total operative times were comparable (median, 293 minutes; interquartile range, 222-411 minutes) for axillary versus (298 minutes; interquartile range, 231-368 minutes) for innominate (P for superiority = .47). Stroke/transient ischemic attack occurred in 4 (7.1%) participants in the axillary versus 2 (3.6%) in the innominate group (P = .43). Thirty-day mortality, seizures, delirium, and duration of mechanical ventilation were similar in both groups. CONCLUSIONS: diffusion-weighted magnetic resonance imaging assessments indicate that antegrade cerebral protection with innominate cannulation is safe and affords similar neuroprotection to axillary cannulation during aortic surgery, although the burden of new neurological lesions is high in both groups.

Further structural characterization of ovine forestomach matrix and multi-layered extracellular matrix composites for soft tissue repair.

Decellularized extracellular matrix (dECM)-based biomaterials are of great clinical utility in soft tissue repair applications due to their regenerative properties. Multi-layered dECM devices have been developed for clinical indications where additional thickness and biomechanical performance are required. However, traditional approaches to the fabrication of multi-layered dECM devices introduce additional laminating materials or chemical modifications of the dECM that may impair the biological functionality of the material. Using an established dECM biomaterial, ovine forestomach matrix, a novel method for the fabrication of multi-layered dECM constructs has been developed, where layers are bonded via a physical interlocking process without the need for additional bonding materials or detrimental chemical modification of the dECM. The versatility of the interlocking process has been demonstrated by incorporating a layer of hyaluronic acid to create a composite material with additional biological functionality. Interlocked composite devices including hyaluronic acid showed improved in vitro bioactivity and moisture retention properties.

Cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health care and cardiac surgery. We report cardiac surgeons' concerns, perceptions, and responses during the COVID-19 pandemic. METHODS: A detailed survey was sent to recruit participating adult cardiac surgery centers in North America. Data regarding cardiac surgeons' perceptions and changes in practice were analyzed. RESULTS: Our study comprises 67 institutions with diverse geographic distribution across North America. Nurses were most likely to be redeployed (88%), followed by advanced care practitioners (69%), trainees (28%), and surgeons (25%). Examining surgeon concerns in regard to COVID-19, they were most worried with exposing their family to COVID-19 (81%), followed by contracting COVID-19 (68%), running out of personal protective equipment (PPE) (28%), and hospital resources (28%). In terms of PPE conservation strategies among users of N95 respirators, nearly half were recycling via decontamination with ultraviolet light (49%), followed by sterilization with heat (13%) and at home or with other modalities (13%). Reuse of N95 respirators for 1 day (22%), 1 week (21%) or 1 month (6%) was reported. There were differences in adoption of methods to conserve N95 respirators based on institutional pandemic phase and COVID-19 burden, with higher COVID-19 burden institutions more likely to resort to PPE conservation strategies. CONCLUSIONS: The present study demonstrates the impact of COVID-19 on North American cardiac surgeons. Our study should stimulate further discussions to identify optimal solutions to improve workforce preparedness for subsequent surges, as well as facilitate the navigation of future healthcare crises.

Studies of the role of basophils in aspirin-exacerbated respiratory disease pathogenesis.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to cyclooxygenase-1 enzyme inhibitors. The underlying mechanisms contributing to AERD pathogenesis are not fully understood, but AERD is characterized by an enhanced type 2 inflammatory phenotype. Basophils are potent type 2 effector cells, but their involvement in AERD pathophysiology remains unclear. OBJECTIVE: We sought to characterize the systemic and local basophil responses in patients with AERD compared with patients with CRSwNP. METHODS: Sinonasal tissues including inferior turbinate and/or nasal polyps (NPs) and peripheral blood were collected from controls, patients with AERD, and patients with CRSwNP. Expression of cell surface (CD45, FcεRI, CD203c), activation (CD63), and intracellular (2D7) markers associated with basophils was characterized using flow cytometry. Clinical data including Lund-Mackay scores and pulmonary function were obtained. RESULTS: The mean number of basophils (CD45+CD203c+FcεRI+CD117-) detected in AERD NPs (147 ± 28 cells/mg tissue) was significantly elevated compared with that detected in CRSwNP NPs (69 ± 20 cells/mg tissue; P = .01). The number of circulating basophils was significantly elevated in patients with AERD (P = .04). Basophils in NPs had significantly higher CD203c and CD63 mean fluorescence intensity compared with blood in both conditions (P < .01). Basophils from AERD NPs had lower expression of the granule content marker 2D7 compared with those from matched blood (P < .01) or NPs of patients with CRSwNP (P = .06), suggesting ongoing degranulation. Basophil 2D7 mean fluorescence intensity significantly correlated with pulmonary function (r = 0.62; P = .02) and inversely correlated with sinonasal inflammation (r = -0.56; P = .004). CONCLUSIONS: Increased basophil numbers and extent of ongoing degranulation in NPs of patients with AERD compared with patients with CRSwNP may contribute to the exaggerated disease pathogenesis and severity unique to AERD.

