...adults who had been hospitalized in the previous year had fewer positive environmental allergen specific IgE tests than those who had not been hospitalized (median 3 vs. 1, p=0.027), while there ...were no differences in number of allergens in children with or without a history of a hospitalization, (p=0.25). Conclusions In adult asthma, sensitization to a greater number of environmental allergens does not increase the risk of asthma exacerbations, and may be protective.
Background and Objective : The ADA increase has been attributed to cell mediated response to Mycobacterium Antigens. Hence, the study was conducted to evaluate the level of ADA in Serum and Pleural ...Fluid to find its role for early diagnosis of Pulmonary Tuberculosis (PTB). Method: The study was conducted on 76 subjects and was divided into two groups. Group-I include 35 subjects as healthy control and Group-II include 41 PTB patients, which has 28 sputum negative (-ve AFB) patients and 13 sputum positive (+ve AFB) patients between the age group of 25-83 years. ADA level was estimated in serum and pleural Fluid in both the groups of patients in tertiary care hospital, Udaipur. Results: The ADA level in Serum and pleural fluid were significantly higher in sputum positive (+ve AFB) patients; 35.62 + or - 2.41 and 29.27 + or - 3.20 as compared to sputum negative (-ve AFB) patients; 57.40 + or - 32.14 and 55.94 + or - 18.60. Further, serum ADA was significantly higher in PTB patients than the healthy control group. Conclusion: ADA determination is as fast and discriminating test for early diagnosis of PTB and may probably reflects differences in cellular immune response to different infectious agent. Keywords : Adenosine deaminase, pulmonary tuberculosis, Pleural Fluid, Acid Fast Bacili
•Full solar-light-spectrum active V-Bi2S3-xSex photocatalyst was prepared for the first time.•Doped and defected endowed the superb photocatalytic activity over bare counterparts.•High Cr(VI) ...reduction and H2O2 generation efficiencies are achieved under illumination.•Both ESR and species trapping analysis reveal the photocatalysis mechanism.
Heterogeneous photocatalysis has been demonstrated as a highly effective approach in addressing the difficulties encountered by conventional technologies in environmental remediation. Herein, for the first time, a novel hierarchical photocatalyst of selenium-doped Bi2S3 (Bi2S3-xSex) was successfully synthesized through a one-spot hydrothermal route followed by a vacancy engineering process (V-Bi2S3-xSex). The photocatalytic reduction of Cr(VI) and in-situ generation of hydrogen peroxide (H2O2) under simulated solar-light irradiation were performed to evaluate the catalytic activity of the as-prepared samples. The catalytic activity of as-prepared samples was evaluated toward the photocatalytic reduction of Cr(VI) and in-situ generation of H2O2 under simulated solar-light irradiation. Notably, V-Bi2S3-xSex (V-BSSe-5, as optimum sample) exhibited a photo-reduction of Cr(VI) at a rate of 97.04% during 150 min, which was 1.53- and 1.39-fold higher than those of pure Bi2S3 and Bi2Se3, respectively. Interestingly, the V-Bi2S3-xSex photocatalyst not only harvested more incident light in the UV–vis and near-infrared (NIR) regions but also supplied many active sites, improving the promotion of photo-generated charge-carriers, inhibiting charge recombination, and thus enhancing the photocatalytic activity. In addition, V-BSSe-5 showed greater photocatalytic efficiency for H2O2 generation, which was 15.69, 10.07, and 1.79 times higher than those of Bi2S3, Bi2Se3, and BSSe-5, respectively. The charge-carrier migration pathway and possible photocatalytic mechanisms were systematically discussed by assisting the electron spin resonance and ultraviolet photoelectron spectroscopy analyses. The findings of this study demonstrate that doping and defect engineering strategies have the potential to be a significant advancement in the development of visible- and NIR-light responsiveness photocatalysts, thereby providing a solution to current environmental and energy challenges.
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Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin ...activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To identify genes that both modulate beta-catenin activity and are essential for colon cancer cell proliferation, we conducted two loss-of-function screens in human colon cancer cells and compared genes identified in these screens with an analysis of copy number alterations in colon cancer specimens. One of these genes, CDK8, which encodes a member of the mediator complex, is located at 13q12.13, a region of recurrent copy number gain in a substantial fraction of colon cancers. Here we show that the suppression of CDK8 expression inhibits proliferation in colon cancer cells characterized by high levels of CDK8 and beta-catenin hyperactivity. CDK8 kinase activity was necessary for beta-catenin-driven transformation and for expression of several beta-catenin transcriptional targets. Together these observations suggest that therapeutic interventions targeting CDK8 may confer a clinical benefit in beta-catenin-driven malignancies.
