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Self-limited Rheumatoid Meningitis as a Presenting Symptom of Rheumatoid Arthritis.
Isr Med Assoc J. 2018 Apr;20(4):262-264
Authors: Finkelshtein V, Lampl Y, Lorberboym M, Kanner A, Ben-Ami Raichman D, Dabby R, Tanay A
PMID: 29629737 [PubMed - in process]
| Related Articles |
The Task Force for the Promotion of the Status of Women in Medicine in Israel.
Isr Med Assoc J. 2018 Apr;20(4):254-259
Authors: Borow M, Levi B, Carmi R
Abstract
BACKGROUND: In this article, we offer a brief summary of the report from the Task Force for the Promotion of the Status of Women in Medicine in Israel. The task force, formed by the Israel Medical Association in 2013, published a comprehensive report in May 2015 dedicated to the promotion of equal opportunities for female doctors in the Israeli healthcare system and in the academic world. The aim of this paper is to present the work of the task force and to highlight its main principles and recommendations against the backdrop of the gender revolution in the Israeli healthcare system and worldwide.
PMID: 29629735 [PubMed - in process]
| Related Articles |
Exercise Hemodynamics for the Diagnosis of Diastolic Dysfunction in Dyspneic Patients with Systemic Sclerosis.
Isr Med Assoc J. 2018 Apr;20(4):245-249
Authors: Graham Cummiskey A, Segev A, Segel M, Buber J, Guetta V, Barbash IM, Elian D, Asher E, Vaturi O, Fefer P
Abstract
OBJECTIVES: To assess the added diagnostic value of using exercise hemodynamics during RHC in assessment of patients with symptomatic SSc.
METHODS: We performed 22 RHCs in 17 SSc patients with dyspnea and/or pulmonary arterial hypertension (PAH). Exercise was performed in 15 RHCs using isotonic arm exercises while holding a 1 kg weight in each hand. Measurements of pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), and cardiac output (CO) were taken at rest and during peak exercise.
RESULTS: Normal resting RHC (PAP 22 3 mmHg, PAWP 11 3 mmHg) was found in seven cases. Of these, exercise induced elevation in PAP was found in three (38 7 mmHg), and exercise induced elevation in PAWP was found in four (24 6 mmHg). Elevated resting PAP was found in 15 (41 11 mmHg) with minor changes in exercise. Of the 22 RHCs, elevation of the PAWP was found in 11 (50%), half of which were in response to exercise.
CONCLUSIONS: In symptomatic SSc patients, exercise hemodynamics provides important information on diastolic dysfunction that is not available with non-invasive testing. Findings on exercise RHC can explain patient symptoms in up to 50% of cases. Earlier and more accurate diagnosis of patient symptoms can aid in tailoring the correct therapy for each.
PMID: 29629733 [PubMed - in process]
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Effect of Tocilizumab on Fatigue and Bone Mineral Density in Patients with Rheumatoid Arthritis.
Isr Med Assoc J. 2018 Apr;20(4):239-244
Authors: Abu-Shakra M, Zisman D, Balbir-Gurman A, Amital H, Levy Y, Langevitz P, Tishler M, Molad Y, Aamar S, Roser I, Avshovich N, Paran D, Reitblat T, Mader R, Savin H, Friedman J, Lieberman N, Ehrlich S
Abstract
BACKGROUND: Chronic fatigue is common among patients with rheumatoid arthritis (RA), affecting quality of life. Osteoporosis is a prevalent co-morbidity in RA patients.
OBJECTIVES: To assess the effect of long-term treatment with tocilizumab on fatigue and bone mineral density (BMD) in RA patients with inadequate response to synthetic or biologic disease-modifying anti-rheumatic drugs.
METHODS: In this multicenter, open-label, non-controlled, single-arm study, patients ≥ 18 years of age received intravenous tocilizumab 8 mg/kg every 4 weeks for 96 weeks. The primary outcome was the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to weeks 24, 48, 72, and 96. BMD was assessed before and 96 weeks after treatment.
RESULTS: The study comprised 145 patients (mean age 53.4 ± 13.4 years, 83.4% women). Of these, 88 (60.7%) completed the 2 year treatment period. The mean FACIT-Fatigue score improved consistently starting from week 4 and showed a statistically significant increase of 5.0 ± 9.7, 6.8 ± 10.5, 7.3 ± 10.9, and 7.3 ± 10.4 from baseline to weeks 24, 48, 72, and 96, respectively (P < 0.0001). Mean BMD of femoral neck and total spine remained stable. Disease activity, acute phase reactants, and composite efficacy measures decreased during the study, while hemoglobin levels increased. Adverse events and serious adverse events were as expected for the known and previously described data.
CONCLUSIONS: Tocilizumab therapy for 2 years significantly and clinically decreased fatigue. BMD remained stable and no new safety issue was reported.
PMID: 29629732 [PubMed - in process]
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The Effect of Mineralocorticoid Receptor Antagonists on Recruitment and Function of Endothelial Progenitor Cells in Patients with Congestive Heart Failure.
Isr Med Assoc J. 2018 Apr;20(4):233-238
Authors: Levi A, Leshem-Lev D, Weissler-Snir A, Hasin T, Mats I, Murninkas D, Kornowski R, Lev EI, Ben-Gal T
Abstract
BACKGROUND: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor.
OBJECTIVES: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure.
METHODS: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability.
RESULTS: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline.
CONCLUSIONS: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.
PMID: 29629731 [PubMed - in process]
| Related Articles |
Depression Among Older Adults with Diabetes in Israel: Pattern of Symptoms and Risk Factors.
Isr Med Assoc J. 2018 Apr;20(4):222-226
Authors: Bashkin O
PMID: 29629729 [PubMed - in process]
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The Impact of Drug Metabolism Gene Polymorphisms on Therapeutic Response and Survival in Diffuse Large B-Cell Lymphoma Patients.
Isr Med Assoc J. 2018 Apr;20(4):217-221
Authors: Pál I, Illés Á, Gergely L, Pál T, Radnay Z, Szekanecz Z, Zilahi E, Váróczy L
Abstract
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of all non-Hodgkin lymphomas (NHL) and 80% of agressive lymphomas. Besides the traditional International Prognostic Index (IPI), some other factors may also influence the prognosis of DLBCL patients.
OBJECTIVES: To study how the genetic polymorphisms in the metabolic pathway influence the event-free and overall survivals and therapeutic responses in DLBCL.
METHODS: The study was comprised of 51 patients (32 men, 19 women). The average age was 53.1 years. DLBCL was diagnosed between 2011 and 2016 and the average follow-up time was 3.78 years. These patients received 1-8 cycles (an average of 6.2 cycles) of rituximab, cyclophosphamide, doxorubicin, vincristin, prednisolon (R-CHOP) immunochemotherapy. Real-time polymerase chain reaction was used to determine the genetic polymorphisms of CYP2E1, GSTP1, NAT1, and NAT2 genes.
RESULTS: Our results showed that the polymorphisms of CYP2E1, GSTP1, and NAT1 genes did not influence the prognosis of DLBCL patients significantly. In terms of the NAT2 gene, GG homozygous patients showed slightly better therapeutic response and survival results compared to those bearing an A allele; however, the differences were not statistically significant.
CONCLUSIONS: Our results could not confirm that genetic polymorphism in metabolic pathways has any predictive role in DLBCL.
PMID: 29629728 [PubMed - in process]
| Related Articles |
The Association of an Elevated Thrombocyte Count with Clinicopathological Prognostic Factors and Survival in Patients with Uterine Carcinosarcoma.