Role of preoperative intravenous iron therapy to correct anemia before major surgery: a systematic review and meta-analysis.

BACKGROUND: Preoperative anemia is a common comorbidity that often necessitates allogeneic blood transfusion (ABT). As there is a risk associated with blood transfusions, preoperative intravenous iron (IV) has been proposed to increase the hemoglobin to reduce perioperative transfusion; however, randomized controlled trials (RCT) investigating this efficacy for IV iron are small, limited, and inconclusive. Consequently, a meta-analysis that pools these studies may provide new and clinically useful information. METHODS/DESIGN: Databases of MEDLINE, EMBASE, EBM Reviews; Cochrane-controlled trial registry; Scopus; registries of health technology assessment and clinical trials; Web of Science; ProQuest Dissertations and Theses; Clinicaltrials.gov; and Conference Proceedings Citation Index-Science (CPCI-S) were searched. Also, we screened all the retrieved reference lists. SELECTION CRITERIA: Titles and abstracts were screened for relevance (i.e., relevant, irrelevant, or potentially relevant). Then, we screened full texts of those citations identified as potentially applicable. RESULTS: Our search found 3195 citations and ten RCTs (1039 participants) that met our inclusion criteria. Preoperative IV iron supplementation significantly decreases ABT by 16% (risk ratio (RR): 0.84, 95% confidence interval [CI]: 0.71, 0.99, p = 0.04). In addition, preoperatively, hemoglobin levels increased after receiving IV iron (mean difference [MD] between the study groups: 7.15 g/L, 95% CI: 2.26, 12.04 g/L, p = 0.004) and at follow-up > 4 weeks postoperatively (MD: 6.46 g/L, 95% CI: 3.10, 9.81, p = 0.0002). Iron injection was not associated with increased incidence of non-serious or serious adverse effects across groups (RR: 1.13, 95% CI: 0.78, 1.65, p = 0.52) and (RR: 0.96, 95% CI: 0.44, 2.10, p = 0.92) respectively. CONCLUSIONS: With moderate certainty, due to the high risk of bias in some studies in one or two domains, we found intravenous iron supplementation is associated with a significant decrease in the blood transfusions rate, and modest hemoglobin concentrations rise when injected pre-surgery compared with placebo or oral iron supplementation. However, further full-scale randomized controlled trials with robust methodology are required. In particular, the safety, quality of life, and cost-effectiveness of different intravenous iron preparations require further evaluation.

In vitro-Constructed Ribosomes Enable Multi-site Incorporation of Noncanonical Amino Acids into Proteins.

Efforts to expand the scope of ribosome-mediated polymerization to incorporate noncanonical amino acids (ncAAs) into peptides and proteins hold promise for creating new classes of enzymes, therapeutics, and materials. Recently, the integrated synthesis, assembly, and translation (iSAT) system was established to construct functional ribosomes in cell-free systems. However, the iSAT system has not been shown to be compatible with genetic code expansion. Here, to address this gap, we develop an iSAT platform capable of manufacturing pure proteins with site-specifically incorporated ncAAs. We first establish an iSAT platform based on extracts from genomically recoded Escherichia coli lacking release factor 1 (RF-1). This permits complete reassignment of the amber codon translation function. Next, we optimize orthogonal translation system components to demonstrate the benefits of genomic RF-1 deletion on incorporation of ncAAs into proteins. Using our optimized platform, we demonstrate high-level, multi-site incorporation of p-acetyl-phenylalanine (pAcF) and p-azido-phenylalanine into superfolder green fluorescent protein (sfGFP). Mass spectrometry analysis confirms the high accuracy of incorporation for pAcF at one, two, and five amber sites in sfGFP. The iSAT system updated for ncAA incorporation sets the stage for investigating ribosomal mutations to better understand the fundamental basis of protein synthesis, manufacturing proteins with new properties, and engineering ribosomes for novel polymerization chemistries.