Abstract only
Background:
Comparisons between Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) have been critiqued, with suggestions that KD Shock Syndrome (KDSS) ...patients may be a more valid comparison. We compared contemporaneous KD and MIS-C patients, both with and without shock at presentation.
Methods:
The International KD Registry enrolled 2144 patients with either KD (site diagnosis confirmed by AHA criteria) or MIS-C (site diagnosis confirmed by CDC criteria) from 40 sites in 7 countries from 01/2020 to 01/2023. Data collected included demographics, clinical features and presentation, management, laboratory values, and outcomes, and diagnosis/shock groups were compared.
Results:
Shock at presentation was noted for 19 of 672 (2.8%) KD patients and 653 of 1472 (38%; p<0.001) MIS-C patients. For both groups, shock patients were significantly more likely to be admitted to ICU, receive inotropes, and have cardiac arrest or arrhythmia. Groups did not differ by sex, but MIS-C patients and shock patients were older. While MIS-C shock patients were less likely to be White, KD shock and MIS-C shock patients more likely to be Black. For inflammatory markers, while shock patients in both groups had higher CRP and ferritin compared to non-shock patients, ESR was similar in both groups to non-shock patients, and higher WBC was only noted for MIS-C shock versus MIS-C non-shock patients. KD shock patients had similar values to MIS-C shock patients, with the exception of lower ferritin. Shock patients had higher NTproBNP (both diagnoses) and Troponin I (MIS-C only). Shock patients had lower LV ejection fraction, more so for MIS-C patients (
Figure A
). KD shock patients had higher max coronary artery Z scores versus MIS-C patients (
Figure B
).
Conclusions:
KD shock patients are more similar to MIS-C patients, particularly those with shock. Shock was associated with worse coronary artery involvement for KD patients, and worse LV dysfunction for both MIS-C and KD.
Abstract only
Introduction:
Despite several years of gender parity entering the field of pediatric cardiology, representation of women leaders trails that of their male colleagues. We sought to ...better understand the variation in women in leadership roles in our field.
Methods:
Pediatric cardiology programs that participate in the Society of Thoracic Surgeons database with > 5 cardiologists were included. Data regarding gender of physicians in 16 leadership positions was collected. We analyzed the association of women in leadership roles with center size (based on surgical volume), geographic region, presence of fellowship, and gender of division chief and department chair.
Results:
Of the 99 centers in this study, a median of 13 (IQR 10-15) roles/center were identified, with 4 (IQR 3-6), 33.3% held by women. The lowest representation was in pediatric cardiology chiefs: 13% (table). Programs led by women chiefs had more women in leadership roles (48% vs 35%, p=0.01). In the US, the Northeast has more %women leaders than the West, South, or Midwest: 43% vs 33, 32, 34% respectively, p=0.035. Fellowship program or a woman department chair were not associated with %women leaders. The %women varied among the different sections: lowest in invasive subspecialties, interventional (17%) and EP (20%), and highest in fetal directors (66%). Fewer cardiac MRI leads in medium or high-volume centers are women compared to low volume centers (16 vs 39%, p=0.02), otherwise no volume-based differences were seen.
Conclusions:
Women hold fewer leadership positions across most subsections of pediatric cardiology programs, with more equitable distribution at centers led by women division chiefs. Future studies will define barriers to leadership equity.
Opinion statement
Assessing the quality of health care delivered is a priority across medical specialties, but it is particularly critical for radiation oncology, a field with rapid introduction of ...new technologies and treatment paradigms. Deviation from acceptable standards can lead to delivery of inferior therapies and medical errors that can directly compromise patient clinical outcome, thus leading to disparities in quality of care. Professional oncologic specialty societies often take ownership of standardizing best practices by issuing evidence-based disease-specific consensus guidelines. They also inform quality indicators that are set as requirements for accreditation, maintenance of certification, and reimbursement. Cooperative groups also create benchmarks for quality radiation therapy through design of clinical protocols that set standard-of-care treatment practices. Pelvic radiotherapy for colorectal and anal cancers has undergone a significant transformation in radiation planning and delivery including increased complexity in contour segmentation with a transition from three-dimensional to intensity-modulated radiation therapy (IMRT). Compliance with quality metrics proposed in national consensus guidelines and participation in clinical trials help keep practicing radiation oncologists up-to-date with advances in our field and well-trained to provide safe and effective high-value care.
Role of HER‐2 in Breast Carcinogenesis Link, Tina; Jain, Supriya; Lu, Allison ...