Isr Med Assoc J. 2018 Apr;20(4):213-216
Authors: Menczer J, Elyashiv O, Ben-Shem E, Peled O, Levy T
Abstract
BACKGROUND: Uterine carcinosarcoma (UCS) is a rare tumor with a poor prognosis. An elevated thrombocyte count and thrombocytosis were found to be associated with poor prognosis in several gynecological tumors. Data regarding an elevated thrombocyte count and thrombocytosis, particularly in UCS, are scarce.
OBJECTIVES: To assess the frequency of a preoperative elevated thrombocyte count and of thrombocytosis in UCS patients and their association with clinicopathological prognostic factors and survival.
METHODS: The preoperative thrombocyte count of 29 consecutive verified USC patients diagnosed in our medical center from January 2000 to July 2015 was recorded, and clinicopathological data of these patients were abstracted from hospital files.
RESULTS: Thrombocytosis was found in two patients (6.8 %) and both died of the disease. An elevated thrombocyte count was found in nine patients (31.0%). The percentage of patients with the poor prognostic factors who had a preoperative elevated thrombocyte count was not statistically different from those without these risk factors. The cumulative survival of patients with an elevated count was 22.1 months and that of those without an elevated count was 31.1 months. This difference was statistically not significant (P = 0.85). There was also no difference between the groups regarding the progression free survival.
CONCLUSIONS: No association between an elevated thrombocyte count and prognosis was found. Larger studies are needed to clarify this issue.
PMID: 29629727 [PubMed - in process]
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The Significance of Routine Computer Tomography in Evaluation of Asymptomatic Postoperative War Trauma Patients Transferred from Syria for Further Treatment.
Isr Med Assoc J. 2018 Apr;20(4):211-212
Authors: Kakiashvili E, Mansour M, Weiss M, Barhoum M, Khatib K, Bickel A
PMID: 29629726 [PubMed - in process]
 | Related Articles |
Radiation protection measures: Implications on the design of neurosurgery operating rooms.
Neurocirugia (Astur). 2018 Apr 07;:
Authors: Delgado-López PD, Sánchez-Jiménez J, Herrero-Gutiérrez AI, Inclán-Cuesta MT, Corrales-García EM, Martín-Alonso J, Galacho-Harriero AM, Rodríguez-Salazar A
Abstract
OBJECTIVE: To describe pros and cons of some radiation protection measures and the implications on the design of a neurosurgery operating room.
MATERIAL AND METHODS: Concurring with the acquisition and use of an O-arm device, a structural remodeling of our neurosurgery operating room was carried out. The theater was enlarged, the shielding was reinforced and a foldable leaded screen was installed inside the operating room. Radiation doses were measured in front of and behind the screen.
RESULTS: The screen provides whole-body radiation protection for all the personnel inside the theater (effective dose <5μSv at 2,5 m from the gantry per O-arm exploration; 0,0μSv received behind the screen per O-arm exploration; and undetectable cumulative annual radiation dose behind the screen), obviates the need for leaded aprons and personal dosimeters, and minimizes the circulation of personnel. Enlarging the size of the operating room allows storing the equipment inside and minimizes the risk of collision and contamination. Rectangular rooms provide greater distance from the source of radiation.
CONCLUSION: Floor, ceiling and walls shielding, a rectangular-shaped and large enough theater, the presence of a foldable leaded screen, and the security systems precluding an unexpected irruption into the operating room during irradiation are relevant issues to consider when designing a neurosurgery operating theater.
PMID: 29636275 [PubMed - as supplied by publisher]
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Subdural hygroma secondary to rupture of an intracranial arachnoid cyst: description of 2cases and review of the literature.
Neurocirugia (Astur). 2018 Apr 04;:
Authors: García Romero JC, Ortega Martínez R, Zabalo San Juan G, de Frutos Marcos D, Zazpe Cenoz I
Abstract
The appearance of a subdural hygroma after the rupture of an arachnoid cyst wall is extremely rare, with very few cases described in the literature. Most cases are due to a traumatic cause. The therapeutic approach in symptomatic cases is controversial, with a current tendency toward conservative management initially. In those cases that require surgical treatment, multiple therapeutic options are available, with fenestration techniques being recommended as first-line treatment. We describe 2cases treated in our centre and review the literature.
PMID: 29627291 [PubMed - as supplied by publisher]
| Related Articles |
Delayed surgical site infection 2 years after cervical disk arthroplasty. Case report and literature review.
Neurocirugia (Astur). 2018 Apr 04;:
Authors: Rosselló A, Sanmillán JL, López-Obarrio L, Pelegrín I, Gabarrós A, Godino O
Abstract
Anterior cervical discectomy has a low non-mechanical complication rate. In our literature review, we found 7 cases of delayed surgical site infection. We report a case of cervical prevertebral abscess due to Propionibacterium acnes 2 years after discectomy and arthroplasty, with a beta-2-transferrin false positive test as a complementary highlighted finding. We discuss the diagnosis and etiology of this rare delayed infectious complication.
PMID: 29627290 [PubMed - as supplied by publisher]
| Related Articles |
Symptomatic delayed coil migration after balloon assisted embolization: An underreported adverse event?
Neurocirugia (Astur). 2018 Apr 03;:
Authors: Fonseca L, Najarro-Quispe R, Rodríguez-Hernández A, Torné R, Gándara-Sabatini D, Arikan F, Baños-Carrasco P
Abstract
Microsurgical clipping is still regarded as the gold-standard treatment for broad-neck intracranial aneurysms. New endovascular techniques like balloon or stent assisted coiling are quickly rising to the challenge and showing promising outcomes. As a result, broad-neck aneurysms are increasingly addressed by these techniques despite they have not been tested against clipping in a randomized controlled trial and long-term complications might be unknown yet. Intraprocedural coil migration has been well documented in the literature, but the same complication in a delayed fashion is scarcely reported. We present a case of delayed coil migration occurring after a balloon-assisted embolization of a wide-necked intracranial aneurysm and we perform a literature review for similar cases. We discuss how, despite seeming an extremely rare complication, with new endovascular techniques increasingly perceived as the safer option in any aneurysm, potential adverse events may become more frequent. Strategies proposed to address this developing scenario are also reviewed.
PMID: 29625853 [PubMed - as supplied by publisher]
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Frontoethmoidal encephalocele. Report of a case.
Neurocirugia (Astur). 2018 Mar 30;:
Authors: Horcajadas A, Palma A, Khalon BM
Abstract
Encephaloceles are uncommon in western countries and most cases are located in the occipital bone. Frontal encephaloceles may involve the ethmoid bone, nasal bones and/or the orbits. Surgical repair is complex and usually requires a multidisciplinary approach. The goal of the surgery is to reconstruct the normal anatomy, to achieve a good cosmetic repair and to avoid a cerebrospinal fluid leak. We present a case of a patient with a large congenital frontoethmoidal encephalocele. Autologous calvarian bone grafts were used to repair of encephalocele defect and for the reconstruction of the frontonasal area. The defect closure and the cosmetic result were satisfactory, and the only complication detected was the infection of a previously performed ventriculoperitoneal shunt. A description of the technique and a review of the literature are presented.