Activation of the 15-lipoxygenase pathway in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirin-tolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD. OBJECTIVE: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD. METHODS: Single-cell RNA sequencing (10× Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence. RESULTS: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r = 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO+ epithelium in NPs from patients with AERD. CONCLUSIONS: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD.

Long-term Outcomes Following Mechanical or Bioprosthetic Aortic Valve Replacement in Young Women.

BACKGROUND: Studies performed to date reporting outcomes after mechanical or bioprosthetic aortic valve replacement (AVR) have largely neglected the young female population. This study compares long-term outcomes in female patients aged < 50 years undergoing AVR with either a mechanical or bioprosthetic valve. METHODS: In this propensity-matched study, we compared outcomes after mechanical AVR (n = 57) and bioprosthetic AVR (n = 57) between 2004 and 2018. The primary outcome of this study is survival. Secondary outcomes include the rate of reoperation, stroke, myocardial infarction, rehospitalization for heart failure, and incidence of serious adverse events. Outcomes were measured over 15 years, with a median follow-up of 7.8 years. RESULTS: In patients receiving a mechanical AVR vs a bioprosthetic AVR, overall survival at median follow-up was equivalent, at 93%. There is a lower rate of reoperation in patients receiving a mechanical AVR vs a bioprosthetic AVR (1.8% vs 8.8%). The rate of new-onset atrial fibrillation was significantly higher in the mechanical AVR group vs the bioprosthetic AVR group (18.2% vs 7.3%). No significant difference was seen in the rate of serious adverse events. CONCLUSIONS: These results provide contemporary data demonstrating equivalent long-term survival between mechanical and bioprosthetic AVR, with higher rates of new atrial fibrillation after mechanical AVR, and higher rates of reoperation after bioprosthetic AVR. These results suggest that either valve type is safe, and that preoperative assessment and counselling, as well as the follow-up, medical treatment and indications for intervention, must be a collaborative decision-making process between the clinician and the patient.

CONTEXTE: Les études réalisées à ce jour portant sur le bilan après un remplacement mécanique ou bioprothétique de la valve aortique (RVA) ont largement négligé la population de jeunes femmes. Cette étude compare le pronostic à long terme chez les patientes âgées de moins de 50 ans qui subissent un RVA par une valve mécanique ou bioprothétique. MÉTHODES: Dans cette étude d'appariement par score de propension, nous avons comparé les résultats après un RVA mécanique (n = 57) et un RVA bioprothétique (n = 57) entre 2004 et 2018. Le principal critère d'évaluation consiste en l'étude de la survie. Les critères d'évaluation secondaires comprennent le taux de réopération, d'accident vasculaire cérébral, d'infarctus du myocarde, de réhospitalisation pour insuffisance cardiaque et l'incidence des événements indésirables graves. Les critères d'évaluation ont été mesurés sur une période de 15 ans, avec un suivi médian de 7,8 ans. RÉSULTATS: Pour les patientes soumises à un RVA mécanique par rapport à un RVA bioprothétique, la survie globale au suivi médiane était équivalente à 93 %. Le taux de réopération est plus faible chez les patientes avec un RVA mécanique que chez celles soumises à un RVA bioprothétique (1,8 % contre 8,8 %). Le taux de fibrillation auriculaire d'apparition récente était significativement plus élevé dans le groupe ayant eu un RVA mécanique que dans le groupe ayant eu un RVA bioprothétique (18,2 % contre 7,3 %). Aucune différence significative n'a été observée concernant le taux d'événements indésirables graves. CONCLUSIONS: Ces résultats fournissent des données actualisées démontrant une survie à long terme équivalente entre les RVA mécaniques et bioprothétiques, avec des taux plus élevés de fibrillation auriculaire d'apparition récente après une RVA mécanique, et des taux plus élevés de réopération après une RVA bioprothétique. Ces résultats suggèrent que chaque type de valve est sûr, et que l'évaluation et le counselling préopératoire, ainsi que le suivi, le traitement médical et les indications d'intervention, doivent être un processus de décision concerté entre le clinicien et le patient.

Aminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family.