The FASEB journal,
April 2018, 2018-04-00, Letnik:
32, Številka:
S1
Journal Article
Recenzirano
Breast cancer has several defining prognostic and predictive markers, one of which is HER‐2. The Human Epidermal Growth Factor Receptor (HER‐2) is a protein which plays a role in cellular ...proliferation and cell survival. The solved structure revealed that the protein has an extracellular ligand binding domain. However, HER‐2 has no known ligand to bind to its active site. Consequently, its known function is to dimerize with its sister receptor (HER‐3) and initiate a cascade pathway for growth. The upregulation of the HER‐2 neu oncogene can result in the overexpression of HER‐2, causing a change in the ratio of HER‐2 to HER‐3 receptors. Because HER‐2 promotes cellular proliferation and survival, uncontrolled expression of this factor has major implications in carcinogenesis. About twenty percent of all breast cancers are diagnosed as HER‐2 positive. Treatments to inhibit HER‐2 include ligand mimetics which bind to HER‐2, preventing its dimerization with HER‐3 and therefore stopping the uncontrolled cellular proliferation that would otherwise occur downstream. The FDA has approved several anti‐HER2 antibody therapies which have been used in combination with chemotherapy in the adjuvant and neoadjuvant setting. Trastuzumab (Herceptin) and Pertuzumab (Perjeta) are two anti‐HER2 antibodies which, in conjunction with chemotherapy, have resulted in improved outcomes for HER‐2 positive breast cancer patients. The Walton High School MSOE Center for BioMolecular Modeling SMART Team used 3‐D modeling and printing technology to examine the structure‐function relationship between HER‐2 as it relates to carcinogenesis.
This is from the Experimental Biology 2018 Meeting. There is no full text article associated with this published in The FASEB Journal.
Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare delayed hyperinflammatory response to SARS-CoV-2 infection and causes severe morbidity in the pediatric age group. Although ...MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic, and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6 to12 years, and specific racial or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurologic complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein—as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens—are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C vs both acute SARS-CoV-2 infection and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine-associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.
Le syndrome inflammatoire multisystémique de l’enfant (SIME) qui s’est révélé une réponse hyperinflammatoire tardive rare à l’infection SRAS-CoV-2 cause une morbidité grave chez les enfants. Bien que le SIME ait en commun plusieurs similarités cliniques avec la maladie de Kawasaki (MK), d’importantes différences dans les facteurs épidémiologiques, cliniques, immunologiques et potentiellement génétiques existent et suggèrent des différences potentielles dans la physiopathologie, et des points à explorer et à expliciter. Les caractéristiques épidémiologiques sont les suivantes : la prédominance masculine, le groupe d’âge le plus touché (de 6 à 12 ans), et les prédispositions raciales et ethniques particulières. Le SIME est caractérisé par de la fièvre, des symptômes gastro-intestinaux marqués, des manifestations mucocutanées, des symptômes respiratoires et des plaintes neurologiques, et les patients sont souvent en état de choc. Les complications cardiaques fréquentes sont les suivantes : la dysfonction ventriculaire, la régurgitation valvulaire, l’épanchement péricardique, la dilatation coronaire et les anévrismes, les anomalies de conduction et les arythmies. De nouvelles données probantes en ce qui concerne les mécanismes immunologiques potentiels suggèrent que la réponse excessive des cellules T à un superantigène sur la glycoprotéine spiculaire du SRAS-CoV-2 ainsi que la formation des autoanticorps contre les antigènes cardiovasculaires, gastro-intestinaux et endothéliaux sont les principaux facteurs qui contribuent au milieu inflammatoire du SIME. D’autres études sont nécessaires pour déterminer la ou les voies immunologiques partagées et distinctes qui sous-tendent la pathogenèse du SIME vs l’infection SRAS-CoV-2 et la MK. Des données probantes suggèrent que le rare risque de myopéricardite plus bénigne associée au vaccin à ARNm l’emporte sur la réduction du risque d’un SIME plus grave. Dans la présente revue, nous faisons la synthèse de la littérature publiée afin de décrire les facteurs associés et les mécanismes potentiels en ce qui concerne le risque accru de SIME et de complications cardiaques, donnons un aperçu de la physiopathologie immunologique sous-jacente et définissions les similarités et les différences avec la MK.
Abstract
Background
Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, ...receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM).
Methods
A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM.
Results
The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors—nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17–28 mo, P = 0.12; HER2, 15–19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27–18 mo, P = 0.02; HER2, 30–18 mo, P = 0.08).
Conclusions
Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly.
Key Points
1. Receptor discordance alters subtype in 32% of BCBM patients.
2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively.
3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment.
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