PMID: 29610064 [PubMed - as supplied by publisher]
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PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The organic matter existing in nature presents as a complex system of various substances. The humic fraction refers to the humic substances (HS) and consists of humic acids (HA), fulvic acids (FA), and humins, according to solubility in aqueous solution. The physical and chemical characteristics of HA, FA, and humins depend on many factors, among which is the type of original organic material. Two processes for the stabilization of organic materials are known worldwide: composting and vermicomposting. Cattle manure, rice straw, sugarcane bagasse, and vegetable wastes from leaves were the organic residues chosen for the composting and vermicomposting processes. In this study, the differences between the HS extracted from such composted and vermicomposted residues were evaluated. The so-extracted HS were evaluated by spectroscopy in the regions of infrared and ultraviolet-visible, and pyrolysis coupled with gas chromatography with mass spectrometric detection is applied. Thus, we expect that the results obtained here indicate which of the two processes is more efficient in the biotransformation of organic residues in a short period with respect to the HS content. It was also observed that the basic units of the humic fractions generated (although they presented different degrees of maturation) are the same. Altogether, the data reported here bring to light that the structures of the HS are very similar, differing in quantities. These results can still be extrapolated to several other raw materials, since the most variable organic matrices were used here to allow this data extrapolation. In addition, the process seems to lead to the formation of more aliphatic substances, counterpoising what is found in the literature.
Publication date: Available online 14 April 2018
Source:Trends in Cell Biology
Author(s): Antonio Totaro, Martina Castellan, Daniele Di Biagio, Stefano Piccolo
How the behavior of cells in living tissues is orchestrated according to tissue needs, size, and developmental stage is still poorly understood. Advances in these directions are essential to understand morphogenesis, 'self-organization' phenomena, to build new tissues for regenerative medicine or to reverse the changes in deranged organs, such as in cancer or in genetic disorders. This review outlines a new scenario by which the crosstalk between the Yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) transcription factors and Notch signaling influences cell self-renewal, stem cell differentiation, cell fate decisions, epithelial–stromal interactions, inflammation, morphogenesis, and large-scale gene oscillations.
https://ift.tt/2HomB6Z
The interleukin (IL)-1 pathway has been identified as being involved in inflammatory and neoplastic skin diseases such as psoriasis, atopic dermatitis, neutrophilic dermatosis, melanoma, and squamous cell carcinoma. Drugs developed to target the IL-1 pathway are currently used to treat these pathologies, and although they are becoming more selective, they are not exempt from adverse events and high costs. Integrating the best research evidence with clinical experience and patient needs has been shown to improve care, health, and cost outcomes. This is because evidence-based guidelines rank interventions according to cost-effectiveness. However, evidence on this topic is scarce for several reasons. First, although randomized clinical trials currently provide the best evidence, they are not always available. Second, there are no secondary scientific studies that summarize the use of IL-1-targeting agents in dermatology. We therefore sought to develop an a priori protocol for broadly reviewing the available evidence on the use of IL-1-targeting drugs in the treatment of dermatological diseases.
We used the latest methodology to perform a scoping review as described in the Joanna Briggs Institute manual.
Developing and applying a methodology for evidence synthesis promotes reproducibility and increases the validity of secondary scientific investigations, making it the optimal strategy for scientifically synthesizing a broad field such as the indications for and the mechanisms of action, efficacies, safety, and costs of IL-1-targeting drugs in the treatment of dermatological diseases. Quantitative synthesis facilitates the detection of knowledge gaps and the identification of new questions that can be addressed through systematic reviews. We present an a priori protocol for exploring the available evidence on this topic.
Publication date: Available online 14 April 2018
Source:The Journal of Emergency Medicine
Author(s): Adam D. Laytin, Martha Shumway, Alicia Boccellari, Catherine J. Juillard, Rochelle A. Dicker
BackgroundMental illness, substance abuse, and poverty are risk factors for violent injury, and violent injury is a risk factor for early mortality that can be attenuated through hospital-based violence intervention programs. Most of these programs focus on victims under the age of 30 years. Little is known about risk factors or long-term mortality among older victims of violent injury.ObjectivesTo explore the prevalence of risk factors for violent injury among younger (age < 30 years) and older (age 30 ≥ years) victims of violent injury, to determine the long-term mortality rates in these age groups, and to explore the association between risk factors for violent injury and long-term mortality.MethodsAdults with violent injuries were enrolled between 2001 and 2004. Demographic and injury data were recorded on enrollment. Ten-year mortality rates were measured. Descriptive analysis and logistic regression were used to compare older and younger subjects.ResultsAmong 541 subjects, 70% were over age 30. The overall 10-year mortality rate was 15%, and was much higher than in the age-matched general population in both age groups. Risk factors for violent injury including mental illness, substance abuse, and poverty were prevalent, especially among older subjects, and were each independently associated with increased risk of long-term mortality.ConclusionMental illness, substance abuse, and poverty constitute a "lethal triad" that is associated with an increased risk of long-term mortality among victims of violent injury, including both younger adults and those over age 30 years. Both groups may benefit from targeted risk-reduction efforts. Emergency department visits offer an invaluable opportunity to engage these vulnerable patients.
https://ift.tt/2Hi7CMb
The aim of this article is to conduct an overview of the current state of knowledge about patients presenting anti-Nmethyl- D-aspartate receptor encephalitis associated with neoplastic process, as well as diagnosis and treatment. This disease concerns mainly young women and correlates with ovarian teratoma. Most important problems seems to be the difficulties in making a proper diagnosis ensuing from the rarity of this syndrome, the period from the appearance the first symptoms to starting treatment and the correct handling of intensive care complications. There are only a few articles describing severe, complicated cases of this type of encephalitis, requiring treatment in an intensive care unit.
https://ift.tt/2HldZOJ
Background: Stress hyperglycaemia is thought to result from a hormonal response (release of catecholamines,
glucocorticoids, glucagon, etc.) following stress, sepsis or trauma. Although stress hyperglycaemia is a very common
finding in critically ill populations, there are many non-diabetic critically ill patients who do not develop a hyperglycaemic
stress response to trauma or acute illness. We suggest that the lack of a hyperglycaemic stress response
during the acute phase of a critical illness may correlate significantly with the clinical outcome of these critically ill
non-diabetic patients.
Methods: This was a retrospective study of 700 non-diabetic critically ill patients admitted to the general intensive
care unit (ICU) at Soroka Medical Center, Beer Sheva, Israel. We analyzed the clinical impact of the blood glucose levels
of these patients measured during their first week of ICU hospitalization on their clinical outcome.
Results: Age, male gender, and the Acute Physiology and Chronic Health Evaluation (APACHE) score were found to
be independent risk factors for new episodes of infection during the patients' stay in the ICU. Age and the APACHE
and Sequential Organ Failure Assessment scores were found to be independent risk factors for intra-ICU mortality. In
contrast, blood glucose analysis performed during the patients' stay in the ICU was not found to be an independent
predictor for new infectious events or for mortality during the ICU stay.
Conclusion: Our study did not demonstrate an association between blood glucose levels and clinical outcomes in
non-diabetic critically ill patients.
Background: Currently, most critical care physicians maintain a patient's haemoglobin levels at 7 to 8 g dL-1. However,
little data have been available on haemoglobin-related outcomes in burn patients. The purpose of this study was
to evaluate inpatients with greater than 20% total body surface area burns and the effects of haemoglobin below
8 g dL-1 on clinical outcomes.
Methods: This study included 70 patients with burns amounting to greater than 20% of total body surface area. Data
were retrospectively evaluated and included age, gender, adult respiratory distress syndrome presence, length of
intensive care unit stay, length of mechanical ventilation, days requiring vasopressors, renal insufficiency, positive
cultures/infections, cardiovascular complications, number of operations, inhalation injury, and mortality. Logistic
regression analyses that were adjusted for age, sex, and percent total body surface area were used to assess the
relationships between haemoglobin and multiple clinical outcomes. Odds ratios (OR) were estimated with 99%
confidence intervals (99% CI).