We have previously reported the discovery of a series of rhodanine-based inhibitors of the PIM family of serine/threonine kinases. Here we described the optimisation of those compounds to improve their physicochemical and ADME properties as well as reducing their off-targets activities against other kinases. Through molecular modeling and systematic structure activity relationship (SAR) studies, advanced molecules with high inhibitory potency, reduced off-target activity and minimal efflux were identified as new pan-PIM inhibitors. One example of an early lead, OX01401, was found to inhibit PIMs with nanomolar potency (15 nM for PIM1), inhibit proliferation of two PIM-expressing leukaemic cancer cell lines, MV4-11 and K562, and to reduce intracellular phosphorylation of a PIM substrate in a concentration dependent manner.

Development of a Gaussian Process - feature selection model to characterise (poly)dimethylsiloxane (Silastic® ) membrane permeation.

OBJECTIVES: The current study aims to determine the effect of physicochemical descriptor selection on models of polydimethylsiloxane permeation. METHODS: A total of 2942 descriptors were calculated for a data set of 77 chemicals. Data were processed to remove redundancy, single values, imbalanced and highly correlated data, yielding 1363 relevant descriptors. For four independent test sets, feature selection methods were applied and modelled via a variety of Machine Learning methods. KEY FINDINGS: Two sets of molecular descriptors which can provide improved predictions, compared to existing models, have been identified. Best permeation predictions were found with Gaussian Process methods. The molecular descriptors describe lipophilicity, partial charge and hydrogen bonding as key determinants of PDMS permeation. CONCLUSIONS: This study highlights important considerations in the development of relevant models and in the construction and use of the data sets used in such studies, particularly that highly correlated descriptors should be removed from data sets. Predictive models are improved by the methodology adopted in this study, notably the systematic evaluation of descriptors, rather than simply using any and all available descriptors, often based empirically on in vitro experiments. Such findings also have clear relevance to a number of other fields.

Multidimensional Top-Down Proteomics of Brain-Region-Specific Mouse Brain Proteoforms Responsive to Cocaine and Estradiol.

Cocaine addiction afflicts nearly 1 million adults in the United States, and to date, there are no known treatments approved for this psychiatric condition. Women are particularly vulnerable to developing a cocaine use disorder and suffer from more serious cardiac consequences than men when using cocaine. Estrogen is one biological factor contributing to the increased risk for females to develop problematic cocaine use. Animal studies have demonstrated that estrogen (17ß-estradiol or E2) enhances the rewarding properties of cocaine. Although E2 affects the dopamine system, the molecular and cellular mechanisms of E2-enhanced cocaine reward have not been characterized. In this study, quantitative top-down proteomics was used to measure intact proteins in specific regions of the female mouse brain after mice were trained for cocaine-conditioned place preference, a behavioral test of cocaine reward. Several proteoform changes occurred in the ventral tegmental area after combined cocaine and E2 treatments, with the most numerous proteoform alterations on myelin basic protein, indicating possible changes in white matter structure. There were also changes in histone H4, protein phosphatase inhibitors, cholecystokinin, and calmodulin proteoforms. These observations provide insight into estrogen signaling in the brain and may guide new approaches to treating women with cocaine use disorder.

Increased thrombin-activatable fibrinolysis inhibitor levels in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease subdivided based on the presence or absence of nasal polyps (NPs). Histologic features of chronic rhinosinusitis with nasal polyps (CRSwNP) include inflammatory cell infiltration and excessive fibrin deposition in NPs. Thrombin-activatable fibrinolysis inhibitor (TAFI) is an enzyme that plays an antifibrinolytic role in the body. The significance of TAFI has been documented in patients with chronic inflammatory diseases, including chronic lung disease; however, it has not been evaluated in the pathogenesis of NPs. OBJECTIVE: The objective of this study was to evaluate the potential role of TAFI in the pathogenesis of NPs. METHODS: Nasal lavage fluid was collected from control subjects and patients with CRS. We measured levels of thrombin/anti-thrombin complex (TATc) and TAFI protein using an ELISA. RESULTS: TATc levels in nasal lavage fluid were significantly increased in patients with CRSwNP and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with control subjects, and TAFI levels in nasal lavage fluid were also significantly increased in patients with CRSwNP compared with those in control subjects and patients with CRSsNP. There was a significant correlation between TATc and TAFI levels in nasal lavage fluid. Interestingly, patients with CRS and asthma showed increased TATc and TAFI levels in nasal lavage fluid compared with those in patients with CRS without asthma, especially patients with CRSwNP. CONCLUSIONS: Increased TATc and TAFI levels in nasal passages of patients with CRSwNP might participate in fibrin deposition in NPs and might play a role in the pathogenesis of CRSwNP and asthma.

Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

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