Results: Haemoglobin below 8 g dL-1 was associated with a need for vasopressors (OR = 2.17; 99% CI = 1.03–8.22).
Furthermore, haemoglobin below 8 g dL-1 was associated with higher positive wound (OR = 2.86; 99% CI = 1.00–34.40),
urine (OR = 4.63; 99% CI = 1.15–67.00), and lung cultures (OR = 2.24; 99% CI = 1.06–5.47). These associations largely
remained after controlling for blood transfusions.
Conclusions: Contrary to most other patient groups, burn patients with burns amounting to greater than 20% of
total body surface area and low haemoglobin levels were more likely to develop positive cultures in urine, wounds,
and the lung and require vasopressor treatment.
Publication date: Available online 9 April 2018
Source:Molecular Immunology
Author(s): Monika Raulf
We are now in the epoch of "molecular allergology" and numerous clinically relevant allergenic molecules are available improving the performance of in vitro allergen tests and allergen detection methods. This review is focusing on characterized occupational allergens and their implementation into the in vitro diagnosis for occupational allergy and in allergen detection methods.More than 400 occupational agents are identified and documented as being 'respiratory sensitizers', but currently only a limited number of them are characterized on the molecular level and available for routine diagnosis as native or recombinant allergens. One exception, however, is natural rubber latex (NRL) from Hevea brasiliensis still remaining an important occupational allergen source. Characterization of 15 NRL allergens led to the development of assays for the determination of allergen content of NRL materials and the implementation of component-resolved diagnosis (CRD) for specific IgE antibody measurement. Microarray or singleplex using recombinant or native allergens are reliable tools for NRL allergy diagnosis. In addition, NRL allergy is an excellent model for improving extract-based specific IgE measurement by amplification of NRL extract preparation with stable recombinant major allergen rHev b 5. Despite the many efforts to characterize the occupationally relevant wheat allergens for baker's asthma, the most frequently occurring forms of occupational asthma, the results are highly diverse. Wheat sensitization profiles of bakers showed great interindividual variability and no wheat allergen could be classified as the major allergen. For diagnosis of baker's asthma, a whole wheat extract is still the best option for specific IgE determination. But single wheat allergens might help to discriminate between wheat-induced food allergy, grass pollen allergy and baker's asthma. For workplace-related allergens like coffee, wood, soybean, seafood and moulds allergens are characterized and few of them are available, but their relevance for occupational sensitization routes should be verified in the further studies.
https://ift.tt/2qzEFAH
Publication date: May 2018
Source:International Journal of Surgery, Volume 53
Author(s): Hongdou Ding, Xiao Song, Linsong Chen, Xinlin Zheng, Gening Jiang
BackgroundThe status of citations can reflect the impact of a paper and its contribution to surgical practice. The aim of our study was to identify and review the 100 most-cited papers in general thoracic surgery.Materials and methodsRelevant papers on general thoracic surgery were searched through Thomson Reuters Web of Science in the last week of November 2017. Results were returned in descending order of total citations. Their titles and abstracts were reviewed to identify whether they met our inclusion criteria by two thoracic surgeons independently. Characteristics of the first 100 papers, including title, journal name, country, first author, year of publication, total citations, citations in latest 5 years and average citation per year (ACY) were extracted and analyzed.ResultsOf the 100 papers, the mean number of citations was 322 with a range from 184 to 921. 19 journals published the papers from 1956 to 2012. Annals of Surgery had the largest number (29), followed by Journal of Thoracic and Cardiovascular Surgery (22) and Annals of Thoracic Surgery (21). The majority of the papers were published in 2000s (48) and originated from United States of America (62). There were 65 retrospective studies, 13 RCTs and 11 prospective studies. Orringer MB and Grillo HC contributed 4 first-author articles respectively. There were 53 papers on esophagus, 36 on lung, 6 on pleura and 5 on trachea.ConclusionsOur study identified the most-cited papers in the past several decades and offered insights into the development and advances of general thoracic surgery. It can help us understand the evidential basis of clinical decision-making today in the area.
https://ift.tt/2vcRrLi
| Related Articles |
[Myasthenia gravis and its association with lymphoproliferative disorders: a case series].
Rev Med Chil. 2017 Dec;145(12):1626-1630
Authors: Cea G, Gallardo V A, Cabrera C ME
Abstract
Myasthenia gravis (MG) is a rare autoimmune disease of the neuromuscular junction. It is characterized by variable weakness and excessive fatigability of skeletal muscles. In the last few years, numerous reports have been published showing the association between autoimmune diseases, such as systemic erythematous lupus or rheumatoid arthritis, with lymphoid neoplasias. The association between MG and lymphoid neoplasia seems to be less frequent. To analyze this association we reviewed the MG patients in the Department of Neurology, Hospital Salvador of Santiago, Chile. During a three-year period we identified four patients who developed different lymphoproliferative disorders: two with B-cell lymphoma, one with chronic lymphocytic leukaemia and one plasmacytoma with an associated amyloidosis. The MG was generalized but mild, all cases classified as type IIa according to the definition proposed by the MG Foundation of America. The neoplasia appeared two to 36 years after the onset of MG. These cases provide additional evidence of the association between MG and lymphoproliferative disorders.
PMID: 29652962 [PubMed - in process]
 | Related Articles |
How we manage patients with Waldenström macroglobulinaemia.
Br J Haematol. 2018 Apr 10;:
Authors: Simon L, Baron M, Leblond V
Abstract
Waldenström macroglobulinaemia (WM) is a rare, indolent B-cell lymphoproliferative disorder characterized by cellular involvement in bone marrow and monoclonal IgM production. Symptoms can be related to cytopenias, tumoural involvement, or IgM-related disorders. Somatic mutations in the MYD88 gene have been described in the majority of WM cases. The mutation is responsible for a gain-of-function and induces activation of nuclear factor-κB, for DNA transcription and cell survival. It seems that MYD88 mutation is associated with better prognosis and better response to some treatment. Treatments are started when WM is symptomatic, following systematic biological and morphological assessments. Therapeutic choice depends on age, frailty and urgent efficacy need. In first line, the majority of patients are treated with monoclonal anti-CD20 antibody-based regimens combined with cytotoxic chemotherapy. Rituximab, cyclophosphamide and dexamethasone remain the most commonly used regimen with good safety. Nevertheless, increasing numbers of new drugs are becoming available or are in development. Proteasome inhibitors, such as bortezomib or carfilzmib, showed good and rapid responses. Bruton tyrosine kinase (BTK) inhibitor demonstrated excellent results and is now available for relapse/refractory disease or as first line for some patients. This review highlights the diagnostic procedures and therapeutic approaches in WM.
PMID: 29637541 [PubMed - as supplied by publisher]
| Related Articles |
Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity through Phospho-Erk1/2 pathway.
Biochem Biophys Res Commun. 2018 03 18;497(4):990-996
Authors: Sun P, Zhou X, He Y, Liu H, Wang Y, Chen Y, Li M, He Y, Li G, Li Y
Abstract
Histone deacetylase inhibitors (HDACi) manifest great potential for treatment of Burkitt's lymphoma (BL), an aggressive B-cell lymphoma. Epidermal growth factor receptor pathway substrate 8 (EPS8) is confirmed overexpressed and associated with poor prognosis in solid tumors and leukemia. However, EPS8 expression and the relationship between EPS8 and HDACi on BL remains obscure. Here, we hypothesized that trichostatin A (TSA), a pan-HDACi, could inhibit BL cells by downregulating EPS8. We demonstrated that TSA reduced cell viability, induced apoptosis and cell arrest at G0/G1. Mechanismly, TSA attenuated EPS8 and downstream Phospho-Erk1/2 pathway. Knockdown of EPS8 resulted in a significant reduction in cellular proliferation and suppressed Phospho-Erk1/2 pathway activity, particularly when combined with TSA. Conversely, overexpression of EPS8 rescued this phenomenon. Then we showed that the combination of TSA and Epirubicin had a more significant effect when compared with TSA or Epirubicin alone. Finally, knockdown of EPS8 and TSA had a synergistic suppression effect on BALB/c nude mice. In conclusion, this study reveals that TSA affects BL cells by suppressing Phospho-Erk1/2 pathway through downregulating EPS8.
PMID: 29462617 [PubMed - indexed for MEDLINE]
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Murine Gammaherpesvirus 68: A Small Animal Model for Gammaherpesvirus-Associated Diseases.
Adv Exp Med Biol. 2017;1018:225-236
Authors: Dong S, Forrest JC, Liang X
Abstract
Murine gammaherpesvirus 68 (MHV68) is a naturally occurring pathogen of murid rodents that is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). Viral, immunologic, and disease parameters following experimental infection of laboratory mice with MHV68 closely resemble what occurs during primary EBV infection of humans, which suggests that MHV68 infection of mice offers a small animal model to study in general the pathogenesis of gammaherpesvirus infections. Diseases elicited by MHV68 infection include lymphoproliferative diseases, idiopathic pulmonary fibrosis, and autoimmune diseases, ailments also associated with EBV infection of humans. Furthermore, MHV68 infection also is linked to the development of vasculitis, encephalomyelitis, and other disorders that resemble pathologies with viral and nonviral etiologies in humans. This review aims to provide an overview of MHV68-associated diseases in infected mice that may provide a model for understanding basic mechanisms by which similar diseases in humans occur and can be treated.
PMID: 29052141 [PubMed - indexed for MEDLINE]
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Development of Epstein-Barr Virus-related Primary Diffuse Large B-cell Lymphoma of the Central Nervous System in a Patient with Peripheral T-cell Lymphoma, Not Otherwise Specified after Mogamulizumab Treatment.
Intern Med. 2017 Oct 15;56(20):2759-2763
Authors: Tanaka H, Aoki H, Sugita Y, Shimizu R, Kiko K, Mochida H, Suzuki Y
Abstract
Mogamulizumab is a defucosylated humanized anti-CC chemokine receptor type 4 (CCR4) antibody that exerts an anti-tumor immune effect against various tumors through a suppressive effect on regulatory T-cells. We herein report a patient with peripheral T-cell lymphoma who developed Epstein-Barr virus (EBV)-related primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) after mogamulizumab therapy. Our experience should alert physicians to the possibility of the development of EBV-related CNS DLBCL in patients treated for primary lymphoma and suggests that the anti-tumor immune effect of mogamulizumab is ineffective for the prophylaxis of EBV-related lymphomas.
PMID: 28924126 [PubMed - indexed for MEDLINE]
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Regulation of Apoptosis during Flavivirus Infection.
Viruses. 2017 08 28;9(9):
Authors: Okamoto T, Suzuki T, Kusakabe S, Tokunaga M, Hirano J, Miyata Y, Matsuura Y
Abstract
Apoptosis is a type of programmed cell death that regulates cellular homeostasis by removing damaged or unnecessary cells. Its importance in host defenses is highlighted by the observation that many viruses evade, obstruct, or subvert apoptosis, thereby blunting the host immune response. Infection with Flaviviruses such as Japanese encephalitis virus (JEV), Dengue virus (DENV) and West Nile virus (WNV) has been shown to activate several signaling pathways such as endoplasmic reticulum (ER)-stress and AKT/PI3K pathway, resulting in activation or suppression of apoptosis in virus-infected cells. On the other hands, expression of some viral proteins induces or protects apoptosis. There is a discrepancy between induction and suppression of apoptosis during flavivirus infection because the experimental situation may be different, and strong links between apoptosis and other types of cell death such as necrosis may make it more difficult. In this paper, we review the effects of apoptosis on viral propagation and pathogenesis during infection with flaviviruses.
PMID: 28846635 [PubMed - indexed for MEDLINE]
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Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.
Oncotarget. 2017 Jul 04;8(27):44266-44280
Authors: Bilger A, Plowshay J, Ma S, Nawandar D, Barlow EA, Romero-Masters JC, Bristol JA, Li Z, Tsai MH, Delecluse HJ, Kenney SC
Abstract
EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.
PMID: 28574826 [PubMed - indexed for MEDLINE]
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Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research.
Arch Toxicol. 2017 Aug;91(8):2763-2780
Authors: Pelkonen O, Terron A, Hernandez AF, Menendez P, Bennekou SH, EFSA WG EPI1 and its other members
Abstract
Infant leukaemia (<1 year old) is a rare disease of an in utero origin at an early phase of foetal development. Rearrangements of the mixed-lineage leukaemia (MLL) gene producing abnormal fusion proteins are the most frequent genetic/molecular findings in infant B cell-acute lymphoblastic leukaemia. In small epidemiological studies, mother/foetus exposures to some chemicals including pesticides have been associated with infant leukaemia; however, the strength of evidence and power of these studies are weak at best. Experimental in vitro or in vivo models do not sufficiently recapitulate the human disease and regulatory toxicology studies are unlikely to capture this kind of hazard. Here, we develop an adverse outcome pathway (AOP) based substantially on an analogous disease-secondary acute leukaemia caused by the topoisomerase II (topo II) poison etoposide-and on cellular and animal models. The hallmark of the AOP is the formation of MLL gene rearrangements via topo II poisoning, leading to fusion genes and ultimately acute leukaemia by global (epi)genetic dysregulation. The AOP condenses molecular, pathological, regulatory and clinical knowledge in a pragmatic, transparent and weight of evidence-based framework. This facilitates the interpretation and integration of epidemiological studies in the process of risk assessment by defining the biologically plausible causative mechanism(s). The AOP identified important gaps in the knowledge relevant to aetiology and risk assessment, including the specific embryonic target cell during the short and spatially restricted period of susceptibility, and the role of (epi)genetic features modifying the initiation and progression of the disease. Furthermore, the suggested AOP informs on a potential Integrated Approach to Testing and Assessment to address the risk caused by environmental chemicals in the future.
PMID: 28536863 [PubMed - indexed for MEDLINE]
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A systematic approach for peptide characterization of B-cell receptor in chronic lymphocytic leukemia cells.
Oncotarget. 2017 Jun 27;8(26):42836-42846
Authors: Díez P, Ibarrola N, Dégano RM, Lécrevisse Q, Rodriguez-Caballero A, Criado I, Nieto WG, Góngora R, González M, Almeida J, Orfao A, Fuentes M
Abstract
A wide variety of immunoglobulins (Ig) is produced by the immune system thanks to different mechanisms (V(D)J recombination, somatic hypermutation, and antigen selection). The profiling of Ig sequences (at both DNA and peptide levels) are of great relevance to developing targeted vaccines or treatments for specific diseases or infections. Thus, genomics and proteomics techniques (such as Next-Generation Sequencing (NGS) and mass spectrometry (MS)) have notably increased the knowledge in Ig sequencing and serum Ig peptide profiling in a high-throughput manner. However, the peptide characterization of membrane-bound Ig (e.g., B-cell receptors, BCR) is still a challenge mainly due to the poor recovery of mentioned Ig.Herein, we have evaluated three different sample processing methods for peptide sequencing of BCR belonging to chronic lymphocytic leukemia (CLL) B cells identifying up to 426 different peptide sequences (MS/MS data are available via ProteomeXchange with identifier PXD004466). Moreover, as a consequence of the results here obtained, recommended guidelines have been described for BCR-sequencing of B-CLL samples by MS approaches.For this purpose, an in-house algorithm has been designed and developed to compare the MS/MS results with those obtained by molecular biology in order to integrate both proteomics and genomics results and establish the steps to follow when sequencing membrane-bound Ig by MS/MS.
PMID: 28467808 [PubMed - indexed for MEDLINE]
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Loss of thyroid hormone receptor interactor 13 inhibits cell proliferation and survival in human chronic lymphocytic leukemia.
Oncotarget. 2017 Apr 11;8(15):25469-25481
Authors: Zhou K, Zhang W, Zhang Q, Gui R, Zhao H, Chai X, Li Y, Wei X, Song Y
Abstract
BACKGROUND: The genetic regulation of apoptosis and cell proliferation plays a role in the growth of chronic lymphocytic leukemia (CLL), the most common form of leukemia in the Western hemisphere. Although thyroid hormone receptor interactors (TRIPs) are known to play roles in cell cycle, the potential involvement of the novel family member TRIP13 in CLL has not yet been investigated.
METHODS: Quantitative PCR (qPCR) was used to detect expression of TRIP13 in 36 CLL patients and 33 healthy donors CD19+ B cells. Loss-of-function (siRNA) assays were used to alter TRIP13 expression levels. The effect of TRIP13 on cell proliferation and apoptosis was measured by MTT, Annexin V-based flow cytometry and Caspase 3/7 activity assay. Affymetrix GeneChip and Ingenuity Pathway Analysis (IPA) were used to describe an overview of TRIP13 potential biological function and downstream pathways. Dual-luciferase reporter assay was performed to assess the promoting effect of c-MYC on TRIP13 transcription.
RESULTS: The qPCR data showed that TRIP13 is significantly over-expressed in CLL patients. Microarray analyses indicated that the biological function of TRIP13 in CLL is majorly cell apoptosis and cell proliferation associated. TRIP13 siRNA expressing cells exhibited a slower cell proliferation rate and underwent apoptosis compared with control cells. TRIP13 knockdown induced CLL cells apoptosis through PUMA independent of p53. TRIP13 up-regulation is induced by c-MYC dependent transcriptional activation.
CONCLUSION: Overall, our data suggest the bio-function of TRIP13 in CLL cell for the first time, and that this gene might be a therapeutic target for CLL.
PMID: 28424416 [PubMed - indexed for MEDLINE]
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High expression of miR-125b-2 and SNORD116 noncoding RNA clusters characterize ERG-related B cell precursor acute lymphoblastic leukemia.
Oncotarget. 2017 Jun 27;8(26):42398-42413
Authors: Vendramini E, Giordan M, Giarin E, Michielotto B, Fazio G, Cazzaniga G, Biondi A, Silvestri D, Valsecchi MG, Muckenthaler MU, Kulozik AE, Gattei V, Izraeli S, Basso G, Te Kronnie G
Abstract
ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL) subtype characterized by aberrant expression of DUX4 and ERG transcription factors, and highly recurrent ERG intragenic deletions. ERG-related patients have remarkably favorable outcome despite a high incidence of inauspicious IKZF1 aberrations.We describe clinical and genomic features of the ERG-related cases in an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan SNORD116 cluster.
PMID: 28415578 [PubMed - indexed for MEDLINE]
Publication date: 15 June 2018
Source:Materials & Design, Volume 148
Author(s): H. Niknam, A.H. Akbarzadeh, D. Rodrigue, D. Therriault
Inspired by natural materials like bamboo and the dentin-enamel junction of tooth, the concept of architected multi-directional functionally graded cellular materials (FGCMs) is introduced. These architected porous materials are made by assembling porous unit cells of dissimilar densities and cell topologies. To evaluate the potential of multi-directional FGCMs for improving the performance of lightweight structural elements, the mechanical properties of functionally graded cellular (FGC) plates are analyzed. For the numerical analyses, standard mechanics homogenization is used to predict the mechanical properties of cells with arbitrary superellipse voids. The homogenized effective properties along with finite element method and shear deformation theory are exploited to predict the mechanical responses of plates made of multi-directional FGCMs. Numerical results reveal substantial improvement in structural responses when FGCMs are appropriately used; e.g. 56% improvement in bending stiffness is found in an FGC rectangular plate compared to a cellular plate with the same weight and with uniform distribution of constitutive cells. Numerical results show that cell variation through the thickness of FGC plates is more effective on the structural responses than variation through the length or width. Finally, multi-objective optimization is implemented to show the maximum improvement achievable via architecture variation within FGC structures.
https://ift.tt/2GYiMGy
Publication date: 5 July 2018
Source:Materials & Design, Volume 149
Author(s): Hongyan Xu, Mohammad Karbalaei Akbari, Zhenyin Hai, Zihan Wei, Lachlan Hyde, Francis Verpoort, Chenyang Xue, Serge Zhuiykov
From the technical and design points of view, it is quite difficult to maintain the integrity of nano-films during the deposition process to fabricate practical devices based on ultra-thin semiconductor films. Thus, defect-free wafer-scaled development of ultra-thin quasi two-dimensional (2D) oxide semiconductor films represents serious challenges. Plasma-enhanced atomic layer deposition (PE-ALD) made it possible to fabricate ultra-thin MoO3 nano-films (4.6nm) over the wafer-scaled granular Au electrode. The detailed ALD recipe for ultra-thin MoO3 film was established and verified. The C12H30N4Mo and O2 plasma were used as Mo precursor and oxygen source, respectively. The growth of crystalline phases was observed when the ALD temperature of 250°C was employed. Higher ALD temperature resulted in an increase of growth rate over Au substrate (1.21Ǻ/cycle). The precise recipe design enabled the scalable fabrication of environmental sensors based on ultra-thin MoO3 films with precise thickness controllability. Electrochemical sensors based on the fabricated MoO3 nanostructures demonstrated reliable performance to hydrazine (N2H4) detection.
Publication date: 5 July 2018
Source:Materials & Design, Volume 149
Author(s): Yunyi Wu, Siu Wing Or
(Na0.85K0.15)0.5Bi0.5TiO3 (NKBT) multilayer thin films with different thicknesses of 100–700nm, corresponding to 2–14 layers with each layer of ~50nm thickness, are synthesized on Pt(111)/Ti/SiO2/Si substrates to form Pt/NKBT/Pt/Ti/SiO2/Si heterostructures using different spin-coating and annealing conditions in a modified aqueous sol-gel process. The multilayer thin films spin-coated by two steps (step 1/2) at 600/4000rpm for 6/30s and annealed at 700°C for 5min with a heating rate of 30°C/s show a dense, uniform, and continuous morphology as well as a pure perovskite structure with a rhombohedral–tetragonal phase transition at ~140°C and no preferential orientation in the heterostructures. Their structural and electromechanical properties exhibit consistent improvement trends with increasing thickness from 100 to 550nm (i.e., 2–11 layers). The 550nm-thick, 11-layer films demonstrate the best ferroelectric, dielectric, piezoelectric, and electric performance in terms of the highest remnant polarization, saturation polarization, dielectric constant, and effective piezoelectric constant of 18.3μC/cm2, 53.6μC/cm2, 463, and 64pm/V, as well as the lowest coercive field, dielectric loss tangent, and leakage current density of 116kV/cm, 0.057, and 27μA/cm2, respectively. The observed thickness-dependent improvement is explained by an interfacial passive layer effect where the motion of both 180° and non-180° domain walls is enhanced in the thicker multilayer thin films by weakening the influence of domain pinning in the interfacial passive layers between the multilayer thin films and the substrates.
Publication date: 5 July 2018
Source:Materials & Design, Volume 149
Author(s): Bin Zhang, Yuping Duan, Yulong Cui, Guojia Ma, Tongmin Wang, Xinglong Dong
Mechanical milling and melting-strip casting-milling have been used to prepare FeCoNiSi0.4Al0.4 high entropy alloy (M-HEA and C-HEA respectively) powders. Both techniques have different solution and phase formation rules. The M-HEA powders have more FCC, and the opposite is true for C-HEA powders. In addition, the C-HEA powders have better elemental uniformity and a larger aspect ratio. Because of this, the C-HEA powders have a smaller Ms and a larger Hc; the Ms range from 93.6emu/g to 104.4emu/g, and the Hc vary from 81.5Oe to 159.6Oe. As the milling time increases, the variety of aspect ratios and uniformity give rise to the change of electromagnetic (EM) parameters for both HEA powders. Versus the EM parameters of M-HEA powders (ranging from 7.5 to 16 and from 0 to 1.4 for ε' and ε", respectively), these C-HEA powders have larger values (ranging from 11 to 26 and from 0 to 8 for ε' and ε", respectively). At the same time, the μ' (varying from 1.78 to 1.90 at 2GHz) and the μ″ (up to 0.52) of C-HEA powders are larger than the M-HEA powders.
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Thyroidosis Mistaken for Thyroid Cancer.
JAMA Otolaryngol Head Neck Surg. 2018 Apr 05;:
Authors: Crawford AR, Martinez-Lage M, Kim CS
PMID: 29621377 [PubMed - as supplied by publisher]
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Survival Outcomes for Patients With T3N0M0 Squamous Cell Carcinoma of the Glottic Larynx.
JAMA Otolaryngol Head Neck Surg. 2018 Apr 05;:
Authors: D'Ascanio L, Piazza F
PMID: 29621368 [PubMed - as supplied by publisher]
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A Child's Complaint of "Throat Freeze"-Not Brain Freeze-and Experiences With Zenker Diverticulum.
JAMA Otolaryngol Head Neck Surg. 2018 Apr 05;:
Authors: Wiebe DJ
PMID: 29621364 [PubMed - as supplied by publisher]
Wenn Ärzte medizinisch nicht gerechtfertigte Wünsche und Forderungen ihrer Patienten ablehnen, bleibt dies mitunter nicht ohne Folgen: Die Enttäuschten sind mit der Behandlung unzufrieden — und kommunizieren dies auch per Mundpropaganda. Mit ein wenig diplomatischem Geschick lassen sich Frustrationen aber oft vermeiden.
Das neue Mutterschutzgesetz ist zum 1. Januar in Kraft getreten. Es gibt einige Detailänderungen, die Praxisinhaber kennen sollten, sonst droht Ärger — inklusive Bußgeldern.
Ärztliche Befundberichte und Briefe sind im gesamten Behandlungsfall nicht neben den üblichen Pauschalen berechnungsfähig. Somit gilt in vielen Praxen der Grundsatz, dass Briefe und Befundberichte prinzipiell nicht berechnungsfähig sind. Ein fataler Irrtum.
Das genetische Tumorprofil bietet bei rezidivierten Speicheldrüsenkarzinomen neben der Histologie wichtige Informationen zum Tumortyp und eröffnet neue Wege für den Einsatz von zielgerichteten Therapien. Dies zeigen Ergebnisse einer aktuellen Untersuchung.
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High-resolution MRI of the inner ear enables syndrome differentiation and specific treatment of cerebellar downbeat nystagmus and secondary endolymphatic hydrops in a postoperative ELST patient.
J Neurol. 2018 Apr 11;:
Authors: Kirsch V, Ertl-Wagner B, Berman A, Gerb J, Dieterich M, Becker-Bense S
PMID: 29644399 [PubMed - as supplied by publisher]
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Gestational Obstructive Sleep Apnea: Biomarker Screening Models and Lack of Postpartum Resolution.
J Clin Sleep Med. 2018 Mar 30;:
Authors: Street LM, Aschenbrenner CA, Houle TT, Pinyan CW, Eisenach JC
Abstract
STUDY OBJECTIVES: To measure prevalence and severity of third trimester obstructive sleep apnea and evaluate postpartum resolution. To assess a novel biomarker for screening for obstructive sleep apnea in pregnancy.
METHODS: This prospective observational study was performed at Wake Forest School of Medicine obstetrics clinics between April 2014 and December 2015. Fractional exhaled nitric oxide measurements and sleep studies were obtained and compared at 32 0/7 to 35 6/7 weeks gestation and postpartum. Exhaled nitric oxide and risk factors for the development of gestational sleep apnea were evaluated for predictive ability independently and in screening models.
RESULTS: Of 76 women enrolled, 73 performed valid sleep studies in pregnancy and 65 had an additional valid study 6 to 15 weeks postpartum. Twenty-four women (37%) had gestational sleep apnea compared with 23 (35%) with postpartum sleep apnea (P> .99). Eight of 11 women (73%) retested 6 to 8 months postpartum had persistent sleep apnea. Exhaled nitric oxide had moderate discrimination screening for sleep apnea in pregnancy (area under the receiver operating characteristic curve = 0.64). A model utilizing exhaled nitric oxide, pregnancy-specific screening, and Mallampati score improved ability to identify women at risk for gestational sleep apnea (sensitivity = 46%, specificity = 91% and likelihood ratio = 5.11, area under receiver operating characteristic curve = 0.75).
CONCLUSIONS: Obstructive sleep apnea is common in the early postpartum period and often persisted at least 6 months. Exhaled nitric oxide as a sole biomarker to screen for sleep apnea in pregnancy has only modest discrimination. Combined with additional parameters sensitivity and specificity improved.
CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Identifier: NCT02100943, Title: Exhaled Nitric Oxide as a Biomarker of Gestational Obstructive Sleep Apnea and Persistence Postpartum, URL: https://ift.tt/2HCeamq.
PMID: 29609706 [PubMed - as supplied by publisher]
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Bispecific antibodies in haematological malignancies.
Cancer Treat Rev. 2018 Apr 04;65:87-95
Authors: Viardot A, Bargou R
Abstract
Bispecific antibodies (bsAbs) combine the binding sites of two monoclonal antibodies in one molecule. The close proximity of a tumor specific antigen and an effector cell antigen results in a targeted activation of effector cells. The mechanism is similar to the chimeric antigen receptor (CAR) T-cells, recently approved in two haematologic cancers. CAR T-cells and bsAb represent the most powerful tools for major-histocompatibility complex (MHC) independent T-cell immune response against cancer. In contrast to CAR T-cells, bsAbs are "off the shelf" drugs. As a drawback, the efficacy is dependent on a prolonged application. More than 40 years of intensive research generate a plethora of bispecific constructs with a remarkable difference in manufacturability, stability, half-life time and receptor affinity. Blinatumomab was the first approved bsAb in relapsed and refractory acute lymphoblastic leukemia. By the mature experience of blinatumomab in more than 10 clinical trials over more than one decade, we learned some lessons on how to use this new principle. The efficacy is higher in patients with less tumor burden, suggesting the use as consolidation more than for initial debulking. Main resistance mechanisms are extramedullary relapses and the expression of the inhibitory PD-L1 molecule, suggesting the value of combination with checkpoint inhibitors. CD19 loss is infrequent after blinatumomab, preserving the option for alternative CD19-direct treatments. New bsAbs in lymphoma, myeloma and acute myeloid leukemia enter phase-I trials, together with many new constructs in solid cancer.
PMID: 29635163 [PubMed - as supplied by publisher]
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Outlooks on Epstein-Barr virus associated gastric cancer.
Cancer Treat Rev. 2018 Mar 31;66:15-22
Authors: Naseem M, Barzi A, Brezden-Masley C, Puccini A, Berger MD, Tokunaga R, Battaglin F, Soni S, McSkane M, Zhang W, Lenz HJ
Abstract
Epstein-Barr virus associated gastric cancer (EBVaGC) comprises approximately 10% of gastric carcinomas. Multiple factors contribute to tumorigenesis, including EBV driven hypermethylation of tumor suppressor genes, inflammatory changes in gastric mucosa, host immune evasion by EBV and changes in cell cycle pathways. The unique molecular characteristics of EBVaGC, such as programmed death ligand 1 (PD-L1) overexpression, highlight the potential for using EBV as a biomarker for response to immunotherapy. Few studies have reported benefit from immunotherapy in EBV positive cancers, and clinical trials investigating the impact of checkpoint inhibitors in EBVaGC are currently underway. This review provides the most recent updates on molecular pathophysiology, epidemiology, clinical features and treatment advances pertaining to EBVaGC.
PMID: 29631196 [PubMed - as supplied by publisher]
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NUT Carcinoma of the Salivary Glands: Clinicopathologic and Molecular Analysis of 3 Cases and a Survey of NUT Expression in Salivary Gland Carcinomas.
Am J Surg Pathol. 2018 Apr 11;:
Authors: Agaimy A, Fonseca I, Martins C, Thway K, Barrette R, Harrington KJ, Hartmann A, French CA, Fisher C
Abstract
NUT carcinoma (NC) represents a rare subset of highly aggressive poorly differentiated carcinomas characterized by rearrangement of the NUT (aka NUTM1, nuclear protein in testis) gene, most commonly fused to BRD4. Originally described as a mediastinal/thymic malignancy, NC has been reported at a variety of anatomic regions including the upper and lower aerodigestive tract. To date, only 7 NC cases of probable salivary gland origin have been reported. We herein describe 3 new cases (all affecting the parotid gland) in 2 women (39- and 55-y old) and 1 man (35-y old). Histologic examination showed poorly differentiated neoplasms composed of poorly cohesive small-sized to medium-sized cells with variable squamoid cell component that was focal and abrupt. Immunohistochemistry showed uniform expression of p63 and distinctive punctate expression of the NUT antigen in the tumor cell nuclei. Review of the reported salivary gland NC cases (total, 10) showed a male:female ratio of 1.5:1 and an age range of 12 to 55 years (median, 29 y). Site of the primary tumor was the parotid (7), sublingual (2), and submandibular (1) glands. All presented as rapidly growing masses treated by surgery followed by adjuvant radiotherapy/chemotherapy. Initial nodal status was positive in 8/10. At last follow-up (1 to 24 mo; median, 5 mo), 7/10 patients died of disease at a median of 5.5 months (1 to 24 mo) and only 2 were disease free at 7 and 14 months. Of 9 cases with genetic data, the fusion partner was BRD4 (n=7), non-BRD4/3 (n=1), or undetermined (n=1). None of 306 carcinomas spanning the spectrum of salivary carcinoma types screened by NUT immunohistochemistry was positive. This is the first small series on salivary NC highlighting the importance to include this rare disease in the differential diagnosis of poorly differentiated salivary gland carcinomas and in cases of presumable poorly differentiated carcinoma of unknown origin.
PMID: 29649019 [PubMed - as supplied by publisher]
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FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer.
Mol Cancer. 2017 Jul 17;16(1):124
Authors: Yang S, Liu Y, Li MY, Ng CSH, Yang SL, Wang S, Zou C, Dong Y, Du J, Long X, Liu LZ, Wan IYP, Mok T, Underwood MJ, Chen GG
Abstract
BACKGROUND: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC).
METHODS: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results.
RESULTS: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial-mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction.
CONCLUSIONS: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.
PMID: 28716029 [PubMed - indexed for MEDLINE]
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Dose-Modifying Factor of Radiation Therapy with Concurrent Cisplatin Treatment in HPV-Positive Squamous Cell Carcinoma: A Preclinical Study.
Radiat Res. 2018 Apr 13;:
Authors: Prevc A, Kranjc S, Cemazar M, Todorovic V, Zegura B, Novak M, Filipic M, Flezar MS, Kirbis IS, Rotter A, Brozic A, Zakelj MN, Poljak M, Hosnjak L, Groselj B, Strojan P, Sersa G
Abstract
Human papillomavirus (HPV) is an important etiological factor in oropharyngeal squamous cell carcinoma (SCC). Compared to HPV-negative tumors, HPV-positive oropharyngeal SCC has shown a better response to nonsurgical treatments. In this study, we determined the dose-modifying factors for HPV-positive tumors with single-dose irradiation, with or without low radiosensitizing doses of cisplatin. In vitro, we determined an increased radiosensitivity of HPV-positive SCC, which might be a consequence of HPV-induced changes in the cell cycle regulation and DNA damage response, leading to increased cell death. Additionally, compared to HPV-negative tumors, 30% higher radiosensitivity of HPV-positive tumors was determined by tumor growth delay monitoring in immunodeficient mice in vivo. Concurrent cisplatin treatment had an additive effect in both HPV-negative and HPV-positive tumors, resulting in 20% better response in HPV-positive tumors than in HPV-negative tumors.
PMID: 29652621 [PubMed - as supplied by publisher]
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NASA GeneLab Project: Bridging Space Radiation Omics with Ground Studies.
Radiat Res. 2018 Apr 13;:
Authors: Beheshti A, Miller J, Kidane Y, Berrios D, Gebre SG, Costes SV
Abstract
Accurate assessment of risks of long-term space missions is critical for human space exploration. It is essential to have a detailed understanding of the biological effects on humans living and working in deep space. Ionizing radiation from galactic cosmic rays (GCR) is a major health risk factor for astronauts on extended missions outside the protective effects of the Earth's magnetic field. Currently, there are gaps in our knowledge of the health risks associated with chronic low-dose, low-dose-rate ionizing radiation, specifically ions associated with high (H) atomic number (Z) and energy (E). The NASA GeneLab project ( https://ift.tt/2uhRrnA ) aims to provide a detailed library of omics datasets associated with biological samples exposed to HZE. The GeneLab Data System (GLDS) includes datasets from both spaceflight and ground-based studies, a majority of which involve exposure to ionizing radiation. In addition to detailed information on radiation exposure for ground-based studies, GeneLab is adding detailed, curated dosimetry information for spaceflight experiments. GeneLab is the first comprehensive omics database for space-related research from which an investigator can generate hypotheses to direct future experiments, utilizing both ground and space biological radiation data. The GLDS is continually expanding as omics-related data are generated by the space life sciences community. Here we provide a brief summary of the space radiation-related data available at GeneLab.
PMID: 29652620 [PubMed - as supplied by publisher]
